Portable Infrared and Raman Spectrometers for On-Scene Analysis of Cocaine Raman Spectroscopy in Biomedicine Resonance Raman Spectroscopy Quo Vadis Raw Data?

December 2018 Volume 33 Number 12 www.spectroscopyonline.com

CORPORATE PROFILES ISSUE THE POWER OF INSIGHT

Introducing the NEW LAB SERVICES

Ocean Optics puts world-class facilities,

machine learning capabilities and

decades of expertise at your

service to take on your toughest

application challenges.

labservices.oceanoptics.com [email protected] • US +1 727-733-2447 • EUROPE +31 26-3190500 • ASIA +86 21-6295-6600 spie.org/pw2019

Attend the premier event for the photonics and laser industries

2–7 February 2019 · San Francisco, California, USA 4 Spectroscopy 33(12) December 2018 www.spectroscopyonline.com

MANUSCRIPTS: To discuss possible article topics or obtain manuscript preparation 485F US Highway One South, Suite 210 guidelines, contact the editorial director at: (732) 346-3020, e-mail: Laura.Bush@ Iselin, NJ 08830 ubm.com. Publishers assume no responsibility for safety of artwork, photographs, or (732) 596-0276 manuscripts. Every caution is taken to ensure accuracy, but publishers cannot accept Fax: (732) 647-1235 responsibility for the information supplied herein or for any opinion expressed. Michael J. Tessalone SUBSCRIPTIONS: For subscription information: Spectroscopy, P.O. Box 6196, Duluth, MN Vice President/Group Publisher 55806-6196; (888) 527-7008, 7:00 a.m. to 6:00 p.m. CST. Outside the U.S., +1-218-740-6477. [email protected] Delivery of Spectroscopy outside the U.S. is 3–14 days after printing. Single-copy price: Stephanie Shaffer U.S., $10.00 + $7.00 postage and handling ($17.00 total); Canada and Publisher Mexico, $12.00 + $7.00 postage and handling ($19.00 total); Other [email protected] international, $15.00 + $7.00 postage and handling ($22.00 total). Edward Fantuzzi CHANGE OF ADDRESS: Send change of address to Spectroscopy, P.O. Box 6196, Associate Publisher Duluth, MN 55806-6196; provide old mailing label as well as new address; include ZIP [email protected] or postal code. Allow 4–6 weeks for change. Alternately, go to the following URL for Michael Kushner address changes or subscription renewal: http://ubmsubs.ubm.com/?pubid=SPEC Senior Director, Digital Media RETURN ALL UNDELIVERABLE CANADIAN ADDRESSES TO: IMEX Global Solutions, P.O. Box [email protected] 25542, London, ON N6C 6B2, CANADA. PUBLICATIONS MAIL AGREEMENT No.40612608. Laura Bush REPRINT SERVICES: Reprints of all articles in this issue and past issues are available Editorial Director (500 minimum). Licensing and Reuse of Content: Contact our official partner, Wright’s [email protected] Media, about available usages, license fees, and award seal artwork at Advanstar@ John Chasse wrightsmedia.com for more information. Please note that Wright’s Media is the only Managing Editor authorized company that we’ve partnered with for Advanstar UBM materials. [email protected] C.A.S.T. DATA AND LIST INFORMATION: Contact Melissa Stillwell, (218) 740-6831; Jerome Workman, Jr. e-mail: [email protected] Senior Technical Editor INTERNATIONAL LICENSING: Jillyn Frommer, (732) 346-3007, [email protected] fax: (732) 647-1104; e-mail:[email protected] Cindy Delonas Associate Editor [email protected] Kristen Moore ecycled R Pa Webcast Operations Manager % p 0 e 5 r

[email protected]

0 e

- t 2 s

0 a % Vania Oliveira W r Po e st Consum Project Manager [email protected] Sabina Advani Digital Production Manager © 2018 UBM. All rights reserved. No part of this publication may be reproduced or transmit- [email protected] ted in any form or by any means, electronic or mechanical including by photocopy, recording, Kaylynn Chiarello-Ebner or information storage and retrieval without permission in writing from the publisher. Authori- Managing Editor, Special Projects zation to photocopy items for internal/educational or personal use, or the internal/educational [email protected] or personal use of specific clients is granted by UBM for libraries and other users registered Dan Ward with the Copyright Clearance Center, 222 Rosewood Dr. Danvers, MA 01923, 978-750-8400 Art Director fax 978-646-8700 or visit http://www.copyright.com online. For uses beyond those listed [email protected] above, please direct your written request to Permission Dept. fax 732-647-1104 or email: Brianne Pangaro [email protected]. Marketing Associate UBM Americas provides certain customer contact data (such as customers’ names, addresses, [email protected] phone numbers, and e-mail addresses) to third parties who wish to promote relevant products, Melissa Stillwell services, and other opportunities that may be of interest to you. If you do not want UBM Amer- C.A.S.T. Data and List Information icas to make your contact information available to third parties for marketing purposes, simply [email protected] call toll-free 866-529-2922 between the hours of 7:30 a.m. and 5 p.m. CST and a customer Thomas W. Ehardt service representative will assist you in removing your name from UBM Americas lists. Outside Executive Vice-President, Senior Managing Director the U.S., please phone 218-740-6477. UBM Life Sciences Group [email protected] Spectroscopy does not verify any claims or other information appearing in any of the adver- tisements contained in the publication, and cannot take responsibility for any losses or other Dave Esola damages incurred by readers in reliance of such content. VP & General Manager UBM Life Sciences Group Spectroscopy welcomes unsolicited articles, manuscripts, photographs, illustrations and [email protected] other materials but cannot be held responsible for their safekeeping or return. Jillyn Frommer To subscribe, call toll-free 888-527-7008. Outside the U.S. call 218-740-6477. Permissions [email protected] Jesse Singer UBM Americas (www.ubmamericas.com) is a leading worldwide media company providing Production Manager integrated marketing solutions for the Fashion, Life Sciences and Powersports industries. UBM [email protected] Americas serves business professionals and consumers in these industries with its portfolio Wendy Bong of 91 events, 67 publications and directories, 150 electronic publications and Web sites, as Audience Development Manager well as educational and direct marketing products and services. Market leading brands and a [email protected] commitment to delivering innovative, quality products and services enables UBM Americas to “Connect Our Customers With Theirs. UBM Americas has approximately 1000 employees and Morgan Hight Audience Support Analyst currently operates from multiple offices in North America and Europe. [email protected] www.spectroscopyonline.com December 2018 Spectroscopy 33(12) 5

v 33 n 12 CONTENTS d 2018 ® COLUMNS December 2018 Focus on Quality ...... 8 Volume 33 Number 12 Quo Vadis Raw Data? R.D. McDowall Regulatory definitions can be confusing, particularly when different agencies seem to contradict each other. But with some digging and clear thinking, we can sort out what the MHRA and FDA really mean by the term raw data, including both static and dynamic data.

Molecular Spectroscopy Workbench ...... 12 Exploring Resonance Raman Spectroscopy David Tuschel Resonance Raman spectroscopy offers a significant signal enhancement—up to 106 compared to normal Raman spectroscopy. Here, we explain how the two types of Raman differ, and illustrate the differences with examples.

Spectroscopy Spotlight The Rise of Raman Spectroscopy in Biomedicine ...... 26 Alasdair Matheson Raman spectroscopy is promising some dramatic breakthroughs in biomedical applications. Juergen Popp and his team are determined to realize that promise, by working to make the technique a powerful tool for cell biology and clinical studies.

Megan Thielges, the 2018 Emerging Leader in Molecular Spectroscopy, Cover image courtesy of Pioneers Protein Studies with 2D IR and Vibrational Probes ...... 30 Ildi/AdobeStock. Jerome Workman, Jr. The 2018 Award winner discusses her career challenges and her research on the use of specially engineered proteins, combined with 2D IR spectroscopy, for investigating protein function dynamics. ON THE WEB PEER-REVIEWED ARTICLE WEB SEMINARS A Comparison of Portable Infrared Spectrometers, Fast and Accurate Sugar, Acid, and Portable Raman Spectrometers, and Color-Based Field Tests Sulfite Analysis Using Automated for the On-Scene Analysis of Cocaine ...... 20 Discrete Analysis David Glutz, Thermo Fisher Scientific Dory Lieblein, Meghann E. McMahon, Pauline E. Leary, Peter Massey, and Brooke W. Kammrath On-scene analysis of illegal drugs is an essential tool for law enforcement. This study How to Streamline Implementation of ICP-MS for Regulated Water Analysis examines how portable IR and Raman spectroscopy compare to color-based tests for Ed McCurdy and Gregory Lecornet, Agilent cocaine identification in terms of accuracy, reliability, cost, and other practical considerations. Technologies

CORPORATE CAPABILITIES SERS Based Raman Module: Technology Overview including 2019 Corporate Capabilities ...... 33 Examples for Pharmaceutical and Law Enforcement Applications John Gilmore and Gary Spingarn, Hamamatsu DEPARTMENTS Hao Wang, Rutgers University News Spectrum ...... 6 Single Cell Mass Spectrometry: Calendar ...... 80 An Emerging Technique for Metabolomic and Metal Content Short Courses ...... 81 Analysis of Single Cells Chady Stephan, PhD, and David Price, PhD, PerkinElmer

Like Spectroscopy on Facebook: Spectroscopy (ISSN 0887-6703 [print], ISSN 1939-1900 [digital]) is published monthly by UBM LLC 131 West First Street, Duluth, MN 55802-2065. Spectroscopy is distributed free of charge to users and specifiers of spectroscopic equipment in the United States. www.facebook.com/SpectroscopyMagazine Spectroscopy is available on a paid subscription basis to nonqualified readers at the rate of: U.S. and possessions: 1 year (12 issues), Follow Spectroscopy on Twitter: $74.95; 2 years (24 issues), $134.50. Canada/Mexico: 1 year, $95; 2 years, $150. International: 1 year (12 issues), $140; 2 years (24 issues), https://twitter.com/spectroscopyMag $250. Periodicals postage paid at Duluth, MN 55806 and at additional mailing offices. POSTMASTER: Send address changes to Spec- troscopy, P.O. Box 6196, Duluth, MN 55806-6196. PUBLICATIONS MAIL AGREEMENT NO. 40612608, Return Undeliverable Canadian Join the Spectroscopy Group on LinkedIn Addresses to: IMEX Global Solutions, P. O. Box 25542, London, ON N6C 6B2, CANADA. Canadian GST number: R-124213133RT001. http://linkd.in/SpecGroup Printed in the U.S.A. 6 Spectroscopy 33(12) December 2018 www.spectroscopyonline.com News Spectrum

Stephen Cramer Receives EAS Award for biological systems and complex materials. Despite Outstanding Achievements in Vibrational heavy involvement with X-rays, vibrational spectroscopy Spectroscopy has remained dear to his heart. His favorite technique, nuclear resonance vibrational spectroscopy (NRVS), Stephen Cramer of the University of California, Davis merges these two field—a synchrotron x-ray experiment was presented with the EAS Award for Outstanding that provides vibrational information. His current Achievements in Vibrational Spectroscopy at the Eastern research emphasizes the enzymes that fix nitrogen Analytical Symposium (EAS), in Princeton, New Jersey, (nitrogenase) or produce hydrogen (hydrogenase). on November 13. Cramer is an advanced light source Cramer has been honored with the ACS Spectrochemical professor at UC Davis. Analysis Award, the Edward Stern Outstanding Achievement Cramer’s PhD thesis work under Keith Hodgson Award from the International X-Ray Absorption Society, the Lu involved the first extended X-ray absorption fine structure Jiaxi Lectureship from Xiamen University, the New York Society (EXAFS) studies of metalloenzymes at the newly founded for Applied Spectroscopy Gold Medal, a Humboldt Foundation Stanford Synchrotron Radiation Project, along with Raman Research Award, and an Einstein Visiting Fellowship at spectroscopy and coherent anti-stokes Raman spectroscopy TU-Berlin, and has been named an AAAS fellow. (CARS) with Bruce Hudson. Following work as a National Institutes of Health (NIH) postdoctoral researcher at California Igor K. Lednev Receives NYSAS for Applied Institute of Technology, Cramer joined Exxon Research Spectroscopy Gold Medal Award in New Jersey, followed by Schlumberger-Doll Research, The New York and New Jersey section of the Society for then continued to the National Synchrotron Light Source at Applied Spectroscopy (NYSAS) will present the Gold Medal Brookhaven National Laboratory. He then joined UC Davis in a Award to Igor K. Lednev at the Eastern Analytical Symposium joint position with the Lawrence Berkeley National Laboratory. (EAS), in Princeton, New Jersey, on November 12. Lednev is Cramer’s research has focused on synchrotron-based spectroscopic techniques for chemical characterization of Continued on page 32

MARKET PROFILE: MASS, MOLECULAR AND ATOMIC SPECTROSCOPY

Mass spectrometry, molecular North America, Europe and Ja- and atomic spectroscopy tech- Government Environmental, Food pan, and demand from emerg- nologies combine to represent & Academia & Other 22% ing markets, particularly China, more than a ﬁ fth of the overall 24% is driving growth for atomic market for laboratory analytical spectroscopy and mass spec- instrumentation. These tech- trometry instruments such as niques are perhaps the most ICP-MS, triple-quadrupole LC/ broadly used instruments, with MS and Orbitrap/FT-MS. utility in pharmaceuticals and Overall, the demand for spec- other life sciences, chemicals, troscopy instruments is expect- environmental, food, clinical/Dx Industrial 28% ed to ride its momentum into and other applications. Collec- Pharmaceutical & next year. It is expected meet tively, these three instrumenta- Biotechnology 26% modest headwinds from some tion sectors are categorized into slowing of production levels, 23 technologies that embody but overall unit shipments are 80+ different product types. 2018 spectroscopy market by application sector. expected to increase in 2019 In 2018, the market showed driven by continued growth from solid growth for industrial markets, which include chemicals, plastics/polymers, metals/minerals, semiconductor/electron- life science research, environmental/food testing and clinical ics and others. This sector represented the largest segment applications. TDA’s with about 28% market share. Pharmaceutical/biotechnol- Market size and growth estimates were adopted from Industry Data ogy labs and the public sector (academia and government , a database of technology market profiles and labs) combine for about half of the spectroscopy demand. benchmarks covering laboratory and process analytical in- The total market for spectroscopy instruments and related strumentation that are updated quarterly. It also includes products accounted for about $12.1 billion in 2017, and is data from the 2019 Instrument Industry Outlook report from on pace to increase eight percent in 2018. Demand was fu- independent market research firm Top-Down Analytics (TDA). eled by growth from environmental, food and applied markets, For more information, contact Glenn Cudiamat, general man- measured at about 22% of the market. Molecular spectros- ager, at (888) 953-5655 or [email protected]. copy techniques such as UV/Vis and IR techniques are ex- Glenn is a market research expert who has been covering the periencing strong growth from developed regions including analytical instrumentation industry for more than two decades. www.spectroscopyonline.com December 2018 Spectroscopy 33(12) 7 Editorial Advisory Board

Fran Adar Horiba Scientific Rachael R. Ogorzalek Loo University of California Los Angeles, David Geffen School of Medicine Russ Algar University of British Columbia Howard Mark Mark Electronics Matthew J. Baker University of Strathclyde R.D. McDowall McDowall Consulting Ramon M. Barnes University of Massachusetts Gary McGeorge Bristol-Myers Squibb Matthieu Baudelet University of Central Florida Linda Baine McGown Rensselaer Polytechnic Institute Rohit Bhargava University of Illinois at Urbana-Champaign Francis M. Mirabella Jr. Mirabella Practical Consulting Solutions, Inc. Paul N. Bourassa Blue Moon Inc. Ellen V. Miseo Illuminate Michael S. Bradley Thermo Fisher Scientific Michael L. Myrick University of South Carolina Deborah Bradshaw Consultant John W. Olesik The Ohio State University Lora L. Brehm The Dow Chemical Company Steven Ray State University of New York at Buffalo George Chan Lawrence Berkeley National Laboratory Jim Rydzak Specere Consulting John Cottle University of California Santa Barbara Jerome Workman Jr. Biotechnology Business Associates Lu Yang National Research Council Canada David Lankin University of Illinois at Chicago, College of Pharmacy

Barbara S. Larsen DuPont Central Research and Development Spectroscopy’s Editorial Advisory Board is a group of distinguished individuals assembled to help the publication fulfill its editorial mission to promote the effec- Bernhard Lendl Vienna University of Technology (TU Wien) tive use of spectroscopic technology as a practical research and measurement tool. With recognized expertise in a wide range of technique and application areas, board members perform a range of functions, such as reviewing manuscripts, suggesting Ian R. Lewis Kaiser Optical Systems authors and topics for coverage, and providing the editor with general direction and feedback. We are indebted to these scientists for their contributions to the publication and to the spectroscopy community as a whole.

The widest range: The Spectroscopy Certiﬁed Deep UV to Infra-red Up to 3.5 Absorbance Specialists Reference NIST Traceable ISO 17034 Reference Materials for Material Producer ISO/IEC 17025 accredited supplier Pathlengths from 0.01mm to 100mm Instrument Lifetime Guarantee Fast Recalibration Service Volumes from 0.6ul to 35ml Meet all International Far UV & NIR Quartz Qualiﬁcation regulatory Standards Glass & Borosilicate

Starna Cells, Inc. StarnaSttarntarrnarnnan CCeCells,ellse s,sIs, InIInc.c.c PO Box 1919 Atascadero, CA 93423 PO BoxB 1919191 9A9 Atascadero,Atasascscs adeero,ro CAC 9342393334234234 3 Phone: (800) 228-4482 USA or (805) 466-8855 outside USA Phone:PhoPhne: (8(800)00) 228-4482 228 4482 USA USA or (805) 466466-8855 8855 outside t id USA [email protected] www.starnacells.com [email protected]@starnacells com wwwwww.starnacells.com starnacells com 8 Spectroscopy 33(12) December 2018 www.spectroscopyonline.com

Focus on Quality Quo Vadis Raw Data?

We revisit raw data following the publication by the UK’s regulatory agency of a new data integrity guidance, where the raw data definition contradicts that in the Good Laboratory Practice regulations. In addition, we discuss static and dynamic data, and examine the impact of these terms on raw data.

R.D. McDowall

aw data is a topic that I have previously discussed records in 21 CFR 211.194(a) (7). The conclusion was in this “Focus on Quality” column, and in my that all records generated during any analysis must be R“Questions of Quality” column in LCGC Europe included as complete data. There is a small clue to help since 1996. Let me give you a brief history of raw data your interpretation with the word complete. In August from my perspective. Then, we will discuss a recent 2016, the FDA published the proposed update to the ex- problem with the definition of raw data with the publi- isting Good Laboratory Practice (8) as the GLP Quality cation of the Medicines and Healthcare products Regu- System (9). This triggered my last discussion of raw data latory Agency (MHRA) of their new GXP data integrity in this column (10), partly because of this new proposed guidance. It raises the question: Where is the definition regulation, but also because the European Union (EU) of raw data going? GMP Chapter 4 on documentation uses the term raw data, but fails to define it (11). Chapter 4 is currently In the Beginning being revised with Annex 11 to reinforce data integrity My first column on raw data, published in December 1996, principles (12). argued that electronic records and not paper printouts from a computerized system were raw data (1). Unfor- Original Raw Data Definition tunately, the timing was just before the publication of 21 Although used in GMP, raw data is a GLP term that was first CFR 11 on electronic records and electronic signatures (2). defined in the 1978 GLP regulations (8) in 21 CFR 58.3(k) as: I revisited the topic in 2000 and considered the impact of the new regulation, but reinforced the position that “any laboratory worksheets, records, memoranda, notes, or electronic records were the raw data rather than paper exact copies thereof, that are the result of original observations printouts (3). Twelve years later, the subject was discussed and activities of a nonclinical laboratory study, and are again (4) with the publication on the FDA’s web site of necessary for the reconstruction and evaluation of the report their explanation of why some in the pharmaceutical in- of that study.” [emphasis added] dustry misinterpret 21 CFR 11 regulations and state that paper printouts are their original records (5). On the web The key points from this definition are that raw data site, the FDA used clauses 211.68(b) and 211.180(d) of the consisted of: Good Manufacturing Practice (GMP) regulations (6) to • original observations state that paper printouts were not representative of the • all data generated, derived or interpreted from that electronic records, as printouts were not “exact and com- point forward to the report of the work plete,” nor “true copies,” respectively. There was much and that by implication, it should also be possible to trace a more information in the electronic records. result in the report back to the original observations. In this column, we have also considered an interpre- In the same column, we were able to equate and harmonize tation of the GMP term complete data for laboratory raw data with complete data. Quod erat demonstrandum! www.spectroscopyonline.com December 2018 Spectroscopy 33(12) 9

But a problem has arisen now with plicable regulations for laboratories In Appendix 2 of the glossary, there the publication of the MHRA GXP operating to Good Manufacturing is the following definition for data data integrity guidance (13). Practice are either EU GMP Parts 1 (raw data): and 2 and are applicable for regu- What’s the Problem? lated laboratories testing finished “The GLP Principles define raw The final version of the MHRA’s products, intermediates and raw data as all laboratory records and GXP data integrity guidance was materials or active pharmaceutical documentation, including data issued in March 2018 (13). This is products respectively. The issue of directly entered into a computer a much better presented and more a lack of raw data definition in EU through an automatic instrument rounded document than the draft GMP Chapter 4 on documentation interface, which are the results of from 2016 (14) and the two versions was discussed in the 2016 column primary observations and activities of the GMP document published in (10). For laboratories operating under in a study and which are necessary for 2015 (15,16). Good Laboratory Practice, the ap- the reconstruction and evaluation of In the new MHRA GXP guidance (13), plicable regulations enforced by the the report of that study.” raw data are defined in section 6.2 as: MHRA’s Good Laboratory Practice Monitoring Authority (GLPMA) are We have from this definition that “the original record (data) which can the Economic Co-operation and De- raw data consist of: be described as the first- capture of velopment (OECD) Principles of GLP • all laboratory records and docu- information, whether recorded on (OECD GLP) regulations and associ- mentation paper or electronically.” ated advisory documents. • data directly entered into a com- OECD Principles of Good Labora- puter through an automated inter- According to the MHRA, raw data tory Practice (17) define raw data in face only consists of the first-capture section 2.2.7 as: • results of primary observations and of information, and this equates to activities in a study original observations in United States “all original test facility records and • [data] necessary for the reconstruc- (US) GLP above (8). In the MHRA documentation, or verified copies tion and evaluation of the report. definition, there is no mention of: thereof, which are the result of the Notice the similarity with the original observations and activities in US GLP definition of raw data (8)? “. . . and activities….necessary for the a study.” Apart from the use of primary obser- reconstruction and evaluation of the vations rather than original observa- report . . .” There is also a paragraph expand- tions, it is virtually the same and has ing the type of records that could be a similar meaning. which leaves a divergence between the generated and are capable of being This now begs a question: The MHRA defi nition and the original retained for the record retention pe- MHRA definition of raw data in GLP defi nition (8) presented above riod for nonclinical studies. You will their new guidance document does and discussed in my 2016 column (10). notice the italic text in the definition not appear to be tenable as it is in To be fair to the MHRA, in the ex- of raw data: original observations and direct contradiction with the OECD planation section for raw data there activities in a study. The definition regulations (17) and advisory docu- is the following statement: does not go quite as far as US GLP ment 17 (18) that the MHRA them- in that the requirement for “recon- selves must enforce. If the MHRA “Raw data must permit full struction and evaluation of the study” cannot interpret the regulations that reconstruction of the activities.” (8) is missing or implied. However, they must enforce, what hope is there it is wider in scope than the MHRA for regulated laboratories? Where do There is the requirement for re- definition of raw data in their 2018 we go from here? construction of activities that comes data integrity guidance (13). closer to the GLP definition in 21 Could the OECD regulations be MHRA to the Rescue? CFR 58 (8). However, the major issue, wrong? After all, the regulations are You may think I have taken leave of from my perspective, is that the ex- 20 years old. Let us consider what my senses having spent time until planation is not incorporated in the is contained in the OECD series of now critiquing the MHRA defini- definition itself. Readers tend only Advisory Documents on Principles tion of raw data. Help is at hand to focus on the definition and rarely of Good Laboratory Practice and and it comes, rather surprisingly, read or remember the explanation. Compliance Monitoring. Advisory in MHRA’s own GXP data integrity Document number 17 is entitled guidance document (13). Fast for- OECD GLP Regulations and Raw Data “Application of GLP Principles to ward through the document and ar- The MHRA is responsible for en- Computerized Systems,” and was rive at section 6.11, which discusses forcing the GXP regulations used by issued in 2016 (18). This document original record and true copy. regulated firms within the UK. Ap- is essentially Annex 11 on steroids. 10 Spectroscopy 33(12) December 2018 www.spectroscopyonline.com

Definition of Original Record? be attributable to an individual (or assurance activities. The suggested The definition of original record is if automatically generated, to the definition above could be a starting original data source).” point for discussions to agree on a “The first or source capture of data or suitable definition. information, e.g. original paper record In the explanation section, it notes of manual observation or electronic that (13): Static versus Dynamic Data raw data file from a computerized • metadata form an integral part of the The terms static data, dynamic data, system, and all subsequent data original record, and and record format appear in the required to fully re-construct the • without the context provided by meta- MHRA, World Health Organization conduct of the GXP activity,” (13). data, the data have no meaning. (WHO), FDA, and Pharmaceuti- Therefore, when considering raw cal Inspection Cooperation Scheme Let us look at this definition in data (or in the context of the MHRA (PIC/S) (14-16, 20-22) data integrity some more detail and see the com- —original record), all metadata, in- guidance documents, as well as re- ponent parts in comparison with the cluding all pertinent audit trail cent MHRA GXP guidance (13). As US GLP definition: entries, are essential for the trans- there are statements about static and • first or source capture of data or parent reconstruction of any GXP dynamic data concerning raw data information: this equates to origi- activity, from initial acquisition to and original record in the MHRA nal observations or primary obser- report vs. record as well as report vs. GXP guidance, it is pertinent to dis- vations record to initial acquisition. This is cuss the terms here and how they • covers both paper and computer- a different way of considering com- impact raw data. ised systems: this is implicit in the plete data—all records and support- Section 6.11 of the MHRA states original GLP definition ing contextual metadata from sam- that “original records can be static • all subsequent data: this is the same pling to reporting. In addition, data or dynamic” (13). as activities governance impacts on raw data such From the discussion above, we can • to fully reconstruct the conduct of as open culture, data integrity poli- equate original records to raw data. the GXP activity: equates to recon- cies and procedures, training, and The difference between static and struct and evaluate the study. roles and responsibilities such as dynamic data needs to be discussed. Ignore the heading; this is a great data ownership, and these are dis- The FDA’s data integrity guidance definition of raw data. It is a pity cussed in more detail in a new book has the following question: How that the definition is called original on Data Integrity and Data Gover- does FDA use the terms static and record. In fact, if you swapped the nance for regulated laboratories (19). dynamic as they relate to record for- titles of the two MHRA definitions mats? (22): (raw data becomes original record Revision of EU GMP Chapter 4 and vice versa), all would be great. As I mentioned earlier in this col- “For the purposes of this guidance, umn, EU GMP chapter 4 uses the ‘static’ is used to indicate a fixed-data Putting Raw Data in Context term raw data, but does not define document such as a paper record or Although this column has discussed it (11). Currently, the European Med- an electronic image, and ‘dynamic’ raw data extensively, it is important icines Agency (EMA) has a project means that the record format allows not to forget the that raw data in- to revise Annex 11 and Chapter 4 to interaction between the user and the cludes all the associated metadata. incorporate more emphasis on data record content.” In addition, the integrity of the re- integrity (12). The revised chapter cords must be complete and consis- must have a definition of raw data Typical examples of static data could tent and accurate throughout the and an option could be to adapt the be a pH measurement, the printout of data life cycle. You will recall that a MHRA’s original record definition, a weight from an analytical balance, flexible analytical data life cycle was such as: a photograph, or a temperature of an presented and discussed in a recent environmental chamber. Although the Focus on Quality column (10). “The first or source capture of data value could be averaged in the case of Metadata is defined by the MHRA or information and all subsequent a set of temperature measurements or guidance section 6.3 (13) as: activities including metadata required involved in further calculations with to fully reconstruct the conduct of a a weight, the record itself cannot be “data that describe the attributes of GXP activity.” changed. In contrast, dynamic data other data and provide context and allows a user interaction such as inter- meaning. Typically, these are data One of the problems with writing pretation of a spectrometer spectrum or that describe the structure, data the existing EU GMP Chapter 4 was chromatogram. Dynamic records carry elements, inter-relationships and the difficulty in agreeing on a defi- a higher regulatory risk, due to the pos- other characteristics of data, e.g. audit nition that would fit with manufac- sibility of interpretation, manipulation, trails. Metadata also permit data to turing, quality control, and quality or falsification into compliance. www.spectroscopyonline.com December 2018 Spectroscopy 33(12) 11

The MHRA section 6.2 on raw (5) FDA Questions and Answers on Cur- (Organisation for Economic Co-oper- data has two statements on dynamic rent Good Manufacturing Practices, ation and Development, Paris, (1998). and static data (13): (Good Guidance Practices, Level 2 (18) OECD Series on Principles of Good Guidance - Records and Reports. Laboratory Practice and Compliance “Information that is originally 2010 27 May 2016). Available from: Monitoring Number 17. Application captured in a dynamic state http://www.fda.gov/Drugs/Guid- of GLP Principles to Computerised should remain available in that anceComplianceRegulatoryInforma- Systems. (Organisation for Econom- state (Definition). Raw data must tion/Guidances/ucm124787.htm. ics Co-Operation and Development, permit full reconstruction of the (6) 21 CFR 211 Current Good Manufac- Paris, 2016). activities. Where this has been turing Practice for Finished Pharma- (19) R.D. McDowall, Data Integrity and captured in a dynamic state and ceutical Products. (Food and Drug Data Governance: Practical Imple- generated electronically, paper copies Administration: Silver Springs, MD, mentation in Regulated Laborato- cannot be considered as ‘raw data’ 2008). ries. (Royal Society of Chemistry, (Explanation).” (7) R.D. McDowall, Spectroscopy 28(4), Cambridge, 2018). 18-25 (2013). (20) PIC/S PI-041 Draft Good Practices Therefore, if data are captured in (8) 21 CFR 58 Good Laboratory Practice for Data Management and Integrity dynamic state, they must remain in for Non-Clinical Laboratory Studies. in Regulated GMP / GDP Environ- that state with obvious implications (Food and Drug Administration: ments. (Pharmaceutical Inspec- for record retention. Printing to Washington, DC, 1978). tion Convention / Pharmaceutical paper is not an option. This is a rein- (9) 21 CFR Parts 16 and 58 Good Lab- Inspection Co-Operation Scheme, forcement of the FDA’s position from oratory Practice for Nonclinical Geneva, 2016). 2010 published on their web site (5). laboratory Studies; Proposed Rule. (21) WHO Technical Report Series No. But, at some point in the future, (Federal Register, 81(164), 58342 - 996 Annex 5 Guidance on Good some of your laboratory records and 58380 (2016). Data and Records Management data might need to be converted to (10) R.D. McDowall, Spectroscopy 31(11), Practices. (World Health Organisa- a static format, due to a lack of suit- 18-21 (2016). tion, Geneva, 2016). able hardware or software to read the (11) EudraLex - Volume 4 Good Manu- (22) FDA Draft Guidance for Industry Data records. That is another discussion facturing Practice (GMP) Guidelines, Integrity and Compliance with cGMP. for another column. Chapter 4 Documentation. (EU (US Food and Drug Administration, Commission, Editor, Brussels, 2011). Silver Spring, MD, USA, 2016). Summary (12) Work plan for the GMP/GDP Inspectors The 2018 MHRA GXP data integrity Working Group for 2018 (European guidance has a definition of raw data Medicines Agency, London, 2017). that conflicts with those in the GLP (13) MHRA GXP Data Integrity Guidance regulations. However, the definition and Definitions. (Medicines and of original record from the guidance Healthcare products Regulatory is an adequate substitute and could Agency, London, 2018). be used instead. The impact of static (14) MHRA GXP Data Integrity Defini- and dynamic data types on raw data tions and Guidance for Industry, are also discussed. Draft version for consultation July 2016. (Medicines and Healthcare Acknowledgements products Regulatory Agency, Lon- R.D. McDowall is I would like to thank Chris Burgess don, 2016). the director of R.D. Mc- and Mark Newton for comments made (15) MHRA GMP Data Integrity Defini- Dowall Limited and the during the writing of this column. tions and Guidance for Industry 2nd editor of the “Questions Edition. (Medicines and Healthcare of Quality” column for References Products Regulatory Agency: Lon- LCGC Europe, Spectros- copy’s sister magazine. (1) R.D. McDowall, LC-GC International, don, 2015). Direct correspondence to: 9(12), 790–793 (1996). (16) MHRA GMP Data Integrity Defini- [email protected] Edit@ (2) 21 CFR 11 Electronic records; elec- tions and Guidance for Industry 1st tronic signatures, final rule, in Title Edition. (Medicines and Healthcare 21 (Food and Drug Administration: Products Regulatory Agency, Lon- Washington, DC, 1997). don, 2015). For more information on this topic, (3) R.D. McDowall, LC-GC International (17) OECD Series on Principles of Good please visit our homepage at: 13(9),: 648–657 (2000). Laboratory Practice and Compliance www.spectroscopyonline.com (4) R.D. McDowall, LCGC Europe 25(2), Monitoring Number 1, OECD Prin- 88-102 (2012). ciples on Good Laboratory Practice. 12 Spectroscopy 33(12) December 2018 www.spectroscopyonline.com

Molecular Spectroscopy Workbench Exploring Resonance Raman Spectroscopy

The scope of this work is to provide you with an overview of the chemical physics of resonance Raman spectroscopy, present and discuss some examples of resonance Raman spectra, and discuss those things to be alert to in recognizing resonance enhancement in your Raman spectra. How does resonance Raman spectroscopy differ from so-called normal Raman spectroscopy? The primary difference is that the scattering strength of those Raman active vibrational modes associated with the electronic transition are greatly enhanced, up to 106 times the signal strength observed when performing normal Raman spectroscopy. The presence of bands attributable to second-order overtone and combination modes in resonance Raman spectra is explained.

David Tuschel

aman spectroscopists are aware of the fact that that level of detail (1–7). How does resonance Raman they have a choice of excitation wavelengths. A fre- spectroscopy differ from so-called normal Raman spec- R quent question that new users have when acquiring troscopy? The primary difference is that the scattering a Raman spectrometer is “What excitation wavelengths strengths of those Raman active vibrational modes as- will I need to perform Raman spectroscopy?” Usually, sociated with the electronic transition are greatly en- the choice of excitation wavelength is dictated by a de- hanced, up to 106 times the signal strength observed sire to avoid absorption and subsequent fluorescence when performing normal Raman spectroscopy. One im- from the sample that can overwhelm the Raman signal. mediate consequence of that phenomenon is that a reso- However, in those instances where fluorescence does not nance Raman spectrum can appear quite different from obscure the Raman spectrum, there can be real benefits a normal or nonresonant Raman spectrum, because of to choosing an excitation wavelength that couples to an the differences in relative intensities of the Raman bands. electronic transition or photon absorption of the mate- Most users of Raman instrumentation are aware of the rial. When that is done, we say that the excitation wave- fact that the Raman spectrum of a material will appear length is in resonance with an electronic transition, and the same even if different excitation wavelengths are used. the result can be resonance enhanced Raman spectra. The band positions and their relative intensities do not Resonance Raman spectroscopy cannot be described change as a function of the excitation wavelength if one properly without invoking quantum mechanics and some incorporates a correction for the wavelength dependent mathematically complicated concepts in chemical phys- instrument response function of the spectrometer. The ics. A detailed explanation of resonance Raman spectros- wavelength independence of the Raman spectrum is true copy is beyond the scope of this installment. We encour- insofar as no absorption occurs for any of the laser excita- age you to consult these good references should you want tion wavelengths. The absence of absorption is the condi- www.spectroscopyonline.com December 2018 Spectroscopy 33(12) 13 tion associated with normal Raman spectroscopy. However, if the excitation wavelength is in resonance with an electronic transition of the sample, then enhancement of the signal strength of some Raman bands can occur. Consequently, the resonance Raman spectrum can appear quite different from the normal Raman spectrum because of the sometimes very significant differences in relative intensities. The band positions in molecular resonance Raman spectroscopy do not in general vary with excitation wavelength because local vibrational modes are the origin of Raman scattering. However, the situ- Figure 1: Molecular structures of pentacene and rubrene. ation is different for phonons in solid state materials. The coupling of phonons of different energies throughout the Brillouin zone to the electronic transition can lead to excitation wavelength dispersion, that is the dependence of the Raman band position on excitation wavelength. The purpose of this installment of “Molecular Spectroscopy Work- bench” is to provide you with an overview of the chemical physics of resonance Raman spectroscopy, present and discuss some examples of resonance Raman spectra, and discuss those things to be alert to in recognizing resonance enhancement Figure 2: Raman spectrum obtained from a grain of pentacene using 633 nm excitation. in your Raman spectra. The first distinction that we want to make is between absorption and a scattering can be emitted through fluorescence from a distorted structure formed phenomenon. An electronic transi- or the molecule can return to the by the mixing of the ground and ex- tion from the ground to a real ex- ground state through radiationless cited states. In those relatively few cited state takes place on the order decay. Light scattering, including (one in 106 to 108 incident photons) of 10-13 s or less. Once the electron Raman scattering, is a fast process instances where a Raman photon is in the excited state, the molecule taking place on a time scale of 10-12 is scattered the vibrational motion has time to rearrange or adjust its to 10-13 s. That difference in time couples to the distorted excited state. nuclear configuration to stabilize the scales between Raman scattering In normal Raman spectroscopy the energy before losing it through emis- and fluorescence (10-9 s or greater) intermediate state is described as a sion (fluorescence) or inter-nuclear is the basis for being able to acquire virtual state, whereas in the case of collisions. Vibrational transitions Raman spectra without interfering resonance Raman spectroscopy that occur on a time scale of approxi- fluorescence through time-resolved intermediate and distorted excited mately 10-9 s, and so we might say Raman spectroscopy. state corresponds to a real state of that a lot of time will pass follow- Further to our discussion of time an electronic transition. ing the initial absorption and tran- scales, we note that in resonance To understand the origins of the sitions to various vibrational states Raman spectroscopy the atoms don’t strengths of the various bands that within the excited electronic state, have time to adjust to new equilib- constitute a Raman spectrum we also known as vibronic states. After rium positions of their excited state consider the Kramers Heisenberg vibrational relaxation to the ground as they do following absorption. Dirac (KHD) equation. vibrational state of the excited elec- Normal and resonance Raman scat- ⟨F | r | E⟩ ⟨E | r | G⟩ ⟨E | r | G⟩ ⟨F | r | E⟩ α = 1 ρ σ + ρ σ ( ρσ )GF ∑ tronic state has occurred, a photon tering processes are fast and occur E ν −ν −iΓ ν +ν −iΓ (1) h GE L E EF L E 14 Spectroscopy 33(12) December 2018 www.spectroscopyonline.com

integrals in bra-ket notation in the customary fashion from right to left, the first term in the numerator describes the mixing of ground and excited vibronic states and the second term accounts for the mixing of the excited and final vibronic states. Hence, Raman scattering is a two photon process which explains why it is inherently weak. One may be tempted to think of the two terms in the numerator as being analogous to an absorption followed by emission but that is not correct. It is more appropriate to think of the integrals in the numerator as the mixing of Figure 3: Raman spectrum obtained from a grain of pentacene using 633 nm excitation. ground, excited, and final states of an electronic configuration distorted by the electric field of the incident light. Turning our attention to the denominator in the first term brings us to the root of resonance enhanced Raman spectroscopy as found in the KHD equation. The closer the laser frequency is to that of an electronic transition the smaller the denominator becomes leaving only the damp-

ing constant, iΓE. Were it not for the addition of the damping constant, the denominator could in principle go to zero when the laser frequency equaled that of the electronic tran- Figure 4: Raman spectra obtained from grains of pentacene using various excitation wavelengths. sition and the Raman polarizability would go to infinity. Of course, that doesn’t happen and actual resonance tion, excited state to final state tran- enhancements over normal Raman The Raman polarizability is given sition, and laser, respectively. The scattering are typically 104 to 106. α ρ σ by the term ( ρσ)GF where and term iΓE is a damping constant and is We stated earlier that the Raman po- are the polarizations of incident and related to the lifetime and therefore larizability depended upon the sum Raman scattered light and the terms the band width of the excited state. of the mixing of all of the ground, G and F correspond to the ground Note that the frequencies of the excited, and final vibronic states. and final vibronic states of the mol- laser and the transition from the However, when the laser excitation ecule. The excited state is indicated excited to final state in the denomi- frequency matches that of a transi- by E, which will be virtual or real de- nator of the second term are added, tion to a real electronic state rather pending upon whether the frequency whereas the frequency of the laser is than a virtual state, the resonance of the exciting radiation matches subtracted from that of the transi- condition obtains, and the interac- that of an electronic transition of tion from the ground to excited state tion described by the KHD expres- the molecule. The polarization de- in the first term denominator. There- sion is for that one resonance state pendent dipole operator is given by fore, the second term will always be and not the sum of all states. either rρ or rσ. The summation sym- smaller than the first term and we Those Raman active vibrational bol indicates that the Raman polar- can neglect it in our consideration modes associated with the electronic izability is given by the sum of all of of Raman polarizability and signal transition will then experience a the vibronic states of the molecule. strength. Considering then the nu- significant increase of their vibra- Planck’s constant is given by h, and merator in the first term, we recog- tionally modulated polarizability

νGE, νEF, and νL are the frequencies nize an expression of a two photon and enhancement of their Raman of the ground to excited state transi- process. Reading the expression of scattering. The result of the enhance- www.spectroscopyonline.com December 2018 Spectroscopy 33(12) 15 ment of those specific modes can be a Raman spectrum that appears different from the normal Raman spectrum of the same compound because of the different relative intensities of the bands. In addition, bands attributable to overtones and combination modes that are not seen in a normal Raman spectrum can become quite intense. Readers may be aware of the fact that the Raman spectrum normally comprises only the fundamental vibrational modes. However, using an excitation wavelength that couples to an electronic transition can give rise to the appearance of overtones to the 11th harmonic (2). Figure 5: Raman spectra obtained from grains of rubrene using various excitation wavelengths. Matters can become even more complicated when the resonance condition occurs in solid state materials. Selection rules dictate that for first-order Raman scattering only those phonons at the Brillouin zone center will be Raman active. That is not the case for second-order Raman scattering involving overtones or combination modes. In second-order Raman scattering, all the phonons throughout the Brillouin zone can be Raman active. For example, that is why the 2TO band at approximately 950 cm-1 in the Raman spectrum of silicon (Si) is so much broader than that of the first-order optical mode Figure 6: Raman spectra of 2D MoS2 taken at the same location with different excitation at 520 cm-1. Under the resonance wavelengths. condition, coupling of phonons of different energies within the Bril- probably be attributed to a combina- cm-1. Raman bands from aromatic louin zone can lead to a change in tion of absorption of blue-green light C-H stretching should appear at en- the peak position of multiphonon and fluorescence of reddish-orange ergies greater than 3000 cm-1, which Raman scattering depending upon light. That these compounds absorb do appear in this spectrum. So how the excitation wavelength (8). light in the visible region of the spec- do we account for the appearance of trum makes them good candidates bands between 1800 and 3000 cm-1? Resonance Raman Spectroscopy for resonance Raman spectroscopy. These bands can be attributed to the of Pentacene and Rubrene A resonance Raman spectrum of resonantly enhanced second-order Pentacene and rubrene are two pentacene acquired using 633 nm combinations and overtones that we compounds of great interest in the excitation is shown in Figure 2. How discussed in the previous section. world of molecular electronics and do we know that the spectrum is No fundamental vibrational modes are solids at room temperature. Both resonantly enhanced? Our first clue of pentacene would be expected in compounds are aromatic, consisting is the appearance of Raman bands in this portion of the spectrum. The entirely of phenyl groups, and are the region between 1800 and 3000 most prominent bands in the spec- colored. Their molecular structures cm-1. The highest energy bands in trum appear at 1158, 1176, 1371, 1532 are shown in Figure 1. Rubrene has the fingerprint region will be due to and 1597 cm-1. The first four of these a bright reddish orange color and aromatic ring vibrational modes at bands have been assigned to the Ag pentacene appears almost black. The approximately 1600 cm-1. There are symmetry species and the 1597 cm-1 rubrene grains have a glow to them no saturated portions of the molecule band to the B3g symmetry species (9– under fluorescent room lighting and and so we would not expect to see 10). It is generally accepted that to- so their reddish orange color can C-H stretching modes below 3000 tally symmetric Ag symmetry species 16 Spectroscopy 33(12) December 2018 www.spectroscopyonline.com

a molecular structure. Furthermore, you can see the risks of basing a library search on a resonance Raman spectrum. All of the spectra that constitute a spectral database can be expected to consist of normal (nonresonant) Raman spectra. It is un- likely that you would obtain an accurate match and identification for the spectrum in Figure 2 by searching a Raman database if it is comprised of normal Raman spectra. Another aspect of resonance Raman spectroscopy is the excitation profile or differences in the Raman spectra as a function of excitation wavelength. Normally, the Figure 7: Raman hyperspectral data set (upper left) of 2D MoS . Reflected white light image 2 peak positions will not change with appears in lower right corner. The color coded resonance Raman image in the lower left hand excitation wavelength for molecu- corner corresponds to the green and red brackets appearing in the hyperspectral data set and lar resonance Raman spectroscopy. cursor spectrum in the upper right corner. However, as we explained earlier, a dependence of band position on excitation wavelength can be observed in spectra of solid state materials where phonons of different energies throughout the Brillouin zone couple to the electronic transition. What do change are the relative intensities of the bands. A profile of Raman spectra of pentacene acquired using 405, 473, 532, 633, and 785 nm excitation is shown in Fig- ure 4. The spectrum acquired with 785 nm excitation can be considered a normal Raman spectrum because the energy of 785 nm light is below the bandgap of pentacene. All of the other excitation wavelengths fall within the absorption spectrum of

Figure 8: Color coded resonance Raman image (left) of 2D MoS2. Raman spectra on the right are pentacene and therefore yield reso- from the locations on the image indicated by the connecting lines. nantly enhanced Raman spectra (11). Although absorption occurs for all that manifest resonance enhance- of the Raman spectrum consisting of of the other laser excitation wave- ment do so through a Franck-Con- overtones and combination modes is lengths, they do not all couple to don coupling. There are other types shown in Figure 3. The peak at 3194 the same electronic transition. Note of vibronic coupling to describe cm-1 can be attributed to aromatic how the Raman spectra excited at resonance enhancement, but those C-H stretching. However, all of the 405 and 473 nm are nearly identical, very detailed and mathematical ex- other bands in Figure 3 can only be thereby indicating that those excita- planations are beyond the scope of assigned to second-order overtones tion wavelengths couple to the same this installment. Assignments of the and combination modes and not to electronic transition. Using a longer symmetry species that undergo reso- any fundamental vibrational modes excitation wavelength at 532 nm, we nance enhancement can often help in of pentacene. Raman spectroscopists see definite changes in the relative understanding the electronic transi- need to be aware of this aspect of intensities of the bands. In particu- tion and explaining the coupling be- resonance Raman spectroscopy lest lar, the strengths of the bands at 1158 tween specific vibrational modes and they attempt to assign these bands to and 1371 cm-1 have increased relative the electronic transition. particular functional groups, lead- to their counterparts in the spectra An expanded view of that portion ing to an incorrect construction of excited at 405 and 473 nm. Also, the www.spectroscopyonline.com December 2018 Spectroscopy 33(12) 17 bands at 1408 and 1456 cm-1 have di- maxima at approximately 440, 465, the assignments of Weinberg-Wolf minished in relative strength at 532 495 and 535 nm. Several of the ab- and coworkers (13). The exceptional nm excitation. Furthermore, all of sorption maxima are well placed band is at 1519 cm-1, which has been -1 the bands below 1000 cm are now for the laser wavelengths available assigned to symmetry species Bg. extremely weak and can barely be to us. However, rubrene (like pen- Thus, all but one of the resonance observed plotted on a scale normal- tacene) is a strong fluorophore and enhanced Raman bands are totally ized to the most intense band. This the emission from this compound symmetric modes belonging to the was not the case for the spectra ob- overwhelms the Raman scattering symmetry species Ag. This observa- tained at 405 and 473 nm excitation. when using 473 and 532 nm exci- tion would lead us to conclude that At 633 nm excitation, the spectrum tation. No Raman bands could be the resonance enhancement at 405 is similar to that obtained with 532 detected superimposed on the very nm excitation is through a Franck- nm excitation, but we observe a small strong fluorescent background. The Condon coupling mechanism. recovery of the strengths of the 1408 Raman spectra that we were able to -1 and 1456 cm bands. Finally, at 785 acquire using 405, 633 and 785 nm Coupling to an Exciton in 2D MoS2 nm excitation we observe a very differ- excitation are shown in Figure 5. The Resonance Raman spectroscopy has ent Raman spectrum with respect to spectra acquired at 633 and 785 nm played an important role in the char- relative intensities because at this wave- excitation are nearly identical as we acterization of two dimensional (2D) length we are now out of resonance. might expect. This is because there is crystals. These novel materials are not The dependence of Raman band just small portions of the bulk mate- strength on the excitation wave- rials carrying the same properties as length as observed in Figure 4 and those of the three dimensional kind. discussed above can seem puzzling Rather, their physical, electronic, without reference to the absorption You can see the and spectral characteristics can be spectrum of pentacene. An absorp- risks of basing a significantly different. Specifically, tion spectrum of a 150 nm thick molybdenum disulfide (MoS2) in its polycrystalline film of pentacene is library search on a bulk form is an indirect bandgap shown in Figure 2 of reference (11). semiconductor, whereas in its mono- That spectrum reveals absorption resonance Raman layer to few-layer forms it becomes a at wavelengths shorter than 740 nm spectrum. direct bandgap semiconductor (14). with absorption maxima at approxi- Splendani and coworkers have stud- mately 540, 580, 630 and 670 nm. We ied an exfoliated MoS2 monolayer and can then infer with reference to that a few-layer flakes by photolumines- absorption spectrum and its multiple cence and have observed direct exci- absorption maxima that we are cou- little if any absorption at these wave- tonic transitions (15). By exciting with pling into different electronic tran- lengths and so there is no resonance 532 nm laser light they have observed sitions with the laser wavelengths enhancement of the Raman scatter- broad photoluminescence centered at available to us. The 405 and 473 nm ing. These excitation wavelengths 627 and 677 nm, whereas these emis- laser light couples to a transition well have energies below the bandgap of sions are completely absent when above the band gap and the 532 and rubrene. The Raman spectrum ac- illuminating bulk MoS2. The room 633 nm laser excitations couple to quired using 405 nm excitation ap- temperature bandgap of bulk MoS2 is the absorption maxima at 540 and pears distinctly different from the approximately 1.7 eV (corresponding 630 nm, respectively. The excitation two excited with 633 and 785 nm to 730 nm) with complex excitonic profile of pentacene offers a good laser light. Here we observe the ef- features between 1.7 and 2.5 eV (16). example of the complexity of reso- fects of resonance enhancement. A The crystalline structure of 2D -1 nance Raman spectroscopy when the band appears at 1616 cm that is very MoS2 belongs to the D6h crystal class, absorption spectrum of a compound weak in the spectra acquired with and factor group analysis predicts one has multiple electronic transitions 633 and 785 nm excitation. Also, you A1g, one E1g and two E2g Raman ac- into which one can couple using dif- can see that the relative intensities tive modes (16-22). The symmetry as- ferent laser excitation wavelengths. of the spectrum excited with 405 nm signments and corresponding Raman Rubrene is another aromatic light differ from those excited at 633 band positions for the fundamental compound that has been exten- and 785 nm. Identification of the site (first-order) phonon modes of bulk -1 sively studied for its use in molec- symmetry species of the prominent hexagonal MoS2 are: E1g (286 cm ), 1 -1 -1 ular electronics. It too is colored, bands in the 405 nm excited spec- E 2g (383 cm ), A1g (408 cm ) and 2 -1 and the absorption spectrum of its trum reveals something very inter- E 2g (32 cm ). Furthermore, it is im- solid form extends from the UV esting. All of the moderate to strong portant to remember that some visible to approximately 590 nm (12). The bands with the exception of one are wavelengths of the laser light used to absorption spectrum manifests of symmetry species Ag, based upon excite Raman scattering correspond 18 Spectroscopy 33(12) December 2018 www.spectroscopyonline.com

to energies of MoS2 electronic tran- acoustic (LA) mode at the M point Raman scattering and photolumines- sitions. The absorption spectrum of the Brillouin zone (A1g(M) LA(M)) cence in one spectral acquisition with- -1 of MoS2 reflects the band gap of 1.7 (24). The band at 417 cm has been out the need for moving the grating to eV, but it also manifests fine struc- designated a so-called “b” mode in- stitch regions together. The hyperspec- ture with narrow absorption peaks volving a polariton and manifesting tral data set appearing in the upper left at 1.9 eV (653 nm) and 2.1 eV (590 wavelength dependent dispersion corner of Figure 7 consists of all the nm) related to d-to-d orbital transi- (25-26). The bands at 462, 598, and spectra acquired during mapping. You tions split by spin-orbit coupling and 642 cm 1 have been assigned to the can see from the variation in the pho- designated A1 and B1 excitons, re- symmetry species A2u(Γ) or E1g(Γ) toluminescence of those spectra that 1 spectively (16,23). Consequently, one + XA, E 2g(M) + LA(M), and A1g(M) the electronic properties of the crys- can observe an excitation wavelength + LA(M), respectively. You can see tal varied spatially. A reflected white dependence of the first-order Raman from these symmetry species and light image of the sample appears in band intensities as well as the appear- band assignments that we have de- the lower right hand corner and a res- ance of Raman bands assigned to sec- parted the more familiar territory of onance Raman image corresponding ond-order overtone and combination molecular spectroscopy and entered to the reflected light image appears to modes when the laser excitation is of the more complex world of solid its left. The upper right hand plot is a wavelength that couples into these state physics. The band positions in of the single spectrum associated with excitonic transitions (16, 20, 22-23). molecular resonance Raman spec- the cross hair location in the Raman

The Raman spectra of 2D MoS2 de- troscopy do not in general vary with and reflected light images. pend upon the excitation wavelength. excitation wavelength because local The resonance Raman image is ac- Spectra acquired at the same location vibrational modes are the origin of tually a rendering of signal strength from the interior of a MoS2 few-layer the Raman scattering. However, the for a particular Raman band as a flake on a Si substrate with different situation is different for phonons in function of position on the sample. excitation wavelengths are shown in solid state materials. The coupling In this case, the resonance Raman Figure 6. The spectrum acquired with of phonons of different energies image is rendered through a color 532 nm excitation is typical of those throughout the Brillouin zone to the coded plot of Raman signal strength reported in the literature; it consists electronic transition can lead to ex- of the corresponding color bracketed 1 -1 primarily of the E 2g band at 383 cm citation wavelength dispersion, that Raman shift positions in the two -1 and the A1g band at 408 cm as well is the dependence of the peak posi- upper traces. Peak intensities were as the Si substrate Raman band at 520 tion on excitation wavelength. Fur- measured incorporating a baseline to cm-1. In contrast, the spectrum gener- thermore, the resonantly enhanced remove any contribution from the un- ated with 633 nm excitation is strik- second-order modes are no longer derlying photoluminescence. There- ing insofar as it consists of the same restricted to only those phonons at fore, the spectral image in Figure 7 first-order bands and those due to the Brillouin zone center (Γ) as are is strictly a resonance Raman image. overtones and combination modes. the first-order fundamental modes. The red brackets surround the sec-

Remember that the absorption spec- Phonons throughout the Brillouin ond-order MoS2 Raman band at 642 -1 trum of MoS2 contains fine structure zone and even those modes that by cm (A1g(M) + LA(M)). This band with narrow absorption peaks at 1.9 eV symmetry (e.g., A2u(Γ)) should not appears only in the two trilayer MoS2 (653 nm) and 2.1 eV (590 nm) related be Raman active can appear through crystal and is absent in the single to d-to-d orbital transitions split by resonance in the Raman spectrum. trilayer MoS2. Consequently, only the spin-orbit coupling and designated A1 The structure of 2D MoS2 often var- two trilayer structure in the center and B1 excitons, respectively (16, 23). ies spatially and the most prominent of the MoS2 crystal appears red. The Consequently, the 633 nm excitation changes appear at the sample edges. green bracket covers the second-or- couples into the A1 transition produc- Resonance Raman imaging of these der Raman scattering near 706 cm-1, ing a resonance enhancement of all of 2D crystals is complementary to pho- which is assigned to the second-order the additional modes observed in Fig- toluminescence imaging and offers a mode A1g(Γ) + E1g(Γ) at the Brillouin ure 6. All of the bands in the spectrum means of imaging the spatially varying zone center. This second-order mode excited with 633 nm light can be ac- electronic structure. The results of res- is prominent in the single trilayer counted for and have previously been onance Raman mapping of 2D MoS2 MoS2 spectrum because of resonance assigned (16, 20, 23-24). crystals on a Si substrate using 633 nm enhancement. Thus, these two reso- The assignment of symmetry spe- excitation are shown in Figure 7. The nantly enhanced Raman bands offer cies of these bands reveals the com- Raman data were acquired using a 100 a means of easily differentiating plexity that can sometimes emerge in x Olympus objective and by moving single from double trilayer MoS2, the resonance Raman spectroscopy the stage in 1 μm spatial increments thereby producing resonance Raman of solid state materials. For example, over an area of approximately 40 μm images with excellent contrast based the band at 178 cm-1 is a combina- x 40 μm. A 300 grove per mm grat- on the number of 2D layers. Note how tion of an A1g and a longitudinal ing was used in order to capture both well the resonance Raman image cor- www.spectroscopyonline.com December 2018 Spectroscopy 33(12) 19 responds to the reflected white light mal Raman spectra. The assignment and T.F. Heinz, Phys. Rev. Lett. 105, image in which the hue and degree of of vibrational mode symmetry spe- 136805 (2010). white light reflectance depend upon cies was shown to be important in (15) A. Splendiani, L. Sun, Y. Zhang, T. the number of MoS2 trilayers. understanding the resonance mecha- Li, J. Kim, C.-Y. Chim, G. Galli and Spectra from the two trilayer nism. Resonance Raman spectra and F. Wang, Nano Lett. 10, 1271-1275 structure in the crystal center and images of 2D MoS2 were also shown (2010). from the single trilayer perimeter are and discussed. It was shown that two (16) A.M. Stacy and D.T. Hodul, J. Phys. shown in Figure 8. Note how intense resonantly enhanced Raman bands Chem. Solids 46, 405-409 (1985). the green color associated with the offer a means of easily differentiat- (17) J.R. Ferraro, Appl. Spec. 29, 418-421 single trilayer 706 cm-1 band is near ing single from double trilayer MoS2, (1975). the perimeter but is dimmer in the thereby producing resonance Raman (18) S. Jimenez Sandoval, D. Yang, R.F. interior of the crystal. This strong images with excellent contrast based Frindt and J.C. Irwin, Phys. Rev. B resonance Raman response at the pe- on the number of 2D layers. The 44, 3955-3962 (1991). rimeter inversely correlates with the combination of resonance Raman (19) T.J. Wieting and J.L. Verble, Phys. diminished photoluminescence regu- and photoluminescence imaging Rev. B 3, 4286-4292 (1971). larly observed at the crystal’s edge. allows investigators to more thor- (20) J.M. Chen and C.S. Wang, Solid State Also, the second-order MoS2 Raman oughly characterize the electronic Commun. 14, 857-860 (1974). -1 band at 642 cm (A1g(M) + LA(M)) properties of these new and techno- (21) S. Sugai and T. Ueda, Phys. Rev. B is much stronger in the two trilayer logically important materials. 26, 6554-6558 (1982). crystal where one also observes dif- (22) D.O. Dumcenco, K.Y. Chen, Y.P. ferences in photoluminescence band References Wang, Y.S. Huang and K.K. Tiong, shape and strength relative to those (1) R.J.H. Clark and T.J. Dines, Angew. J. Alloys Compounds 506, 940-943 from a single trilayer. Thus, the com- Chem. Int. Ed. 25, 131-158 (1986). (2010). bination of resonance Raman and (2) R.J.H. Clark and B. Stewart, Struct. (23) B.C. Windom, W.G. Sawyer and photoluminescence imaging allows Bond. 36, 1-80 (1979). D.W. Hahn, Tribol. Lett. 42, 301-310 investigators to more thoroughly (3) D.P. Strommen and K. Nakamoto, (2011). characterize the electronic proper- J. Chem. Educ. 54, 474-478 (1977). (24) M. Placidi, M. Dimitrievska, V. Ez- ties of these new and technologically (4) E. Smith and G. Dent, Chapter 4: quierdo-Roca, X. Fontane, A. Cas- important materials. Resonance Raman Scattering in tellanos-Gomez, A. Perez-Tomas, N. Modern Raman Spectroscopy: A Mestres, M. Espindola-Rodriquez, Conclusion Practical Approach (John Wiley & S. Lopez-Marino, M. Neuschitzer, V. Resonance Raman spectroscopy Sons, Chichester, England, 2005), Bermudez, A. Yaremko and A. Perez- cannot be described properly with- pp. 93-112. Rodriguez, 2D Mater. 2, 035006 out invoking quantum mechanics (5) A.B. Myers, Chem. Rev. 96, 911-926 (2015). and some mathematically compli- (1996). (25) K. Golasa, M. Grzeszczyk, R. Bozek, cated concepts in chemical physics. (6) S.A. Asher, Analyt. Chem. 65, 59A- P. Leszczynski, A. Wysmolek, M. Po- A detailed explanation of resonance 66A (1993). temski and A. Babinski, Solid State Raman spectroscopy is beyond the (7) S.A. Asher, Analyt. Chem. 65, 201A- Commun. 197, 53-56 (2014). scope of this installment and so we 210A (1993). (26) B. Chakraborty, H.S.S. Ramakrishna provided an overview of the phenom- (8) P.Y. Yu and M. Cardona, Fundamen- Matte, A.K. Sood and C.N.R. Rao, J. enon. The primary difference be- tals of Semiconductors: Physics and Raman Spectrosc. 44, 92-96 (2013). tween normal and resonance Raman Materials Properties (Springer, Ber- spectroscopy is that the scattering lin, 1996), pp. 403-406. David Tuschel is a strengths of those Raman active (9) Y. Yamakita, J. Kimura and K. Ohno, Raman Applications Sci- vibrational modes associated with J. Chem. Phys. 126, 064904 (2007). entist at Horiba Scientific, the electronic transition is greatly (10) K. Seto and Y. Furukawa, J Raman in Piscataway, New Jersey, enhanced, up to 106 times the signal Spectrosc. 43, 2015-2019 (2012). where he works with Fran strength observed when performing (11) M.W.B. Wilson, A. Rao, B. Ehrler and Adar. David is sharing authorship of this column normal Raman spectroscopy. Reso- R.H. Friend, Acc. Chem. Res. 46, with Fran. He can be nance Raman spectra of pentacene 1330-1338 (2013). reached at: Spectroscopy- and rubrene were presented and dis- (12) P. Irkhin, A. Ryasnyanskiy, M. [email protected] cussed. These spectra demonstrate Koehler and I. Biaggio, Phys. Rev. B that second-order Raman scattering 86, 085143 (2012). from overtones and combination (13) J.R. Weinberg-Wolf, L.E. McNeil, S. For more information on modes can be resonantly enhanced Liu and C. Kloc, J. Phys. Condens. this topic, please visit: to appear in resonance Raman spec- Matter 19, 276204 (2007). www.spectroscopyonline.com/adar tra whereas they are absent in nor- (14) K.F. Mak, C. Lee, J. Hone, J. Shan 20 Spectroscopy 33(12) December 2018 www.spectroscopyonline.com

A Comparison of Portable Infrared Spectrometers, Portable Raman Spectrometers, and Color-Based Field Tests for the On-Scene Analysis of Cocaine

The majority of inmates in the United States are incarcerated for drug-related offenses. It is important that the technology used to test for controlled substances be accurate and reliable. For on-scene presumptive testing, color-based field tests are commonly employed. Numerous cases have been discovered where positive color-based field tests were later proven to be false positives via confirmatory laboratory testing. Portable infrared (IR) and Raman spectroscopy are capable of providing accurate and reliable identifications at the scene, but are not generally utilized for this purpose. This research evaluated important performance characteristics of these methods to determine which is best for conducting on-scene testing of cocaine HCl. This research concluded that although portable spectrometers require a large initial financial investment, their high performance characteristics (such as ease of use, rapid analysis, non-destructive capability, acceptable limit of detection, and minimal false positives and negatives) make them a superior tool to the color-based field tests for the on-scene presumptive analysis of cocaine HCl. Portable IR spectroscopy was determined to be better than portable Raman because of the lower limit of detection, less severe adulterant interferences, and Raman fluorescence of common drugs (such as heroin or additives).

Dory Lieblein, Meghann E. McMahon, Pauline E. Leary, Peter Massey, and Brooke W. Kammrath

detailed online investigation into field-based presump- color test, and yielded a positive result for cocaine, although tive tests for illicit drugs revealed many cases where Albritton claimed innocence. Albritton was arrested, and pres- A false-positive color tests at the scene resulted in the sured into taking a plea deal by her court-appointed defense law- incarceration of innocent people. The case of Amy Albritton yer, as he insisted that the test proved she was in possession of was detailed in a New York Times Magazine article, and demon- controlled substances and, thus, she would be better off taking strates the problem and its significance (1). A white “crumb” the plea deal. She eventually complied, served her time in county found in her vehicle was tested using the cobalt thiocyanate jail, and went back to her life. It was not until months later that www.spectroscopyonline.com December 2018 Spectroscopy 33(12) 21 any confirmatory testing was done on the suspect crumb, and when it was conducted, it was concluded that the crumb was not a controlled substance. This, among other cases including those of Janet Lee (2), Antonia Carranza (3), and Karlos Casche (4), brings into question the reliability of color tests and indicates a need for finding superior methods for on-scene testing of controlled substances. There is a significant need for field drug testing to be accurate and reliable. This is because, in drug possession cases, outcomes are often decided before they even reach a trial through the use of plea bargains to obtain a conviction. Many US Figure 1: Color-based field test results showing a positive result with 25% cocaine HCl in lidocaine Courts accept guilty pleas based solely on (left) and a negative control (right). the results of field tests, such as those in nine of the ten jurisdictions of North Carolina, and the cities of Atlanta, Dal- (a) las, Jacksonville, Las Vegas, Los Angeles, Newark, Philadelphia, Phoenix, Salt Lake City, San Diego, Seattle, and Tampa. Research indicates that at least 90 % of drug convictions are obtained through plea deals, with some even higher (94 and 97% in Tennessee and Kansas, respectively) (1). Due to the significant errors (such as false positives and interferents) associated with color tests, portable vibrational spectroscopy, including IR and Raman methods, may provide a superior (b) alternative for field testing of illicit substances, especially since these methods offer a higher level of confirmation of the illicit substance. Portable IR and Raman spectrometers are both capable of identifying controlled substances, but have not seen widespread deployment by law enforcement for field testing, primarily because of the cost of the instrumentation. Another concern of the forensic science community is that nonscientist investigators would be exe- Figure 2: Screen readout after a mixture of 25% cocaine HCl in lidocaine was analyzed, with the cuting scientific analyses at crime scenes, portable IR spectrometer showing (a) the component list and (b) the spectrum for cocaine HCl. and may incorrectly conduct the test or misinterpret the results, or both. For field testing in order to provide background of this landscape study, as it was deter- portable instrumentation to become a information for law enforcement who mined that portable technologies provide viable presumptive test for illicit drugs are interested in these technologies (5). general benefits (versatility, objectivity, by law enforcement officers, the instru- This study is an excellent resource for specificity, safety, chain of custody col- ments need to not only be rugged, but information, but the authors did not laboration, technical support, and ability simple to use by nonscientist personnel. perform any specific laboratory or field to be used for multiple applications), and Recently, the National Institute of Jus- research for comparisons of the vari- challenges (high up-front cost, complex- tice (NIJ)’s Forensic Technology Center ous technologies, and instead relied on ity, maintenance, limited mixture inter- of Excellence (FTCoE) published a land- literature searches, manufacturer spec- pretation, and library dependence), and scape study of portable and handheld ifications, and interviews with current each jurisdiction has its own needs and instrumentation for presumptive drug users. There was no ultimate conclusion circumstances. 22 Spectroscopy 33(12) December 2018 www.spectroscopyonline.com

were conducted, samples of 35% and 15% were subsequently made to obtain more precise limits of detection. A positive result for cocaine HCl with the NIK test, as shown in the left side of Figure 1, was indicated by “blue or pink with blue speckles after breaking the first ampoule, a pink result after breaking the second ampoule and a pink layer over a blue layer after breaking the third ampoule (6).” If the proper color change did not occur (right side of Fig- ure 1), this was noted as a negative result. A positive result for cocaine HCl with the portable IR and Raman instruments was indicated by a “hit” for cocaine HCl using the library search function on the instrument (Figures 2 and 4, respec- Figure 3: Spectra of 15% cocaine HCl in baby formula (blue) below the limit of detection for tively). If a “hit” was not provided, this the instrument’s library search algorithm, but containing characteristic peaks for cocaine (red) was noted as a negative result. identified by manual spectral analysis. Results and Discussion Color-Based Field Testing (a) (b) Before experimentation, pure samples of cocaine HCl, as well as each adulterant, were analyzed to establish controls, as well as ensure the adulterants were not false positives for cocaine HCl. It was found that lidocaine was a false positive for cocaine HCl with the color- based field test. Therefore, only the sample sets containing the other four adulterants were used for color testing experimentation. The limit of detection determined for the color-based field test was at a 10% concentration of cocaine HCl with all Figure 4: Screen readout after a mixture of 25% cocaine HCl in lidocaine was analyzed with the four adulterants tested. Sources have portable Raman spectrometer, showing (a) the component list and (b) the spectrum for cocaine HCl. conflicting reports on the average purity of cocaine HCl found in street samples. Experimental included a limit-of-detection study, an in- In 2016, it was reported by the Colom- Performance characteristics were as- vestigation into specificity (potential false bian National Police that the purity of sessed and compared for each tech- positives, false negatives, and adulterant cocaine leaving their country was ap- nique: the Narcotics Identification Kit interactions), and evaluation of the ease proximately 85%, but by the time the (NIK) Test G for cocaine produced by of use, speed of analysis, skill required of cocaine reached the UK, the purity was Safariland, a Smiths Detection HazMa- the operator, and destructive nature of approximately 60% and dropped to about tID Elite portable IR spectrometer with the method. 30% at the retail level (7). The US De- a diamond attenuated total reflection Two-component mixtures were cre- partment of Justice released an article in (ATR) sampling element, and a Smiths ated by using pure cocaine HCl (Sig- February 2010 indicating that from 2006 Detection ACE-ID portable Raman ma-Aldrich) as well as the following five to 2009, cocaine purity had decreased spectrometer. These instruments were adulterants: lidocaine, mannitol, caf- from 68.1% to 46.2%. Even if the lowest used due to their availability, but the feine, Sweet ‘N Low artificial sweetener, reported concentration of 30% were used research could be applied to any com- and Enfragrow powdered baby formula. as a reference, this would make the limit pany’s comparable portable instrumen- Samples with concentrations of 0.1, 0.5, of detection for the color-based field test tation. 1, 5, 10, 25, and 50% by mass of cocaine acceptable. The specific performance characteris- HCl were prepared for experimentation. An extensive literature review revealed tics that were evaluated for all methods When portable IR and Raman analyses numerous known substances that would www.spectroscopyonline.com December 2018 Spectroscopy 33(12) 23 provide a positive result with the cobalt Table I: Substances that produced false positives with the cobalt thiocyanate test, thiocyanate test other than cocaine HCl according to a literature search (8) (Table I), which is the basis for the color- Adiphenine Hydrochloride Meperidine Hydrochloride based field test for cocaine. One article Alphaprodine Hydrochloride Methamphetamine Hydrochloride from the Journal of Forensic Sciences Amitriptyline Hydrochloride Methscopolamine Bromide listed 73 different compounds, indicating a large quantity of potential false positive Antipyrine Methylphenidate results with the test (8). Atropine Sulfate Nalorphine Hydrochloride The color-based field test is a destruc- Azapetine Naphazoline Hydrochloride tive method that prevents any further Benactyzine Hydrochloride Nortriptyline Hydrochloride experimentation from being conducted Benoxinate Hydrochloride Oxymetazoline Hydrochloride on the sample used. It is simple to use, Benzilonium Bromide Oxyphenonium Bromide with directions provided in each box. The Benzphetamine Hydrochloride Pentobarbital Sodium color changes are very obvious at high concentrations of cocaine HCl; however, Benzquinamide Phencyclidine Hydrochloride at lower concentrations it can be difficult Benztropine Mesylate Phendimetrazine Tartrate to discern the color of the bottom layer. Bromodiphenhydramine Hydrochloride Phenindamine Tartrate The subjectivity of determining a positive Butacaine Sulfate Phenoxybenzamine Hydrochloride result is a problem when there is ambi- Carbinoxamine Maleate Phentermine base guity at low concentrations. This method Chloroprocaine Hydrochloride Pipenzolate Bromide would also not be viable for operators Chloropheniramine Maleate Piperocaine Hydrochloride with a color-determination deficiency. A single analysis is fast, taking only a few Chloropromazine Hydrochloride Prilocaine Hydrochloride minutes, and there is little adulterant in- Cinchocaine Hydrochloride Procainamide teraction that affects the limit of detec- Clorazepate Dipotassium Prochlorperazine Dimaleate tion. However, one sample may require Codeine Phosphate Promazine Hydrochloride several different tests to identify the illicit Codeine Sulfate Promethazine Hydrochloride drug, thus taking more time than just a Debrisoquine Sulfate Propantheline Bromide single analysis. Additionally, this test re- Desipramine d-Propoxyphene Hydrochloride quires sampling of the specimen for test- Dexbrompheniramine Maleate Psilocin ing, thus potentially exposing the user to Diethylpropion Hydrochloride Quinine Sulfate an unknown substance. There is also no N,N-Diethyltryptamine Ravocaine Hydrochloride reproducible record of the testing, and the color results may degrade over time, Diphenhydramine Hydrochloride Scopolamine Hydrobromide although detailed documentation with Ephedrine Sulfate Sparteine Sulfate photography is a possibility. Fenﬂ uramine Hydrochloride Tetracycline Hydrochloride The cost for the color-based field test Finratzepam Dyhydrochloride Tetrahydrozoline Hydrochloride for cocaine, crack, and free base is $25.50 Glutethimide Thebaine for a box of ten tests. Other commer- Hexocyclium Methylsulfate Thiopropazate Hydrochloride cially available color tests cost between Hexylcaine Hydrochloride Thioridazine Hydrochloride $2 and 5 dollars per test (5). As these Hydroxyzine Hydrochloride Tofranil tests are one-use only, whomever is em- Hydroxyzine Dihydrochloride Triﬂ uoperazine Dihydrochloride ploying the tests must buy a large quan- Ibogaine Tripelennamine Hydrochloride tity each year. The NIJ’s landscape study estimated that a large metropolitan area Iprindole has approximately 500 drug-related ar- rests per year, with two color tests being juana, PCP, or opiates. These tests do someone who has been falsely con- used for each arrest, resulting in a have expiration dates, and cannot be victed of drug possession. A person total cost of $30,000 per year. How- stored indefinitely. Consequently, the could file a civil suit, and those litiga- ever, this does not take into account $30,000 per year calculation is likely tion fees could far outweigh the cost of the number of cases where no arrest an underestimate of the actual cost. investing in a more reliable method of was made, due to a negative results The perceived low cost of these tests presumptive testing at crime scenes. with the color test. Further, the tests is considered by law enforcement to This does not include the non-mone- are only specific to a particular drug be a significant benefit over portable tary costs that come along with being “group,” so law enforcement person- instrumentation. falsely charged with drug possession nel require separate color-based field Another factor is the potential due to a faulty test result, causing con- tests for cocaine HCl than for mari- litigation fees that could arise from siderable personal distress. 24 Spectroscopy 33(12) December 2018 www.spectroscopyonline.com

Table II: Performance characteristics comparison of color-based tests and portable ponent. There were also false identifica- IR and Raman spectroscopy for the presumptive field testing of cocaine HCl tions made in which an extra component Parameter Color-based Portable IR Portable Raman was identified in addition to the known Complexity Easy to use Easy to use Easy to use components that were not actually pres- 1 day, ent in the mixture (called a “false hit”). Training a component of 1 day ½ day Mistaken identifications are potentially narcotics training a large point of concern, but only if these Sample Consumption Destructive Nondestructive Nondestructive incorrectly identify or prevent the identification of a controlled substance. In this Time for analysis 1–3 minutes 1–3 minutes 1–3 minutes research, the majority of these false hits were extra identifications that were de- Each test is specif- Capable of Capable of ic for a drug class, identifying a identifying a termined to be of innocuous substances. Versatility thus different il- large range of large range of Ultimately, as long as the cocaine HCl licit drugs require compounds in a compounds in a is still being identified, an extra hit for separate tests mixture mixture something because of the adulterant Subjective: based Objectivity on perception of Objective Objective being used does not necessarily affect color the test results. 5–25%, IR spectroscopy is a nondestructive 5–25%, depending Limit of Detection 10% depending on on the adulterant method. Portable IR instruments are the adulterant simple to operate. Step-by-step prompts No false positives with icons are shown throughout an or negatives reported, however analysis. Although these instrument are Prone to false No false fl uorescence of easy to use and can be operated with little Specifi city positives and positives or nega- adulterants and negatives tives reported dark-colored training, scientific knowledge is required samples prohibit for sample selection, evaluating the spec- illicit drug identifi cation tral quality, and trouble shooting. A large Chain of custody benefit over the color tests is the chain of No Yes Yes corroboration custody corroboration in that when a Reduction of sample is tested, the results are automat- exposure to ically stored and time-stamped in the in- Testing requires Testing requires unknown chemi- Safety exposure to un- exposure to un- strument to be exported or reviewed later. cals because of known chemicals known chemicals analysis through Similar to the color tests, portable IR with containers ATR sampling requires direct testing of $2–5 per $25,000–$65,000 $12,500–$25,000 the specimen, thus potentially exposing Cost single-use test; per instrument, no per instrument, the user to an unknown substance. >$30,000 per year consumables no consumables Formal training would be required for the operation of a portable IR spectrom- Portable IR Spectroscopy This indicates that, even if the instrument eter. However, it is simple to operate, so The limit of detection for portable IR does not provide a positive “hit,” the user the training could easily be incorporated using the on-board library search algo- can receive technical support to assist into that already provided for officers. rithm for mannitol, caffeine, and baby with interpretation and troubleshooting. The analysis overall does not take more formula were at 25%. Below 25%, the in- The spectra could also be sent to a foren- than a few minutes for each sample being strument did not provide positive “hits” sic laboratory for interpretation, depend- run, which is comparable to the speed of for cocaine HCl. For artificial sweetener, ing on the agency’s protocols. Addition- the color-based field test. the instrument was able to detect cocaine ally, as previously mentioned, the lowest Though prices on portable IR spec- HCl at 15%, and, for lidocaine, it consist- concentration of street cocaine HCl was trometers vary by company, model, and ently had limits of detection at 5%. When reported to be 30%, which is higher than add-ons (such as libraries, attachments, manual spectral analysis was conducted the limit of detection for the portable IR and service), the price can range from by an educated chemist in spectral inter- with all adulterants tested. $25,000 to $65,000. There are no con- pretation, cocaine HCl was identified in There were no false positives or nega- sumables required for portable IR spec- all of the spectra below the established tives identified with the portable IR spectrometers, so this is a one-time, up-front limit of detection for the instrument’s trometer; however, there were a number cost. Additionally, these instruments search algorithm (Figure 3). This in- of misidentifications found with the are built to be rugged and used in high strument provides a Reachback feature, portable IR spectrometer. A misidentifi- stress situations; this means that, though where the user can electronically send a cation is any substance identified by the repair on the instruments may be neces- spectrum to a trained spectral interpreter instrument that was wrongly identified sary, they will not break easily and could for technical support at any time and day. in place of an authentic mixture com- be used for several years. Also, portable www.spectroscopyonline.com December 2018 Spectroscopy 33(12) 25 spectrometers have the capability to iden- fluorescence, it is important to recognize for all three methods, taking less than 3 tify a large number of controlled sub- that other illicit substances (such as her- min for each analysis. Portable IR and stances. Instead of buying ten different oin) or adulterants may fluoresce, which Raman spectroscopy methods are nonde- color-based field tests and making sure a would interfere with the ability for chem- structive, objective, and create a reviewable police department is stocked for an entire ical identification of any of the mixture record for use as evidence in adjudications, year with all of these options, one porta- components. Dark-colored samples pro- which are significant advantages over ble spectrometer could conduct the same hibit Raman analysis because they absorb color tests. Color tests are also more prone analysis. Finally, an increased demand for the incident radiation, thus potentially to false positives and negatives than tests these instruments would encourage com- destructively burning the sample. In this using portable spectroscopy, thus the latter panies to increase production, which could situation, an orbital-raster-scanning (ORS) are more reliable for the on-scene analysis lead to a cost reduction, thus making it a Raman was used to minimize the transfer of cocaine HCl. Portable Raman also has more affordable technology. of incident radiation, but not all portable the ability to identify cocaine HCl through Raman systems use ORS Raman. These some plastic bags, reducing the potential Portable Raman Spectroscopy issues may prohibit Raman analysis for for contamination and risk of exposure The limit of detection for the portable the identification of cocaine or other illicit to unknown chemicals by analysts. Color Raman spectrometer using the on-board drugs in the field. tests require less knowledge or skill from library search algorithm was consistently Similar to IR spectroscopy, Raman the operator, however, inserting training 25% cocaine HCl for all adulterants. In spectroscopy is nondestructive, requires on the different spectrometers during gen- most trials, the instrument could not only a few minutes for analysis, and cre- eral training for officers would be simple detect cocaine HCl at lower percentages; ates a reviewable record of the analysis that and feasible because the instruments are however, it was able to detect as low as provides chain-of-custody corroboration. created to be user-friendly. Although color 5% with the artificial sweetener, and 10% Much like the portable IR spectrometer, tests are generally thought to be less ex- with the baby formula. The ability to elec- it is a push-button method, with step-by- pensive than portable spectrometers, the tronically send spectra to Reachback or to step instructions on the screen. However, total cost over several years is comparable, a forensic laboratory for manual spectral there is a small spot size for analysis, and if not greater than, an instrument with interpretation is also available for portable focusing the LASER can be challenging at only a one-time up-front cost. Raman spectrometers. However, for these times. Sometimes, a few attempts are nec- Of the two portable spectroscopic samples, manual Raman spectral analysis essary to get a viable spectrum of the sam- methods, the authors concluded that, did not enable lower detection limits. ple. As with the portable IR spectrometer, although both technologies have similar One of the advantages of Raman spec- formal training would be required for the performance characteristics, there are troscopy is the ability to analyze sam- operation of the portable Raman, which some features of portable IR spectroscopy ples without making contact, analyzing could be simply incorporated into general that make it the preferred technique for through some containers made of clear training that officers are given. The same on-scene cocaine HCl identification. The glass and plastic bags. The ability to ana- caveat applies for both portable spectrom- long and reputable history of IR spectros- lyze substances contained within clear eters: Despite their ease of use, there is a copy means that there are more spectral plastic bags was tested, and the limit of de- need for educated users for proper sam- libraries and the technology has had more tection was unaffected, remaining at 25%. pling and analysis. time to be evaluated and perfected. Ad- This limit of detection would be acceptable Portable Raman spectrometers are gen- ditionally, fluorescence and the inability to detect the lowest reported concentration erally less expensive than most portable IR to analyze dark samples lessens the util- of cocaine HCl in street samples. Conse- spectrometers, although there are some ity of the portable Raman spectrometers, quently, unlike color tests and portable IR exceptions; thus prices range from $12,500 whereas a portable IR spectrometer is able spectroscopy, portable Raman does not to $60,000. Similarly to IR spectrometers, to produce interpretable spectra for all require direct testing, thus reducing ex- these instruments are built to be rugged specimens. Although these limitations posure to unknown substances. and do not require consumables, so this is were not a problem in the specific anal- There were no false positives or nega- a one-time, up-front cost. yses tested in this research, they could tives identified with the portable Raman prove to be prohibitive for identification spectrometer. As with the portable IR Conclusions by portable Raman of cocaine mixed with spectrometer, there were a number of Portable spectrometers have excellent other adulterants and for the analysis of “false hits” and misidentifications that potential to be employed for the on-scene other drugs, like heroin. Portable Raman occurred during analysis. The portable analysis of cocaine HCl. Performance spectrometers have the advantages of Raman analysis had significantly fewer characteristics were compared (Table II), being generally less expensive than port- misidentifications and false hits than and the advantages of portable spectros- able IR spectrometers, as well as being the portable IR, with a likely explanation copy over traditional color testing were able to analyze samples through some being the smaller onboard Raman spec- demonstrated. The limit of detection for clear glass and plastics, thus providing tral library, which limits misidentifica- all three methods would be acceptable at greater safety for the analyst. Ultimately, tions and false hits. Although none of the the lowest reported purity of street cocaine adulterants tested suffered from Raman HCl. The speed of analysis is comparable Continued on page 28 26 Spectroscopy 33(12) December 2018 www.spectroscopyonline.com

SPECTROSCOPY SPOTLIGHT

The Rise of Raman Spectroscopy in Biomedicine

In recent years, more and more academic research has been conducted on the use of Raman spectroscopy for biomedical applications. Effectively moving the technique from the research laboratory to the clinic, however, requires overcoming a number of challenges, ranging from dealing with fluorescence interference to automating the process enough to make it easy for medical staff to implement. Juergen Popp and his team at the Leibniz Institute of Photonic Technology and the Friedrich-Schiller University, in Jena, Germany, have been working to address these challenges, with the aim of making Raman spectroscopy a powerful, comprehensive tool for cell biology and clinical studies. He recently spoke to Spectroscopy about this work.

Alasdair Matheson

What are the main challenges associ- The last point is of great importance, be- need this information as quickly as possi- ated with using Raman spectroscopy in cause the differences in the Raman spec- ble. Microbiological standard procedures biomedical applications? What specific tra of different biological cells or tissue normally take more than 24 h because of benefits can the technique offer? types are very small and invisible to the the cultivation period required. With the Raman spectroscopy has become one of naked eye, and therefore require research chip-based Raman microspectroscopic the most academically researched analyt- on tailored statistical evaluation methods solution we have developed, this time can ical methods in the last decade. Raman (chemometric models). In the last few be reduced to between 2 to 3.5 h (1). In spectra depict molecular vibrations that years, my research team and I have suc- this scenario, doctors are in a position to are characteristic of the molecular sys- cessfully addressed all of these challenges. find the optimal therapy for their patients. tem under investigation. In other words, My team, together with the team of Raman spectra can be seen as a kind of You recently developed a simple and fast Prof. Dr. Ute Neugebauer, also from the “molecular fingerprint.” Raman spectros- Raman spectroscopy method to identify Leibniz Institute of Photonic Technology, copy enables label-free detection of the antimicrobial susceptibilities and deter- developed an approach for the automated molecular composition of complex sam- mine minimal inhibitory concentration identification of single bacteria. This ap- ples with little or no sample preparation. (1). Can you tell us more about the aims proach also allows the characterization The major challenge in the application of of this project and the benefits of the ap- of a possible (phenotypic) antibiotic re- Raman spectroscopy to investigate bio- proach you devised? sistance, as well as the determination of medical samples, such as cells and tissue, Infectious diseases are on the rise glob- the minimum inhibitory concentration is the possible occurrence of an interfer- ally, and threaten the health of people (MIC) that is necessary to kill infec- ing fluorescence background and the low all over the world. Using currently ap- tious agents. The unique selling point signal yields, compared to, for example, proved microbiological methods, the of this chip-based Raman approach is fluorescence spectroscopy. causative pathogens and their potential a dramatic reduction in the diagnosis However, decisive technical advances antibiotic resistance can usually only be time. The germs can be unambiguously have been made to overcome these unambiguously identified when it is too identified, and their resistance properties limitations in recent years, particularly late to treat them accurately. This is why determined in only 2–3.5 h with a very through the realization of highly efficient broad-spectrum antibiotics are often small number of microbial pathogens spectrometers and filters, and the imple- used. However, this type of therapy leads (a few hundred bacteria are sufficient). mentation of novel detector technologies. to more and more pathogens becoming Based on the information obtained, the These advances have led to a significant resistant to one or more antibiotics. The physician can tailor the patient therapy reduction in the recording times of challenges for the healthcare system, as to the specific pathogen. Raman spectra for biological samples. well as for society and the economy, are Further challenges toward a routine ap- enormous. The fight against infections What is novel about your approach? plication of Raman spectroscopy for bio- in Germany, for example, costs taxpay- We had to automate the approach to such medical analysis are the automation of ers billions of euros every year. To suc- an extent that it could be applied directly the complete process chain, that is, from cessfully treat an infection, doctors need in a hospital; this is the basis for the devel- sampling to measurement toward an au- information about the type of pathogen opment of chip-based Raman microscopy.

tomated analysis of the Raman spectra. and its antibiotic resistance, and they The combination of a Raman apparatus TOM FULLUM/GETTY IMAGES www.spectroscopyonline.com December 2018 Spectroscopy 33(12) 27 and an optical microscope allows for a required, and living cells can be stud- cell can be monitored for a better under- label free, noninvasive, culture-free, op- ied without perturbing the native cel- standing of the pathways, onset of action, tical and spectroscopic characterization, lular environment. Moreover, different and other pharmacodynamic param- and the identification of bacteria down types of analysis can be performed on eters. New therapeutic methods, such to the single-cell level. Each molecule the same device without any particular as stem-cell therapies, will require the generates an individual signature in the changes. Here, we specifically exploit injection of enriched and purified cells Raman spectrum, resulting in a specific these advantages of Raman spectros- into the human body, and in this type of molecular fingerprint for each bacterium. copy for the analysis and character- therapy efficacy largely depends on the Statistical evaluation algorithms enable ization of single cells, by developing a purity of the injected cells. Fluorescence- automated classification and identifica- device that can differentiate apoptosis based methods are at a clear disadvantage, tion of bacteria and antibiotic resistance. and necrosis, identify circulating tumor because they require labeling of cells for Additionally, the integration of chip- cells, and evaluate the cell cycle. This differentiation. Raman spectroscopy based enrichment methods in miniatur- extensive variety of applications opens can perform the identification and the ized microfluidic structures covers the new avenues for Raman spectroscopy enrichment of these cells label-free. entire process chain from sampling to as a convenient “go-to” tool in single- the final result. The uniqueness of the cell research and clinical investigations. What other projects have you been approach lies in its culture independence Traditionally, researchers in the field working on using Raman spectroscopy and the scalability of the approach. of Raman spectroscopy acquire Raman for biomedical applications? What images to characterize individual eukary- do you regard as the most innovative You also developed a high-throughput otic cells, or acquire individual Raman developments in this area of research? screening Raman spectroscopy (HTS-RS) spectra from subcellular regions in cells. Our other projects focus on research- platform for rapid and label-free macro- While the former results in a very long ing Raman approaches to solve current molecular fingerprinting of tens of thou- acquisition time and low throughput, the challenges in clinical pathology, such as sands of eukaryotic cells. (2). Why is the latter results in very high spectral varia- the determination of the tumor type and analysis of eukaryotic cells important? tion as a result of the significant intracel- grade and intraoperative delineation of In single cell research, Raman spectros- lular variation, which is commonly higher tumor margins (3–8). Reliable cancer di- copy has proven itself in many applica- than interclass differences between cells. agnosis is a complex process and requires tions, including the identification of cir- To overcome this problem, my team, led a number of diagnostic approaches, in- culating tumor cells, the characterization by Dr. Iwan Schie, has developed the cluding endoscopy, ultrasound, and mul- of drug–cell interactions, and the differ- new high-throughput screening Raman tidetector computed tomography. entiation of apoptotic and necrotic cells. spectroscopy (HTS-RS) platform, which However, the current “gold standard” So far, however, many Raman studies allows the acquisition of Raman spectra for making a definitive diagnosis is the have been performed on a limited num- from the entire cell at once, overcoming histopathological examination, that is, ber of cells, that is, in the order of 100 the problem of intracellular heterogene- the microscopic analysis of specially cells, which does not completely cover the ity. By combining this approach with a stained tissue biopsies. For a fast and statistical variability of cell experiments. self-developed, fully automated acquisi- safe in vivo or near in vivo intraopera- In contrast, for typical cytometric experi- tion and data processing strategy, we can tive diagnosis, however, new methods ments based on scattering or fluorescence, significantly increase the throughput of and approaches are urgently needed. In 10,000 cells for each sample can be ana- the Raman measurements. These im- this context, we explored the potential lyzed. By fully automating the process provements help move Raman spectros- of Raman spectroscopy to address these chain—that is, cell detection, Raman copy from being a niche technology to a challenges through the implementation spectrum recording, and chemometric powerful all-around tool for cell biology of optical molecular pathology. We in- analysis for online cell classification, in and clinical studies. troduced novel Raman fiber probes for multiwell plates or microfluidic environ- in vivo tissue screening to differentiate ments—this limitation can be overcome. What other applications would HTS- between healthy and malignant tissue Such an automated Raman platform en- RS be useful for? (3). However, scanning relatively large ables the measurement of a large num- Because Raman spectroscopy can be areas is quite difficult because of the ber of cells, for example 10,000, within used with living cells without affecting relatively long acquisition times of 30 min without sample preparation (2). them, it allows the investigation of cells in Raman spectroscopy. their native environment, opening novel The combination of Raman spectros- What benefits does this HTS-RS and intriguing research opportunities copy with fast imaging techniques such method offer and what is novel about in single cell research. Now, individual as optical coherence tomography (OCT) your approach? cells can be tracked over an extended or fluorescence lifetime imaging (FLIM) The advantage of Raman spectroscopy period of time to investigate changes can circumvent this problem (4). In addi- over other traditional staining-based of the molecular makeup as a result of tion, we work on multicontrast imaging methods, such as fluorescence micros- environmental effects at any timepoint. with nonlinear imaging techniques ex- copy, is that no sample preparation is Drug-induced effects on an individual hibiting similar imaging times. In partic- 28 Spectroscopy 33(12) December 2018 www.spectroscopyonline.com ular, we focus on multimodal nonlinear J. Popp, Anal. Bioanal. Chem. 407, 8291–8301 where he finished his habilitation in 2002. coherent anti-Stokes Raman scattering (2015). Since 2002, he has held a chair for phys- (CARS), two-photon excited fluorescence (5) T. Meyer, M. Chemnitz, M. Baumgartl, T. ical chemistry at the Friedrich-Schiller (TPEF), and second harmonic generation Gottschall, T. Pascher, C. Matthaus, B.F.M. University in Jena, Germany. Since 2006, (SHG) imaging with the potential for a Romeike, B.R. Brehm, J. Limpert, A. Tunner- he has also been the scientific director of reliable intraoperative tumor margin mann, M. Schmitt, B. Dietzek, and J. Popp, the Leibniz Institute of Photonic Tech- detection. Here, we developed a compact Anal. Chem. 84, 6703–6715. (2013). nology in Jena, Germany. His research and easy-to-use CARS–SHG–TPEF mul- (6) S. Heuke, O. Chernavskaia, T. Bocklitz, F.B. Le- interests are mainly concerned with bi- timodal nonlinear microscope combined gesse, T. Meyer, D. Akimov, O. Dirsch, G. Ernst, ophotonics. In particular, he focuses on with a novel fiber laser source for use in F. von Eggeling, I. Petersen, O. Guntinas-Li- the development and application of inno- clinics (5). The application of this micro- chius, M. Schmitt, and J. Popp, Head Neck 38, vative Raman techniques for biomedical scope, combined with advanced image 1545–1552 (2016). diagnosis. processing algorithms, offers great po- (7) T. Bocklitz, F.S. Salah, N. Vogler, S. Heuke, O. He has published more than 800 jour- tential to overcome current limitations Chernavskaia, C. Schmidt, M. Waldner, F.R. nal papers, and has been named as an of frozen section analysis with respect to Greten, R. Bräuer, M. Schmitt, A. Stallmach, inventor on 12 patents. He is the Edi- achieving a reliable intraoperative tumor I. Petersen, and J. Popp, BMC Cancer 16, tor-in-Chief of the Journal of Biophoton- margin detection (6–8). 534/1–1 (2016). ics. In 2012, he received an honorary doc- (8) O. Chernavskaia, S. Heuke, M. Vieth, O. Frie- toral degree from Babes-Bolyai University References drich, S. Schuermann, R. Atreya, A. Stallmach, in Cluj-Napoca, Romania. Professor Popp (1) J. Kirchhoff, U. Glaser, J.A. Bohnert, M.W. Pletz, M. F. Neurath, M. Waldner, I. Petersen, M. is the recipient of the 2013 Robert Kellner J. Popp, and U. Neugebauer, Anal. Chem. 90, Schmitt, T. Bocklitz, and J. Popp, Sci. Rep. 6, Lecture Award and the 2016 Pittsburgh 1811–1818 (2018). 29239 (2016). Spectroscopy Award. In 2016, he was (2) I.W. Schie, J. Rüger, A.S. Mondol, A. Ramoji, elected to the American Institute for Med- U. Neugebauer, C. Krafft, and J. Popp, Anal. Juergen Popp studied ical and Biological Engineering (AIMBE) Chem. 90, 2023-–2030 (2018). chemistry at the uni- College of Fellows. In 2018, Popp was (3) C. Matthäus, S. Dochow, G. Bergner, A. Latter- versities of Erlangen awarded the renowned Johannes Marcus mann, B.F. Romeike, E.T. Marple, C. Krafft, B. and Würzburg. After Marci Medal of the Czechoslovak Spectros- Dietzek, B.R. Brehm, and J. Popp, Anal. Chem. completing his PhD in copy Society. He also won the third prize 84, 7845–7851 (2012). chemistry, he joined of the Berthold Leibinger Innovation- (4) S. Dochow, D. Ma, I. Latka, T. Bocklitz, B. Hartl, Yale University to do spreis and was also awarded the “Kaiser- Juergen Popp J. Bec, H. Fatakdawala, E. Marple, K. Urmey, S. postdoctoral work. He Friedrich-Forschungspreis”. ◾ Wachsmann-Hogiu, M. Schmitt, L. Marcu, and then returned to Würzburg University,

Continued from page 25 thinking-it-was-cocaine-n-c-police- (7) United Nations Office on Drugs and Crime. jail-man-for-cheese-and-tortilla- World Drug Report 2012. United Nations both portable IR and Raman spectros- dough?ft=1&f=1001&sc=tw&utm_ Publication, New York (2018). copy are viable alternatives for crime source=twitterfeed&utm_medium=twitter. (8) S. Johns, A. Wist, and A. Najam, J. Forensic scene identification of cocaine HCl. (4) S. Jeong, “Man Spends Three Months In Jail Sci. 24(3), 631-649 (1979). After False Positive On Police Drug Test” References: (June 28, 2017). Retrieved April 28, 2018, Dory Lieblein, Peter Massey, and (1) R. Gabrielson and T. Sanders, “How a from https://www.cnn.com/2017/06/28/ Brooke W. Kammrath are with the $2 Roadside Drug Test Sends Innocent us/drug-test-drywall-positive-arrest-trnd/ Henry C. Lee College of Criminal Justice People to Jail” (July 7, 2016). Retrieved index.html. and Forensic Sciences at the University of April 28, 2018, from https://www.ny- (5) Forensic Technology Center of Excellence. New Haven, in West Haven, Connecticut. times.com/2016/07/10/magazine/how- Landscape Study of Field Portable Devices Meghann E. McMahon is with a-2-roadside-drug-test-sends-innocent- for Chemical and Presumptive Drug Test- the Wisconsin State Crime Laboratory, people-to-jail.html. ing. U.S. Department of Justice, National in Milwaukee, Wisconsin. Pauline (2) J. Kelly, “False Positives Equal False Justice” Institute of Justice, Office of Investigative E. Leary is with Smiths Detection, in (2008). Retrieved April 28, 2018, from and Forensic Sciences (2018). Edgewood, Maryland. Direct correspondence https://www.mpp.org/issues/criminal- (6) Safariland Group. NIK Test G- Cocaine, to: [email protected]. justice/false-positives/. Crack, & Free Base (2018). Retrieved (3) E. Peralta, “Thinking It Was Cocaine, N.C. August 29, 2018, from http://www.safa- Police Jail Man For Cheese And Tortilla riland.com/products/forensics/field-drug- For more information on this topic, Dough” (May 16, 2011). Retrieved April 28, tests/nik-test-g---cocaine-crack-and-free- please visit our homepage at: 2018, from https://www.npr.org/sections/ base-1006155.html#sm0000624lqmake www.spectroscopyonline.com thetwo-way/2011/05/16/136359770/ rfrm2cnczoduu2. The Visible Difference In Laboratory Science Expositions Join thousands of chemists and scientists in your specialty and beyond at Pittcon, the leading annual conference and exposition for laboratory science. This all-in-one event ŅýåųŸ±ĘĜčĘěÏ±ĬĜÆåųƋåÏĘĺĜÏ±ĬŞųŅčų±ĵ±ĺÚŸĩĜĬĬěÆƚĜĬÚĜĺčŸĘŅųƋÏŅƚųŸåŸüå±ƋƚųĜĺčƋŅŞĜÏŸ such as atomic spectroscopy, LIBS, UV/Vis, NMR, Raman, vibrational spectroscopy and ĵŅųåţ{ĬƚŸØåƻŞĬŅųå±ÚƼĺ±ĵĜÏĵ±ųĩåƋŞĬ±ÏåŅüƋĘåĬ±ƋåŸƋĜĺŸƋųƚĵåĺƋ±ƋĜŅĺ±ĺÚŸåųƴĜÏåŸţ Ƌ±ųƋÏŅĬĬ±ÆŅų±ƋĜĺčƵĜƋĘƼŅƚųÏŅĬĬå±čƚåŸüųŅĵ±ųŅƚĺÚƋĘåƵŅųĬÚƋŅĀĺÚŸŅĬƚƋĜŅĺŸƋŅƼŅƚų greatest laboratory challenges at Pittcon 2019. Pennsylvania Convention Center | Philadelphia, PA | March 17 - 21 | www.pittcon.org 30 Spectroscopy 33(12) December 2018 www.spectroscopyonline.com

SPECTROSCOPY SPOTLIGHT Megan Thielges, the 2018 Emerging Leader in Molecular Spectroscopy, Pioneers Protein Studies with 2D IR and Vibrational Probes

Protein engineering may be used to insert infrared-active groups, such as CNF, at specific sites within protein molecules. When combined with 2D infrared (IR) spectroscopy, these engineered probes, such as plastocyanin, enable the study of protein microenvironments and binding properties. This specialized technique provides details on site-specific protein heterogeneity and dynamics. Megan Thielges, an associate professor of chemistry at Indiana University, is a pioneer in the development and use of such probes with 2D IR. She is also the recipient of the 2018 Emerging Leader in Molecular Spectroscopy Award presented by Spectroscopy magazine. Thielges recently spoke with us about her work demonstrating the application of site-specific 2D IR spectroscopy for investigating protein function dynamics. She also talked about her career development and the biggest challenges and rewards in her daily work.

Jerome Workman, Jr.

Please tell us about some of your earliest theoretical basis of this technol- WWe uncovered multiple IR absorp- research interests. How did you get started ogy, while at the same time we ttions for single vibrational modes, in science? What has kept you motivated? have to make and handle delicate indicatingi multiple populated Honestly, since I can remember, I have protein samples and address im- states.s We then prepared the same wanted to be a scientist. When we gradu- portant questions about complex systems labeled with 13C to facili- ated from elementary school, my teacher systems. Juggling the disparate tatet NMR spectroscopy. The same wrote predictions for each student’s ca- and difficult aspects of our work bondsb that showed multiple states reer; I was to become a cancer researcher is a constant challenge. Megan Thielges via IR spectroscopy showed single and create my own designer line of lab- resonances via NMR spectroscopy, due to coats. As I was exposed to new areas, You did postdoctoral research at Stanford their being too fast to resolve on the NMR my interests evolved from microbiology University with Professor Michael D. Fayer. timescale. I think this work clearly showed to biochemistry to physical chemistry, What was the highlight of that work? the power of the inherently fast timescale essentially becoming more focused on I first demonstrated 2D IR spectroscopy of IR spectroscopy to uncover all poten- smaller-scale phenomena and more fun- of an IR probe introduced as an unnatural tially important conformational states. damental descriptions. My goal always amino acid as an approach to protein 2D The second paper I would choose fo- has been to have a career doing some- IR. Personally, the highlight of my post- cused on the role of dynamics in the re- thing I love, which has motivated me doctoral studies was the self-improvement gioselectivity of P450 catalysis. We char- throughout my life. gained from working with Mike and the acterized the dynamics of the P450 and a research group he had assembled. Inter- mutant in complex with several substrates What have been the most difficult aspects acting with such an intelligent group of that are acted upon with varying regiose- of your research to date? How have you people was inspiring. I consider it to be lectivity and found that the spectral dy- worked to overcome these challenges? one of the best times of my life. namics, but not the average frequency of Our work is highly interdisciplinary. It the IR probe, correlated with activity. The makes my work fun, but challenging. We Of all your research papers so far, what are idea that motion on fast timescales con- study protein dynamics via highly tech- two of the most meaningful papers you tributes to protein function is controver- nical methods, with the ultimate goal would like to highlight for our readers? sial. However, the environment of a chemi- of uncovering whether and how protein One of our studies employed infrared cal in solution fluctuates on picosecond dynamics are tailored by evolution for (IR) spectroscopy to characterize carbon timescales. I think of an enzyme active function. This endeavor requires that our deuterium IR probes for investigating the site as an evolved path, so I consider such group operate a femtosecond laser system binding of peptides with proline recogni- very fast motions of protein side chains are

and understand the fairly challenging tion motifs to an Src homology 3 domain. likewise to be important to our complete TOM FULLUM/GETTY IMAGES www.spectroscopyonline.com December 2018 Spectroscopy 33(12) 31 understanding of protein function. I think What new discoveries has your work slow dynamics. The extent the complex our study contributed to experimentally revealed in the basic understanding of populated one or the other states corre- demonstrating that idea. biological systems? lated with the regioselectivity of P450 on Generally, we have contributed to experi- the substrate, with fast dynamics associ- What is the most difficult or challeng- mentally uncovering rapidly interconvert- ated with lower selectivity. The activity did ing aspect of your current research and ing states of proteins and assessing their not correlate with the average frequency teaching role? relation to function. In the example of of the spectra, which is reflective of the Balancing all my time commitments is a proline-rich motif recognition by Src ho- average electrostatic environment at the challenge. I am working on the art of say- mology 3 domains, a long-standing ques- IR probe, suggesting that dynamics in the ing “no” to requests, but I am still not very tion regards the molecular basis of the conformation were the important factor. good at it. I am also constantly working to typically unfavorable entropy of binding. We are currently working on testing our be more effective mentor and to manage By IR spectroscopy, we found evidence model with different IR probes located and inspire a group of varying personalities. for multiple rapidly interconverting states at various sites in the enzyme, as well as associated with backbone configurations with different P450 enzymes, including What is the most exciting part of your of proline residues that change upon com- the human isoforms that are important work day? plexation in a manner that helps to explain to pharmaceutical development. Interacting with my students. Even when I the variation in the binding entropies mea- feel drained, I find myself rejuvenated after sured for different sequences. Another ex- How is your work in advanced coherent 2D talking with them. ample of new information from site-spe- IR spectroscopy relevant to fundamental cific IR spectroscopy came from our study understanding of enzymology and signal- Are the opportunities in the scientific arena of the metal site in the blue copper protein ing structure and functions? changing for women? What would you say plastocyanin, and how the complexation A focus of our research is elucidating how to young girls with an interest in science that with electron transfer partner cytochrome motions of proteins contribute to molec- may hesitate to pursue their aspirations? f affects it. We used carbon deuterium ular recognition; the recognition of sub- There is increasing support of females in bonds incorporated at the axial ligand as strates by enzymes and of linear sequence science, perhaps more so than in other a non-perturbative way to monitor the motifs by signaling domains are two ex- career areas, and I would say that I rarely binding-induced changes of the metal site amples. Due to the complexity of proteins, experience overt bias or harassment. I also and found that increased ionic interaction investigating the role of dynamics in their find that younger scientists have less inher- between the axial ligand and copper ion function requires experimental measure- ent bias from being raised from birth in a resulted from the protein–protein interac- ment with both high spatial and temporal society that at least claims to view women tion, providing a mechanism for the long resolution. IR spectroscopy provides an and men as equals. As the older genera- known decrease in redox potential in the approach that can be used to characterize tions retire over time, the climate will get complex. the environments at specific locations in continually better, just as is occurring in proteins and their dynamics on very fast the greater society. Would you briefly describe your work of timescales, while the protein is in solution detailed functional studies on cytochrome at room temperature. However, the extent Your research focuses on the use of vi- P450s? Have you been able to determine that 1D IR spectra can be interpreted in a brational probes, with two-dimensional that different substrate binding configura- rigorous manner is limited. 2D IR spec- IR spectroscopy (2D IR), to investigate tions and the fast dynamics of conforma- troscopy can provide richer information, the structures and dynamics of proteins. tional interchange will be key to under- including the spectral dynamics. Why did you decide to pursue this area standing the drug-degradation products in of research? promiscuous enzymes? What made you choose the path of two I am interested in the biophysics under- We have data that support that fast dy- distinct chemistry disciplines, these being lying protein function and think that the namics are important to the specificity protein and enzyme biochemistry and bio- dynamics are a major deficient aspect of of cytochrome P450 catalysis, but our physics, and ultrafast laser spectroscopy? our current understanding. As a gradu- work thus far is just a start. We prepared I’ve always been amazed by the complex- ate student I measured protein dynam- the enzyme with a carbon monoxide ity of living systems and how it could ics using nonlinear visible spectroscopy. bound at the active site to use as a vibra- evolve. My undergraduate major was Visible chromophores are huge and not tional probe, and then characterized the biochemistry, and all my work since natively found in most proteins, and their vibrational spectra and dynamics via 1D has focused on proteins. I also find the spectroscopy is much more complicated and 2D spectroscopy when the enzyme quantitative nature of physical chemis- to theoretically describe than IR chromo- was in complex with substrates that are try satisfying. Together these formed my phores. I considered pursing NMR spec- acted upon with varying regioselectivity. interests in biophysics and spectroscopy. troscopy, but the technique is so powerful The spectra indicated that the enzyme– Multidimensional spectroscopy is more because it is so well developed. I thought substrate complexes varyingly populated powerful than linear, and its implemen- that a different approach might be able to two conformational states–one with fast tation requires ultrafast lasers. I also re- uncover new aspects of protein biophysics. dynamics among substates, the other with ally enjoy working with optical systems, 32 Spectroscopy 33(12) December 2018 www.spectroscopyonline.com building and optimizing the instrument, We are always working to improve and enzymatic action that you would hope to like a kid with a really expensive set of extend the experimental approach of achieve over your lifetime? Legos. 1D and 2D IR spectroscopy on biomol- I hope to understand the mechanisms ecules. We are just beginning to inves- by which dynamics are tuned through How do you go about building a research tigate the human cytochrome P450s evolution for function, and through our team for this specialized work? that are important to human health. understanding, design protein dynamics All of our group thinks about proteins Our studies of proline-rich motifs are for selective or promiscuous activity. We and spectroscopy, but some focus more tied to a general interest in intrinsically can rationalize how to introduce enthalpic on the ultrafast 2D IR spectroscopy, disordered parts of proteins. They are contributions to binding through display while others focus on the biophysical very common, but less well understood of chemical functionality, but controlling questions, the biochemical aspects of than structured proteins, and their dy- entropic contributions is more challeng- labeling proteins with IR probe groups, namics are inherently key to function. ing. Regarding method development, my and the challenge of detecting weak ab- Another continued interest is biologi- hope is that biomolecular 2D IR spectros- sorptions by 1D IR spectroscopy. I try to cal electron transfer and photosyn- copy could be used to directly follow all the excite prospective members by interest thesis. We have plans to implement interactions and their dynamics among all in the questions we address and the fun non-equilibrium 2D IR experiments possible carbon deuterium labeled parts and challenge of building the ultrafast to investigate how proteins mediate and the rest of the functional groups in a spectroscopic system. electron transfer. protein, providing a spatially complete pic- ture nearing the level currently provided by Where would you like to see this research What is your most optimistic view of the NMR spectroscopy, but with faster tempo- expand into the future? fundamental understanding of proteins or ral resolution. ◾

Continued from page 6 hair, and trace evidence from a crime to Cambridge in 2009, maintaining an scene. He has co-authored more than adjunct position at Stony Brook. She a professor at the University at Albany, 200 peer reviewed publications with was director and associate director State University of New York. media coverage including TV and radio of the Northeastern Chemical Energy After receiving his PhD from the interviews, the Wall Street Journal, Storage Center, a Department of Energy Moscow Institute of Physics and Chemical & Engineering News, and (DOE) Energy Frontier Research Center Technology, Lednev was a group leader Forensic Magazine. Additionally, Lednev and is currently the director of the at the Institute of Chemical Physics, has served as an advisory member EPSRC Centre for Advanced Materials for Russian Academy of Sciences. He has on the White House Subcommittee Integrated Energy Systems. worked in several leading laboratories for Forensic Science, and is currently a Grey’s recent honors and awards including York University and, Durham Fellow and Governing Board member of include the Research Award from University, both in the UK, and the the Society for Applied Spectroscopy. the International Battery Association University of Tsukuba, Japan. In 1997, (2013), the Royal Society Davy Award Clare P. Grey Receives EAS Lednev came to the United States and (2014), the Arfvedson-Schlenk-Preis Award for Outstanding joined Sanford Asher’s laboratory at from the German Chemical Society Achievements in Magnetic the University of Pittsburgh, where (2015), the Société Chimique de France, Resonance they built the first nanosecond time French-British Prize (2017), and the resolved temperature-jump apparatus The EAS Award for Outstanding International Solid State Ionics Galvani- with ultraviolet Raman spectroscopic Achievements in Magnetic Resonance Nernst-Wagner Mid-Career Award detection and utilized it for the kinetic was presented to Clare P. Grey at the (2017), of which she is the first recipient. studies of protein folding. Lednev Eastern Analytical Symposium (EAS) on She is a Fellow of the Royal Society accepted an assistant professor position November 14 in Princeton, New Jersey. and in 2017 was elected as a Foreign at the University at Albany in 2002, was Grey is the Geoffrey Moorhouse-Gibson member of the American Academy promoted to full professor in 2013. professor of chemistry at Cambridge of Arts and Science and Fellow of the Lednev’s research focuses on University and a fellow of Pembroke Electrochemical Society. Her current the development of novel laser College Cambridge. research interests include the use of spectroscopy for medical diagnostics After post-doctoral fellowships in the solid state nuclear magnetic resonance and forensic purposes. He has presented Netherlands and at DuPont CR&D in (NMR) and diffraction-based methods a new approach for the noninvasive, Wilmington, Delaware, Gray joined the to determine structure–function early diagnostics of neurodegenerative faculty at Stony Brook University (SBU) relationships in materials for energy diseases such as Alzheimer’s and as an assistant professor in 1994, and storage (batteries and supercapacitors), Parkinson’s, and novel methods for was promoted to associate professor in conversion (fuel cells), and carbon the detection and characterization 1997, and then to professor in 2001, a capture. ◾ of biological stains, gunshot residue, position she held until2015. She moved www.spectroscopyonline.com December 2018 Spectroscopy 33(12) 33 2019 Corporate Capabilities

Corporate Profiles

ABB Measurement & Analytics 34 RedShiftBio 63

Amptek, Inc. 36 Rigaku Corporation 64

art photonics GmbH 38 Savillex 66

BaySpec, Inc.. 39 Specac Inc. 67

CEM Corporation 40 Shimadzu Scientific Instruments 68

Cobolt AB 42 Spellman High Voltage Electronics Corp. 70 Edinburgh Instruments 43 Starna Cells Inc. 71 EDAX Inc. 44 StellarNet, Inc. 72 Electro-Optics Technology, Inc. 46 Wasatch Photonics 73 Harrick Scientific Products, Inc. 47 WITec GmbH 74 International Centre for Diffraction Data 48

Inorganic Ventures 49 Application Notes Malvern Panalytical 50 Glass Expansion, Inc. 76 Ocean Optics 51 LECO Corporation 78 Milestone Inc. 52 Applied Rigaku Technologies 79 Moxtek Inc. 54

Ondax, now a Coherent company 56

OptiGrate Corp. 57

PerkinElmer, Inc. 58

PHOTONIS USA 59

PIKE Technologies, Inc. 60

Power4, LLC 62 34 SPECTROSCOPY CORPORATE CAPABILITIES DECEMBER 2018 www.spectroscopyonline.com ABB Measurement & Analytics

Markets Served Proud of our scientific and technological innovations for more than 45 years, ABB designs, manufactures, and markets high-performance analytical instruments for several key industries such as:

⦁ Academic & Research ⦁ Chemicals ⦁ Environment ⦁ Food and Beverage ⦁ Metals ⦁ Oil & Gas ⦁ Power ⦁ Semi-conductors ⦁ Space and Defense ⦁ Water and Wastewater

Company Description Facility ABB’s Measurement & Analytics business unit (www.abb.com/ Our high-tech manufacturing facility, located measurement) is one of the world’s leading manufacturers in Quebec City, Canada, employs more than and suppliers of smart instrumentation and analyzers. With 250 people, including R&D, manufacturing, thousands of experts around the world and high-performance marketing, sales, and administrative groups. digital technologies, ABB is on a mission to write the digital future and make measurement easy for our customers. ABB (NYSE: ABB) is a pioneering technology leader in electrification products, robotics Chief Techniques Supported and motion, industrial automation and Based on a solid foundation of innovative engineering and power grids, serving customers in utilities, manufacturing inherited from our roots in spectroscopy, the industry, and transport & infrastructure ABB Measurement & Quebec manufacturing site recently diversified its portfolio by globally. Continuing a history of innovation Analytics adding new product lines such as laser level transmitters and spanning more than 130 years, ABB today is 3400, Rue Pierre-Ardouin guided-wave radars, for high-precision level measurement; writing the future of industrial digitalization Quebec, (Quebec) G1P 0B2 Canada sensors that enable the detection of defects and perfor- and driving the Energy and Fourth Industrial mance issues, for power transformer health monitoring; and Revolutions. As title partner of Formula E, TELEPHONE new TDL ICOS instruments that measure gas and isotopes, the fully electric international FIA motorsport (418) 877-2944 for environmental, research and industrial applications. class, ABB is pushing the boundaries of FAX e-mobility to contribute to a sustainable (418) 877-2834 future. ABB operates in more than 100

E-MAIL countries with about 136,000 employees. [email protected]

WEB SITE www.abb.com/analytical

NUMBER OF EMPLOYEES 250

YEAR FOUNDED 1973 — TALYS™ for real-time control of chemical processes TALYS™ ASP500

The TALYS™ ASP500 is a new generation of process analyzer for the chemical industry. It is designed for in-line monitoring and control of batch or continuous processes. This high performance FT-NIR analyzer is flexible and supports various sampling accessories to meet wide measurement needs for liquid and powder applications. With small footprint and an embedded processor, TALYS™ is a robust industrial analyzer that minimizes cost of ownership. Learn more at abb.com/analytical or contact us at [email protected] 36 SPECTROSCOPY CORPORATE CAPABILITIES DECEMBER 2018 www.spectroscopyonline.com Amptek, Inc.

Also offering improved performance are Amptek’s SDD and Si-PIN detectors. Amptek detectors are offered in a wide range of configurations with their Preamplifiers and Digital Pulse Processors (DPP) for complete XRF portable solutions.

Applications ⦁ X-Ray fluorescence ⦁ Process control ⦁ OEM instrumentation ⦁ RoHS/WEEE compliance testing ⦁ Nondestructive analysis with XRF Company Description ⦁ Restricted metals detection Amptek, Inc., is a recognized world leader in the design and ⦁ Environmental monitoring manufacture of state-of-the-art X-ray and gamma ray detectors, ⦁ Medical and nuclear electronics preamplifiers, instrumentation, and components for portable ⦁ Heavy metals in plastics instruments, laboratories, satellites, and analytical purposes. ⦁ Lead detectors These products provide the user with high performance and ⦁ Toxic dump site monitoring high reliability together with small size and low power. ⦁ Semiconductor processing ⦁ Nuclear safeguards verification Chief Spectroscopic Techniques Supported ⦁ Plastic & metal separation X-ray fluorescence (EDXRF), direct spectral mea- ⦁ Coal & mining operations surements, EDS XRF, PIXE, and TXRF. ⦁ Sulfur in oil and coal detection ⦁ Smoke stack analysis Markets Served ⦁ Plating thickness Amptek serves wherever X-ray detection is used; for example, ⦁ Oil logging handheld and table-top XRF analyzers produced by OEMs; ⦁ Electro-optical systems research facilities in universities, commercial enterprises and ⦁ Research experiments & teaching the military; nuclear medicine; space; museums; environmental ⦁ Art and archaeology Amptek, Inc. monitoring; and geological analysis of soils and minerals. ⦁ Jewelry analysis 14 DeAngelo Drive ⦁ SEMs Bedford, MA 01730 Major Products/Services TELEPHONE Amptek recently brought silicon wafer manufacturing in- (781) 275-2242 house and improved the process. The results are detectors FAX with lower noise, lower leakage current, better charge (781) 275-3470 collection, and uniformity from detector to detector. ® E-MAIL The FAST SDD represents Amptek’s highest [email protected] performance silicon drift detector (SDD), capable of count rates over 1,000,000 counts per second (CPS) WEB SITE Amptek.com while maintaining excellent resolution. The FAST SDD® is also available with our patented C-Series NUMBER OF EMPLOYEES (Si N ) low energy windows for soft X-ray analysis. 47 3 4 Amptek has developed a 70 mm² FAST SDD® YEAR FOUNDED Detector in a TO-8 package. This is the same package 1977 that is used with all Amptek detectors. This makes the 70 mm² a drop-in replacement (same package, same pin-out, same voltages). Triple the count rate versus the 25 mm² SDD with the same performance. State-of-the-Art X-Ray Solutions •FAST SDD® •SDD •Si-PIN In-house manufacturing = The highest performing detectors available

The best detector for optimal results Amptek Detector Comparison: Si-PIN, Standard SDD, and FAST SDD® 55Fe FWHM vs Peaking Time at 210 K 300

280 FAST SDD® Detector

260 25 mm2 Si-PIN >2,000,000 CPS and 122 eV FWHM Resolution 240

220 13 mm2 Si-PIN Options: 2 2 200 • 25 mm collimated to 17 mm 6 mm2 Si-PIN 2 2 Fe FWHM @ 5.9 keV Fe

55 180 • 70 mm collimated to 50 mm 160 25 mm2 • Windows: Be (0.5 mil) 12.5 μm, or C Series (Si N ) Standard SDD 3 4 140 25 mm2 FAST SDD® • TO-8 package fits all Amptek configurations 120 0 10 20 30 Tpeak (μs)

Confi gurations to meet your needs

XR-100 and PX5 Digital Pulse Processor X-123 Complete X-Ray Spectrometer XRF Experimenters Kit

OEM Confi gurations

A sample of detectors with preamplifi ers Digital Pulse Processors and Power Supplies and heat sinks

® For XRF amptek.com 38 SPECTROSCOPY CORPORATE CAPABILITIES DECEMBER 2018 www.spectroscopyonline.com art photonics GmbH

Applications ⦁ Remote reaction monitoring in–line ⦁ Process spectroscopy for industrial process analytical technologies (PAT) used in chemical, petrochemical, atomic, food, and pharma industries ⦁ In-situ control of gluing, drying, and polymer curing processes ⦁ Crystallization process screening ⦁ Full automated fermentation process control with process-interfaces ⦁ Biomedical diagnostics in-vivo with spectral fiber sensors

Major Products/Services FlexiSpec® product line includes innovative fiber optic probes, bundles, and fiber couplers designed for in-line process-spectroscopy of a broad spectral range: from 200 nm to 16 μm. FlexiSpec® Probes design family enables measurement of ATR-absorption, transmission, or transflec- tion spectra; to run diffuse reflection, fluorescent, or multi-spectral analysis when coupled to any FT-IR, Company Description FT-NIR, or grating spectrometer; LED, QCL, MEMS, art photonics GmbH is the world’s leading manufacturer of or other type spectral sensor to be used in-field or unique fiber optics for mid IR-range, pioneering the patented in PAT-applications, eliminating the need for time technology of Polycrystalline PIR-fibers from Silver Halides consuming sample collection or preparation. and assembling a variety of specialty laser cables, bundles, FlexiSpec® industrial probes of standard 12 and spectroscopy probes from all types of Silica and IR-glass mm diameter are compatible with process plus PIR-fibers—to cover the broad spectral range 0.2–16 μm. interfaces required to clean probe optics in art photonics GmbH art photonics was founded in 1998 in Berlin to develop contaminating media in full or semi-automated Rudower Chaussee 46 and produce specialty fiber products under the motto “broad mode. Probes can comply with ATEX standards 12489 Berlin, Germany spectra fiber solutions.” To match fast business growth when used with SensoGate-FOS or Ceramat-FOS TELEPHONE in 2013 production, space was tripled to run ISO-9001 process interfaces—to be retracted, cleaned, and + 49 30-6779 887-0 certified production with a full range of production and test calibrated during chemical process for remote FAX equipment—to provide complete quality control in-house. molecular analysis of any liquid, gas, or solid + 49 30-6779 887-99 A team of highly skilled professionals enables fabrication mixtures under harsh process conditions. ® E-MAIL and sales of standard and customized products, while the FlexiSens product line includes innovative [email protected] R&D group develops in multiple projects the new types of Multi-Spectral Fiber System—a powerful tool fiber systems for spectral process-control in biotechnologies, to differentiate cancerous and healthy tissue. WEB SITE and in space, industrial chemical, petrochemical, and Raman, NIR, and MIR spectroscopy fiber www.artphotonics.com pharma applications. The latest projects are focused on probes were used to analyze samples from NUMBER OF EMPLOYEES biophotonics—to develop low cost spectral sensors with a kidney tumors. The differentiation between 30 tiny fiber probe to be used in clinics and ambulatories for cancer and healthy samples was successfully YEAR FOUNDED biomedical in-vivo diagnostics of tissues—like tumor margin obtained by multivariate data analysis. 1998 definition, early detection of cancer, or other diseases by endoscopy methods, and so on. www.spectroscopyonline.com DECEMBER 2018 SPECTROSCOPY CORPORATE CAPABILITIES 39 BaySpec, Inc.

Markets Served ⦁ Biomedical ⦁ Pharmaceutical ⦁ Chemical ⦁ Food & Agriculture ⦁ Semiconductor ⦁ Homeland Security ⦁ Oil & Gas ⦁ Fiber Sensing ⦁ Optical Telecommunication

Major Products/Services BaySpec provides a full line of spectroscopy products: ⦁ OEM Components: mini-light source, CCD cameras, InGaAs detectors, and custom optical modules. Company Description ⦁ UV-VIS–SWIR Spectrometers BaySpec, Inc., founded in 1999 with 100% manufacturing ⦁ VIS/SWIR OCT imaging spectrometers in the USA (San Jose, California), is a vertically integrated ⦁ Hyperspectral imagers: OCI series spectral sensing company. BaySpec brings the lab to aerial imagers for 400–1700 nm the sample by designing and manufacturing advanced spectral range, multi-bands and spectral instruments with an emphasis on compact size, continuous bands models, push broom light weight, and low power consumption. Our miniature and snapshot operating modes. UV-VIS-NIR-SWIR spectrometers, Raman analyzers, ⦁ Transportable mass spectrometer hyperspectral imagers, portable mass spectrometers, and with battery operation OEM spectral engines and components have been deployed in a wide range of markets such as Food & Agriculture, Facility Pharmaceuticals, Semiconductor, Safety & Security, BaySpec’s facility occupies an area of Healthcare, Telecommunications, and Research & Science. 48,000 sq ft, and is equipped with semi clean room, electronic, optical laboratory, BaySpec, Inc. Chief Spectroscopic Techniques Supported and instrument demo show room. All 1101 McKay Drive ⦁ Hyperspectral imaging for VIS/SWIR BaySpec’s products are 100% made at San Jose, CA 95131 USA ⦁ Portable mass spectrometry the San Jose facility in California, USA. TELEPHONE ⦁ Fluorescence (408) 512-5928 ⦁ FBG sensing ⦁ FAX Optical module for telecommunications (408) 512-5929 ⦁ Fiber-optic remote/on line sensing ⦁ OCT E-MAIL ⦁ [email protected] Reflectance ⦁ Absorbance/transmittance WEB SITE www.BaySpec.com

YEAR FOUNDED 1999 40 SPECTROSCOPY CORPORATE CAPABILITIES DECEMBER 2018 www.spectroscopyonline.com CEM Corporation

Major Products/Services CEM offers two platforms, a variety of vessels, and options for microwave digestion to ensure fast, complete, and reproducible digestions for a wide range of sample types. Run up to 40 samples simultaneously with the MARS 6 with One Touch™ Technology, a series of smart features that help automate the digestion process. MARS 6 automatically identifies and counts vessels, determines all of the parameters, adjusts power output, and performs the digestion for all major sample types. Discover® SP-D digests most samples in 10 min or less including cooldown. Discover SP-D offers individual parameter programming for each sample and an optional autosampler.

Company Description Facility CEM Corporation is a leading global company specializing CEM’s global headquarters, research in scientific solutions for critical laboratory applications. laboratories, and manufacturing fa- We design and manufacture systems for analytical cilities are located in Matthews, North laboratories, bioscience applications, life sciences, and Carolina. The company has subsidiaries processing plants worldwide. Our product portfolio in the United Kingdom, Ireland, Ger- includes innovative instrumentation for sample preparation many, Italy, France, and Japan as well as for elemental or chromatographic analysis, chemical more than 50 distributors worldwide. synthesis, peptide synthesis, and other applications.

CEM Corporation Chief Spectroscopic Techniques Supported PO Box 200, ⦁ ICP-MS Matthews, NC 28106 ⦁ ICP-OES ⦁ TELEPHONE Atomic Absorption ⦁ (704) 821-7015 GFAA FAX Markets Served (800) 726-3331 CEM instrumentation is used by chemists, scientists, E-MAIL and technicians in private industry, as well as leading [email protected] universities, analytical laboratories, and research facilities WEB SITE around the world. We support numerous markets, including www.cem.com the pharmaceutical, chemical, environmental, applied

NUMBER OF EMPLOYEES materials, food, and petroleum industries, among others. USA: 245 Elsewhere: 65

YEAR FOUNDED 1978 MARS 6 Better digestions. Better analyses.

The best technologies for the best results.

iPrep™ iWave™ iLink® One Touch™ The world’s most Accurate, contactless Remote system It’s like having a robust vessel temperature control operation chemist in a box

MARS 6™ cem.com/mars6 The leader in microwave digestion 42 SPECTROSCOPY CORPORATE CAPABILITIES DECEMBER 2018 www.spectroscopyonline.com Cobolt AB

Markets Served Cobolt AB supplies cutting-edge compact lasers with exceptional optical performance specifications and proven reliability and lifetime capability for OEM integration into analytical instrumentation for process control, biomedical research, clinical diagnosis, and industrial metrology, as well as for scientific research. Applications within these markets include Raman spectroscopy, interferometry, particle analysis, laser Doppler velocimetry, fluorescence microscopy, flow cytometry, LIBS, laser ultrasonics, and trace gas analysis.

Major Products/Services Cobolt lasers are all high performance lasers, typically with single frequency performance, excellent power stability, perfect beams, and very low noise. All Company Description Cobolt lasers are manufactured using Cobolt AB develop, manufacture, and supply high performance proprietary HTCure™ technology, and the diode-pumped lasers and modulated laser diodes in the resulting compact hermetically sealed UV, visible and near-infrared spectral ranges. The company’s package provides a very high level of laser products are key enabling components in advanced immunity to varying environmental analytical instrumentation equipment used in life science, conditions, along with exceptional process control, and industrial metrology applications. The reliability. Lasers built using the HTCure™ customer base is highly international, consisting of leading technology have been shown to withstand instrument manufacturers and research labs worldwide. multiple 60G mechanical shocks in Cobolt was founded in 2000 and has its headquarters operation without any sign of degraded in Solna, Sweden. Since December 2015, Cobolt AB is a performance. With demonstrated fully owned subsidiary of the HÜBNER Group, a market- lifetime capability of >60,000 hours Cobolt AB leading supplier of industrial mobility solutions for the and thousands of installed units in the Vretenvägen 13 transport industry recently branching into photonics. field, HTCure™ has proven to be one of Solna 171 54 the most reliable methods for making Sweden Chief Spectroscopic Techniques Supported industrial-grade lasers and is reflected with ⦁ Raman spectroscopy market leading warranty terms. TELEPHONE ⦁ Fluorescence spectroscopy +46 8 545 91230 ⦁ Laser induced breakdown spectroscopy (LIBS) Facility E-MAIL ⦁ Photo acoustic spectroscopy (PAS) Our head office is located in Stockholm, [email protected] Sweden, where all production, R&D, WEB SITE administration and sales is conducted www.cobolt.se in a top-modern facility, including a 2 YEAR FOUNDED >700 m clean room environment. 2000 www.spectroscopyonline.com DECEMBER 2018 SPECTROSCOPY CORPORATE CAPABILITIES 43 Edinburgh Instruments

Major Products/Services Research grade fluorescence spectrometers, analytical spectrofluorometers, dedicated fluorescence lifetime spectrometers, pulsed diode lasers and LEDs,

terahertz, and CO2 gas lasers. Facility Edinburgh Instruments are part of the Techcomp Europe group, with all manufacturing facilities in Scotland. Sales, service, and applications facilities are located around the world.

Company Description Edinburgh Instruments has become one of the world’s largest manufacturers of leading edge spectroscopic instrumentation. Edinburgh Instruments has over 33,000 sq. ft. of manufacturing and office space just outside Edinburgh, where it employs more than 90 people. The company is involved in the development, manufacture, and sale of a wide range of high technology products for the scientific research and Edinburgh Instruments industrial markets. Product ranges include research grade 2 Bain Square, Kirkton fluorescence spectrometers, analytical spectrofluorometers, Campus, Livingston, EH54 dedicated fluorescence lifetime spectrometers, pulsed 7DQ, United Kingdom diode lasers and LEDs, terahertz, and CO2 gas lasers. TELEPHONE +44 (0)1506 425 300 Chief Spectroscopic Techniques Supported FAX ⦁ Fluorescence spectroscopy +44 (0)1506 425 320 ⦁ Fluorescence lifetime ⦁ E-MAIL Phosphorescence lifetime [email protected] ⦁ Luminescence ⦁ Photoluminescence WEB SITE ⦁ Transient absorption spectroscopy www.edinst.com NUMBER OF EMPLOYEES Markets Served USA: 2 Academia and fundamental research in a wide range UK: 93 of fields, including photochemistry, photobiology, YEAR FOUNDED various applications in life science and physical 1971 chemistry, industrial applications such as food science, environment/water monitoring, and solar cells. 44 SPECTROSCOPY CORPORATE CAPABILITIES DECEMBER 2018 www.spectroscopyonline.com EDAX Inc.

renewable energy, pharmaceuticals, mining, forensics, petrochemicals, metallurgy, and manufacturing operations.

Major Products/Services ⦁ Energy dispersive X-ray fluorescence: EDAX manufactures XRF analyzers both for the laboratory and for coating analysis in industry. ⦁ Electron backscatter diffraction: EDAX supplies instrumentation for materials structural analysis on scanning electron microscopes (SEM). ⦁ Energy dispersive spectroscopy: EDAX provides a full range of EDS products for elemental analysis on SEMs. ⦁ Wavelength dispersive spectroscopy: EDAX offers parallel beam WDS products for elemental analysis on SEMs. Company Description EDAX is a leading provider of innovative materials characterization systems encompassing energy dispersive spectrometry (EDS), wavelength dispersive spectrometry (WDS), electron backscatter diffraction (EBSD), and X-ray fluorescence (XRF). EDAX products include standalone tools for EDS, EBSD and WDS, and integrated tools for EDS/EBSD, EDS/WDS, and EDS/EBSD/WDS. The company offers several XRF and micro-XRF elemental analyzers for small and microspot X-ray analysis and mapping. The XLNCE X-ray metrology line provides in-line instrumentation for process control and yield management for coating applications. EDAX develops the best solutions for micro- and nano-characterization, EDAX Inc. where elemental and/or structural information is required, 91 McKee Drive making analysis easier and more accurate. EDAX designs, manu- Mahwah, NJ 07430 factures, distributes, and services products for a broad range of Facility TELEPHONE industries, educational institutions, and research organizations. EDAX headquarters is located in Mahwah, (201) 529-4880 New Jersey, housing sales, engineering,

FAX Chief Spectroscopic Techniques Supported technical support, and operations. EDAX (201) 529-3156 ⦁ Energy dispersive spectroscopy (EDS) is committed to providing the best pos- ⦁ Energy dispersive X-ray fluorescence (XRF) sible support for our customers world- E-MAIL ⦁ [email protected] Electron backscatter diffraction (EBSD) wide with sales, service, and applications ⦁ Wavelength dispersive spectroscopy (WDS) support offices located in Japan, China, WEB SITE Singapore, The Netherlands, Germany, the www.edax.com Markets Served United Kingdom, and the United States. YEAR FOUNDED EDAX instrumentation for elemental and structural analysis 1962 is found in a broad spectrum of industrial, academic, and government applications from the field or production line to the most advanced research and development laboratory. Typical markets served include semiconductor and microelectronics, academic and industrial R&D laboratories, RoHS/WEEE New XRF Metrology Tool for Composition and Thickness Measurement The SMX benchtop analyzer is a complete non-destructive XRF tool for total process control from R&D and process development to manufacturing.

• Optimized process control and yield management • Non-destructive bulk sample and thin coating analysis • Comprehensive failure analysis and quality control • Applications include photovoltaic manufacturing, protective coatings, layer measurements, corrosion/wear and thermal barrier analysis

edax.com 46 SPECTROSCOPY CORPORATE CAPABILITIES DECEMBER 2018 www.spectroscopyonline.com Electro-Optics Technology, Inc.

Facility EOT recently moved to a brand new, 40,000 sq. ft. manufacturing facility located in Traverse City, Michigan, which includes a 15,000 sq. ft. state-of-the-art cleanroom and on-site machine shop.

Company Description Electro-Optics Technology, Inc. has been supplying innovative, high quality enabling components and diagnostic equipment worldwide for manufacturers and users of high power laser systems since 1987. Current products include: Faraday rotators and optical isolators for use with laser diodes, fiber lasers, and solid-state lasers. EOT also stocks a complete line of photodetectors used to monitor the output of pulsed, mode-locked, and externally modulated CW lasers.

Chief Spectroscopic Techniques Supported ⦁ Electro-Optics Raman Spectroscopy Technology, Inc. ⦁ DNA Sequencing 3340 Parkland Ct. ⦁ Imaging Traverse City, MI 49686 ⦁ Environmental Sensing ⦁ Mapping TELEPHONE ⦁ (231) 935-4044 Microscopy ⦁ 3D Metrology E-MAIL [email protected] Markets Served WEB SITE ⦁ Life Sciences www.eotech.com ⦁ Biotechnology NUMBER OF EMPLOYEES ⦁ Medical 85 ⦁ Materials Science ⦁ Research & Development YEAR FOUNDED 1987 Major Products/Services ⦁ Faraday Rotators ⦁ Optical Isolators ⦁ Photodetectors www.spectroscopyonline.com DECEMBER 2018 SPECTROSCOPY CORPORATE CAPABILITIES 47 Harrick Scientific Products, Inc.

Major Products/Services Harrick Scientific offers the most complete line of spectroscopy sampling products, including: ⦁ Video MVP—a diamond micro ATR accessory with built-in camera ⦁ DiaMaxATR—an affordable monolithic diamond ATR accessory ⦁ ConcentratIR2—a compact, multi reflection horizontal ATR micro-sampler that utilizes a Si or diamond ATR ⦁ Praying Mantis—a diffuse reflectance accessory available with environmental chambers/reaction cells ⦁ Seagull—a variable angle specular reflection and ATR accessory ⦁ VariGATR—a variable angle grazing angle ATR accessory for monolayers on Gold and Silicon substrates ⦁ FiberMate 2—an interface between spectrometers and fiberoptic applications ⦁ MultiLoop, Omni-Diff, and Omni-Spec— fiberoptic probes for ATR, diffuse reflection, and specular reflection Company Description ⦁ A variety of liquid and gas Harrick Scientific Products specializes in designing and transmission cells manufacturing instruments for optical spectroscopy. Since ⦁ Custom design development being established in 1969, Harrick Scientific has advanced the frontiers of optical spectroscopy through its innovations Facilities Harrick Scientific in all spectroscopic techniques. The founder of the company, Harrick Scientific Products is located Products, Inc. Dr. N.J. Harrick, pioneered attenuated total reflection (ATR) 30 miles north of New York City in 141 Tompkins Ave, spectroscopy and became the principal developer of this Pleasantville, New York. Our products 2nd Floor technique. Harrick Scientific offers a complete selection of are also available through FT-IR and Pleasantville, NY 10570 sampling accessories, including both standard and custom UV–vis spectrometer manufacturers, TELEPHONE designs, as well as an extensive line of optical elements. as well as distributors in the United (800) 248-3847 States and throughout the world. FAX Chief Spectroscopic Techniques Supported (914) 747-7209 ⦁ Transmission ⦁ E-MAIL Specular reflection [email protected] ⦁ Diffuse reflection ⦁ ATR WEB SITE ⦁ www.harricksci.com Fiber optics NUMBER OF EMPLOYEES Markets Served 25 Harrick Scientific serves analytical markets worldwide. Harrick’s YEAR FOUNDED customers typically are from research or quality control labo- 1969 ratories of industrial, governmental, research, and academic institutions throughout the world. Industries served include chemical, electronic, pharmaceutical, forensics, and biomedical. 48 SPECTROSCOPY CORPORATE CAPABILITIES DECEMBER 2018 www.spectroscopyonline.com International Centre for Diffraction Data

Major Products/Services PDF-4+ is designed to support rapid phase identification and quantitative analysis by providing key reference data required for these analyses. It combines the world’s largest sources of inorganic data from crystals and powders into a single database. PDF-4+ contains an array of tools, including a full suite of data simulation programs enabling the analysis of neutron, electron, and synchrotron data, in addition to X-ray. PDF-4+ features digitized patterns, molecular graphics, and atomic coordinates to enhance the ability to do quantitative analysis by any of three methods: Rietveld Analysis, Reference Intensity Ratio (RIR) Method, or Total Pattern Analysis.

Company Description ICDD is a non-profit scientific organization dedicated to collecting, editing, publishing, and distributing powder diffraction data for the identification of crystalline materials. Our mission is to continue to be the world center for quality diffraction and related data to meet the needs of the technical community. We promote the application of materials characterization methods in science and technology by providing forums for the exchange of ideas and information. We sponsor the Pharmaceutical Powder International Centre for X-ray Diffraction Symposium (PPXRD); the Denver X-ray Diffraction Data Conference; its proceedings, Advances in X-ray Analysis; 12 Campus Boulevard and the journal Powder Diffraction. ICDD and its members Newtown Square, PA 19073 conduct workshops and clinics on materials characterization at our headquarters in Newtown Square, Pennsylvania, TELEPHONE (610) 325-9814 and at X-ray analysis conferences around the world. Toll Free U.S.: (866) 378-9331 Chief Spectroscopic Techniques Supported ⦁ X-ray Diffraction FAX ⦁ Electron Diffraction (610) 325-9823 ⦁ Electron Backscatter Diffraction E-MAIL ⦁ Neutron Diffraction [email protected] ⦁ Synchrotron Diffraction WEB SITE www.icdd.com Markets Served ™ YEAR FOUNDED The Powder Diffraction File is designed for materials 1941 identification and characterization. ICDD databases are used worldwide by scientists in academia, government, and industry who are actively engaged in the field of X-ray powder diffraction and related disciplines. www.spectroscopyonline.com DECEMBER 2018 SPECTROSCOPY CORPORATE CAPABILITIES 49 Inorganic Ventures

Major Products/Services Inorganic Ventures specializes in the manufacture of the industry’s most accurate inorganic certified reference materials. Our offering of products includes ISO Guide 34 compliant ICP (OES and MS), IC, AA, water QC, wet chemistry, conductivity, pH buffer, and USP standards. After 20 years of data gathering and careful research, we were proud to unveil in early 2015 our Transpiration Control Technology (TCT), a new packaging system that drastically extends the shelf life of our CRMs. For more information on TCT, please visit our website at inorganicventures.com. TCT is just one more way we flex to your specs.

Facility Inorganic Ventures proudly distributes Company Description CRM solutions worldwide via a Since 1985, Inorganic Ventures has been manufacturing a distribution network that includes higher class of analytical inorganic standards at a fair price. North America, Europe, Asia, South Our certified reference materials (CRMs) are engineered to be America, Africa, and Australia. stable, compatible, and NIST traceable, and are manufactured ⦁ U.S. Headquarters: 300 Technology and tested under ISO Guide 34 and ISO 17025 guidelines Drive, Christiansburg, VA 24073, USA. (A2LA 883.01 & 883.02). We make almost any inorganic CRM for ICP, ICP-MS, IC, atomic absorption (AA), wet chemistry, and QC applications. In fact, custom standards are our specialty. As an ISO 9001 registered company (QSR-1034), our goal is to provide the highest-quality product with the most exceptional Inorganic Ventures customer service and technical support in the industry. 300 Technology Drive Christiansburg, VA 24073 Chief Analytical Techniques Supported TELEPHONE ⦁ ICP (OES and MS) (800) 669-6799 ⦁ AA FAX ⦁ IC (540) 585-3012 ⦁ Water quality ⦁ E-MAIL Wet chemistry [email protected] Markets Served WEB SITE Inorganic Ventures serves any market worldwide seeking inorganicventures.com the most accurate inorganic certified reference materials NUMBER OF EMPLOYEES available today. Markets seeking CRMs for ICP, ICP-MS, 65 IC, atomic absorption, wet chemistry, and QC applications YEAR FOUNDED can include: pharmaceutical (USP <232>), nuclear 1985 (10CFR50), food and beverage, mining, environmental (EPA), transportation, research, and medical. 50 SPECTROSCOPY CORPORATE CAPABILITIES DECEMBER 2018 www.spectroscopyonline.com Malvern Panalytical

Markets Served Malvern Panalytical products and solutions for Discovery, Research & Development, Process Control, and Product Quality Assurance are sold primarily into four market sectors: Pharma/Food/Bio, Metals/ Mining/Minerals, Chemicals/Petrochemicals, and Advanced Materials sector, which includes many academic and government research facilities around the world.

Major Products/Services ⦁ Dynamic Light Scattering (DLS) – particle size and zeta potential [Zetasizer] ⦁ X-ray Powder Diffraction (XRPD) – crystal phase/structure [Empyrean, Aeris] ⦁ Gel Permeation Chromatography (GPC)/ Size Exclusion Chromatography Company Description (SEC) – molecular weight, size Malvern Panalytical is a strong player in the materials and structure [OMNISEC] characterization market, providing expert solutions for ⦁ Image Analysis – particle size, shape actionable insight. Our technologies are used by scientists and chemical ID Morphologi 4 and engineers in a wide range of industries and organizations ⦁ Isothermal Titration Calorimetry (ITC) – to solve challenges associated with maximizing productivity, protein binding affinity [MicroCal ITC] developing better quality products, and getting them to market ⦁ Laser Diffraction – particle size faster. Our mission is to create superior, customer-focused distribution [Mastersizer 3000] solutions and services to deliver economic impact through ⦁ X-ray Fluorescence (XRF) – Malvern Panalytical chemical, physical, and structural analysis of materials. elemental analysis, USP<232> 117 Flanders Road [Zetium, Epsilon 1, Epsilon 4] Westborough, MA 01581 Chief Spectroscopic Techniques Supported ⦁ Nanoparticle Tracking Analysis TELEPHONE ⦁ X-ray diffraction (XRD) for phase identification and (NTA) – nanoparticle size/ +1 (508) 647-1100 quantification, determination of residual stress, concentration [NanoSight] ⦁ FAX texture, SAXS, WAXS, PDF, CT, non-ambient Resonant Mass Measurement +1 (508) 647-1115 ⦁ X-ray fluorescence (XRF) for elemental (RMM) – particle size and analysis and small spot mapping concentration [Archimedes] E-MAIL ⦁ ⦁ [email protected] Laser diffraction for the determination Rheometry – rheological properties of particle size distribution and viscosity [Kinexus] WEB SITE ⦁ Dynamic light scattering to analyze ⦁ Taylor Dispersion Analysis (TDA) www.malvernpanalytical.com nanoparticle size and zeta potential – molecular size and relative NUMBER OF EMPLOYEES ⦁ Rotational rheology to determine viscosity and viscoelasticity viscosity [Viscosizer TD] Global: 2000 ⦁ Image analysis for particle size, shape,

YEAR FOUNDED and chemical identification Facility 2017* (merger of two ⦁ Sample preparation by fusion Malvern Panalytical employs over 2,000 companies with a combined ⦁ Remote sensing and near-infrared spectroscopy people worldwide. With R&D and 100 years experience for materials identification manufacturing sites in North America, serving the laboratory Europe and China and a global sales instrumentation market) and service presence, we provide un- rivalled levels of customer support. www.spectroscopyonline.com DECEMBER 2018 SPECTROSCOPY CORPORATE CAPABILITIES 51 Ocean Optics

instruments an integral part of each student’s learning experience. Ocean Optics solutions are part of both everyday measurement needs and bigger technical challenges related to issues such as population growth and climate change.

Major Products/Services Spectrometers: General-purpose UV, Visible and NIR spectrometers; fluorescence spectrometers; Raman instruments; industrial spectrometers; teaching lab spectrometers; reflectometers; field spectrometers; spectral sensors; spectroradiometers; thin film systems Light Measurement Solutions: Smartphone- ready tools for quantifying light Multispectral Sensors and Precision Filters: Micro-patterned optical filters; multispectral sen- Company Description sors; multispectral cameras; filters, mirrors and Ocean Optics combines savvy system design, integration capabilities optical coatings; optical measurement and refer- and applications knowledge to help people solve problems using ence standards light measurement. We offer a suite of modular spectroscopy OEM Offerings: Spectrometers, sen- products, multispectral sensing solutions and software development sors, fibers; multispectral cameras, acces- for diverse applications in industrial settings, research and science, sories and sub-assemblies for embedding food and agriculture, applied biotechnology and life sciences, into OEM applications; custom software illumination and color measurement, and safety and security. Optical Sensors: Oxygen sensors, pH sensors, Also, Ocean Optics provides a comprehensive range of temperature sensing, transducing materials complementary technologies, including chemical sensors, Sampling Accessories: Collimating lenses, cu- Raman analyzers, metrology instrumentation, optical fibers vettes and holders, standards, filters and holders, and probes, optical filters, and spectroscopy accessories. The flow cells, cosine correctors, integrating spheres consolidation of PIXELTEQ multispectral sensing and imaging Light Sources: Deuterium, tungsten Ocean Optics offerings has further enhanced the company’s spectral imaging halogen, LED, calibration sources, 8060 Bryan Dairy Road design and manufacturing expertise in support of researchers, excitation sources, lasers, xenon Largo, FL 33777 developers, and OEMs across a wide range of applications. Optical Fiber and Probes: Fiber optic patch TELEPHONE cords; bare fiber; custom options; reflection and +1 (727) 733-2447 Chief Spectroscopic Techniques Supported transmission probes; vacuum feedthroughs FAX UV, Visible and NIR; absorbance, transmission and reflectance; +1 (727) 733-3962 laser characterization; LED quality control; Raman; SERS; Facility

E-MAIL fluorescence; irradiance; spectroradiometry; color determination; Ocean Optics has sales, service, engineering [email protected] fiber optic chemical sensing; chemometrics; end-point detection; and manufacturing operations in Florida, and headspace monitoring; nondestructive testing; remote monitoring; has full-service locations throughout Europe, WEB SITE multispectral sensing and imaging; and optical coating India and China. Ocean Optics is a subsidiary OceanOptics.com of Halma plc, an international market leader NUMBER OF EMPLOYEES Markets Served in safety, health and sensor technology. 200 Ocean Optics technologies are connected to a diverse range of YEAR FOUNDED industries and disciplines. Our products are used by innovators, 1989 researchers, educators, scientists, and OEM suppliers in lab settings, field research, and process environments worldwide. First respond- ers and security professionals have incorporated Ocean Optics products into their equipment. Science educators have made our 52 SPECTROSCOPY CORPORATE CAPABILITIES DECEMBER 2018 www.spectroscopyonline.com Milestone Inc.

Markets Served ⦁ Academic ⦁ Cannabis Testing ⦁ Clinical ⦁ Commercial Testing ⦁ Consumer Products ⦁ Environmental ⦁ Food Testing ⦁ Metals & Mining ⦁ Petrochemical ⦁ Pharmaceutical ⦁ Polymers ⦁ Specialty Chemicals

Major Products/Services Ethos UP: The most advanced closed vessel microwave digestion system offering Wi-Fi enabled extended control UltraWAVE: Single reaction chamber microwave digestion in a benchtop package for unmatched capabilities UltraCLAVE: Single reaction chamber microwave digestion offering ultimate throughput DMA-80: Direct mercury analysis with Company Description results in 5 minutes per sample Laboratories performing trace metals analysis today are DuoPUR: On-demand acid purification challenged to process more samples at lower detection TraceCLEAN: Acid steam cleaning system levels with fewer resources. Often, the limitations of existing for trace metal analysis accessories sample preparation approaches for metals analysis such as PYRO: Fast microwave ashing large consumption of acids, safety and handling problems, inconsistent recoveries, and limited throughput create a Facility Milestone Inc. “bottleneck” in productivity. To help break these bottlenecks, Milestone’s global headquarters are based in Ber- 25 Controls Drive Milestone offers a complete suite of microwave sample prep gamo, Italy, with manufacturing and R&D facilities Shelton, CT 06484 and clean chemistry productivity tools, backed by over 30 years in Germany and Switzerland. We support our global TELEPHONE of industry experience, and an unmatched portfolio of over 50 customers through direct offices in China, Japan, (866) 995-5100 patents. As a world leader in microwave technology, Milestone and Korea, as well as distributor networks in over 70 FAX is known for providing safe, reliable, and flexible platforms that countries. Milestone’s North American headquarters (203) 925-4241 enhance the productivity of metals testing labs. The key to this are located in Shelton, Connecticut, to provide ap- technological leadership lies in bringing together individuals plications, technical, and customer service support E-MAIL [email protected] from diverse scientific and engineering disciplines to solve real to our clients. We stock a full range of consumables, world problems with innovative microwave instrumentation. accessories, and service parts. Our applications lab is WEB SITE Over 20,000 customers worldwide look to Milestone to equipped with a full range of productivity tools and www.milestonesci.com improve their metals digestions, organic extractions, mercury a team of application chemists to provide customer www.milestonesrl.com analysis, and synthetic chemistry processes. We partner with our demonstrations as well as method development. NUMBER OF EMPLOYEES customers to meet their challenges now and well into the future. With a full service, support, and field sales team, 30 (in the US) Milestone can quickly respond to customer needs. 100 (outside the US) Chief Spectroscopic Techniques Supported YEAR FOUNDED ⦁ ICP mass spectrometry (ICP-MS) 1988 ⦁ Inductively coupled plasma (ICP-OES) ⦁ Atomic absorption (AA) ⦁ Mercury analysis Expectations surpassed. Quality assured.

Unrivaled technology Milestone sets the standard for microwave Safety by design digestion excellence.

Maximum throughput You make important choices for your lab every day – decisions that can impact the quality of your analyses, the efficiency of your processes and Lower operating costs the reliability of your operation. With three decades of technology firsts, including over thirty patents, Milestone instruments offer the most innovative metals prep technology on the market today.

With a complete digestion product line that includes the revolutionary UltraWAVE and powerful Ethos UP, Milestone is the first choice of laboratories that rely on quality sample prep for superior ICP/ICP-MS analyses. See what Milestone can do for your lab. Learn more about Milestone digestion products at www.milestonesci.com or call us at 866.995.5100.

MILESTONE

Ethos UP UltraWAVE UltraCLAVE

Markets Served ⦁ EDXRF and WDXRF ⦁ XRD ⦁ Microanalysis ⦁ Radiographic Inspection ⦁ Medical Imaging ⦁ X-ray Imaging ⦁ Security ⦁ Non-destructive testing (NDT) ⦁ 2D and 3D projection display ⦁ HMD/HUD ⦁ Polarimetric imaging ⦁ UV, visible, and IR spectroscopy

Company Description Moxtek is a leading supplier of advanced nano-optical and X-ray components used in display electronics, imaging, and analytical instrumentation. Moxtek provides innovative, solution-based products and services focused on performance, quality, and value. Moxtek products enable many new scientific discoveries and improve the quality of everyday life. Moxtek optical polarizers and polarizing beamsplitters enable advancements in projection display and analytical instrumentation including: 2-D and 3-D projection display, near-eye display, and optical analysis instrumentation. Moxtek Moxtek X-ray products empower compact handheld 452 West 1260 North and benchtop elemental analysis for positive material Orem, UT 84057 identification. Moxtek products are used in various EDXRF, WDXRF, and XRD systems for environmental screening, TELEPHONE hazardous substance analysis, and sorting and recycling. (801) 225-0930

FAX (802) 221-1121

E-MAIL [email protected]

WEB SITE www.moxtek.com

MOXTEK® Polarizers MOXTEK X-ray

Wire Grid Polarizers Portable X-Ray Sources and Beamsplitters

ICE Cube ™ Pin-Diode Polarizing Beamsplitters X-ray Detectors

Wire Grid Polarizers X-Ray Windows Custom Sizes

452 West 1260 North / Orem, UT 84057 Phone 801.225.0930 / Fax 801.221.1121 www.moxtek.com [email protected] 56 SPECTROSCOPY CORPORATE CAPABILITIES DECEMBER 2018 www.spectroscopyonline.com

Ondax, now a Coherent company

Major Products/Services ⦁ Low-Frequency THz-Raman® spectroscopy systems ⦁ Automated well plate/high- throughput screening tools ⦁ Wavelength stabilized and single frequency laser sources

Markets Served ⦁ Pharmaceutical ⦁ Materials science ⦁ Defense and security ⦁ Life science ⦁ Academic ⦁ Forensic science ⦁ Geological ⦁ Oil and gas ⦁ Research and development

Facility All products are U.S. manufactured at our Southern California headquarters in Mon- rovia, CA, 10 miles east of Pasadena and about 30 miles from the Los Angeles airport.

Company Description Ondax, now a Coherent company, is the leader in high-performance, low-frequency/THz-Raman® Spectroscopy systems and wavelength stabilized laser sources for a wide range of spectroscopy, industrial, scientific, defense, and life science applications. Ondax patented THz-Raman® spectroscopy sys- Ondax, Inc. tems combine chemical composition and structural analysis 850 E. Duarte Road into one instrument. Fast, easy capture of the entire Raman Monrovia, CA 91016 spectrum, including the complete chemical fingerprint along TELEPHONE with both Stokes and anti-Stokes low-frequency Raman signals (626)-357-9600 down to ~5 cm-1, improves sensitivity and reliability for poly-

FAX morph identification and screening, crystallization and phase (626) 513-7494 monitoring, semiconductor and 2D materials characterization, explosives forensics, and advanced materials analysis. Our E-MAIL SureLock™ and CleanLine™ Series single frequency lasers set [email protected] the price-performance standard for Raman laser sources. WEB SITE www.coherent.com Chief Spectroscopic Techniques Supported ⦁ Raman Spectroscopy ⦁ High-Throughput Screening www.spectroscopyonline.com DECEMBER 2018 SPECTROSCOPY CORPORATE CAPABILITIES 57 OptiGrate Corp.

diagnostics and treatment; and more.

Main Product Lines ⦁ Ultra-narrow band optical notch and bandpass filters with linewidth less than 10 cm-1 ⦁ Laser resonator mode selection filters/mirrors for spectral narrowing and thermal stabilization of lasers ⦁ Deflectors — transmitting volume Bragg gratings for angular filter- ing and deflection of laser light ⦁ Chirped volume Bragg gratings for compact and robust stretchers and Company Description compressors of ultra-short laser pulses OptiGrate Corp. designs and manufactures ultra-narrow band ⦁ Spectral beam combiner — angular optical filters based on volume Bragg grating (VBG) technologies and spectral filters for high-power in proprietary photo-thermo-refractive glass. Filters with ultra- laser spectral beam combining narrow bandwidth are formed by holographic techniques in the bulk of glass material, and demonstrate superior optical Facilities quality, outstanding durability, environmental stability, and OptiGrate moved to a new location in high optical damage threshold. OptiGrate is a pioneer and Oviedo, Florida, to accommodate an world leader in VBG technologies. For over 15 years, OptiGrate increased demand for the firm’s volume has delivered holographic optical elements (HOE) to a large Bragg grating (VBG) products and allow number of government contractors and OEMs in optoelectronics, for future expansion. The new 10,000 sq. analytical, medical, defense, and other industries. Since May ft., state-of-the-art facility was specially 2017, OptiGrate is a part of the IPG Photonics Family. designed and engineered for production of VBG filters. The facility—the only Markets vertically integrated VBG production plant OptiGrate supplied ultra-narrow band filters to hundreds of in the world—includes a photo-thermo- OptiGrate Corp. customers on five continents. These filters are used for: Raman refractive glass production unit, a VBG 562 South Econ Circle spectroscopy and microscopy; semiconductor, solid state, holographic production unit, and a VBG Oviedo, FL 32765 and fiber lasers; hyperspectral and Raman imaging systems; laser application development lab. TELEPHONE ultrafast laser systems; optical recording and storage; medical (407) 542-7704

FAX (407) 542-7804

E-MAIL [email protected]

WEB SITE www.optigrate.com

NUMBER OF EMPLOYEES 40

YEAR FOUNDED 1999 58 SPECTROSCOPY CORPORATE CAPABILITIES DECEMBER 2018 www.spectroscopyonline.com PerkinElmer, Inc.

Major Products/Services PerkinElmer, Inc. offers a wide breadth of instrumentation and solutions to meet your analytical measurement needs: ⦁ Atomic spectroscopy: AA, ICP-OES, ICP-MS ⦁ Chromatography: GC and GC custom solutions, and GC–MS/MS, GC–MS, HPLC and UHPLC, LC–MS, and LC–MS/MS ⦁ Hyphenated techniques: HPLC–ICP-MS, GC–ICP-MS, HS-GC, HS-GC–MS, TD-GC, TD-GC–MS, TG-IR, TG-MS, TG-GC–MS. ⦁ Mass spectrometry: ICP-MS, GC–MS, LC–MS ⦁ Molecular spectroscopy: FT-IR and FT-NIR, UV–vis and UV–vis–NIR, Company Description fluorescence spectroscopy PerkinElmer is a global leader focused on improving human ⦁ Thermal analysis: DSC, TGA, and environmental health, for the better. We provide our STA, DMA, TMA customers with critical knowledge, expertise, and innovative ⦁ Organic elemental analysis: CHNS/O detection, imaging, software, and service solutions so that ⦁ Consumables: Atomic spectroscopy, they can make better decisions for better outcomes. At chromatography, mass spectrometry, PerkinElmer, we make a difference every day, helping molecular spectroscopy, thermal scientists, clinicians, and governments detect earlier and analysis, organic elemental analysis more accurately to improve the health and safety of people ⦁ OneSource® Laboratory Services and the environment. Our solutions range from enabling the discovery of more effective diagnostics and therapies, Facilities to making sure that the food we eat, the water we drink, PerkinElmer, Inc. operates globally in and our environment are safe from contaminants. 150 countries.

PerkinElmer, Inc. Chief Spectroscopic Techniques Supported 940 Winter Street ⦁ Atomic absorption Waltham, MA 02451 ⦁ Inductively coupled plasma (ICP-OES and ICP-AES) TELEPHONE ⦁ ICP mass spectrometry (ICP-MS) (781) 663-6900 ⦁ Infrared (FT-IR and FT-NIR) spectroscopy FAX ⦁ UV–vis and UV–vis–NIR (781) 663-6052 ⦁ Fluorescence spectroscopy

E-MAIL [email protected] Markets Served PerkinElmer is a leading provider of precision instrumentation, WEB SITE reagents and chemistries, software, and services for a wide www.perkinelmer.com range of scientific and industrial laboratory applications, NUMBER OF EMPLOYEES including environmental monitoring, food and beverage 11,000 quality/safety, and chemical analysis, as well as genetic YEAR FOUNDED screening, drug discovery, and development. 1937 www.spectroscopyonline.com DECEMBER 2018 SPECTROSCOPY CORPORATE CAPABILITIES 59 PHOTONIS USA

Markets Served Mass spectrometry, nuclear detection, medical instrumentation, pharmaceutical safety, industrial instrumentation, and image intensification, as well as the custom design and manufacture of detectors, sensors, and ion mobility analyzers.

Major Products/Services PHOTONIS offers a complete range of high performance scientific and medical detector products. Our market includes electron multipliers, microchannel plates, mass spectrometry fiber optics and resistive glass, advance performance time-of-flight detectors, image intensifiers, ion mobility analyzers, neutron imagers, and other related products. Our detection products are found in most of today’s technology-based markets, including analytical instrumentation, medical diagnostics, chemistry, drug discovery, high-energy physics, space exploration, and scientific research. PHOTONIS is the largest supplier of standard, retrofit, and custom Company Description detectors in the mass spectrometry, residual PHOTONIS is a multinational high-technology group, with gas analyzer, and electron microscope more than 40 years of experience in manufacturing, sales, markets providing advanced detector designs and innovation, specializing in charged particle and photon for the highest sensitivity through superior sensor technology. The group operates internationally in the signal collection and noise reduction. PHOTONIS USA 660 Main Street night vision, industrial, scientific, and medical markets. Sturbridge Business Park Facilities Sturbridge, MA 01566 Chief Techniques Supported Sturbridge, MA; Lancaster, PA; Frisco, ⦁ Liquid chromatography detectors TX; Brive, France; Roden, Netherlands. TELEPHONE ⦁ Ion mobility spectrometry (508) 347-4000 ⦁ Mass spectrometers FAX ⦁ UV–vis fixed wavelength (508) 347-3849 ⦁ UV–vis variable wavelength E-MAIL ⦁ Gas chromatography detectors and accessories [email protected] ⦁ Detector accessories ⦁ Mass spectrometers: high-resolution WEB SITE ⦁ Mass spectrometers: low-resolution www.photonis.com ⦁ Mass spectrometers, residual gas analysis, magnetic NUMBER OF EMPLOYEES ⦁ Mass spectrometers, residual gas analysis, quadrupole US: 150 ⦁ ICP-MS Elsewhere: 900 ⦁ Time-of-flight mass spectrometry ⦁ YEAR FOUNDED Other detectors and accessories 1937 ⦁ Supercritical fluid chromatography detectors and accessories ⦁ Radioactivity ⦁ Neutron imaging 60 SPECTROSCOPY CORPORATE CAPABILITIES DECEMBER 2018 www.spectroscopyonline.com PIKE Technologies, Inc.

Markets Served PIKE products serve a broad range of markets including the petrochemical, food testing, forensic, optical, agricultural, and material science industries. We also specialize in the custom design of products and optical components for specific applications. Visit our website and take advantage of our unique, interactive FT-IR Calculator and Crystal Properties program.

Major Products/Services ⦁ MIRacleTM – patented “universal” sampling accessory (Diamond, ZnSe, Ge, and Si) ⦁ HATR – multiple reflection horizontal ATR ⦁ GladiATRTM, GladiATR VisionTM – Company Description highest performance diamond ATR PIKE Technologies specializes in the design and manufacture ⦁ VeeMAXTM – patented variable angle of accessories and optical systems that enhance the specular reflection and ATR accessory performance of commercial spectrometers. Our goal is to ⦁ ATRMaxTM – variable angle multiple make the lives of laboratory personnel easier with a wide reflection horizontal ATR range of FT-IR, NIR and UV-Vis spectroscopic sampling ⦁ Gas Cells – long and short path accessories that deliver greater energy throughput, higher ⦁ Valu-LineTM Kits – the most often spectral quality, and faster results. Our products are built with used sampling accessories, sample craftsmanship and care to exceed customer expectations. holders, cells, and optics combined ⦁ A wide range of fully automated Chief Spectroscopic Techniques Supported FT-IR and NIR products with easy- PIKE Technologies, Inc. PIKE products are compatible with most FT-IR and molecular to-integrate AutoPROTM software 6125 Cottonwood Drive spectrometers and are based upon the principles of Madison, WI 53719 spectroscopic measurement via: Facility TELEPHONE ⦁ Attenuated total reflectance (ATR) PIKE Technologies, Inc. is located in (608) 274-2721 ⦁ Diffuse reflectance Madison, Wisconsin. We distribute directly FAX ⦁ Specular reflectance to our customers worldwide and to OEMs (608) 274-0103 ⦁ Transmission, including sample cells and IR windows for packaging with spectrometers of all ⦁ E-MAIL Remote sensing manufacturers. Please call, or visit our [email protected] ⦁ High-throughput automation website for additional product information. ⦁ Integrating spheres WEB SITE ⦁ Polarization control www.piketech.com ⦁ IR microscopy NUMBER OF EMPLOYEES ⦁ Microsampling 60 ⦁ Gas cells YEAR FOUNDED 1989

62 SPECTROSCOPY CORPORATE CAPABILITIES DECEMBER 2018 www.spectroscopyonline.com Power4, LLC

Major Products/Services Power4 offers an in-depth product portfolio of power protection equipment and clean effective power conditioning solutions so that your analytical equipment operates efficiently and free from power issues. Power4’s uninterruptible power supply (UPS) solutions protect your electronic equipment in the event of an outage. Power4’s power conditioning solutions protect your system from noise, spikes, and transients that cause operational disruption and degrade system components, resulting in lost data, inaccurate test data, communication errors, and “no trouble found” service calls. In addition, Power4 provides specialized education, training, and Company Description technical assistance along with the Power4 understands there are many variables that determine client-specific tools and resources the success of an organization, business, or manufacturer. The to ensure long-term success. uninterrupted flow of clean, efficient power is one major variable and vital for the performance of mission critical systems and Facility equipment. When downtime, service calls, hardware failures, Power4 is located on the campus and inaccurate results threaten your customer experience of the Pennsylvania Biotechnology and bottom line, you need an innovative power quality Center of Bucks County in Doylestown, strategy backed by superior solutions, service, and support. Pennsylvania. The center seeks to Experts at diagnosing, remedying, and preventing power advance biotechnology in Bucks County Power4, LLC quality issues, Power4 is your prescription for success. Power4 and the surrounding region, maximize Pennsylvania Biotechnology Ctr. can eliminate these issues to improve profitability and give synergies between nonprofit scientists 3805 Old Easton Road, you the competitive advantage in your marketplace. and their commercial colleagues, and Doylestown, PA 18902 launch new ideas and discoveries Chief Spectroscopic Techniques Supported that will make a difference. TELEPHONE (267) 614-4847 All techniques and system configurations E-MAIL Markets Served [email protected] Focusing on the Analytical Instrumentation industry, Power4 WEB SITE develops customized power protection solutions to meet www.power4llc.com the specific power needs of critical systems in: Corporate

NUMBER OF EMPLOYEES and University Research Laboratories; Biotechnology USA: Team of Trusted Partners Centers; Pharmaceutical Companies; Drug Development Elsewhere: Team of Companies; Life Sciences Companies; and more. International Trusted Partners Power4 creates and implements personalized power

YEAR FOUNDED quality strategies for clean, uninterrupted power that 2015 improves profitability and reduces downtime. www.spectroscopyonline.com DECEMBER 2018 SPECTROSCOPY CORPORATE CAPABILITIES 63 RedShiftBio

Major Products/Services AQS3 pro Built on MMS technology. With its greater sensitivity, it enables the characterization of proteins from 0.1 mg/mL to over 200 mg/mL, the concentration range found across the drug development spectrum. No other technique (FTIR, circular dichroism and other spectrometry systems) is capable of this range of analysis, providing the ability to see changes that scientists could currently miss. The AQS3pro is a true walkaway instrument, capable of running through well plates automatically to provide characterization of aggregation, quantitation, similarity, stability and biophysical structure in one instrument.

AQS3 delta Bioanalytics software. Company Description The innovative and flexible analytics RedShiftBio is the developer of Microfluidic Modulation suite automates the routine analysis Spectroscopy (MMS). MMS addresses the limitations of of spectroscopic data, while providing current technologies and provides direct, label-free protein improved tools for gaining insights into analysis. It uses a tunable mid-infrared quantum cascade structural change and its implications. laser to generate an optical beam 1000 times brighter than those used in conventional FTIR, enabling the measurement of more concentrated samples, and the use of simpler detectors with no requirement for nitrogen cooling. The unique optical configuration of MMS delivers high sensitivity measurements over a wide concentration range of 0.1–200 RedShiftBio mg/mL to 0.01 mg/mL, giving MMS a wider dynamic range 131 Middlesex Turnpike, than alternative protein characterization techniques. Burlington, MA 01803 TELEPHONE Chief Spectroscopic Techniques Supported (781) 345-7300 ⦁ IR-Based Microfluidic Modulation Spectroscopy FAX ⦁ IR Spectroscopy (781) 345-7301

E-MAIL Markets Served [email protected] ⦁ Pharmaceutical Development ⦁ Pharmaceutical R&D WEB SITE www.RedShiftBio.com

NUMBER OF EMPLOYEES 20

YEAR FOUNDED 2010 64 SPECTROSCOPY CORPORATE CAPABILITIES DECEMBER 2018 www.spectroscopyonline.com Rigaku Corporation

⦁ SmartLab® series— Intelligent X-ray diffraction (XRD) systems ⦁ Ultima IV — Multipurpose X-ray diffraction system ⦁ NEX CG — Cartesian geometry EDXRF spectrometer ⦁ NEX QC — Low cost benchtop EDXRF elemental analyzer ⦁ NEX QC+ — Benchtop EDXRF elemental analyzer ⦁ Nex QC+ Quant EZ — Benchtop EDXRF with Windows® software ⦁ NEX DE — Fast SDD EDXRF ⦁ NEX DE VS — Variable spot size EDXRF spectrometer ⦁ NEX OL — On-line process EDXRF analyzer ⦁ NEX LS — Scanning multi-element process coatings analyzer ⦁ ZSX Primus — 4 kW sequential WDXRF Company Description spectrometer Since its inception in 1951, Rigaku has been at the forefront ⦁ ZSX Primus III+ — 3 kW tube-above of analytical and industrial instrumentation technology. Today, sequential WDXRF with hundreds of major innovations to their credit, the Rigaku ⦁ ZSX Primus IV — 4 kW tube-above Group of Companies are world leaders in the fields of protein sequential WDXRF and small molecule X-ray crystallography, general X-ray diffraction ⦁ Simultix 15 — High-throughput, (XRD and PXRD), X-ray spectrometry (EDXRF and WDXRF), X-ray simultaneous WDXRF spectrometer optics, semiconductor metrology, Raman spectroscopy, laser ⦁ ZSX Primus 400 — Large sample induced breakdown (LIBS) spectrometry, automation, computed sequential WDXRF spectrometer tomography, nondestructive testing, and thermal analysis. ⦁ Progeny — Handheld Raman spectrometer ⦁ Progeny ResQ — 1064 nm handheld Chief Spectroscopic Techniques Supported Raman for rapid chemical identification ⦁ X-ray spectrometry ⦁ Progeny ResQ FLX — Advanced Narcotics ⦁ Laser induced breakdown (LIBS) spectrometry Analyzer Rigaku Corporation ⦁ Raman spectroscopy ⦁ KT-100S — Handheld laser induced 4-14-4, Sendagaya ⦁ Energy dispersive X-ray fluorescence (EDXRF) breakdown (LIBS) spectrometer Tokyo 151-0051, Japan ⦁ Wavelength dispersive X-ray fluorescence (WDXRF) TELEPHONE ⦁ Related: X-ray diffraction (XRD) Facility +1(281) 362-2300 ⦁ Related: X-ray reflectometry (XRR) Based in Tokyo, Japan, Rigaku is a global FAX organization with offices, laboratories, and +1(281) 364-3628 Markets Served production facilities around the world. Major

E-MAIL Cement, petroleum, mining, refining, pulp and paper, wood production facilities are located in Auburn [email protected] treating, chemicals, pharmaceuticals, biotechnology, forensics, Hills, Michigan; Austin, Texas; Boston, homeland security, defense, aerospace, energy, metals and Massachusetts; Carlsbad, California; Osaka, WEB SITE www.rigaku.com alloys, life sciences, polymers and plastics, inks and dyes, Japan; Prague, Czech Republic; Tokyo, Japan; cosmetics, nanomaterials, photovoltaics, semiconductors, Wroclaw, Poland; Tucson, Arizona; The NUMBER OF EMPLOYEES chemistry, geology and minerals, physics, teaching, and academy. Woodlands, Texas; and Yamanashi, Japan. Worldwide: 1400 YEAR FOUNDED Major Products/Services 1951 ⦁ Miniflex™— High-power benchtop X-ray diffractometer (XRD) ⦁ NANOHUNTER II benchtop TXRF spectrometer ⦁ NANOPIX - Mini Benchtop small angle X-ray scattering (SAXS) instrument ⦁ Supermini200 — Benchtop WDXRF spectrometer Applied Rigaku Technologies, Inc. www.RigakuEDXRF.com | [email protected] 66 SPECTROSCOPY CORPORATE CAPABILITIES DECEMBER 2018 www.spectroscopyonline.com Savillex

Major Products/Services C-Flow PFA Microconcentric Nebulizers ⦁ From 200 μL/min down to 35 μL/min uptake rate ⦁ High sensitivity, low RSDs ⦁ Unique two-piece body design ensures excellent reproducibility from nebulizer to nebulizer ⦁ Easily backflushed without tools ⦁ Constant ID sample uptake path C-Flow d-Type PFA Nebulizers ⦁ With removable uptake line ⦁ From 0.2 mL/min to 1.2 mL/min uptake rate (pumped) ⦁ Extreme matrix tolerance: up to 25% salt and 80 μM diameter particulates ⦁ Easily backflushed without tools ⦁ Suitable for routine applications of both ICP-MS and ICP-OES X-Flow PFA Nebulizer Company Description ⦁ Ultimate matrix tolerance: virtually Savillex has been manufacturing fluoropolymer laboratory uncloggable products since 1976, and has unmatched expertise in the ⦁ One piece all PFA cross-flow design molding and machining of perfluoroalkoxy alkanes (PFA). All ⦁ Removable uptake line with Savillex zero our design, tooling, molding, manufacturing, and testing is dead volume connector done in-house, giving us complete control of product quality. PFA Cyclonic Spray Chamber Our products are widely used in trace metals analysis—from ⦁ World’s first blow molded cyclonic spray sample collection through to ICP sample introduction. chamber ⦁ All PFA with interchangeable exit ports Chief Spectroscopic Techniques Supported to suit different ICP instruments The sample introduction system is a critical component of ⦁ Unmatched sensitivity for an inert cyclonic Savillex both ICP-OES and ICP-MS instrumentation. The design of the ⦁ Translucent side walls allow user to see 10321 West 70th Street sample introduction system affects all aspects of performance, inside during operation Eden Prairie, MN 55344-3446 including sensitivity, stability, washout, matrix tolerance, and PFA Inert Kits TELEPHONE also oxide level and isotope ratio precision in ICP-MS. Also, the ⦁ True double pass Scott type design (952) 935-4100 cleanliness of the materials that come into contact with the ⦁ O-ring free end cap ⦁ FAX sample directly impact the quality of the analytical blank. Our Used as OEM equipment (952) 936-2292 ICP sample introduction products are manufactured using the ⦁ Platinum or sapphire injectors highest purity grades of PFA resin. With over 40 years experi- E-MAIL [email protected] ence in fluoropolymer molding and unmatched expertise in Facility the design and molding of PFA components, Savillex is bringing Based in Eden Prairie, Minnesota, WEB SITE new products and capabilities to ICP-MS and ICP-OES, includ- we serve thousands of customers in www.savillex.com ing the world’s first blow molded PFA cyclonic spray chamber. over 60 countries worldwide through YEAR FOUNDED our partners and distributors. 1976 Markets Served Savillex sample introduction systems are used across a wide range of ICP-MS and ICP-OES applications, including semiconductor, geochemistry, pharmaceutical, environmental, biomedical, and petrochemical. www.spectroscopyonline.com DECEMBER 2018 SPECTROSCOPY CORPORATE CAPABILITIES 67 Specac Inc.

Major Products/Services Specac’s range (fit most spectrometers) includes: ⦁ Pearl liquid FTIR ⦁ Golden Gate ATR ⦁ Quest ATR ⦁ Omni-Cell liquid FTIR ⦁ Gas Cells ⦁ Atlas Manual Hydraulic Press (0–25 ton) ⦁ Atlas Autotouch Automatic Hydraulic Press (8–40 ton) ⦁ Free-standing Wire Grid FTIR Polarizers ⦁ Demountable Wire Grid FTIR Polarizers

Facility Specac has offices in the USA, UK, Company Description and China, and has a global network Specac is a leading manufacturer of high quality FT-IR of dealers and distributors. accessories and FT-IR/XRF sample preparation products. They regularly bring new and innovative solutions to the market. Nobody makes more user-friendly or accurate products. ATR, diffuse reflectance, specular reflectance, and transmission are among the techniques served. Pellets, discs, or films are covered by Specac’s Atlas range of automated/manual benchtop pressing and grinding solutions. From small low tonnage manual hydraulic presses to 40-ton fully programmable powered presses with programmable loads, the Specac Inc. Atlas range covers FT-IR, XRF, and more. 414 Commerce Dr. #175, Specac products serve universities, Fort Washington, PA 19034 research and development, forensics, TELEPHONE pharmaceutical, oil industries, and more. +1 (866) 726 1126 Get in touch with us at Specac.com/contact/quote to FAX receive information and pricing on a specific application (215) 793-4011 or product, and to try out the equipment with a free

E-MAIL visit from an experienced member of our team. [email protected] Chief Spectroscopic Techniques Supported WEB SITE ⦁ Infrared transmission www.specac.com ⦁ Infrared reflectance YEAR FOUNDED ⦁ Wire grid polarizers 1971 ⦁ Process cells ⦁ XRF sample preparation ⦁ FT-IR sample preparation ⦁ Bespoke optics solutions 68 SPECTROSCOPY CORPORATE CAPABILITIES DECEMBER 2018 www.spectroscopyonline.com Shimadzu Scientific Instruments

that meet scientists’ needs for ruggedness, ease of use, validation, and applications. Key instruments include the high-resolution, ultrafast, easy-to-use, double-beam UV- 1900, high-performance UV-2600/2700, and three-detector UV-3600/3700. FT-IR: From research to routine tasks, our systems, including the fast, sensitive IRTracer-100, new portable IRSpirit, and fully automated AIM-9000 microscope, deliver stable, reliable, high-precision infrared analysis for a wide range of applications. Fluorescence: Delivering outstanding speed, stability, and sensitivity, and incorporating intuitive software, the high-performance RF-6000 spectro- fluorophotometer offers ultimate performance for challenging applications Company Description in such markets as chemicals, environ- Shimadzu Scientific Instruments (SSI) is the North American mental, pharmaceutical, and foods. subsidiary of Shimadzu Corp., headquartered in Kyoto, Ja- AA/ICP-MS: Simultaneous ICP, efficient, pan. SSI was established in 1975 to provide analytical solu- sensitive ICPMS-2030, and our series tions to a wide range of laboratories in the Americas. With of high-quality AA spectrometers a vast installed base and preferred vendor status at many offer superior reliability, precision, institutions, SSI’s instruments are used by top research- sensitivity, and throughput to deliver ers across the globe, customers who can count on the maximum performance and value. stability, experience, and support only Shimadzu offers. X-ray: Our EDX/XRF/XRD systems are Shimadzu Scientific packed with powerful features to provide Instruments Chief Spectroscopic Techniques Supported users with versatile, easy-to-use solutions. ⦁ 7102 Riverwood Drive UV–vis Columbia, MD 21046 ⦁ FT-IR Facility ⦁ Fluorescence Shimadzu’s US headquarters includes TELEPHONE ⦁ (800) 477-1227 Atomic (AA/ICP-MS) a customer service and training ⦁ (410) 381-1227 X-ray (EDX/XRD/XRF) center, a solution center to showcase ⦁ GC–MS-MS technologies, and an innovation center FAX ⦁ LC–MS-MS for promoting collaborative projects (410) 381-1222 with customers. Shimadzu’s regional E-MAIL Markets Served facilities, strategically located around [email protected] Shimadzu offers more spectroscopy instrumentation, with the US, provide customers with local WEB SITE more software and accessory options, than any other com- sales, service, and technical support. www.ssi.shimadzu.com pany. This flexibility enables spectroscopists in virtually any NUMBER OF EMPLOYEES laboratory, from biotechnology, pharmaceutical, and industrial US: 480 to academic, forensic, and environmental, to select the instru- Worldwide: 11,900 ment best suited to their application. Shimadzu provides free technical support for the life of the instruments, and encour- YEAR FOUNDED Shimadzu Scientific ages customer alliances to further product development. Instruments: 1975 Shimadzu Corporation: 1875 Major Products/Services UV–vis: Shimadzu has been developing UV–vis spectrophotometers for over 60 years, and continues to manufacture instruments IRSpirit, Ready to Run

5OCNNCPFNKIJVYGKIJV5JKOCF\WoUIRSpirit FTIR spectrophotometerRTQXKFGUWPOCVEJGF HWPEVKQPCNKV[KPKVUENCUUQHEQORCEVKPUVTWOGPVUYJKNGFGNKXGTKPIGZEGRVKQPCNTGNKCDKNKV[KP EQPVCOKPCPVCPCN[UKUKFGPVKƂECVKQPVGUVUCPFSWCPVKVCVKXGOGCUWTGOGPVU

5RCEG'HƂEKGPV&GUKIPYKVJ5VCPFCTFUK\GF5CORNG %QORCTVOGPV – Ensures Portability and Versatility )WKFGF9QTMƃQY$CUGF5QHVYCTG +42KNQV – Ensures Quick and Accurate Measurements *KIJ4GNKCDKNKV[ – Ensures the System Can Be Utilized with %QPƂFGPEG 9KFG5GNGEVKQPQH#EEGUUQTKGU –+PENWFGU#64CPF%QPƂIWTCVKQP 1RVKQPUHQT7UGKP*KIJ*WOKFKV['PXKTQPOGPVU

.GCTPOQTGCDQWV5JKOCF\WoU+45RKTKV8KUKVWUQPNKPGCVwww.ssi.shimadzu.com/Spirit

1TFGTEQPUWOCDNGUCPFCEEGUUQTKGUQPNKPGCVJVVRUVQTGUJKOCF\WEQO5JKOCF\W5EKGPVKƂE+PUVTWOGPVU+PE4KXGTYQQF&T%QNWODKC/&75# 70 SPECTROSCOPY CORPORATE CAPABILITIES DECEMBER 2018 www.spectroscopyonline.com

Facilities Spellman High Voltage Spellman maintains centers of excellence, manufacturing, and support in key regions around the world. Electronics Corp. Our 100,000 sq. ft. main facility and global headquarters in New York includes engineering, service, administration, and manufacturing. Spellman’s low cost manufacturing center in Mexico is a state of-the-art, 228,500 sq. ft. complex devoted to high volume production. A 50,000 sq. ft. production facility in China provides high quality products at competitive prices to Asian and worldwide OEM customers, and is ISO 13485 certified. Spellman’s United Kingdom operation is a 27,500 sq. ft. facility and is our global center of excellence for high- precision analytical power supply design and production. Spellman’s ISO 9001 and 14001 certified production centers in New York, Mexico, China, the UK, and Germany utilize lean manufacturing techniques such as value stream mapping, focused factories, mixed and single Company Description model cells, and visual control systems When OEM system manufacturers around the world rein order to reduce cost and lead time. quire precision, well-regulated high voltage power, one Service centers in New York, Mexico, name most often comes to mind: Spellman High Voltage. Germany, United Kingdom, China, Korea, Over the past 70 years, Spellman has provided innovative and Japan provide Spellman’s global system developers with custom designed high voltage DC OEM customers local technical expertise power supplies to meet their unique application requirements. and rapid response repair capability. Spellman boasts the world’s largest and most experienced high voltage engineering staff, with world-class project teams experienced in specific applications and technologies, dedicated not only to new designs but also to sus- taining engineering throughout the life of each product. Spellman High Voltage Electronics Corp. Markets Served 475 Wireless Blvd. We offer high voltage power supplies with well-regu- Hauppauge, NY 11788 lated outputs from 62 V to 500 kV, and from 200 mW TELEPHONE to 200 kW. High stability, extremely low ripple, and +1 (631) 630-3000 low partial discharge features are available. ® FAX Spellman is also a world leader in Monoblock integrated +1 (631) 435-1620 X-ray sources, CT gantry-mounted generators, telecom sub- marine power feed systems, and a large array of generators E-MAIL and power converters used in critical medical, analytical, [email protected] scientific, and industrial applications. WEB SITE Spellman offers the broadest range of products for the www.spellmanhv.com mass spectrometry, analytical instrumentation, and biotechnology fields. Specific applications include MS, TOF, MALDI, ICP, chromatography, CZE, SEM, ion sources, and a vast array of other analytical techniques. High stability, fast switching, multiple outputs, and RoHS compliance are a few of the key features of our comprehensive product range. www.spectroscopyonline.com DECEMBER 2018 SPECTROSCOPY CORPORATE CAPABILITIES 71 Starna Cells Inc.

Markets Served Starna Cells Inc. supplies a wide range of markets within North, Central, & Latin America and the Caribbean. These include the life sciences (pharmaceutical, biopharmaceutical, and healthcare), food, drinks, and wine industries, chemical industry, oil and gas, space, and water, as well as numerous universities and research institutes.

Major Products/Services Starna Cells Inc. supplies a complete range of precision quartz and glass spectrophotometer cells, including standard or custom items for analytical methods using spectroscopy, fluorimetry, and refractometry; from macro to sub-micro volumes; for static, temperature, and/or flow applications. Spe- cialized optics including Toroid mirrors and Company Description Deep UV coatings. Ultra-low volume acces- Starna Cells Inc. is based in California, and is a member of the sory: DMV-Bio Cell. international Starna Group. The Starna Group is a key Starna are the world leading supplier manufacturing partner and supplier of spectrophotometer of UV-vis-NIR certified reference materials cells and spectroscopy accessories. It is the world leader in and are accredited to ISO 17025 and ISO the provision of certified reference materials for the 17034 through UKAS for the calibration verification of UV-visible-NIR spectrophotometers, accredited and manufacture of standard and bespoke by UKAS to ISO/IEC 17025 for calibration and ISO 17034 for reference materials. The range also includes the manufacture of certified reference materials. references for plate readers, fluorimeters, FT-IR, and micro-volume applications. Chief Spectroscopic Techniques Supported ⦁ UV-visible spectroscopy Facility Starna Cells Inc. ⦁ NIR spectroscopy Sales, stock, and support facility in Cali- P.O. Box 1919, ⦁ Fluorimetry fornia, USA. This facility imports and ex- Atascadero, CA 93423 ⦁ Micro-well plate analysis ports regular consolidated shipments to TELEPHONE ⦁ Colorimetry the primary Starna manufacturing facility (800) 228-4482 ⦁ Polarimetry in the UK and maintains a large inde- ⦁ FAX Circular dichroism pendent stock of many products. It also (805) 461-1575 ⦁ Dynamic light scattering provides a logistics center for handling ⦁ Particle size analysis certified reference materials facilitating E-MAIL ⦁ [email protected] Cytometry quick and efficient recalibration service. ⦁ On-line flow applications WEB SITE ⦁ Tablet dissolution www.starnacells.com ⦁ Ultra-high vacuum YEAR FOUNDED ⦁ Blood analysis 1975 ⦁ DNA/protein analysis ⦁ Microscopy ⦁ Cryogenic applications 72 SPECTROSCOPY CORPORATE CAPABILITIES DECEMBER 2018 www.spectroscopyonline.com StellarNet, Inc.

lamp and lighting, LED and laser, optical paint, solar, semiconductor, UV process manufacturing, and, of course, OEM.

Major Products/Services Complete Systems – Delivered either modular, portable, or even handheld, StellarNet offers complete systems such as SpectroChemical Absorbance meters, Raman systems, fluorometers, NIR component analyzers, SpectroCol- orimeters, and SpectroRadiometers. Spectrometers – General purpose UV, Vis, and NIR spectrometers. StellarNet has many different spectrometer options with high resolution models with less Company Description than 0.1 nm resolution, TE cooled models StellarNet provides low cost miniature spectrometer for extreme sensitivity, and our flagship systems and spectroscopy software for product analysis, BLACK-Comet Concave grating spectrom- research, education, and OEM. StellarNet instrumentation eter for the best optical performance. is rugged for any environment—lab, process, or field. Light Sources, Spheres, and Most items are in stock with immediate delivery and Accessories – Excitation LEDs and lasers, customer service and support is a top priority. broadband and calibrated spectroscopy In 1991, StellarNet developed a mini fiber optic spectrometer lamps, cuvette holders, optical fibers, that connected to a computer’s printer interface, a revolutionary probes, flow cells, integrating spheres, advancement of the time in size, speed, and functionality. Over lenses, and everything you may need. the years, StellarNet has continued the trend of ingenuity and Software – FREE SpectraWiz spectros- has become a global leader in optical sensing and miniature copy software including Spectral ID, spectrometer systems with unmatched price performance. ChemWiz Concentration, Color, Ra- diometry, SDK, and much more! Chief Spectroscopic Techniques Supported StellarNet, Inc. ⦁ UV, Vis, and NIR absorbance chemistry Facility 14390 Carlson Circle ⦁ Raman spectroscopy (532, 785, 830, and 1064 nm) StellarNet is headquartered in Tampa, Tampa, FL 33626 ⦁ Raman microscopy and SERS Florida, where it’s currently expanding its TELEPHONE ⦁ Fluorescence spectroscopy staff. Its new 10,000 square-foot facility hosts 1 (813) 855-8687 ⦁ NIR chemometrics and spectral ID manufacturing, research and development, ⦁ FAX Colorimetry and all US sales and support. StellarNet has 1 (813) 855-0394 ⦁ Radiometry (LED, solar, laser, display, plasma) a team of over 30 international distribu- ⦁ OES and laser induced breakdown spectroscopy (LIBS) tion partners providing technical sales and E-MAIL ⦁ [email protected] Optical metrology and thin film thickness support to every region of the globe. WEB SITE Markets Served www.StellarNet.us StellarNet’s low-cost, high-performance systems are YEAR FOUNDED designed without moving parts and are shock tolerant. 1991 Additionally, miniaturization with a focus on portability enables StellarNet to serve many markets, including: aerospace, agriculture, food and beverage, biomedical, pharmaceutical, chemical, forensics, cosmetics, educational and research, semiconductor and thin film, www.spectroscopyonline.com DECEMBER 2018 SPECTROSCOPY CORPORATE CAPABILITIES 73 Wasatch Photonics

Major Products/Services Raman: Get cleaner, faster spectra for any application. Choose from 405, 532, 638, 785, 830 & 1064 nm. NIR: Superior sensitivity and SNR for rapid measurements, 900-2500 nm. Superb thermal stability & repeatability. Fluorescence: Benchtop fluorimeter sensitivity in a fraction of the footprint. UV-VIS-NIR: High efficiency & low stray light for 350-1100 nm. Ideal for low light applications, kinetics monitoring, and high-throughput quality control. Customization: All products offered as fiber coupled/free-space spectrometers or integrated systems; choice of slit size and detector cooling. Custom in-house gratings created upon request for OEMs. OEM modules: Compact, robust, Company Description thermally stable modules for Raman, Wasatch Photonics creates products that enable the next visible, and NIR spectroscopy. generation of spectroscopy solutions to make the leap from the laboratory to the field, the clinic, and industry. Facility We offer researchers 10x more speed, sensitivity, and SNR Wasatch Photonics is proud to announce than traditional compact spectrometers, and deliver a rapid a new, expanded facility in Morrisville, path to commercialization with our matched OEM-ready NC. This 10,500 sq. ft. (975 m2) facility is modules – all based on the same rugged, repeatable, ISO 9001:2015 certified and equipped thermally stable optical bench. We’re fascinated by the many with an applications lab and a volume ways light can be used to understand nature and solve the manufacturing production line. Our patented Wasatch Photonics problems that touch our lives each day, and it shows in and proprietary VPH gratings are developed Systems Division our applications expertise and experience. Whether you’re and manufactured in Logan, Utah. 808 Aviation Parkway, solving a problem in research, industry, or creating your own Suite 1400 OEM product, we want to help you build a better future. Morrisville, NC 27560 USA Chief Spectroscopic Techniques Supported ⦁ TELEPHONE Raman spectroscopy +1 (919) 544-7785 ⦁ UV, visible, and NIR spectroscopy ⦁ Fluorescence/photoluminescence E-MAIL ⦁ Absorbance, transmission & reflectance [email protected] WEB SITE Markets Served wasatchphotonics.com ⦁ Food safety & authentication NUMBER OF EMPLOYEES ⦁ Biomedical, chemical & pharmaceutical 70 ⦁ Homeland security & anti-counterfeiting ⦁ YEAR FOUNDED Semiconductor & materials science 2002 ⦁ Environmental monitoring ⦁ Research & development ⦁ OEM manufacturing 74 SPECTROSCOPY CORPORATE CAPABILITIES DECEMBER 2018 www.spectroscopyonline.com WITec GmbH

Major Products/Services WITec alpha300 Confocal Raman Microscope: The alpha300 R is a Raman imaging system focusing on high-resolution as well as high-speed spectra and image acquisition. The acquisition time for a single Raman spectrum is in the range of 1 ms or even below; thus, a complete Raman image consisting of tens of thousands of spectra can be obtained in 1 min or less. Differences in chemical composition, although completely invisible in the optical image, will be apparent in the Raman image and can be analyzed three-dimensionally with a spatial resolution down to 200 nm.

Correlative Raman Microscopy: WITec instruments can combine different techniques for a more comprehensive Company Description understanding of a sample. Raman WITec is a manufacturer of high-resolution optical and scan- imaging integrated with AFM links chemical ning probe microscopy solutions for scientific and industrial characterization with surface characteristics. applications. A modular product line allows the combination The inverted Raman microscope alpha300 of different microscopy techniques such as Raman, NSOM, or Ri can be complemented with fluorescence AFM in one instrument. The company’s product line features a microscopy. Raman Imaging and Scanning near-field scanning optical microscope, using unique cantilever Electron (RISE) microscopy, pioneered technology, a confocal Raman microscope designed for high- by WITec, correlates nm-range structures WITec GmbH est sensitivity and resolution, and an AFM for material research detected by SEM with chemical Raman Main Address: and nanotechnology. Focusing on innovations and constantly imaging data acquired from the same Lise-Meitner-Str. 6, 89081 introducing new technologies, WITec is the leading expert for a sample area, within the same vacuum Ulm, Germany wide variety of optical, structural, and chemical imaging tasks. chamber, in a streamlined measurement. WITec Instruments Corp. 130G Market Place Blvd. Chief Spectroscopic Techniques Supported Facilities Knoxville, TN 37922 ⦁ Raman spectroscopy WITec headquarters is located in Ulm, TELEPHONE ⦁ Confocal 3D Raman imaging Germany, and includes the R&D department, +49 (0) 731 140 700 ⦁ Ultrafast confocal Raman imaging production, sales and marketing, and US: (865) 984-4445 ⦁ Confocal and near-field fluorescence spectroscopy administration. WITec Instruments Corp. FAX ⦁ Upgradable with atomic force and near-field in Knoxville, Tennessee, is responsible for +49 (0) 731 140 70200 microscopy capabilities North American sales and service activities. US: (865) 984-4441 ⦁ Topographic Raman imaging ⦁ E-MAIL RISE microscopy (Raman imaging & scanning electron microscopy) [email protected]

WEB SITE Markets Served www.witec.de WITec products are delivered worldwide to academic and industrial research labs focusing on high-resolution chemical NUMBER OF EMPLOYEES imaging and materials characterization. Areas of application 50 for WITec’s confocal Raman imaging systems include polymer YEAR FOUNDED sciences, pharmaceutics, life science, geoscience, thin films 1997 and coating analysis, semiconductors, and nanotechnology. 3D Raman image of a pharmaceutical ointment.

3D Ram gg Turn ideas into discoveries

Let your discoveries lead the scientiﬁ c future. Like no other system, WITec’s confocal 3D Raman microscopes allow for cutting-edge chemical imaging and correlative microscopy with AFM, SNOM, SEM or Proﬁ lometry. Discuss your ideas with us at [email protected].

Raman AFM SNOM RISE www.witec.de

MADE IN GERMANY 76 Atomic Spectroscopy APPLICATION NOTES – DECEMBER 2018

Inert High-Performance ICP Sample Introduction System Ryan Brennan, Glyn Russell, and Terrance Hettipathirana, Glass Expansion, Inc.

This report highlights the superior performance of an inert Glass Expansion ICP sample introduction system compared to two alternative sample introduction systems. The Glass Expansion conﬁ guration consisted of the DuraMist nebulizer coupled with a PTFE Twister spray chamber (Figure 1), whereas the alternative conﬁ guration consisted of two different non-concentric nebulizers coupled with a Scott-type spray chamber.

or ICP samples that contain hydrofl uoric acid (HF), a glass F or quartz ICP sample introduction system is unsuitable. Glass or quartz is also unsuitable for the ultra-trace determination of some elements by ICP-MS (for example, silicon or boron). For these types of ICP analyses, an inert sample introduction system, consisting of a spray chamber and nebulizer made from various plastic materials, is used. Figure 1: Glass Expansion DuraMist nebulizer and PTFE Twister Common polymers used in the manufacture of inert spray spray chamber. chambers and nebulizers include: • Polytetrafluoroethylene (PTFE) • Perfluoroalkoxy alkane (PFA) • Polyphenylene sulfide (PPS) • Polypropylene (PP) • Polyether ether ketone (PEEK) • Polyimide (PI) A common problem with spray chambers made from these materials is they do not wet completely, causing large droplets to col- lect on the inside walls. Th is degrades ICP performance, leading to erratic drainage, poor precision (RSD), and poor signal stability. A major breakthrough in the performance of inert spray chambers came with Glass Expansion’s proprietary Stedifl ow surface treatment in 2006 (1). Th e Stedifl ow treatment improves the wettability of the surface, ensuring effi cient drainage, and delivering sensitivity and precision comparable to a glass cyclonic spray chamber. In a 2014 Figure 2: Sensitivity of NCPN with Scott-type and CrossFlow with application note (2), the advantages of a cyclonic spray chamber were Scott-type relative to DuraMist and PTFE Twister (relative sensitivity = 1). examined, highlighting sensitivity gains and reduced washout times compared to Scott-type spray chambers. Choosing an inert nebulizer is just as important as selecting a remainder of the discussion. Th e CrossFlow and NCPN provide proper spray chamber. Key criteria include: chemical resistance tolerance to HF and particulates, but suff er from poorer precision, to HF, purity, tolerance to particulates, and overall performance reduced sensitivity and enhanced matrix eff ects. Th ese nebulizers (sensitivity and precision). Th is way the best nebulizer is chosen typically produce an aerosol that has larger droplets with a wider for the application and sample matrix. droplet size distribution. Larger droplets can pass through the Glass Expansion currently off ers two inert concentric nebulizer plasma without desolvating or completely evaporating, resulting designs, the OpalMist and DuraMist. Other popular inert in poor precision, reduced nebulization effi ciency, increased nebulizer models include the cross-fl ow and a polymeric, parallel matrix eff ects, and reduced plasma robustness. A smaller droplet path, “v-groove” nebulizer referred to as NPCN throughout the size, as produced by concentric nebulizers, provides higher transport effi ciency (sensitivity) and improved precision (RSD). APPLICATION NOTES – DECEMBER 2018 Atomic Spectroscopy 77

Th e DuraMist nebulizer, released by Glass Expansion in 2011 Figure 2 depicts the sensitivity obtained with the NCPN paired (3), is a concentric, self-aspirating inert nebulizer that consists of with the PPS Scott-type and CrossFlow paired with the Scott- a PEEK body and PEEK capillary insert. At the time of its release, type, relative to the sensitivity of the DuraMist DC nebulizer the DuraMist was compared to Glass Expansion’s SeaSpray, paired with the PTFE Twister. Th e combination of the DuraMist OpalMist, and a non-Glass Expansion NCPN. Characteristics and PTFE Twister provided an increase in sensitivity by 50% or studied included sensitivity, precision, stability, robustness, and more for all elements examined (4). tolerance to high TDS (3). In this report, the DuraMist nebulizer Th e best indicator of analytical detectability for ICP-OES had comparable performance to the SeaSpray and outperformed using a solid-state detector is the SRBR. Similar to what was the NCPN in both precision and sensitivity. observed when comparing sensitivity, the DuraMist DC nebulizer and PTFE Twister spray chamber provided close to a 50% Experimental improvement in SRBR when compared to the other two inert A Perkin Elmer Avio 200 sequential ICP-OES was used for this sample introduction systems (4). Th e fi nal merit of performance work, with experimental conditions listed in Table I. Integration examined was short-term analytical precision, which also indi- times were manually set to 2 s to maintain consistency for all cates that the DuraMist DC nebulizer and PTFE Twister provide confi gurations tested. A multielement solution containing 0.5 ppm superior %RSD, well below 1.0% (4). Cu and Mn; and 1 ppm As, Se, Mg, Na and K was used. Each sample introduction system was evaluated based on sensitivity, Conclusions signal-to-root background ratio (SRBR), and precision. For A comparative evaluation of a Glass Expansion sample introduction sensitivity and SRBR calculations, net signal counts in ppm were system, consisting of the DuraMist DC nebulizer coupled with the used. Precision of the net signals was estimated by analyzing the Twister PTFE spray chamber against the NCPN and CrossFlow multielement solution 10 times and calculating the average %RSD. nebulizers coupled with a PPS Scott-type spray chamber, indicates that the Glass Expansion sample introduction system yields the Table I: PerkinElmer Avio 200 Operating Conditions best sensitivity, SRBR and precision. Experimental Parameter Setting RF Power 1.2 kW References Nebulizer gas fl ow rate 0.7 L/min (1) “Improving the Performance of ICP Spectrometers,” Glass Expansion Plasma gas fl ow rate 12.0 L/min Newsletter, February (2006). Auxiliary gas fl ow rate 1.0 L/min (2) “ICP Spray Chamber Update,” Glass Expansion Newsletter, October Read time 2 sec (2014). Replicates 3 (3) “Evaluation of a New High Performance Inert Nebulizer,” Glass Expan- Viewing mode Axial sion Newsletter, October (2011). Pump speed 0.7 mL/min & 1.4 mL/min (4) “Inert-High Performance ICP Sample Introduction System,” Glass Ex- Pump tubing Black-Black, 0.76 mm ID pansion Newsletter, July (2018). Torch Fully ceramic D-Torch

Th e Glass Expansion inert sample introduction system consisted of the DuraMist DC nebulizer and PTFE Twister cyclonic spray chamber, which was compared to both a CrossFlow nebulizer paired with a PPS Scott-type spray chamber and an NCPN paired with a PPS Scott-type spray chamber. Th e NCPN was operated at the recommend liquid fl ow rate of 1.4 mL/min, whereas the DuraMist and CrossFlow nebulizers were run at 0.7 mL/min. Glass Expansion, Inc. Although a range of nebulizer gas fl ows were examined, in order 31 Jonathan Bourne Dr., Unit # 7, Pocasset, MA 02559 USA to simplify the data comparison, the results presented were col- tel. (508) 563-1800; fax (508) 563-1802 lected at a nebulizer gas fl ow rate of 0.7/mL/min. Website: www.geicp.com; email [email protected] 78 Atomic Spectroscopy APPLICATION NOTES – DECEMBER 2018

Determination of the Bulk Elemental Composition of Cast Iron with Glow Discharge Optical Emission Spectrometry (GD-OES) Allen Metz and Aaron Walczewski, LECO Corporation

ast irons are a family of ferrous alloys containing percent levels Spectrometer C of carbon and silicon. Alloying elements such as chromium LECO GDS900-RC and nickel enhance the physical properties of the metal while the structure maintains a rich carbon phase. Whether the objective is Experimental Conditions to improve the strength, abrasion resistance, corrosion resistance, Lamp: Grimm-style DC 4 mm or hardness of the basic iron, the chemical composition must be Voltage: 1250 V controlled in order to achieve the desired physical properties. Current: 45 mA Glow discharge spectrometry (GD-OES) is an analytical method for direct determination of the elemental composition of solid Conclusion samples like cast iron. Th rough a process called cathodic sputter- GD-AES was used to measure the bulk elemental composition of ing, kinetic energy is transferred from the inert gas ions to the three cast iron samples with exceptional accuracy and precision. atoms on the sample surface, which causes some of these surface Even real world samples, with less homogeneity than certifi ed atoms to be ejected into the plasma. Once the atoms are ejected reference materials, return consistent results. Th e glow discharge into the plasma, they are subject to inelastic collisions with ener- technique is more than capable to meet the analytical require- getic electrons or metastable argon atoms. Energy transferred by ments of foundries and metals processing fi rms. such collisions causes the sputtered atoms to become excited. Th e excited atoms quickly relax to a lower energy state by emitting Reference photons. A spectrometer is used to measure the emission signals (1) K.A. Marshall, J. Anal. At. Spectrom. 14, 923–928 (1999). from the glow discharge. Since the number of photons emitted by each element is proportional to its relative concentration in LECO Corporation the sample, analyte concentrations can be deduced by calibration 3000 Lakeview Avenue, St. Joseph, MI 49085 with reference samples of known composition. tel. (269) 985-5496, fax (269) 982-8977 Results Website: www.leco.com

n = 5 BS 286AC - Nodular Cast Iron Element C Si Ni Cr V Mo Cu Mg Ti B Average 3.23 2.06 1.350 0.166 0.153 0.247 0.336 0.039 0.049 0.0083 Certiﬁ ed 3.24 2.03 1.360 0.165 0.151 0.258 0.341 0.034 0.054 0.0085 % Diff -0.3% 1.5% -0.7% 0.6% 1.3% -4.5% -1.5% 12.8% -10.2% -2.7% Stdev 0.01 0.009 0.004 0.0003 0.0003 0.001 0.001 0.001 0.0003 0.0001 RSD 0.45 0.44 0.32 0.21 0.21 0.41 0.31 2.7 0.62 1.3

n = 5 BS 291DE - Chill Cast Iron Element C Si Ni Cr V Mo Cu Mg Ti Al Nb Co B Average 3.35 2.34 0.17 0.159 0.015 0.0201 0.192 0.047 0.0244 0.0065 0.0024 0.0082 0.0083 Certiﬁ ed 3.35 2.32 0.17 0.159 0.013 0.0220 0.189 0.040 0.0265 0.0089 0.0024 0.0062 0.0089 % Diff 0.0% 0.9% 2.3% 0.0% 10.3% -9.5% 1.6% 14.2% -8.6% -36.5% 0.0% 24.7% -7.2% Stdev 0.02 0.008 0.002 0.001 0.0006 0.0005 0.0009 0.0007 0.0004 0.00009 0.0004 0.0006 0.00006 RSD 0.48 0.35 1.2 0.48 4.4 2.5 0.48 1.6 1.7 1.4 16.1 7.3 0.78

n = 5 Common Brake Rotor Element C Si Ni Cr V Mo Cu Mg Ti Al Nb Co Average 3.74 1.87 0.063 0.140 0.0069 0.060 0.228 0.0052 0.0085 0.0031 0.0042 0.0132 Stdev 0.01 0.01 0.001 0.005 0.0004 0.004 0.004 0.0003 0.0006 0.0001 0.0005 0.0003 RSD 0.36 0.73 1.6 3.6 5.7 7.2 1.8 5.6 7.2 3.3 11.5 2.5 APPLICATION NOTES – DECEMBER 2018 Atomic Spectroscopy 79

Calibration Because a high degree of accuracy is desired in the industry, the empirical regression calibration method is used. An empirical calibration was built using a set of 12 commercially available standards from AMIS (African Mineral Standards) that model used ore materials. Using the empirical approach, an overlap correction was employed to automatically compensate for the spectral overlap of the Zn-Kβ Gold Recovery by EDXRF line on the Au-Lα line. Appropriate alpha corrections were enabled to Applied Rigaku Technologies, Inc. compensate for various absorption and enhancement matrix effects.

Repeatability To demonstrate the repeatability and recovery of the measurement, The measurement of gold is demonstrated in used three standards were measured 10 times each in static position. The ore material such as from ore dumps and tailing piles. average results and standard deviations are shown here. This App Note also shows the recovery of uranium from the used ore material. Sample: Standard 412 Units: ppm Sample ID Standard Value Average Value Std Dev % Relative Dev ecovering gold and other valuable metals from used ore materials Au 5.7 6.3 0.4 5.70% can be a profi table recovery venture. In the processing of ores, R U 205 209 1 0.30% the desired metals and other base metals are extracted, leaving mostly Sample: Standard 245 Units: ppm silicates, minerals, and the other base ore materials. Gold and other Sample ID Standard Value Average Value Std Dev % Relative Dev precious metals can be recovered by further processing and extraction Au 88.4 86.9 1.7 1.90% of the ore material from used ore dumps or old tailing piles. To screen U 491 496 1 0.10% and measure the gold content, Applied Rigaku off ers the NEX DE Sample: Standard 369 Units: ppm EDXRF system with high throughput SDD detector to give superior Sample ID Standard Value Average Value Std Dev % Relative Dev measurement of trace valuable metals in various used ore materials. Au 26.36 27.3 0.9 3.40% U 1340 1346 1 0.11% Experimental Conditions Instrumentation Detection Limits (LLD—Lower Limit of Detection) Model: Rigaku NEX DE In the empirical method, ten repeat analyses of a blank powder sam- X-ray tube: 12W 60kV Ag-anode ple (boric acid, Chemplex SpectroBlend, or other appropriate blank Detector: High Th roughput SDD, 500,000+ cps powder) are taken with the sample in static position, and the standard Film: Prolene 4 μm (Mylar 6 μm also suitable) deviation (σ) is determined. Th e LLD (Lower Limit of Detection) is Analysis Time: 400 s then defi ned as 3σ. Th e total measurement time for the LLDs shown Environment: Air below is 400 s per analysis. Sample Tray: 15-position Autosampler Element LLD Recycled Ore Samples Options: Manual Compaction Press Au 1 g/ton U 0.6 ppm Sample Preparation Detection limits are dependent on many factors, including Ensure each sample is homogeneous and stable. Simply fill a measurement time, background removal, detector throughput, 32-mm XRF sample cup with 4.0 g of sample. sample preparation, and calibration concentration range. For A sample is prepared by grinding the material to a dry, ho- example, optimum detection limits can be achieved using longer mogeneous medium powder approximately 200 mesh (~75 μm analysis time, calibrating only over a low concentration range. particle size). Simply fi ll a sample cup with powder and compact using the Rigaku Manual Compaction Press. Conclusions Th e NEX DE off ers analysts and technicians a simple yet powerful and versatile system for quantifying elemental composition. Th e results of this study indicate that, given matrix-matched calibration and proper sampling, the Rigaku NEX DE EDXRF can achieve excellent results for monitoring and measuring the concentration of gold and other valuable elements in the recovery of used ore materials.

Applied Rigaku Technologies, Inc. 9825 Spectrum Drive, Bldg. 4, Suite 475, Austin, TX 78717 tel. (512) 225-1796; fax (512) 225-1797 Website: www.rigakuEDXRF.com 80 Spectroscopy 33(12) December 2018 www.spectroscopyonline.com

Calendar– of Events– January 2019 3 6 International Forum on 22 26 Materials Research Society Process Analytical Chemistry Spring Meeting 24–27 Sanibel Conference on Mass (IFPAC) Annual Meeting Phoenix, AZ Spectrometry—Chemical Cross- Bethesda, MD https://www.mrs.org/spring2019 linking and Covalent Labeling: From http://www.ifpacglobal.org Proteins to Cellular Networks May 2019 Fort Myers, FL 3–7 http://www.asms.org/conferences/ Practical Applications of NMR 5–10 CLEO 2019 sanibel-conference in Industry Conference San Jose, CA Hilton Head, NC https://www.cleoconference.org/home/ https://www.panicnmr.com about-cleo/ 24–28 Pacific Conference on Spec- troscopy and Dynamics (PSCD) June 2019 12–14 San Diego, CA ARABLAB 2019

https://www.westernspectroscopy.org Dubai, United Arab Emirates 2–6 ASMS 2019 https://www.arablab.com Atlanta GA February 2019 https://www.asms.org 17–21 2–6 Society for Laboratory The Pittsburgh Conference

Automation and Screening on Analytical Chemistry and 24–27 Laser World of Photonics (SLAS 2019) Applied Spectroscopy Munich, Germany Washington, DC (Pittcon 2019) https://world-of-photonics.com/index-2. https://www.slas2019.org/ Philadelphia, PA html https://pittcon.org August 2019 2–7 SPIE Photonics West 2019

San Francisco, CA 31–April 4 ACS Spring National 5–9 Denver X-ray Conference http://spie.org/conferences-and-exhibi- Meeting and Exposition Lombard, IL, tions/photonics-west?SSO=1 Orlando, FL www.dxcicdd.com https://www.acs.org/content/acs/en/ meetings.html

3–8 European Winter Conference on 11–15 SPIE Optics + Photonics Plasma Spectrochemistry April 2019 San Diego, CA Pau, France http://spie.org/conferences-and-exhibi- 7–11 https://winterplasma19.sciencesconf.org/ 52nd Annual International tions/optics-and-photonics resource/page/id/1 Meeting of the ESR Spectroscopy Group of the Royal Society of September 2019 Chemistry

25–27 Photoptics 2019: 7th Interna- Glasgow, Scotland, UK 8–13 COLA 2019: tional Conference on Photonics, http://www.esr-group.org/ The 15th International Optics, and Laser Technology conferences/2019-conference-glasgow Conference on Laser Ablation Prague, Czech Republic Maui, Hawaii http://photoptics.org https://cola2019.org/ 14–18 SPIE Defense + Commercial March 2019 Sensing October 2019 Baltimore, MD

2–6 Biophysical Society 63rd Annual http://spie.org/conferences-and-exhibi- 13–18 SciX Conference Meeting tions/defense--commercial-sensing Palm Springs, CA Baltimore, MD www.scixconference.org http://www.biophysics.org/annual- meeting# www.spectroscopyonline.com December 2018 Spectroscopy 33(12) 81 Short Courses March 2019 Philadelphia, PA 18 LIMS, ELN, and LES: How to https://pittcon.org/plan-your-pittcon Plan and Select the Right Lab- 16 Practical NMR Spectroscopy oratory Software Solution for Pittcon 2019 Your Organization Philadelphia, PA 18 Essentials of LC–MS Pittcon 2019 https://pittcon.org/plan-your-pittcon Pittcon 2019 Philadelphia, PA Philadelphia, PA https://pittcon.org/plan-your-pittcon https://pittcon.org/plan-your-pittcon 16 Analytical Ionic Liquids in GC and Mass Spectrometry 19 Enhancing Your Lab Pittcon 2019 18 Understanding GXP Require- Informatics System through Philadelphia, PA ments for Data Integrity in Lean Lab Principles https://pittcon.org/plan-your-pittcon Laboratories Pittcon 2019 Pittcon 2019 Philadelphia, PA Philadelphia, PA https://pittcon.org/plan-your-pittcon 16 On-The-Job and Soft Skills https://pittcon.org/plan-your-pittcon for Technologists (Things You Were Not Taught in School) 19 Long-Term Archival of Pittcon 2019 18 Keeping Your Analytical Pro- Laboratory Data Philadelphia, PA cedures in Compliance with the Pittcon 2019 https://pittcon.org/plan-your-pittcon FDA: Validation, Documenta- Philadelphia, PA tion, and Change Management https://pittcon.org/plan-your-pittcon Pittcon 2019 17 An Introduction to Scanning Philadelphia, PA Electron Microscopy (SEM) and https://pittcon.org/plan-your-pittcon 19 Analytical Sampling and Associated Energy Dispersive Sample Preparation for X-ray Spectroscopy (EDS) Chromatography Pittcon 2019 18 Elemental Analysis via Laser Pittcon 2019 Philadelphia, PA Induced Breakdown Spectros- Philadelphia, PA https://pittcon.org/plan-your-pittcon copy and X-ray Fluorescence https://pittcon.org/plan-your-pittcon Pittcon 2019 Philadelphia, PA 17 Characterization of Biologics https://pittcon.org/plan-your-pittcon 20 Handheld Vibrational by HPLC, CE, and Mass Spec- Spectrometers: State-of-the- trometry Art Instrumentation and their Pittcon 2019 18 Introduction to Gas Chroma- Realistic Application Potential Philadelphia, PA tography/Infrared Spectros- Pittcon 2019 https://pittcon.org/plan-your-pittcon copy and its Application to the Philadelphia, PA Cannabis Industry https://pittcon.org/plan-your-pittcon Pittcon 2019 17 Modern Portable Analytical Philadelphia, PA Spectroscopy https://pittcon.org/plan-your-pittcon 20 Improving Handheld Raman Pittcon 2019 Performance: From Philadelphia, PA Pharmaceuticals to Forensics https://pittcon.org/plan-your-pittcon 18 Injection Techniques in Gas Pittcon 2019 Chromatography Philadelphia, PA Pittcon 2019 https://pittcon.org/plan-your-pittcon 17 Language and Matter: Tech- Philadelphia, PA nical Writing for Analytical Sci- https://pittcon.org/plan-your-pittcon entists and Managers Pittcon 2019 82 Spectroscopy 33(12) December 2018 www.spectroscopyonline.com Call for Papers

Spectroscopy invites researchers to submit their work for publication.

eaders interested in sharing tions. Use the following format for ICP–OES & ICP–MS supplement, the results of their research references: September 2019 R with more than 27,000 other (1) R. Salzer and H.W. Siesler, Infrared Submission deadlines: spectroscopists are encouraged to sub- and Raman Spectroscopic Imaging Abstracts: March 1, 2019 mit manuscripts for review and possible (Wiley-VCH, Weinheim, 2009), pp. Manuscripts: May 8, 2019 publication. 90–103. Spectroscopy publishes articles deal- (2) P. Matousek, Appl. Spectrosc. 60, Current Trends in Mass ing with practical applications of 1341 (2006). Spectrometry supplement series modern spectroscopic techniques and Our supplement series on mass spec- instrumentation. Contributed manu- Author Benefits trometry appears four times a year: scripts commonly address any of the Publishing your work in Spectros- in March, May, July, and October. following topics: copy has many advantages. The size Manuscripts for this series should be • emerging techniques of Spectroscopy ’s audience, with more approximately 3500–4500 words long, • new applications of spectroscopic than 27,000 readers, makes Spectros- including an abstract of approximately instrumentation copy the ideal vehicle for communicat- 150–200 words, plus up to eight figures • current trends in hot research areas ing information of broad significance and tables. We are still accepting sub- • improved methods for common to the spectroscopy community. Con- missions for the following issues: applications tributed technical papers published in • data-handling strategies Spectroscopy have passed a thorough Submission Deadlines: • solutions to sample-handling peer-review process. Our pool of refer- March 2019 issue problems. ees includes the members of our distin- Abstracts: November 8, 2018 The full range of atomic spectros- guished Editorial Advisory Board. Manuscripts: January 11, 2019 copy, molecular spectroscopy, and mass spectrometry techniques is suitable for Special Supplements May 2019 issue coverage in Spectroscopy. A number of supplemental issues are Abstracts: January 11, 2019 planned for 2019, for which we also Manuscripts: March 1, 2019 Manuscript Preparation invite contributions. Manuscripts for Manuscripts for regular issues should the supplements on Raman technol- July 2019 issue be approximately 3500–4500 words ogy, IR spectroscopy, and ICP-OES & Abstracts: February 8, 2019 long, plus figures and tables as needed, ICP-MS should be 2500–3000 words Manuscripts: April 12, 2019 including an abstract of approximately long, with up to six figures and tables 150–200 words. Figures and tables, combined, and should include an October 2019 issue along with their captions, should ap- abstract of approximately 150–200 Abstracts: April 1, 2019 pear at the end of the manuscript, and words. We are accepting submissions Manuscripts: June 7, 2019 figures also must be sent as separate for the following issues: files, preferably in JPG, TIF, PNG, or Contact Us XLS format. Raman Technology supplement, For more information about contrib- References. Number the literature June 2019 uting to Spectroscopy, please contact citations in the text consecutively Submission deadlines: in order of appearance and indicate Abstracts: January 11, 2019 them by Arabic numerals in paren- Manuscripts: March 15, 2019 Laura Bush, Editorial Director theses. Number each reference sepa- Spectroscopy rately. Group the references at the IR Spectroscopy supplement, +1.732.346.3020 end of the manuscript in the order August 2019 [email protected] of their appearance in the text, not Submission deadlines: www.spectroscopyonline.com ◾ alphabetically. Abstracts: February 1, 2019 Use Chemical Abstracts Service Manuscripts: April 5, 2019 Source Index for journal abbrevia- CONNECT WITH SPECTROSCOPY ON SOCIAL MEDIA

Join your colleagues in conversation, respond to hot topic questions, and stay up-to-date on breaking news. “Like” and follow us on Twitter, LinkedIn, and Facebook today!

www.spectroscopyonline.com/SpecConnect Copyright © 2017 PerkinElmer, Inc. 400372_01 All rights reserved. PerkinElmer® is a registered trademark of PerkinElmer, Inc. All other trademarks are the property of their respective owners. EXPAND YOUR RANGE EXTEND YOUR RESOURCES EXTEND YOUR Avio 500ICP-OES For moreinformation,visitperkinelmer.com/avio500 It’s everythingyouwantinanICP-OESsystem. High throughput.Lowcostofownership.Superiorperformance. comes togethertoexpandtherangeofwhatyoucanaccomplish. and highthroughputenabledbyDualViewtechnology,itall consumption ofanyICP,simultaneousbackgroundcorrection, dealing withthemostdifficultsamples.Andlowest argon superior resolution,yourlabcanaccomplishmore,evenwhen investment yourworkdemands.Withhighsensitivityand need withthehigh-qualityperformanceandfasterreturnon The Avio®500ICP-OEScombinestheproductivityyou with lowcostofownership The NewAvio500ICP-OES-Highthroughput