Analytical Scientist

Home , Koichi Tanaka, Mark Wightman, Richard Zare

OCTOBER 2013 # 09 the Analytical Scientist

Upfront In My View Feature Solutions Is it time to trace Out of sight should Three gurus of SFC How to increase access fracking contamination? not mean out of mind extol its virtues to dioxin analysis

14 16 38 – 43 44 – 46 Gain a new perspective

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www.markes.com Who’s Who on the Cover? In no particular order. Turn to page 23 for The Power List 2013

1. Richard Smith 21. Joseph Wang 41. Douglas A. Berthiaume 61. Kurt Wüthrich 81. Alan G. Marshall 2. Mark Wightman 22. Peter Roepstorff 42. Milos Novotny 62. Klavs F. Jensen 82. Robert Kennedy 3. Milton Lee 23. Dianping Tang 43. Gert Desmet 63. Hian Kee Lee 83. Wolfgang Lindner 4. Guowang Xu 24. Albert van der Berg 44. Matthias Mann 64. Emily Hilder 84. Peter Schoenmakers 5. Tuan Vo-Dinh 25. Allen J. Bard 45. Detlef Günther 65. Michal Holcapek 85. Ed Yeung 6. Hanfa Zou 26. Yoshinobu Baba 46. Andrew deMello 66. Richard Zare 86. Takeshi Yasumoto 7. R. Graham Cooks 27. Mike MacCoss 47. Norman Dovichi 67. Colin Poole 87. Gui-bin Jiang 8. Susan Lunte 28. Royce W. Murray 48. Attila Felinger 68. James W. Jorgenson 88. George Whitesides 9. Gary Christian 29. Chad Mirkin 49. Barry Karger 69. Michael Quilliam 89. John Yates III 10. Wilhelm Schänzer 30. Charles M. Lieber 50. Brendan MacLean 70. Gerald Hopfgartner 90. Ruedi Aebersold 11. Yi Chen 31. Claudio Soto 51. John Justin Gooding 71. Nobuo Tanaka 91. Jonathan Sweedler 12. Ian Wilson 32. Ulrich Tallarek 52. David McCalley 72. Jack Kirkland 92. Lutgarde Buydens 13. Frank Laukien 33. Gary Hieftje 53. Christian Griesinger 73. Pavel Jandera 93. Frank Svec 14. David Walt 34. Mike Ramsey 54. Catherine Fenselau 74. William Hancock 94. Akira Nakamoto 15. Marc N. Casper 35. Richard Stadler 55. Monika Dittman 75. Albert Heck 95. Georges Guiochon 16. Jean-Luc Veuthey 36. Michael Lämmerhofer 56. Paul Haddad 76. Hans H. Maurer 96. Ulrich Panne 17. Koichi Tanaka 37. Janusz Pawliszyn 57. Luigi Mondello 77. Fred Regnier 97. Jeanne E. Pemberton 18. Davy Guillarme 38. Ron Majors 58. Scott E. Fraser 78. Pat Sandra 98. Fasha Mahjoor 19. Nicholas Winograd 39. Marja-Liisa Riekkola 59. Mary Wirth 79. Andreas Manz 99. Daniel Armstrong 20. William P. (Bill) Sullivan 40. Michel Nielen 60. Alexander Makarov 80. Gerard Rozing 100. Yukui Zhang

9 10 11 13 17 18 20 5 7 12 4 14 15 16 24 3 6 8 33 19 21 22 23 2 32 29 31 35 39 1 27 37 28 30 34 40 44 36 38 42 50 41 43 26 49 52 47 51 55 46 54 59 25 48 58 53 56 57 45 67 73 66 71 72 68 74 64 69 70 76 65 60 61 62 63 89 91 75 77 85 87 88 90 92 93 80 83 94 82 84 96 98 78 81 86 95 79 97

99 100 Contents

07 Editorial Upfront In My View The Top Ten Reasons For Doing the Power List, 10 Analytical Tattoo 16 Emily Hilder questions the lack by Frank van Geel of analytical symposia in the 11 Lipstick on Your Collar? Southern Hemisphere

12 Onions Under E-Scrutiny 17 How do we guarantee quality 08 Contributors from lab tests?, asks 13 Bug ID by Mass Spec Peter Kootstra

14 Tracking Fracking 18 Joan-LLuis Vives Corrons On The Cover Cover makes a rare request for those 15 What’s that Smell? suffering from anemia

OCTOBER 2013 # 09 the Power List pastiche of Sir Peter Analytical Scientist

Upfront In My View Feature Solutions Blake’s “Sgt. Pepper’s Lonely Is it time to trace Out of sight should Three gurus of SFC How to increase access fracking contamination? not mean out of mind extol its virtues to dioxin analysis

14 16 38 – 43 44 – 46 Hearts Club Band” album cover (1967).

the Analytical Scientist the Analytical Scientist

ISSUE 09 - OCTOBER 2013

Editor - Rich Whitworth [email protected] Editorial Director - Richard Gallagher [email protected] Scientific Director - Frank van Geel [email protected] Graphic Designer - Marc Bird [email protected] Managing Director - Andy Davies [email protected] Director of Operations - Tracey Peers [email protected] Publishing Director - Lee Noyes [email protected] Audience Development Manager - Tracey Nicholls io B s [email protected] e n Editorial Advisory Board Monika Dittman, Agilent Technologies, Germany s Norman Dovichi, University of Notre Dame, USA Emily Hilder, University of Tasmania, Australia o Tuulia Hyötyläinen, VTT Technical Research r Centre of Finland Hans-Gerd Janssen, Unilever Research and Development, The Netherlands Ian Jardine, Thermo Fisher Scientific, USA Robert Kennedy, University of Michigan, USA Samuel Kounaves, Tufts University, USA Marcus Macht, Bruker Daltonik, Germany Luigi Mondello, University of Messina, Italy Peter Schoenmakers, University of Amsterdam, 10 The Netherlands Robert Shellie, University of Tasmania, Australia Ben Smith, University of Florida, USA Frantisec Svec, University of California at Berkeley, USA Ian Wilson, Imperial College London, UK

Features Departments Published by Texere Publishing Limited, Booths Hall, Booths Park, 23 The Power List 2013 44 Solutions: Dioxin Analysis Chelford Road, Knutsford, Cheshire, So let us introduce to you Access, by Jayne de Vos and WA16 8GS, UK The one and only John Yates III Peter Gorst-Allman And The Analytical Scientist’s General enquiries: www.texerepublishing.com Top 100 Band. [email protected] 47 Application Notes +44 (0) 1565 752883 38 Three Gurus of Supercritical [email protected] Fluid Chromatography Isabelle François, Davy Distribution: Guillarme, and Eric Lesellier Sitting Down With The Analytical Scientist is distributed challenge SFC naysayers and worldwide through 21,000 printed copies to a targeted European mailing make a strong case for the 50 Mike Grayson, Archivist at the list of industry professionals and 61,250 reappraisal of the technique in American Society for Mass electronic copies, including 27,583 to the context of modern systems. Spectrometry North/South America, 26,509 to Europe, and 4,658 to the Rest of the World. ISSN 2051-4077 ® 2 AZURA Compact HPLC We think a cuboid of 36 x 15 x 52 cm should be enough space for a whole HPLC system … AZURA Compact HPLC is available in isocratic or high pressure gradient conﬁ gurations. Due to its small dimensions, this HPLC ﬁ ts on any laboratory bench. Nevertheless, it offers high technical performance and is suitable for a wide range of HPLC applications. Different control options and a choice of accessories make it very adaptable.

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www.knauer.net/azuraedu The Top Ten Reasons For Doing the Power List Why we’ve added to the craze of “a list for everything”. Editorial

fter some (quite heated) debate, we have developed and now humbly present The Analytical Scientist Power List 2013 – our catalog of the 100 most influential people in the field – on page 23. Why generate a Top 100? Because, quite simply, you are a fascinating bunch, doing interesting and useful work that serves society – and you are doing it without much ado, humbug or pretention. The Power List is a contribution to the third part of our mission to record, scrutinize and celebrate analytical science, and applauds some of the self-effacing giants of the field. To develop the list we requested nominations from our readers and then organized a jury to select the Top 100. Our editorial team represented one-fifth of the jury; the others were well-respected scientists who prefer to remain anonymous and were modest enough not to vote for themselves. Let’s be clear – we don’t pretend that this list is definitive: it’s subjective and may have shocking omissions (do let us know). We’ll use any discussion, dissention and disagreement as fuel for 2014 list. Lastly, in the spirit of list-mania, here are our Top 10 reasons for doing the Power List: 10. Survival. “We like lists because we don’t want to die” - Umberto Eco (http://tas.txp.to/0913-lists) 9. Trendiness. Lists are pervasive, especially in this Internet age. Why resist? 8. Sophistication. The Power List lends the list craze an intellectual leg-up (not that the bar is set very high by “the highest-earning celebrities” and “worst movies of all time”). 7. Devilment. The idea of taking a complex subject and reducing it to a tabloidesque list of characters fulfills a need for mischief. 6. Habit. Readers gravitate toward almost any list (so they say); magazines publish lists for that very reason. 5. Kinship. A list of like-minded souls reminds us that we’ re not alone. 4. Variety. From paper-based diagnostics to high-pressure mass spectrometry, the diversity of the field is amazing. 3. Serendipity. Lists act as a great source of information that you didn’t even know you were looking for. 2. Imitation. If it’s good enough for the Smithsonian, it’s good enough for analytical science (www.aaa.si.edu/exhibitions/lists) 1. Celebration! The list includes contributions to many fields of science and practical improvements to the lot of humankind. We should all be proud of that.

Frank van Geel Scientific Director Contributors

Jayne De Vos & Peter Gorst-Allman “Watching countless episodes of Quincy on television directed my career aspirations towards becoming a forensic scientist,” says Jayne De Vos, who started out in serology in the late 1980s before an interest in drug analysis, toxicology, and arson chemistry grabbed hold. A career shift took Jayne from qualitative chemistry to accurate measurement (metrology). Her interest in separation science and environmental monitoring led to a collaboration in 2008 with Peter Gorst- Allman and Jean-Fransçois Focant (University Liége, Belgium), which provided the platform to establish and develop dioxin capability for South Africa. But Jayne is still a forensic analyst at heart.

“Environmental analysis has always been a passion for me,” says Peter Gorst-Allman. After early work on the contamination of food and feedstuff by mycotoxins (using primarily NMR spectroscopy), Peter has been in the field of chromatography and mass spectrometry for over 30 years. The last 13 years have been spent with LECO Africa where he is the Director of Separation Science Applications for Africa and Asia Pacific. “Collaborating with Jayne on developing alternative methods for POPs analysis in South Africa has resulted in some of the most personally satisfying work I have done.” Read about the collaboration on page 44.

Joan LLuis-Vives Corrons The professor of medicine and head of the haematology laboratory department of the Hospital Clinic i Provincial (University of Barcelona) since 1976, Joan LLuis-Vives Corrons has been influential in haematology research, education and diagnosis. “My main focus has been on the development of new procedures for the diagnosis of anaemias and haematological malignancies (acute and chronic leukaemias and lymphomas) as well as in the standardization and quality assessment of haematology laboratory practice”. Joan requests your input on anaemia diagnosis on page 18.

Peter Kootstra Laboratories can no longer have secrets with Peter Kootstra on the case. After more than 25 years working for the government, Peter, who has a background in medical and analytical chemistry, is now a consultant on analytical chemistry and quality assurance. He is co-owner of Lab-QAcademy, a provider of training courses and workshops on the quality assurance in laboratories. Peter believes that, by following a practical approach, the quality of laboratories can be improved: “If analyst know why rules are necessary, quality will be improved,”he says. Read more of his views on page 17.

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continuous monitoring for fitness, Analytical healthcare and military applications,” says Upfront Wang, who also features on The Power Tattoo List (see page 30). The sensor comprises of three screen- Reporting on research, Non-invasive lactate printed electrodes, one of which is coated personalities, policies and monitoring adds function to with lactate oxidase to provide chemical partnerships that are form for athletes on the edge selectivity. The conversion of lactate into pyruvate releases two electrons – a wired shaping analytical science. The lactate threshold (the work device monitors the resulting current. rate beyond which blood lactate The metabolite biosensing tattoo We welcome information concentration increases exponentially) readily flexes with movement and was is a better predictor of performance able to accurately measure lactate levels on interesting than maximal aerobic capacity and a in ten exercising volunteers. “Such collaborations or research better indicator of exercise intensity electrochemical devices are low cost, that has really caught than heart rate (1) so its measurement low power, and portable – and hence is of significant clinical importance in highly attractive for such on-body your eye, in a good or monitoring extreme athletes – or military operations,” Wang concludes. To prove bad way. Email: personnel being put through their paces. the point, start-up company Electrozyme [email protected] But measuring lactate levels usually (www.electrozyme.com) is currently requires a small blood sample – more than seeking funding to further develop and a mildmild inconvenienceinconveni mid-marathon. commercialize the technology. RW Now, a research teamteam led by Joseph Wang at the DepartmenDepartmentt of Nanoengineering, References University of CaliforniaCalifo San Diego, have 1. J. Wenzhao Jia et al., “Electrochemical Tattoo ddevelopedeveloped a biosenbiosensors that can be applied Biosensors for Real-Time Noninvasive Lactate to the skin much likelik a temporary tattoo to Monitoring in Human Perspiration”, Anal. measure laclactatet levels in sweat (2). Chem., 85, 14, (2013). “We coupleco our printable 2. M. L. Goodwin, “Blood Lactate Measurements flflexibleexible e lelectrochemicale sensors and Analysis during Exercise: A Guide for with arartistict tattoo-transfer Clinicians”, J. Diabetes Sci. Technol., 1 (4), ttechnology,echnology and use it for 558–569 (2007).

10.0

8.0 Lactate

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4.0 ios

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the Analytical Scientist with a Horiba LabRAM-HR Raman Lipstick on spectrometer using three different lasers operating at wavelengths of 473, 633, and Your Collar? 784 nm. The lipstick data was pretreated to reduce noise and remove the baseline, The non-destructive nature of and then principal component analysis Raman spectroscopy is a boon was applied to reduce the dimensionality. to forensic evidence continuity The data were subsequently used to construct a simple k-nearest neighbours A practical advantage of Raman (kNN) classifier. Our analysis spectroscopy was recently was implemented in provided by researchers MATLAB R2012a using from the University the Statistics Toolbox.” of Kent, UK, in the forensic analysis of How reliable is lipstick (1). They were the data? able to differentiate “We achieved up to samples found on 98.7 percent correct cigarette ends and classification over 30 tissues without the need spectra of 10 lipstick to remove the items from samples. Spectra from evidence bags, thus reducing trace lipstick deposited on the risk of “compromised continuity”. fibres were also analysed – with 100 Professor Michael Went of the percent correct classification.” University’s School of Physical Sciences fills in the details. Any surprises? “We found that Raman spectroscopy Why lipstick? could be used to obtain spectra of the “There is a general principle in forensic lipstick smears deposited on a variety science that every contact leaves a trace, of surfaces – even through evidence so we became interested in the transfer of bags, with little or no interference from cosmetic evidence between individuals the bag.” and between individuals and objects. We had previously looked at Raman Any further forensic opportunities? spectroscopy for the trace detection of “We have certainly further drugs, so we began exploring its use in demonstrated Raman spectroscopy’s the analysis of foundation powders, skin ability to non-destructively obtain creams and eyeliners, but have made the highly discriminating data from most progress with lipsticks.” microscopic samples without removal from transparent containers. We will Is this a forensic first? continue to work on other forms of “While Raman spectroscopy has been cosmetic evidence.” RW used before for lipstick analysis, we have arguably demonstrated its potential in References forensically important situations.” 1. F. Salahioglu, M. J. Went, and S. J. Gibson, “Application of Raman spectroscopy for the How does it work? differentiation of lipstick traces”, Analytical “The experiments were conducted Methods, 5, 5392-5401 (2013). Are you happy with your IC System? Switch to Metrohm now and save – Onions Under guaranteed! E-Scrutiny Save thousands of $ Italian researchers tackle over the lifetime of the unlikely issue of red your instrument! onion counterfeiting with m No syringe filters and an electronic-nose-based filter caps required approach to ﬂavor proﬁling. m 10 year suppressor warranty m Fully automated sample The prevention of deceptive, fraudulent, ‘fingerprint’ preparation or downright dangerous practices is a or ‘pattern’ rather m Success guaranteed: constant and major challenge facing than as a set of spectral features.” A typical Metrohm Application the food industry. Now, a team from the E-Nose system mimics the mammalian Guarantee Laboratory of Food Chemistry at the olfactory system with an array of partially University of Reggio Calabria led by specific artificial electrical ‘receptors’ – 12 switch-now.metrohm.com the (appropriately named) Mariateresa metal oxide semiconductor sensors in Russo has unveiled a new E-Nose system this particular case – coupled with pattern and data analysis approach that could recognition techniques to process the strengthen the field’s defensive armory signals. “It doesn’t decompose the aroma (1). The product under analysis? Not red fraction of the matrix into its constitutive wine, for which Italy is rightly famed, but components,” says Russo, “rather, it red onions. supplies a global evaluation of the aroma “The Cipolla Rossa di Tropea [red in an attempt to provide objectivity”. Ask for onion of Tropea], produced in the Italian As with any system of this nature, a free demo region of Calabria, has been recognized it is perhaps the data analysis that by the EU Protected Geographical provides the biggest challenge. The team now! Indication thanks to its unusually sweet used Discriminant Function Analysis aroma and low level of pungency – and (DFA) to convert the large amounts of hence its quality,” explains Russo. Like information generated by the sensors. many other goods covered by specific “DFA transforms data using linear European protection, the cyanidin- discriminant functions (LDFs) in a rich bulbs prove too tempting to similar manner to PCA. However, where counterfeiters. “The implementation PCA attempts to maximize all variances of simple, affordable, power efficient, present in the data, DFA generates reliable, and sensitive devices for real- an LDF to maximize the distance time analysis is a current priority for between two given centroids within food quality and authentication,” the data, taking the variances of the two Russo says. While some research groups into account,” says Russo. “So, groups are attempting to convert where PCA could be seen as part of an advances in microtechnology into viable unsupervised classification system and miniaturized gas chromatographs is used to explore the data and to assess and mass spectrometers, Russo and discrimination performance, DFA forms colleagues believe that nature offers a part of a supervised classification system more affordable template: “the alternative – groups must be known a priori to is a biology-inspired approach where gas perform DFA.” In other words, DFA is composition is recognized as an odor used to categorize unknown samples into Rediscover Your Passion

one of several already known groups. that they have US Food and Drug Russo’s approach yielded an impressive Administration (FDA) 510(k) de novo 97.5 percent correct classification rate clearance for clinical use of the technology (CR) overall. “The discrimination is is big news. It could signal a mass adoption considered ‘excellent’ if the percentage of MALDI-TOF MS, which can of recognition is higher than 90%. The dramatically simplify and increase the DFA of our onion samples showed a clear speed of microorganism identification. separation among the four onion groups The Vitek MS connects Biomérieux’s assessed. Such a high recognition rate identification and antibiotic susceptibility confirms our hypothesis based on results testing platform (Vitek 2) to a MALDI- from classical analytical techniques, which TOF MS, automatically combining the You care about making a demonstrated clear qualitative differences two sets of results to bring identification difference. between the types of onions compared.” time down from hours to minutes. Whether your work helps protect Whether the approach can be To gain FDA clearance, 7,068 considered truly non-destructive, as the clinical isolates from several categories, clean waterways, ensure food title of the paper suggests, is up for debate; including anaerobic bacteria, fastidious safety, or develop life-saving the onion’s edible parts were homogenised Gram-negative bacteria, and yeast, were drugs, it doesn’t just generate a and filtered before the addition of 5 percent analyzed and identified with 93.6 percent paycheck; it improves lives. Be- trichloroacetic acid to terminate allinase overall accuracy when compared with activity. It is not reported how good the red 16S Ribosomal RNA gene sequencing – cause so much depends on your onion marmalade tasted after that… RW the current gold standard. data, you need tools that deliver Researchers from the Washington deﬁnitive results and consistent Reference University School of Medicine also performance. 1. M. Russo et al., “Non-destructive flavour rigorously tested the new system with evaluation of red onion (Allium cepa L.) Ecotypes: An a ten-year collection of clinical samples electronic-nose-based approach”, Food Chemistry 141, that were difficult to identify using We specialize in innovative, 896–899 (2013). traditional methods. According to Carey- high-quality chromatography Ann Burnham, Assistant Professor of products and support them with Pathology and Immunology and Medical Director of Microbiology at Barnes expert technical service, so you Bug ID by Jewish Hospital, nearly all of the isolates have the tools you need to were identified with high accuracy in a rediscover your passion and Mass Spec matter of moments. create a better world. No small wonder that the Cleveland FDA approval of a MALDI-TOF Clinic, USA, has named the technique MS-based system for bacteria one of the Top Ten Breakthrough and yeast identiﬁcation brings Medical Technologies of 2013. Which analytics to the clinic brings us nicely to The Analytical Want to learn more Scientist 2013 Innovation Awards… RW about how Restek The detection of microbes using matrix- products can help assisted laser desorption ionization–time To be published in our final issue of you make a difference? of flight mass spectrometry (MALDI- 2013, The Innovation Awards will TOF MS) isn’t new; Bruker’s MALDI celebrate the Top Ten innovations of Sign up to receive free the year. Nominations are now open literature in your area at Biotyper has been on the market for some www.restek.com/rediscover time. However, the Biotyper product – email the editor: rich.whitworth@ page states that it is “For research use only. texerepublishing,com. Please ensure you Not for use in diagnostic procedures!” are signed up online for updates and more So the announcement from Biomérieux information: tas.txp.to/0913/subs

Rediscover Restek 14 Upfront

configurations that can Tracking act as tracers while remaining chemically Fracking and biologically inactive. We decided Startup company BaseTrace to enter the Duke applies DNA tracer technology Startup Challenge to to track contamination from see how far it would take hydraulic fracturing us and won some money. We also secured a Duke Fracking is a hot-button issue. So, when Environmental Innovation they co-invented a technology to identify and Entrepreneurship grant. associated contamination problems, That’s what gave us the cash and Justine Chow and Jake Rudolph saw courage to get some lab space and make an opportunity. They set up a company our tracer technology a reality.” together, BaseTrace (www.basetrace. com), to commercialize it. Here, they What technology choices did you make formulas, but testing for potentially answer our questions. and why? hundreds of different chemicals is hard Jake: “Detection is performed using PCR, on state and local regulators.” Could you describe how the system works? so you have to know what you’re looking Jake: “BaseTrace uses unique DNA for to find it. It was an obvious choice, What are the main challenges from a sequences, designed around a proprietary both for its versatility and for its wide business perspective? oligonucleotide configuration, to confer a availability; eventually, we’d like to be able Justine: Funding, to a certain extent. We fingerprint to unique fluid sources – these to license out our detection capabilities, haven’t actively sought or obtained any could be in situ or in a tank in an industrial so that any lab with PCR capabilities is funding from oil and gas companies, setting. We can test samples for the set up for our detection protocol, given so this technology has been developed presence of that unique tracer to determine our proprietary chemistry.” independently through local startup whether there’s been connectivity where competition money and investments there shouldn’t have been.” Were there any unexpected challenges in from friends and family. creating a robust system? What’s your background and why the Jake: “Justifying the BaseTrace system Where do you see the company in five or interest in hydraulic fracturing? has been both challenging and exciting ten year’s time? Justine: “I studied biology at Harvard because of the problem’s cross- Justine: “Hopefully, we'll have expanded and came to Duke University for disciplinary nature – we’ve had to draw on into different applications and possibly graduate school, where I began to learn expertise in hydrogeology, engineering, other countries, and the tracer will be more about hydraulic fracturing. In geography, and petroleum geology, as present in most oil and gas wells, and carrying out research for a nonprofit well microbiology, bioinformatics, and certain underground storage tanks. in Washington DC I realized that, machine learning. This convergence Because our technology uses DNA, regardless of which side people took on creates a very exciting work environment, we’re able to generate many trillions of the arguments surrounding hydraulic and allows us to bridge new gaps.” different sequences, each of which can be fracturing, they were all looking for a tool assigned to an individual potential source to help objectively determine whether the Did you face any opposition to the of contamination or leakage.” process causes contamination. concept? Jake: “The beauty of the BaseTrace Justine: “No. The companies we’ve technology is its simplicity, but I’d Where did the inspiration behind talked with see it as a way to prove their love to see additional technological BaseTrace come from? innocence. Right now companies are advancement of the tracer design for Justine: “In part, from my background in being pushed to disclose trade secret niche markets and perhaps more extreme biology. We have patent-pending DNA fracking fluid ingredient lists and environments.” RW

the Analytical Scientist Upfront 15

Karnataka State Pollution Control Does this smell What’s that Board (KSPCB) officials charged into like a cover up to the local area with a volatile organic you? Have you Smell? compound meter to check levels, the heard about other mystery odor was described simply as such analytical A “nauseating odor” a “smell” but quantified at 50 parts per failures? Let us that alarmed citizens of million before dispersing. know by commenting: Mangalore, India, apparently Two days later, and the source of the tas.txp.to/0913-smell remains unidentiﬁed despite “pungent smell” could still not be traced laboratory analysis. despite the KSPCB sending air samples Sources for laboratory examination – the results 1. http://newindianexpress.com/states/ Friday, 20 September, 2013, saw panic allegedly did not show the presence karnataka/Mystery-odour-sends-Mangalore- on the streets of Mangalore as a gas-like of any chemical substance. A KSPCB into-tizzy/2013/09/21/article1795640.ece smell caused people to seek open space spokesperson told The Times of India: 2. http://articles.timesofindia.indiatimes. and safety, checking their own LPG “Samples were sent to Mangalore com/2013-09-21/mangalore/42271546_1_ canisters en route, according to several Refineries Petrochemicals Limited, odour-state-pollution-control-board-new- Indian news outlets (1, 2). but it was already diluted by the time mangalore-port Within hours of initial reports and it reached the lab" (3). Gas sample 3. http://articles.timesofindia.indiatimes. amongst a flood of further panicked collection, it appears, is an art form, com/2013-09-22/mangalore/42291957_1_ calls to police and fire control rooms, after all. RW smell-state-pollution-control-board-kspcb

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HPLC series. This is often reflected in HPLC Down Under the challenge of providing a forum for In My those long-established in the field while, Isn’t it time for a change of at the same time, offering opportunities scenery? Isn’t it time for a for young, up-and-coming scientists View different perspective? Isn’t it and those from non-traditional or time for a shake up? By limiting developing regions. In fact, these are major symposia to the Northern both issues that the HPLC meetings In this opinion section, Hemisphere, you’re missing have actively tried to address over the experts from across the half the world’s potential. past few years. The introduction of the world share a single Horvath Award from 2006, honoring the achievements of a young researcher strongly-held view or (under 35), has not only created key idea. recognition but also highlighted the contributions that young scientists can Submissions are welcome. make to the meetings. Moreover, such a commitment effectively mandates the Articles should be short, By Emily Hilder, Professor and ARC inclusion of oral presentations from a focused, personal and Future Fellow, University of Tasmania, younger crowd. The Hobart organizing passionate, and may Hobart, Australia. committee has made the same promise to those at the beginning of their career deal with any aspect of The HPLC meeting series began in 1973 with a truly inclusive program. analytical science. with annual meetings held alternately in Since 2008, the HPLC Permanent They can be up to 600 Europe and North America. Although Committee has included additional well established, it has been accused, meetings in Asia. Now, Australasia is words in length and in the past, of being old-fashioned or in the mix, with HPLC2013-Hobart written in the first person. conservative – even unwilling to change. providing the perfect example of the To some readers, HPLC2013-Hobart potential that new geography can bring. probably looks like “yet another one of And the support of the international Contact the editors at those separation science meetings” – hard community is proven by the quality of [email protected] to distinguish from any number of similar the plenary and keynote speakers secured symposia. As a regular participant of the (many of whom appear on The Power List HPLC meeting series since 2000 and, in this issue, see page 23). Such support is more importantly, co-chair of the Hobart absolutely critical for the future growth meeting, I’ve been reflecting on what of separation science in this region and, makes this one any different and what led arguably, worldwide. It also differentiates to it being held in Tasmania – the first time this HPLC meeting from others. Why? the meeting will cross the equator into the Well, as an Australian, attending an Southern Hemisphere. Here, I answer international meeting usually requires those questions but also suggest that it over 24 hours of travel – and a generous bodes very well for a vibrant future for travel budget that is prohibitive for many. separation science right across the globe. The opportunity to hear from and interact When faced with stiff competition, with the best scientists in the field without I believe that the ability to thrive stems such a travel burden is a huge advantage. from innovative thinking in the context Conversely, we have endeavored to of wisdom gained from previous construct a program that also includes successes – a delicate balance to strike many speakers from the local region. with established meetings like the For regulars of HPLC meetings, this

the Analytical Scientist F-DGSi introduces its “Clever Sensor” to eliminate the risks in using Hydrogen as a Carrier gas in GC or GCMS analysis. The advantages of hydrogen are clear (fast provides an exciting opportunity to Centre for Research on Separation analysis, high efficiency, reduced costs and prolonged column life time), but it does listen to perspectives from a new, fresh- Science (ACROSS) at the University of have one really big disadvantage! thinking crowd. For scientists within the Tasmania. How ACROSS has grown to region, it provides an opportunity to truly a team of over 50 researchers in separation Hydrogen is an explosive gas! contribute to the direction of separation science is another story in itself, but is an An undetected gas leak can occur with a broken science from an international perspective. example of what can happen when you column or a leaking connection. The danger is that Given current growth within Asia and think differently and aren’t afraid to take an undetected gas leak could result in an explosion Australasia, these scientists will represent risks. I feel the same excitement about in the GC oven placing laboratories and their a big part of the field and its future, and HPLC2013-Hobart, but you should personnel at risk. I believe that we must engage more come and see for yourself. effectively with them. With our H2 Clever Multi- Sensor ensures the safe use of hydrogen in GC analysis. The final question: why Hobart, The 40th International Symposium on High The measured gas concentration is shown on the Tasmania? As a native Tasmanian, I Performance Liquid Chromatography and LCD screen of the external controller. When the could simply say, why not?! Given its Related Techniques (HPLC2013-Hobart) hydrogen concentration reaches the user defined untouched wilderness, superb food and will take place at the Hotel Grand Chancellor, level, typically between 25% and 50% LEL (equal to wine, and lashings of contemporary Hobart, Tasmania, Australia from 18-21 1%-2% by Vol H2), the LCD screen starts flashing, art, Tasmania has much to offer. But November 2013. For more information, visit: an acoustic signal is transmitted and the carrier gas Hobart is also home to the Australian www.hplc2013-hobart.org Q will automatically be switched to an inert gas. This important feature eliminates the risks and at the same time ensures safety. The external box is able to support up to 4x sensors and operates as individual channels: it will Pragmatic Red Tape a kilogram to vary – money is involved, stop the H2 gas only for the GC in which there is a afterall. Likewise, laboratory results play leak detected. Documentation does not ensure an important role in our society. Juries rely effective, efficient or consistent on forensic laboratories for evidence, we Features of our H2 Clever Multi- Sensor: performance. Paper is not a all have faith in food and environmental replacement for motivation, analyses, and we trust the findings of k#VNJMQGMLPGQICJGKGL?RCB competence, and capable medical test results. But can these results k*MUCPMNCP?RGLEAMQRQ employees, working within always be trusted? Unfortunately, the k-NRGA?J ?AMSQRGA?J?PKQGLAJSBGLE?L1+1?J?PK well-designed processes. So, answer is not clear-cut. text message k SRMK?RGA?J?PK?ARGT?RGML how do we guarantee quality Our belief in pharmaceutical k SRMK?RGAA?PPGCPE?QQUGRAFGLEDPMK&RM, from lab tests? laboratories started to falter around 1970. k SRMK?RGAQRMNQGEL?JQCLRRM%! Following cases of fraud in data submitted k#?QWA?JG@P?RGML by toxicology labs to the US Food and k#?QWRMGLQR?JJ Drug Administration (FDA), 1972 saw k!MKN?RG@JCUGRF?JJ%!Q the introduction of Good Laboratory k*C?IBCRCARGMLGLBGA?RCQ?L?JWQGQGQAMKNPMKGQCB Practice (GLP) – the framework within k+SJRG 1CLQMPA?N?@GJGRWQSNNMPRQSNRMQCLQMPQ which laboratory studies are planned, performed, monitored, recorded, By Peter Kootstra, co-owner of Lab-Q reported, and archived. GLP makes Academy, Amsterdam, The Netherlands everything traceable to original raw data and helps assure regulatory authorities To guarantee a ‘standard’ kilogram, that the data submitted are a true meter, or any other SI unit, a network reflection of the results obtained during of metrological laboratories exists. The the study. GLP was one of the first quality competence of this network means we management systems for laboratories. generally trust ‘the system’. Certainly, it In 1978, the US Environmental would not be acceptable for the mass of Protection Agency initiated a certification¶

www.f-dgs.com e-mail: [email protected] 18 In My View

program for laboratories that analyze From an analyst’s point of view, quality manipulation of the parameters to acquire drinking water. Similar projects started in relates to the analysis of a given sample the desired result, especially when a ratio is several other countries, which resulted in – and can mean finding an answer that just outside the required limits. ISO/IEC 17025: General requirements meets their own expectations. If the Going back to the laboratory quality for the competence of testing and result indicates that the product is out management system, remember that it calibration laboratories. of specifications, the analyst is likely to was based on GLP – and the bureaucracy It was simple. The quality manager reanalyze the sample until the result is has become a kind of tradition. Often, defined what ‘quality’ was and wrote within specifications. Surprised? A doping nobody in the laboratory (except the procedures. Analysts were expected to laboratory, which acts in compliance quality manager) has bothered to read, understand, and act accordingly. with the World Anti-Doping Agency read ISO/IEC 17025. It is the quality But ‘quality’ is a relative term. Here’s (WADA) international standard, can be manager alone that translates the clauses the International Organization for similarly flawed by confirmation bias (the into standard operating procedures Standardization (ISO) definition: “The tendency of people to favor information (SOPs). The only feedback he or she totality of features and characteristics of a that confirms their hypotheses and reject receives is that it is too bureaucratic. product or service that bear on its ability that which does not) because “the objective Have you asked your analysts what to satisfy stated or implied needs”. In of the confirmation assay is to accumulate their SOPs would look like, if they were other words, a product is deemed to be of additional information regarding an involved in their inception? How about good quality when it complies with the adverse finding”. providing flow charts rather than long requirements specified by the client. When Furthermore, the identification procedures? Quality also means taking projected onto analytical work, quality criteria described in technical documents the time to think about the design can be defined as the delivery of reliable leaves plenty of room for interpretation. of your processes and evaluating and information within an agreed time span, Anyone who has worked with liquid improving current practice. Certainly, it under agreed conditions, at agreed costs, chromatography-tandem mass takes more effort, but a well-designed and with necessary aftercare – a long way, spectrometry (LC-MS/MS) data analysis and accessible system benefits one and perhaps, from daily laboratory practice. will be aware that it requires only trivial all – including quality. Q

Rare Analytical Need Anemia, defined as a decrease of of professional experience, and social or hemoglobin (Hb) concentration in blood, cultural barriers, a large percentage of RAs Anemia becomes much more is a common condition in humans. It has a remain undiagnosed. The clear need to serious in countries where rare wide variety of causes, both congenital and mobilize resources will only be achieved hereditary forms can remain acquired, but it is always a manifestation of through coordinated multi-centre and undiagnosed. A symposium an underlying disease, not a disease in itself. multi-disciplinary action. The European aims to tackle the issue head on Iron deficiency (in women and children) Commission (EC) is, therefore, co- – and analytical science has its and chronic diseases (in adults and the financing the European Network for Rare part to play. elderly), are the most frequent causes of and Congenital Anaemias (ENERCA). mild to moderate anemia in developed One activity is the 5th European countries. Diagnosis of decreased Hb Symposium on Rare Anaemias*, a forum levels is relatively easy and inexpensive; all on diagnosis and clinical management of modern automated and semi-automated RA, and a workshop to explore the types analyzers measure Hb concentration with of tests that could provide correct diagnosis great precision and accuracy. most quickly. However, another group of anemia For RAs, the pivotal diagnostic tests By Joan-LLuis Vives Corrons, Head of the sufferers occurs at a frequency of less than are red blood cell (RBC) morphology Red Cell Pathology Unit and ENERCA one in 2,000 in Europe. Up to 80 percent examination and reticulocyte count. The Project; Professor of Medicine (Hematology) of these rare anemias (RA) are hereditary. latter allows differentiation between at the University of Barcelona, Spain. Due to the low number of patients, a lack a central (bone marrow) or peripheral ¶

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(hemolytic) origin of the anemia. Peripheral on the other hand, result from decreased alpha thalassemia and gene sequencing for blood film examination and osmotic synthesis of normal globin chains. The the identification of specific mutations. fragility tests (OFT) can sometimes two conditions can overlap. In Europe, The two key discussion points at the confirm the diagnosis of hereditary certain populations of southern countries symposium of greatest relevance for spherocytosis, one of the inherent causes of are particularly at risk of thalassaemia – those in the analytical sciences are (a) rare anemias. When the OFT is negative, the cause of so-called ‘Mediterranean preventive programs for SCD control, RBC enzyme assays are required for the Anemia’. But increasing migration to such as neonatal screening, and (b) new diagnosis of a hereditary enzymopathy, Europe from African and Asian countries methodologies for diagnosis and genetic with glucose-6-phosphate dehydrogenase has drastically changed this scenario: counseling, and genetic characterization (G6PD) or pyruvate kinase (PK) being the sickle-cell disease (SCD) is becoming in cases where laboratory ‘blind most common. an important challenge for public health spots’ are caused by co-inheritance of Hemoglobinopathies, which lead to care. Diagnostic approaches for these hemoglobinopathies and other RBC moderate or severe anemia, are the most disorders range from electrophoresis and genetic defects. The organizers would common genetic defects worldwide, high performance liquid chromatography welcome your input! with an estimated number of 269 million (HPLC) for hemoglobin fractionation *The 5th European Symposium on Rare carriers. These hereditary conditions are in beta thalassemia and structural Anaemias takes place 15–16 November, the consequence of mutations that result haemoglobinopathies (sickle cell anaemia) 2013, in Ferrara Italy. For more in abnormal hemoglobin. Thalassaemias, to polymerase chain reaction (PCR) for information, visit: www.enerca.org. Q GCXGC-QTOF $/ö9/5ö(!6%ö#/-0,%8ö-!42)#%3 ö&/2ö4(%öö '#8'#ö1 4/&ö./ö#/-0/3)4)/.ö)3ö4//ö#/-0,%8 The ZOEX GCXGC modulatorsodulators in combination with thehe NEW! Agilent 7200 QTOF makes it possible to realize a very powerfulul analysis solution.

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&ŽůůŽǁhƐĨŽƌƐƉĞĐŝĂůĂŶŶŽƵŶĐĞŵĞŶƚƐ Who are the 100 most influential people in the analytical sciences? That’s the question we posed to ourselves – and then to you – over two months ago, ahead of open nominations and a painstaking judging process. Here, without further ado, we celebrate the answer. 24 Feature

Yoshinobu Baba Allen J. Bard Professor, Department of Advanced Medical Professor and Director, Center for Science, Graduate School of Medicine, Nagoya Electrochemistry, University of Texas, USA University, Japan Highlight: “Development of the scanning Research: Nanobiosicence and electrochemical microscope.” nanobiotechnology for genomics, proteomics, glycomics, systems biology, Research: Application of electrochemical methods to the study of single molecule manipulation, and medical applications. chemical problems, including investigations in electro-organic chemistry, www.apchem.nagoya-u.ac.jp/III-2/baba-ken photoelectrochemistry, electrogenerated chemiluminescence, and electroanalytical chemistry. bard.cm.utexas.edu Douglas A. Berthiaume Chairman, President and Chief Lutgarde Buydens Executive Officer Professor and Head, Analytical Chemistry/ Waters Corporation, Massachusetts, USA Chemometrics, Radboud University Revenue: $1.64 billion (2010) Nijmegen, The Netherlands Employees: 5,700 Research: Chemometrical techniques for www.waters.com optimization of molecular structures with respect to (bio) chemical activity and for the processing/interpretation of (medical) multivariate images. www.ru.nl/science/analyticalchemistry Marc N. Casper President and Chief Executive Officer Thermo Fisher Scientific, Yi Chen Massachusetts, USA Professor and Laboratory Director, Institute Revenue: $13 billion of Chemistry. Chinese Academy of Sciences, Employees: 39,000 Beijing, China www.thermofisher.com

Andrew deMello Gary Christian Professor of Biochemical Engineering Emeritus Professor of Chemistry, Department ETH Zurich, Switzerland; Imperial College of Chemistry, University of Washington, USA London, UK Research: Flow and sequential injection Highlight: “The development of microfluidic analysis and related techniques. systems for high-throughput chemical and biological analysis. Further highlights include the first demonstrations of microfluidic combinatorial chemistry, chip-based nanoparticle synthesis, continuous flow PCR, Gert Desmet the application of high-contract fluorescence lifetime imaging to Professor and Head, Department of Chemical microfluidic environments, and pioneering developments in droplet- Engineering, Vrije Universiteit Brussel, based microfluidics.” Belgium Research: Microfluidics and nanoscale science. Research: Miniaturization of separation www.demellogroup.ethz.ch methods and modeling of flow effects in chromatographic systems. vubchemicalengineering.be

Monika Dittman Principal Scientist, R&D Norman Dovichi Agilent Technologies, Germany Grace-Rupley Professor of Chemistry and Highlight: “The introduction of the HP Biochemistry, University of Notre Dame, Capillary-Electrophoresis System in 1992. Indiana, USA This was the first instrument that I accompanied as an R&D scientist Highlight: “Ultrasensitive laser-induced from the early investigation stage to manufacturing release. The fluorescence has driven a wide swath of research in the biological and technology was extremely exiting at the time and we were very proud physical sciences. Most notably, ultrasensitive fluorescence detection when the instrument finally sold to customers.” enabled both capillary array and next-generation DNA sequencers. This technology also laid the foundation for single molecule detection and imaging.”

the Analyticalnalytical Scientist 20-100 (in alphabetical order)

Attila Felinger Catherine Fenselau Professor, Department of Analytical and Professor, Chemistry and Biochemistry Environmental Chemistry Unviversity of Maryland, USA University of Pécs, Hungary Highlight: “Being a thought leader and an Highlight: “We were able to extend and apply experimental contributor to the extension of the microscopic theory of chromatography to model the details of the mass spectrometry to the analysis of biological molecules, including polar chromatographic process at the molecular level. With that tool a large molecules, such as phospholipids and glucuronides, and biopolymers, such number of phenomena, including the adsorption on heterogeneous as DNA adducts, carbohydrates, and protein complexes.” surfaces or the size exclusion process, are now described.” www2.chem.umd.edu/groups/fenselau Research: Characterization of the retention mechanism, thermodynamics and kinetics of adsorption-desorption in HPLC, multivariate chemometrics. John Justin Gooding Scientia Professor; Co-Director of The Australian Centre for NanoMedicine, University of New Scott E. Fraser South Wales, Australia Director, Biological Imaging Center Highlight: “We developed sophisticated Caltech, California, USA surface chemistries that allow biosensors to operate in complex biological Research: Patterning of cell lineages, cell fluids, which has enabled us to make antibody-based electrochemical migrations and axonal connections during biosensors and photonics crystal cell chips to monitor the response of live vertebrate embryogenesis. bioimaging.caltech.edu immune cells to pathogenic stimuli.” tas.txp.to/901-Gooding

Christian Griesinger Davy Guillarme Group Leader, NMR-Based Structural Senior lecturer, School of Pharmaceutical Biology; Director and Scientific Member Sciences, University of Geneva, Switzerland Max Planck Institute for Biophysical Highlight: “During the last few years, I Chemistry, Göttingen, Germany have worked actively in the field of liquid Highlight: “It has always been a dream of mine to use NMR chromatography. I have tried to demonstrate the potential of state-of- spectroscopy for the clarification of absolute configuration of molecules the-art instruments and columns (high temperature UHPLC, core-shell, in organic chemistry. With the usage of residual dipolar coupling SFC), for fast and/or high resolution analysis of small molecules and enhanced NMR spectroscopy, this is in reach.” www.nmr.mpibpc.mpg.de large biomolecules.” (see page 38)

Detlef Günther Paul Haddad Head, Department of Chemistry and Applied Distinguished Professor, Chemistry; Director Biosciences; Group Leader: Trace Element of the Australian Centre for Research on and Micro Analysis, ETH Zurich, Switzerland Separation Science (ACROSS), and Director Research: Ion molecule and plasma of the Pfizer Analytical Research Centre, induced gas phase reactions, laser-induced ablation processes, plasma University of Tasmania, Australia formation, ultra trace multi-element analysis, nano-depth layer ablation. Highlight: “The most satisfying achievement of my research career has chemistry, chip-based nanoparticle synthesis, continuous flow PCR, been the privilege to collaborate with, mentor and support the careers of the application of high-contract fluorescence lifetime imaging to PhD students and postdoctoral researchers of extraordinarily high caliber microfluidic environments and pioneering developments in droplet- and dedication. It has been their accomplishments that have given me the based microfluidics. greatest professional reward.” www.utas.edu.au/across

William Hancock Albert Heck Faculty Fellow, Bradstreet Chair in Head, Biomolecular Mass Spectrometry and Bioanalytical Chemistry, Northeastern Proteomics Group, Utrecht University, University, Massachusetts, USA (Editor- The Netherlands in-Chief, Journal of Proteome Research.) Research: Development of mass spectrometric Research: Glycoproteomics and glycans associated with cancer and methods applicable to the structural characterization of biomolecular infectious disease. www.northeastern.edu/barnett/research/hancockgroup.html systems, in relation to their biological function. bioms.chem.uu.nl 26 Feature

Gary Hieftje Emily Hilder Distinguished Professor; Robert and Marjorie Professor and ARC Future Fellow, School of Mann Chair in Chemistry; and Group Leader, Chemistry, University of Tasmania, Australia Laboratory for Spectrochemistry, Indiana Highlight: “The most satisfying achievement University, USA of my career to date has been to develop new Highlight: “The 65 PhD students who have graduated from materials through fundamental research that have since been applied in our laboratory.” commercial products.” Research: Investigation of basic mechanisms in atomic emission, Research: Synthesis of novel polymeric monolithic materials as selective absorption, fluorescence and mass spectrometric analysis, and the adsorbents for sample preparation/pretreatment, chromatographic development of instrumentation and techniques for atomic methods of stationary phases and other applications in analytical chemistry. analysis. www.indiana.edu/~gmhlab Development of miniaturised analytical systems, particularly for applications in clinical diagnostics and remote monitoring. (see page 16)

Michal Holcapek Professor, Analytical Chemistry, Faculty of Gerald Hopfgartner Chemical Technology, University of Pardubice, Full Professor, Analytical Pharmaceutical Czech Republic Chemistry, Life Sciences Mass Spectrometry, Research: Mass spectrometry and its coupling University of Geneva, University of Lausanne, with HPLC, specializing in structural analysis of organic, bioorganic Switzerland and organometallic compounds, mainly lipidomics, metabolomics, drug Highlight: “To apply mass spectrometry for life sciences research from metabolite identification.holcapek.upce.cz elements to macromolecules.” Research: Bioanalysis, metabolism, miniaturization of sample preparation, multi-component analysis, rationalization of fragmentation Pavel Jandera mechanisms for metabolites ID. www.unige.ch/sciences/pharm/lsmv Professor, Analytical Chemistry, Faculty of Chemical Technology, University of Pardubice, Czech Republic Klavs F. Jensen Highlight: “Development of unified theory of Warren K. Lewis Professor of Chemical gradient elution in reversed-phase, organic normal-phase and HILIC Engineering and Department Head, systems, later extended to two-dimensional LCxLC techniques. Massachusetts Institute of Technology, USA. Elaboration of new approaches for characterization of particulate and Highlight: Having worked with and educated a monolithic stationary phases; prediction and optimization of large number of hard working and bright graduate students and postdocs. HPLC separations.” Research: Microsystems for chemical and biological applications, materials synthesis and processing multiscale simulation of reactive processes. web.mit.edu/jensenlab Gui-bin Jiang Director, State Key Laboratory of Environmental Chemistry and Ecotoxicology, Michael Lämmerhofer Chinese Academy of Sciences, Beijing, China Professor, Pharmaceutical Analysis Research: Analytical development and and Bioanalysis, University of Tuebingen, environmental characterization of persistent organic pollutants (POPs), Germany and the speciation of organometallic compounds. english.rcees.cas.cn/au/bi Hian Kee Lee Frank Laukien Professor, Department of Chemistry Chairman, President and Chief Executive National University of Singapore, Singapore Officer. Bruker Corporation Highlight: “I have been fortunate to have been able to train so many students in miniaturized Revenue: $1.79 billion (2012) sample preparation and extraction. More importantly, that I have learnt Employees: >6,000 www.bruker.com more from them than they have gained from our interactions in my laboratory has really been my greatest satisfaction.”

thethe AnalyticalAnalytical Scientist 20-100 (in alphabetical order)

Milton Lee Charles M. Lieber H. Tracy Hall Professor of Chemistry, Mark Hyman Professor of Chemistry, Department of Chemistry and Biochemistry. Department of Chemistry and Brigham Young University, Utah, USA Chemical Biology, Harvard University, Highlight: “Learning of the ongoing activities Massachusetts, USA of my ninety-plus talented former graduates and postdoctoral researchers Highlight: “Making groundbreaking advances in the synthesis, who not only performed spectacular research while in my laboratories, characterization and assembly of semiconductor nanowires, and but have assumed or are assuming responsible positions around the pioneering their applications in nanomedicine through the creation of world, making significant contributions in a variety of ways.” nanoelectronic biosensors and cell interfaces that blur the distinction between digital electronics and living systems.” Research: Nanoscale science and technology, using novel synthesized Susan Lunte building blocks to push scientific boundaries in diverse areas from Director Ralph N. Adams Institute for biology/medicine to energy and computing. Bioanalytical Chemistry; Director COBRE cmliris.harvard.edu Center Molecular Analysis of Disease Pathways, The University of Kansas, USA Highlight: “Mentoring students and postdocs in bioanalytical chemistry through the development of separation-based methods for the Mike MacCoss determination of peptides, drugs and neurotransmitters in biological Associate Professor, Genome Sciences; fluids, single cells and freely roaming animals.” sluntegroup.ku.edu Group Leader, MacCoss Lab, University of Washington, USA Research: Development of stable isotope Brendan MacLean and mass spectrometry based approaches to improve understanding of biology on a molecular, cellular, and whole organism level. maccosslab.org Lead Developer, MacCoss Lab University of Washington, USA Career: Managed development of Skyline; Fasha Mahjoor one of the key programmers responsible for Founder, President, and Chief Executive Officer, the Computational Proteomics Analysis System (CPAS); significant Phenomenex, California, USA contribution to the development of X!Tandem and the Trans Proteomic Revenue: not listed Pipeline; and created the LabKey Enterprise Pipeline. Employees: >700 brendanx-uw1.gs.washington.edu www.phenomenex.com

Ron Majors Matthias Mann Senior Scientist Director, Department of Proteomics and Agilent Technologies, Delaware, USA Signal Transduction, Max Planck Institute of Highlight: “I was one of the early workers in Biochemistry, Munich, Germany HPLC, especially in column technology. I Research: Developing and applying methods packed the first high performance columns and studied early bonded of mass spectrometry-based proteomics in a variety of biological areas. phases. I have been an editor for LCGC for over 30 years.” www.biochem.mpg.de/en/rd/mann

Hans H. Maurer Alan G. Marshall Full professor, Toxicology and Pharmacology; Robert O. Lawton Professor, Chemistry & Head, Department of Experimental & Clinical Biochemistry; Director, Ion Cyclotron Resonance Toxicology, Saarland University, Homburg/ Program, Florida State University, USA Saar, Germany Highlight: “I am the co-inventor and leading Highlight: “My most satisfying achievement is to have established innovator in Fourier transform ion cyclotron resonance mass spectrometry mass spectrometry in clinical and forensic toxicology documented by (FT-ICR-MS). I am now pioneering mass-based structural analysis of numerous papers, review articles, and handbooks/libraries of reference biomacromolecules and complex chemical mixtures.” GC-MS and LC-MS spectra. This led to various major scientific awards www.magnet.fsu.edu/usershub/scientificdivisions/icr and the honorary doctorate of the University of Ghent in Belgium 2007.” 28 Feature

David McCalley Chad Mirkin Professor, Bioanalytical Science Director, International Institute for University of the West of England, Bristol, UK Nanotechnology; George B. Rathmann Highlight: “While I have been fortunate Professor, Chemistry; Professor, Chemical in receiving research funding from industry and Biological Engineering, Biomedical (particularly pharmaceutical companies), I was very pleased to receive Engineering, Materials Science & Engineering, and Medicine. UK Research Council funding for an (ongoing) study of hydrophilic Northwestern University, Illinois, USA interaction liquid chromatography in 2012, against strong competition Research: Developing strategic and surface nano-optical methods for from projects in the traditional areas of organic, inorganic and controlling the architecture of molecules and materials on a 1-100 nm scale. physical chemistry.” sites.weinberg.northwestern.edu/mirkin-group Research: Fundamental mechanisms and applications of HPLC and GC especially in biomedical and pharmaceutical science. www.indiana.edu/~gmhlab Royce W. Murray Kenan Professor, Chemistry The University of North Carolina, USA Luigi Mondello Research: Electrochemistry, molecular Full Professor, Analytical Chemistry, design, sensors. School of Pharmacy, www.chem.unc.edu/people/faculty/murray University of Messina, Italy Research: Development of analytical methods Michel Nielen for the characterization of complex samples. Project Manager, Professor, Special chair on www.sepsci.unime.it Analytical Chemistry, RIKILT Wageningen UR (University & Research centre), The Akira Nakamoto Netherlands Research: Bioactivity-related detection and identification technologies President and Chief Executive Officer for chemical contaminants in the food chain, ultimately leading to the Shimadzu, Kyoto, Japan identification of emerging unknown bioactive contaminants. Net sales: ¥264 billion ($2.67 billion, 2012) Employees: 10,395 www.shimadzu.com Ulrich Panne President, BAM Federal Institute for Materials Research and Testing; Professor, Instrumental Milos Novotny Analytical Chemistry, Humboldt University of Distinguished Professor Emeritus, Lilly Berlin, Germany Chemistry Alumni Chair, Department Highlight: “The establishment of the graduate School of Analytical of Chemistry, Indiana University Sciences, SALSA, in Berlin Adlershof, for a renaissance and renewal Bloomington, USA of analytical sciences. The vision that SALSA will be the place where students and scholars discover analytical sciences to answer their key Research: Improving resolution of complex biological mixtures and identification of the separated compounds through techniques such scientific questions.” as electrospray mass spectrometry (MS) and matrix-assisted laser Research: Analytical chemistry with focus on spectro-chemical analysis. desorption/ionization MS. www.indiana.edu/~novweb

Colin Poole Professor, Department of Chemistry Jeanne E. Pemberton Wayne State University, Michigan, USA Professor, Chemistry, Highlight: My contributions to the The University of Arizona, USA development of the solvation parameter Research: Chemistry at interfaces in model for method development in chromatography and as a tool for the electrochemistry and electrochemical devices, estimation of environmental distribution and fate of industrial compounds.” chromatography, organized molecular assemblies, and environmental Research: Design of novel stationary phases; design and construction of systems. www.chem.arizona.edu/faculty_profile/pemb small devices to be added to existing equipment to enhance analytical utility. www.chem.wayne.edu/faculty/poole

the Analytical Scientist 20-100 (in alphabetical order)

Michael Quilliam Mike Ramsey Principal Research Officer, Measurement Minnie N. Goldby Distinguished Professor, Science and Standards, National Research Chemistry; Professor, Biomedical Engineering; Council, Nova Scotia, Canada Professor, Genome Sciences, University of Highlight: “The reduction of shellfish North Carolina at Chapel Hill, USA poisoning incidents worldwide and improved international trade Highlight: “I am most proud of the teams of outstanding scientists following the development of an improved approach to the monitoring that I have been fortunate enough to assemble over my career. of shellfish toxins, based on LC-MS and certified reference materials.” These teams have made seminal contributions to the development of microfabricated devices for chemical and biochemical analysis, particularly in the areas of microfluidics, nanofluidics, and high- Marja-Liisa Riekkola pressure mass spectrometry (HPMS).” Professor, Analytical Chemistry; Head, Laboratory of Analytical Chemistry, University of Helsinki, Finland Peter Roepstorff Highlight: “The applicability of fused Professor, Protein Chemistry silica capillaries coated with human biomaterials in CEC. Moreover, University of Southern Denmark, Denmark the development of a special sample valve for in-situ aerosol MS Highlight: “In 1982, I saw a signal from my measurements is another innovation also useful in other instrumental protein flying in a mass spectrometer at the techniques.” www.helsinki.fi/kemia/analyyttinen Tandem accelerator Laboratory at the Uppsala University in Sweden. This fulfilled a 15-year-old dream of mine and opened up the world of proteomics.” Gerard Rozing Research: Development of methodology for mass spectrometric protein Research fellow (retired: September, 2012) analysis with focus on post translational modifications including protein Agilent Technologies, Germany oxidation as a function of aging; the use of mass spectrometric protein Highlight: “Being part of a culture shift analysis in the biotechnological and pharmaceutical industry. – viewing academic researchers not as demanding customers (high discounts, special requirements and many complaints!) but as partners in the development of new analytical technology, and as a pool of excellent young scientists with potential as Wilhelm Schänzer future employees and customers.” rozing.com Head, Institute for Biochemistry, German Sport University Cologne, Germany www.dopinginfo.de Claudio Soto Professor of Neurology; Director, Mitchell Center for Alzheimer's Disease and Related Richard Stadler Brain Disorders, University of Texas Medical Group Expert, Chemical Food Safety at Nestlé School at Houston, USA Quality Assurance Centres, Highlight: “The invention and development of Protein Misfolding Nestec Ltd, Vevey, Switzerland Cyclic Amplification (PMCA) technology. This technology was first published in a Nature article in 2001 and is today widely considered as a major breakthrough in science and technology. PMCA enabled for the first time the ability to cyclically amplify the folding and biochemical Ulrich Tallarek properties of a protein in a manner conceptually analogous to the Full Professor, Analytical Chemistry amplification of DNA by PCR.” Philipps-Universität Marburg, Germany Highlight: “My recent personal research highlight was to elucidate the formation William P. (Bill) Sullivan and properties of the water-rich layer at the mesoporous silica President and Chief Executive Officer surface. Now, we have a molecular-level picture of the conditions Agilent Technologies, California, USA under which analytes partition from the acetonitrile-rich mobile Revenue: $6.9 billion phase into the retentive water-rich layer in hydrophilic interaction Employees: 20,500 liquid chromatography.” www.agilent.com 30 Feature

Koichi Tanaka Nobuo Tanaka General Manager, Mass Spectrometry Technical Advisor, GL Sciences, Inc. (Professor Research Laboratory, Emeritus, Kyoto Institute of Technology) Shimadzu Corporation, Kyoto, Japan Highlight: “Gaining an understanding of Highlight: Nobel Prize in Chemistry (2002) the solute-stationary phase interactions in “for the development of soft desorption ionisation methods for mass reversed-phase HPLC systems leading to the proposals for a column spectrometric analyses of biological macromolecules”. characterization method and preparation of monolithic silica columns.”

Dianping Tang Albert van der Berg Full Professor, Analytical Chemistry Professor, Nanotechnology and Lab-on-a-Chip Fuzhou University, Fujian, China systems; Chair, BIOS Lab-on-a-Chip Group, Highlight: “I received the Alexander von University of Twente, Enschede, The Netherlands Humboldt Fellowship in 2008, and worked at Highlight: Fabrication and characterization of Technische Universitat München, Germany, from 2008 to 2009. I am FlowFET, a microdevice to control fluid flows by field-effect influence currently a member of the editorial board of “Advanced Material Letters” of the electrical double layer in a thin-walled microchannel. The same and “The Open Systems Biology Journal”. Up to now, more than 100 field-effect principle was recently applied to generate highly charged publications under my authorship appeared in reviewed international microdroplets that directly convert hydraulic energy in electrical energy. scientific journals.” Research: Microanalysis systems and nanosensors, nanofluidics and Research: Nano-electrochemical biosensor design and application in single cells and tissues on chips. Applications in personalized health care, clinical immunology, food and environmental immunological analysis. drug development and development of sustainable (nano)technologies. www.utwente.nl/ewi/bios

Jean-Luc Veuthey Vice-rector; Professor, School of Tuan Vo-Dinh Pharmaceutical Sciences, PR. Eugene and Susie E. Goodson University of Geneva, Switzerland Distinguished Professor; Professor, Chemistry; Research: Developing pharmaceutical Director, The Fitzpatrick Institute for photonics, separation by liquid chromatography, as well as by capillary Duke University, North Carolina, USA electrophoresis, coupled with various detectors. Research: Bio/nanophotonics, plasmonics, laser-excited luminescence www.unige.ch/sciences/pharm/fanal/lcap spectroscopy, room temperature phosphorimetry, synchronous luminescence spectroscopy, SERS, nanosensors, biosensors and biochips. www.vodinh.pratt.duke.edu David Walt Robinson Professor of Chemistry; Professor, Howard Hughes Medical Institute, Joseph Wang Tufts University, Massachusetts, USA Distinguished Professor; Vice Chair, Highlight: “Successfully commercializing Nanoengineering . University of California technologies that were discovered in my laboratory. These technologies San Diego (UCSD), USA are enabling researchers to make new discoveries, protecting and Highlight: “Making pioneering contributions enhancing the food supply, and saving lives by changing the way people to the development of electrochemical biosensors, nanoscale are diagnosed and health care is administered. Obviously, this is a team bioelectroanalysis, modified electrodes, wearable sensing devices, and effort by many talented individuals.” synthetic nanomachines.” joewang.ucsd.edu (see page 10) ase.tufts.edu/chemistry/walt

Ian Wilson Mark Wightman Professor, Drug Metabolism and Molecular W.R. Kenan, Jr. Professor of Chemistry; Toxicology, Department of Surgery and Director of Undergraduate Studies, Cancer, Imperial College London, UK The University of North Carolina at Chapel Highlight: “The achievement that has given Hill, USA me the most, long-term, satisfaction is to have helped train some 30 Research: Ultramicroelectrodes, electrochemistry, neurochemistry. postgraduate students in the art of research up to the point where they www.chem.unc.edu/people/faculty/wightman/group were able, with increasing confidence, to make their own contributions to their respective fields of scientific endeavor.”

the Analytical Scientist 20-100 (in alphabetical order)

Nicholas Winograd Mary Wirth Evan Pugh Professor of Chemistry W. Brooks Fortune Distinguished Professor, Penn State University, Pennsylvania, USA Department of Chemistry Highlight: “The development of MS imaging Purdue University, Indiana, USA at the submicron level using cluster ion beams Research: Developing new materials for is a satisfying achievement for me. It now appears that we will have the protein separations in characterization of protein drug heterogeneity, top- spatial resolution and the chemical specificity to learn something about down proteomics, and trace protein biomarkers discovery for screening of fundamental biochemical pathways at the level of a single biological cell.” early aggressive cancer. tas.txp.to/0913-Wirth Research: Molecular imaging of biomaterials - single cells, surface chemistry studies with ion beams and lasers, chemical imaging with cluster ion beams and lasers. winograd.psu.edu Guowang Xu Director of Metabonomics Research Center; Deputy director of CAS Key Laboratory of Kurt Wüthrich Separation Science for Analytical Chemistry, Professor of Biophysics, ETH Zürich, Zürich, Dalian Institute of Chemical Physics, Chinese Switzerland; Cecil H. and Ida M. Green Academy of Sciences, Dalian, China. Professor of Structural Biology, Highlight: “I have published more than 300 peer-reviewed papers, co- Scripps Research Institute, California, USA written four books, and hold 20 Chinese patents.” Highlight: “The first protein structure determination in solution.” Research: “My main research field is in the method development of Nobel prize in Chemistry: “for his development of nuclear magnetic chromatography and mass spectrometry and their applications in resonance spectroscopy for determining the three-dimensional structure metabolomics, especially for disease biomarker discovery, traditional of biological macromolecules in solution” Chinese medicines and food safety.” www.402.dicp.ac.cn Research: Molecular structural biology, protein science, and structural genomics. www.scripps.edu/wuthrich Ed Yeung Distinguished Professor, Liberal Arts and Takeshi Yasumoto Sciences, Iowa State University, USA Academic Advisor, Japan Food Research Highlight: “Developing sensitive imaging Laboratories (Inc. Foundation); Distinguished techniques for tracking the behaviors of single Research Fellow, National Research Institute biological cells and single molecules in real time. I elucidated biological of Fisheries Science, Fisheries Research processes, including neuronal signaling, enzymatic activity, gene Agency; Professor emeritus, Tohoku University, Japan expression, and endocytosis.” Presentation: tv.campusdomar.es/en/video/1853 Research: Identification, development, evaluation, and application of new measurement concepts through an in-depth understanding of the associated fundamental chemical and physical principles. Richard Zare Marguerite Blake Wilbur Professor in Natural Science. Stanford University, California, USA Yukui Zhang Research: cell imprinting, reaction dynamics, President, Chinese Chromatography Society; mass spectroscopy, nanoparticles. Professor, Applied Chemistry, Dalian Institute www.stanford.edu/group/Zarelab of Chemical Physics, Chinese Academy of Sciences, Dalian, China Hanfa Zou Research: Biological analysis by modern analytical methods (multidimensional separation techniques); genetic engineering projects, Professor; Vice Director of Biotechnology including cell expression, separation and purification of human kallikrein; Division, Dalian Institute of Chemical Physics and establishment of display library of cDNA of liver cancer cell. Chinese Academy of Sciences, Dalian, China Research: Stationary phases for liquid chromatography, capillary electrochromatography and chiral separation; Novel matrices for analysis of low-mass compounds by MALDI-TOF MS; screening and analysis of bioactive compounds in TCMs by biochromatography; hphenated technology of 2D-HPLC with MS/ MS detection. 32 Feature

20 Fred Regnier 19 Frank Svec Founder, Perfinity Biosciences; Senior Scientist; Facility director at John H. Law Distinguished the Molecular Foundry Professor of Chemistry Lawrence Berkeley National Purdue University, Indiana, USA Laboratory, California, USA

Research: Targeted glycoproteomics Highlight: “Invention of polymer-based monolithic columns Snapshot: “Among the many Purdue faculty who have used and development of monolithic materials that inspire other their research to make a direct impact on our quality of life, people, leading to a number of follow ups focused on new Fred Regnier is a renowned pioneer […] His research on chemistries, approaches, and applications.” chromatography is directly responsible for the development Main motivation: “I have always been trying to break new of many life-saving biopharmaceuticals. The entire world has ground. I am opposed to following the old paradigms and benefited from his vision and expertise.” - Martin C. Jischke, seek ways to come up with new ones. I like face-to-face 10th President of Purdue University (2006). discussions with people from around the world that often lead Perfinity.com to friendships and interesting ideas.” Future aspiration: “I would like to stay in the “business” of research for the foreseeable future and attract young people to follow in my foot steps.” svec.lbl.gov Sitting Down With... theanalyticalscientist.com/issues/0413/601

18 17 Jack Kirkland Andreas Manz Vice-President, Research and Professor, Microfluidics for the Life Development Sciences, Mechatronics Department; Advanced Materials Technology (AMT), Delaware, USA Head of research, Korea Institute of Science and Technology (KIST), Saarland University, Saarbrücken, Germany. Highlight: “Since 1966, I have had an interest in the unique Snapshot: “Andreas Manz is one of the pioneers in microchip properties of superficially porous particles for HPLC columns. technology used for chemical applications. He was involved in the The strongly positive scientific and commercial response to the development of high speed analyzers based on CE, LC and flow introduction of unique sub-3 μm Halo fused-core (core-shell) injection. These analyzers are based on the microfabrication know- particles by AMT in 2006 has been quite satisfying as it verified my how originally developed for microelectronics. continued interest in this technology.” Main motivation: “I have always been interested in solving problems “He developed a novel concept for Miniaturized Total Analysis and developing new technology. The intellectual challenge of this Systems (μ-TAS), which involves sampling, sample pretreatment, has been stimulating. Some positive scientific results have been separation, and detection performed in an integrated microsystem, sufficiently gratifying so as to lead to additional efforts on projects for with a chemical parameter (for example, the concentration of a new technology that would assist scientists.” compound) that is periodically transformed into an electronic or Future aspiration: “My intention is to continue to develop new an optical signal. Such a system is in fact a hybrid, which offers the technology largely in separation science. Of particular interest are advantages of a sophisticated analysis system within the size of a better approaches for analytical separations in the biosciences. This chemical sensor.” difficult area presents unique challenges, but technology gains would (Source: Freiburg Institute for Advanced Studies; tas.txp. have an important impact on health and environmental issues.” to/0913-Manz) www.advanced-materials-tech.com ww.kist-europe.com

the Analytical Scientist Feature 33

16 Daniel Armstrong 15 Barry Karger Robert A. Welch Professor of Director, Barnett Institute of Chemistry & Biochemistry, Chemical and Biological Analysis and University of Texas at Arlington, USA James L. Waters Chair in Analytical Chemistry, Northeastern University, Massachusetts, USA

Highlight: “Developing many of the earliest chiral phases for HPLC Highlight: “Scientifically, my most satisfying achievement was the and GC ranks high. Our chiral HPLC work provided much of the development of linear polyacrylamide matrices used in sequencing impetus for the FDA to pass new drug development guidelines – 40 percent of the genome in the Human Genome Project by and that changed the pharmaceutical industry worldwide. Our GC capillary electrophoresis. I get great satisfaction from the success of columns have been sent on space missions to comets, Mars the close to 200 students, post docs and staff who’ve worked in and Venus.” my lab.” Main motivation: “My main motivation has always been to Main motivation: “I find science exciting and I am interested in do, develop and/or explain things that are new, interesting and not only analytical chemistry but the problems it must address. I potentially useful – and to teach others to do likewise. This is the try to integrate various technologies into separations and detection, enjoyable and most gratifying part of research. Another aspect is the especially LC- and CE-MS. I try to understand what’s important in chance to solve problems and the mysteries of nature.” the areas where we apply our technology, for example, biotechnology Future aspiration: “My goal is to continue to innovate and be as or clinical research.” useful and productive as possible with the time I have – and to have Future aspiration: “I have been a professor for a very long time. I as good a time as possible doing so!” am the founding director of the Barnett Institute of Chemical and tas.txp.to/0913-Armstrong Biological Analysis, which just celebrated its 40th year. My goal is to see that it flourishes for many years into the future.” www.northeastern.edu/barnett/research/kargergroup.html

14 Richard Smith 13 Robert Kennedy Battelle Fellow, Chief Scientist, Hobart H. Willard Professor of Biological Sciences Division Chemistry; Professor, Pharmacology, Pacific Northwest National University of Michigan, USA Laboratory, Washington, USA

Highlight: “The greatest satisfaction has been derived from Highlight: “Although most of our work has been in chemical my efforts to develop improved capabilities based upon various separations, our development of an electrode to measure insulin combinations of high performance separations with high resolution secretion at single cells was a surprising success that led to many mass spectrometry, and the broad impacts these techniques are discoveries about insulin regulation. A close second is the r having upon our abilities to characterize the constituents (e.g. ealization of the potential for rapid separation in many areas of proteomes and metabolomes) of biological systems.” chemical analysis.” Main motivation: “My primary motivation has been the need to Main motivation: “I have always been fascinated by biology. I am better characterize biological systems, and provide the information motivated by the excitement generated from harnessing the power of needed to understand how they operate. I have long believed that new chemical instrumentation to answer both curiosity and disease- approaches based on separations and mass spectrometry would be centered questions in biological systems.” ideally suited for this purpose, and this has guided many of Future aspiration: “In the next 10 years, I hope that we can prove my efforts.” the potential of droplet microfluidics for drug discovery, make our Future aspiration: “I am interested in exploring completely new in vivo neurochemical analysis methods routine so that they can paradigms in which the gas phase ions can be manipulated in be used to study the regulation of neurotransmitters, and improve complex ways and in a lossless fashion, and using such approaches metabolomics to discover underlying causes of diabetes.” for greatly increasing the measurement throughput and sensitivity kennedygroup.lsa.umich.edu possible, for the characterization of biological systems.” Sitting Down With... theanalyticalscientist.com/issues/0713/601 34 Feature

12 James W. Jorgenson 11 Janusz Pawliszyn W. R. Kenan, Jr. Professor of Professor; Canada Research Chair, Chemistry, University of North Department of Chemistry, Carolina at Chapel Hill, USA University of Waterloo, Ontario, Canada

Highlight: “The development of capillary zone electrophoresis. Highlight: “Inventions which were accepted by the scientific This work offered an unexpected and unique alternative to liquid community: Solid Phase Microextraction (SPME), Capillary chromatography for the separation of substances of all kinds. CE Isoelectric Focusing with Column Imaging Detection (CIEF/ ended up bringing together a remarkable group of highly creative WCID) and Needle Trap (NT).” people from a wide variety of scientific disciplines, all trying to make Main motivation: “My group is actively pursuing solvent-free, use of this apparently simple separation method.” “green” approaches that can integrate both sampling and sample Main motivation: “I enjoy working together with bright and preparation steps. This effort will lead to high throughput laboratory talented young students in an effort to try to make sense of how determination, as well as convenient on-site and in-vivo analysis.” chemical separations work and how they can be improved. It’s a Future aspiration: “The long-term objective of our efforts is to move delight to watch a student work hard for many years and finally see analytical chemistry ‘on-site’ – where the sample is located – to them achieve success in what they set out to do.” facilitate low cost, rapid and accurate measurement and monitoring.” Future aspiration: “To better understand the causes of peak uwaterloo.ca/pawliszyn-group broadening in chromatographic columns, to use that knowledge to design and prepare columns that can achieve even more remarkable separations, and to have plenty of fun in the process.” jjorg.web.unc.edu

10 Georges Guiochon 9 Wolfgang Lindner Distinguished Professor, Analytical Professor Emeritus, Analytical Chemistry, Department of Chemistry Chemistry, University of Vienna, The University of Tennessee, Austria Knoxville, USA

Snapshot: “In 1984, I decided to come to the US. There were too Highlight: “My most rewarding intellectual achievement relates many smart people in LC and GC, so I decided to go into something to a deeper understanding in molecular recognition phenomena that no-one else was doing seriously – preparative chromatography. in separation sciences, which is the basis for “selectivity” in Chemical engineers had no idea about the subtleties of the stationary chromatography, electrophoresis, etc. In this context, the phase, for instance, and analysts had no ideas about chemical development of highly dedicated stereoselective chiral selectors engineering. I didn’t have much idea either but I knew enough to and chiral stationary phases (CSPs), which eventually got marry them together. commercialized, are highlights.” Main motivation: “My main scientific motivation has always been “Computers were starting to play a bigger role and I was able to driven by the curiosity and the desire to discover correlations. I was solve numerically the mass balance equation for mass transfer in very fortunate to share this passion with excellent co-workers and chromatography. I published a lot of papers and made my reputation students with whom I had the pleasure of cooperating. Chemistry with that [...] Now I’m doing supercritical fluid chromatography.” was already my dream when I was at high school.” Future aspiration: “My aspiration was and still is to combine several Main motivation:“Understanding phenomena, solving problems, aspects: (i) to dedicate all efforts to basic research, (ii) to translate and training people.” the gained knowledge to the development of novel products and www.chem.utk.edu/Faculty/guiochon methodologies useful for the public, (iii) to work as a teacher and to Sitting Down With... theanalyticalscientist.com/issues/0613/601 stimulate young people to find fascination in science – academia and industry.” www.univie.ac.at/rg_lindner

thethe AnalyticalAnalytical Scientist Feature 35

8 Alexander Makarov 7 Peter Schoenmakers Director of Research, Life Science Education Director COAST; Editor, Mass Spectrometry, Thermo Fisher Journal of Chromatography A; Scientific, Bremen, Germany Professor, Analytical Chemistry/ Forensic Science, University of Amsterdam, The Netherlands

Highlight: “I am known for being the inventor of the Orbitrap Highlight: “One single (non-scientific) achievement is the creation mass analyzer, which allowed the introduction of high-resolution, of COAST – the national collaboration on analytical sciences in The high mass accuracy MS into thousands of laboratories around the Netherlands, which has more than sixty partners already. It has taken world. Orbitrap-based instruments have revolutionized proteomic more than ten years, but our field is starting to get the recognition it research and enabled significant progress in screening, toxicology deserves. Hopefully, it sets an example for other countries or regions.” and forensic analysis.” Main motivation: “My motivation is definitely the bigger picture Main motivation: “The desire to make the very high performance of analytical chemistry and a longer time scale (which is why details of large, difficult-to-use mass spectrometers available to all analytical sometimes suffer and I may be less adept at celebrating moments). labs – not only high-end research but also routine labs. This could Consciously or unconsciously, I try to fit everything in my own only be achieved by using different physical principles – and that picture. It may bring a bit of coherence to my work – or a bit of bias.” resulted in the novel ion optics of the Orbitrap analyzer.” Future aspiration: “In my group we finally have a somewhat Future aspirations: “I want to make MS as extensively used as coherent program on (multi-dimensional) liquid chromatography, optical spectrometry and apply it to as wide variety of analyses as with a nice bunch of students and post-docs. I am counting on some possible. My dream is to have an Orbitrap-based MS in every major great results in the next two or three years. Specifically, let’s see if we hospital and clinic to enable more reliable, more sensitive and faster can move from time to space.” disease diagnostics.” Sitting Down With... theanalyticalscientist.com/issues/0513/601

6 R. Graham Cooks 5 Pat Sandra Henry B. Hass Distinguished Emeritus Professor, Organic Professor, Analytical Chemistry Chemistry, Ghent University; Purdue University, Indiana, USA Founder and President Research Institute for Chromatography, Kortrijk, Belgium

Snapshot: “The subject for which I am being recognized has Highlight: “The foundation of the Research Institute for been decades in the making and many labs and individuals have Chromatography (RIC). Through the activities of RIC, I got in contributed. I feel fortunate to have been part of this long-running touch with the real analytical needs of the industry and we could campaign and to have experienced mass spectrometry when it was help in providing solutions that are economically relevant. Moreover, more a game with expensive toys and lots of promise than a it allowed me to keep my best PhD students around me, which real science. resulted in high scientific output in a non-academic environment.” Main motivation: “My main motivation was linked to the high “All my work goes back to simplifying the process of complex impact of our field on developments within different disciplines. No mixture analysis – this includes the MS/MS experiments on plant other field is so broad that the same instrumental development could material and biofluids that we did in the mid-1970s and the recent be applied to solve different challenges – for example, the application ambient ionization experiments and the attempts to do on-site of GCxGC to unravel the complexity of a synthetic kerosene, measurements by mass spectrometry. The latter requires a miniature to elucidate pesticide residues in food, or to detect biomarkers of mass spectrometer.” chronic kidney diseases in biological fluids.” (Source: theanalyticalscientist.com/issues/0713/mass-spec-approval) Future aspiration: “My aspirations are two-fold: improving my aston.chem.purdue.edu knowledge and knowhow in fields related to life sciences and contributing to the education (knowledge and knowhow) of neophytes in separation sciences and mass spectrometry.” www.richrom.com Sitting Down With... theanalyticalscientist.com/issues/0213/601 36 Feature 2

Jonathan Sweedler Ruedi Aebersold Editor-in-Chief, Analytical Chemistry; James R. Eiszner Family Professor, Institute of Molecular Systems Biology, Chair in Chemistry, University of Illinois at Urbana-Champaign, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland USA What do you consider to be your biggest impacts on the field? “The Highlight: “My highlight is the graduate and postdoctoral students development of techniques to analyze the complexities of the proteome. that I have mentored who have gone on to successful careers in ICAT (Isotope-Coded Affinity Tag) labeling is one of them. We then education and research.” developed a whole range of computational tools to analyze MS data Main motivation: “I am passionate about mentoring and training culminating in the open-source Trans-Proteomic Pipeline (TPP). More students to become successful scientists, about developing new tools recently, we have contributed new analytical workflows for targeted that can make unique measurements from complex samples, and in proteomics to more precisely observe the quantitative behavior of sets of using these new tools to understand how our brain works. Being an proteins across many samples.” analytical chemist and a university professor is a great career!” The Power List’s top two spots go to proteomics pioneers...“I think it’s Future aspiration: “I am enjoying my new challenge of being editor clear to everyone that the genome is only part of the picture in terms of Analytical Chemistry. I want to ensure the journal stays the of how biological systems function. It’s also clear that most of the cell’s preeminent journal in its field and serves the analytical community’s executive molecules are proteins. That’s why there is enormous interest in needs as our field and scientific publishing evolves.” being able to comprehensively and quantitatively analyze the proteome.” www.scs.illinois.edu/sweedler What keeps you excited about your work and at the leading edge? “What’s most exciting is that through technology development we generate the ability to see a completely new and different picture of what’s going on in biological systems. There are very few research fields 3 – or jobs – that enable you to see something for the very first time. We are in a privileged position.” Future aspirations? “I want to continue to make headway in understanding how the proteome relates to function. We are only at the beginning of this journey. We need to understand how multiple proteins cooperate and organize themselves in living cells – and how changes in George Whitesides this organization affects cell health.” Woodford L. and Ann A. Flowers University Professor, Department Where do you see the field of proteomics in ten year’s time? of Chemistry and Chemical Biology, Harvard University, “The goal will be to understand the dynamics of the proteome in Massachusetts, USA time and space – an enormous task. I think MS will continue to play a substantial role, but single cell and imaging approaches will also What do you consider to be your biggest impacts on the field? be essential. We need to know how healthy and diseased cells differ “In science: methods that are simple: self-assembled monolayers, mechanistically and how we can pharmacologically reset those cells in a micro-contact printing, microfluidics, paper diagnostics, cells-in- diseased state. That will be the future of proteomics.” Further comments? “We have been very fortunate to lead research gels-in-paper, soft robotics/actuators.” programmes with long-term perspectives and relatively good funding, What keeps you excited about your work and at the leading edge? which is essential for the development of breakthrough techniques. “Starting new areas. Working with graduate students/postdocs.” In the current climate, investment is in jeopardy because funders are What are you hopes for your research projects over the next few pushing for immediate translation of results into the health sector, years? “That they are useful/stimulating to others.” which is great... if you have something to translate. My hope is that How do you anticipate the area of analytical science developing over some funding agencies will continue to support basic technology the next five/ten years?“More emphasis on problems that require development, because, if successful, it can have an enormous impact by systems approaches, and integration of information of a number of opening new avenues for scientific research.” different sorts.” gmwgroup.harvard.edu www.imsb.ethz.ch/researchgroup/rudolfa

the Analytical Scientist 1

John Yates III we and others have developed in quantitative proteomics to enable the Professor, Department of Cell Biology, study of all kinds of new things. As new questions come up in biology it The Scripps Research Institute, California, USA often requires technology development to get a real insight, and that’s made life fun over the last 20 years.” Congratulations on topping The Power List! So is life science today first and foremost a technology-driven venture? “It’s quite an honor. Surprising too, given that there are so many good “In my view it always has been. Generating questions from biological analytical chemists out there.” research is of course important but when new technologies come What do you consider to be your biggest impacts on the field? around that can be applied to biology it can open up whole areas that “There are two, and they are connected. One is the development hadn’t previously been thought of.” of software methods to search tandem mass spectrometry data for Do the technologies get the credit that they deserve for this? sequence databases. That enabled the other, shotgun proteomics, which “No, not at all. Most of the high profile awards are given for biological allows large-scale analysis of proteomes.” and medical discoveries; very few go to people who develop technology. What keeps you excited about your work and at the leading edge? Maybe we need an Oscar’s-type ceremony for technologists!” “Besides fear of losing funding? It’s the power of the technology that fields.scripps.edu Three Gurus of Supercritical Fluid Chromatography

Is the ongoing resistance to SFC a simple misunderstanding and the legacy of past disappointments? Here, Isabelle François, Davy Guillarme, and Eric Lesellier highlight the positive aspects of this underused technique and urge sceptics to re-evaluate the potential of modern SFC systems.

ssure of 9.2 MPa and a temp at a pre erature o dioxide f 464 rbon °C, m nt ca akin erce g a p .5 p lan 96 et- of wid ed e s pos upe om rcr is c itica us l n fl u Ve id of sea re a he re sp a o l p m o at ss e ibi ac li rf ty u . (s s o ear u n rc e e: n Th ss ? d w c o .g n sfc k u .n o as y a id .g o D v )

theththee AnalyticalAnaAnAnanalylytlltyytticaiiccacallS ScientistScicieciei ntnntititistst Isabelle François completed her PhD in Davy Guillarme holds a PhD degree in Eric Lesellier is Associate Professor at the 2009 in Pat Sandra’s lab at the University analytical chemistry from the University of University of Paris sud (Orsay), researching of Ghent. Isabelle currently works at Waters, Lyon, France. He is now senior lecturer at at the ICOA (Institut of Organic and where she has recently become involved the University of Geneva in Switzerland. Analytical Chemistry, Orléans). Eric tries to in the introduction and support of new Davy has authored over 80 journal articles better understand the behavior of compounds technologies, using her expertise in ultra- related to pharmaceutical analysis and being carried by sub/supercritical fluid high performance LC, SFC, comprehensive is editor of a recent book: UHPLC in life through varied stationary phases. “Just like in and heart-cutting two-dimensional fluid sciences (RSC, 2012). His expertise includes Richard Fleicher’s ‘Fantastic voyage’,” he says, based chromatography (LC×(2)LC and HPLC, UHPLC, HILIC, LC-MS, “I would like to be reduced in size to introduce SFC×LC) in combination with optical SFC, SFC-MS, analysis of proteins and myself into the fluid entering the column, to detectors and MS. monoclonal antibodies. discreetly observe the subtle interactions”.

What are the main advantages offered by SFC?

Isabelle François: SFC can be used in a compounds, certainly when coupled with purification of enantiomers. However, wide range of industries. In laboratories time-of-flight mass spectrometry. based on its kinetic performance and where organic synthesis is carried out, the In the petrochemical industry, applying orthogonal interaction mechanism medium used for synthesis is very often an a pressure gradient allows the density compared to RPLC, I believe it apolar solvent, which can be easily injected of the mobile phase to be increased, will become more and more widely into an SFC system. The pharmaceutical resulting in enhanced solvent strength, used, even for the analysis of achiral industry is significantly benefitting which allows the implementation of substances in pharmaceutical, food, and in this respect from this technology. flame-ionization detection (FID). environmental fields. Achiral SFC provides an alternative method to RPLC to search for additional Davy Guillarme: SFC becomes a Eric Lesellier: It is almost impossible to impurities present in the sample, good alternative to NPLC when write an exhaustive list of the benefits whereas enantiomers are separated by large amounts of toxic and expensive of SFC systems. All of the classical chiral SFC. Chiral separations are the solvent can be substituted by a mixture separation problems are handled, niche application for SFC. SFC is even of supercritical carbon dioxide and a with the exception of water-soluble more advantageous when separations polar co-solvent, such as methanol. It is compounds. It handles interactions are scaled up to preparative mode. superior to RPLC and NPLC for chiral through mobile/stationary phase Compared with normal-phase liquid separations; here, SFC has a high success couplings, it allows coupling of columns chromatography (NPLC), preparative rate, particularly with polysaccharide for higher theoretical plate number, and SFC uses less solvent, produces less stationary phases. At the preparative it provides the natural concentration of waste, and requires less time for fraction scale, SFC has some advantages over the mobile phase for fraction collection. evaporation. The result is a greener, more other chromatographic techniques, Of all the benefits, I would highlight cost-effective solution. since the main mobile phase component isomer separation. Such compounds In the food industry, SFC can be used evaporates easily, leaving only the analyte differ only by subtle geometry, so their for the analysis of nutrients, vitamins, lipids and a small volume of polar co-solvent. separation requires high efficiency and and so on. In nutriceutical applications, Today, SFC is mostly used in the interaction specificity – requirements it can aid in the search for interesting pharmaceutical industry for the that are easily met by SFC. 40 Feature

What are the barriers to implementation of SFC?

Since the introduction of SFC in At the analytical scale, there are several Working with a compressible fluid raises the 1960s, popularity has seen highs ‘historical’ shortcomings of SFC. These theoretical questions. Compressibility and lows. From a user perspective, issues, which really only apply to old- also occurs in GC, but because of a lack I think that resistance is a legacy of generation devices, include: of solute–mobile phase interactions, past negative experience. Major issues there are no serious consequences. have included a lack of robustness and R5 )155 . .#)(5- (-#.#0#.3 In HPLC, liquids are generally repeatability (particularly detrimental R5 )15,)/-.( --5(5, &##&#.3 considered to be uncompressible. for implementation into QA/QC R5 ( *.& 5+/(.#..#0 5 However, in SFC, compressibility environments), and low sensitivity performance (precision and means that fluid properties can vary – when using UV detection. Instrument accuracy) for rigorous firstly along the column and secondly builders have addressed these problems method validation. when changing other parameters. in the latest SFC equipment, and will Some of these can be surprising. undoubtedly continue to develop the There is also a general lack of SFC Due in part to that compressibility, technology, if interest is maintained. education. This makes people reluctant the retention factor can vary when The limited understanding of the to adopt it, even when the advantages changing the flow rate or column fundamental theory of SFC is one of are obvious. Recently, two important dimensions, which can be disturbing the barriers against uptake. Certainly, providers of chromatographic systems for those used to working with LC. when adopting SFC, interaction have entered the SFC market. Given It also promotes different method mechanisms are not always easily the promotional capabilities of these development practices, isopycnic or understood – a fact that is even more providers, curiosity and knowledge not, which lead to straightforward challenging in chiral SFC, where about SFC will steadily grow. approaches in the first case – far from method development is performed by the reality of SFC practice, but more trial-and-error. rigorous in a ‘university sense’ for studying specific theoretical points. Solubility in supercritical fluids – and the methods of measuring it – can also be challenging. Though we understand “Though we the non-polar characteristics of carbon understand dioxide, the effects of 5 or 10 percent the non-polar modifier on elution can be surprising. Moreover, we are far from modeling characteristics of carbon (and understanding) the relationships dioxide, the effects of 5 between solubility in organic solvents “The and carbon dioxide/modifier mixtures. or 10 percent modifier retention factor on elution can be can vary when surprising.” changing the flow rate or column dimensions, which can be disturbing for those used to working with LC.”

the AnalyticalAnalytical ScientistScientit st Feature 41

What are the analytical challenges?

As identified earlier by Eric, density In the beginning, SFC was dedicated The utopia? Separation of proteins plays a crucial role in SFC – if it is not to the analysis of lipophilic compounds and highly polar compounds. managed properly, solvent strength using capillary columns, supercritical However, capillary electrophoresis for can differ between analyses, leading carbon dioxide and FID detectors protein, and hydrophilic interaction to shifting retention times. In SFC (similar to GC). It has always been chromatography (HILIC) for very systems, pressure is maintained by a reference standard for analyzing polar compound separation already do the backpressure regulator (BPR), so apolar substances, such as lipids and these jobs rather well. excellent design is essential for maximal lipo-solublepv,w vitamins, but was less From a pppractical point of view, , the ccontrol.ontrol. ChChangesanges in incominincomingg carboncarbon appropriate for polar compounds. rrealeal challenge for SFC is method ddioxideioxide temtemperatureperature aalsolso resuresultlt in a TToday,oday, this has been corrected to a largelarge develodevelopment;pment; firstly, because of the sshifthift in retention times, so rerepeatablepeatable eextentxtent since SFC is now performed in mmanyany pparametersarameters acting on retention ccoolingooling ofof thethe carboncarbon ddioxideioxide ppumpump tthehe presence ooff a popolarlar co-soco-solvent,lvent, usinusingg and separation,separation, and secondly, because hheadseads is aalsolso crcrucial.ucial. a pacpackedked cocolumnlumn anandd UV detectiondetection the stationary pphasehase choice is huge, As with LC, good batch-to-batch (similar to LC). HoweverHowever,, because a covering all those used in RPLCRPLC,, ccolumnolumn rereproducibilityproducibility is essential.essential. ppolarolar stationary pphasehase is ooftenften useusedd NPLC, and HILIC. For RPLC, it FFurthermore,urthermore, whenwhen scalingscaling upup to iinn SFC,SFC, polarpolar substancessubstances may not is rather easy: choose a C18 phase,phase, ppreparativereparative mode,mode, thethe selectivityselectivity ofof thethe eeasilyasily eluteelute fromfrom tthehe cocolumnlumn witwithouthout 335°C,5°C, 1 ml/min and then pperformerform aanalyticalnalytical sub-2μm or 5 μm pparticlesarticles ssignificantignificant amounts amounts o fof co-so co-solvent.lvent. two or four water/methanol or water/ aandnd the ppreparativereparative 5,5, 10 or 20 μm AAnothernother challenchallengege for SFC is the acetonitrile gradients, at two pH valuesvalues,, pparticlesarticles mumustst bbee ididentical.entical. anaanalysislysis ooff susubstancesbstances in bbiologicaliological at wwhichhich ppoint,oint, dedidedicatedcated sosoftwareftware InjeInjectionction voluvolumeme flexflexibilityibility was was li limitedmited mmatrices,atrices, wwhichhich is clearlyclearly ofof primeprime can calculatecalculate the optimaloptimal point.point. ButBut iinn olderolder generationsgenerationss ofof SFCSFS C equipment,equiipmene t, iimportancemportancec fforor clinical,clinical, fforensic,orensic, andand in SFC,SFC, choosingchooosiing thethe stationarystationnary phasephase wwhichhich indicatesindicates thatthat designingdeesigningn thethe partialpartial totoxicologicalxicological applications.applicationss. SoSo far,far, onlyonly ((fromfrom pupureure ssilicailica too bbondedono ded d C1C18),18)), thtthee lloopoop injector was a seseriousriious chchallengehallenge – notnot a lilimitedmited nunumbermbere ooff susuchch applicationsappliccations mmodifierodifier (f(fromrom mem methanolthannoll t oto heh ehexane),xax nee),) sursurprising,prisingn , if you cconsideronsider ththee differendifferentt hahavevev bbeeneen deddemonstrated.moonsstrtratedd. ththee modifiermodifieer pepercentagercentat ge ((fromfrom 3 3t oto 505 50 ststatestatess ofof thetht e solventssoolvents used (injection(injection ppercent),ercent)t , ththee tetemperaturempperata ure (from(ffroom 100 sosolventlvvenent andannd mobilemobilel phasephase are under lliquidiqquid to 60°C),60°C)C , andaand thethe backpressurebackkprpressusure (from(fromm anaandd supersuuper (or(or sub)suub) critical conditions,conddiitioi ns, 8 to 4040 MPa),MPa), in a systemsystem wherewhhere e flowflow rerespectively)esps ecectit vely) andanand thethhe changeschanges in pressurepresssuru e rarrate,tee, particlepartticlel diameterdiameter andand columncolul mnmn (a(aspirationsppirratatiion off tthehhee ssampleample is ddoneonne in lliquidiquid didimensionsimensnsionss aactct oonn flufluiduid d ensidensityty – –a ndand mommode,odede, anaandd whwhenheen pplacinglacing the lloopooop offoff-line-llinne ththerefore,here efeforree, retentionretenentionn – cancana getget vveryery frfromrom tthehhe mmobileobile phasephase flow,flow, e xpexpansionpana sionn cocomplicatedmmpliicatet d anandd ddadaunting.uuntiingg. ococcurscuurs andandn carbon dioxide gagasas is ppresentreesesentn iinn the loop).loop). “In SFC FFromrom a detection pperspective,errspspectitive, systems, pressure ththerehere araree vavariousrious opoptionstionns ffoforr MSS is maintained by the hhyphenation,yphenatioi n,, bbututut ffurtheruru tht ere ddevelopmentevevelelooppmem ntn iiss alwaysalways wwewelcome.lcome. IInn UV ddetection,ettecctitiono , backpressure regulator rereductiondud ction oof the nnoiseoio se llevelevvel ((linkedlinkkedd ttoo (BPR), so excellent design ththee differencedifference iinin rrefractiveefrar cttive iinindexesdexes of of is essential for maximal ththee mobilemom bile phasephases cconstituents)onstiituents) nneedseedsd to beb ooptimized.ptp imi izede . control.” 42 Feature

Any other potential pitfalls?

Instrument manufacturers have made capability rather than hydrophobicity of potential pitfall. For instance, the effect huge investments in countering the main the molecule. Secondly, the relationship of temperature increase is dependent on pitfalls. And development has not only between retention and lipophilicity is other analytical conditions: when working been devoted to instrumentation but also poor in SFC and can result in some with 5 percent modifier and a backpressure to column technology, for example, the surprising behavior. Interestingly, SFC’s of 10 MPa, a rise in temperature increases introduction of typical SFC stationary retention mechanism and the chemical retention, which is typical SFC behavior. phases in sub-2 μm particles. nature of its stationary phases are similar On the other hand, at 10 percent modifier The future will bring a focus on to those employed in HILIC for polar and a backpressure of 15 MPa, an increase overall system performance (in terms of compound analysis, but HILIC cannot in temperature decreases retention – individual parts and their integration), be considered a green technology. Thirdly, typical LC behavior. The transition and on pushing pressure and flow rate the dissolution solvent must contain as percentage (from SFC to LC behavior) is boundaries to fully exploit the features of low an amount of polar solvent (water dependent on the nature of the modifier. using a supercritical fluid as the mobile or methanol) as possible, to maintain Confusion also arises from the (large) phase (low viscosity and low resistance to reasonable peak shape. Finally, in modern amount of mobile phase that is adsorbed mass transfer). Accessibility and flexibility SFC, up to 30-40% MeOH can be onto the stationary phase in SFC, as must also be improved, both in terms of added to the mobile phase. Under such it can induce unexpected retention hardware and software. conditions, the kinetic advantage of SFC and separation effects. In fact, SFC (low viscosity) is no longer valid and (as with NPLC in the past) is subject The biggest pitfalls are related to performance becomes close to that of LC. to many subtle phenomena that can understanding the interaction be underestimated when switching mechanism in SFC. Firstly, it is To echo Davy, a misunderstanding of from RPLC in which the acidic and important to understand that retention the fundamental theory and retention/ hydrophobic properties of water are the in SFC is mostly driven by H-bond separation behavior is probably the biggest main drivers of retention.

Do separation scientists need to change their attitude/focus/scope, if they want to stay in tune with developments in their field?

To dispel the negative connotations advantages of SFC, it has never really been employed for a wider range of the past, there needs to be a shift taken off. due to the historical lack of compounds than RPLC (except in mentality or a re-education. The of robustness, repeatability, and low therapeutic biomolecules, for which it advantages of SFC include: sensitivity when using UV detection. is clearly unsuitable). In an analytical Furthermore, the simple introduction laboratory, having at ones disposal a R5 /"5 -. ,5- *,.#)(-651#."5 of a new analytical instrument can be a ratio of five HPLC systems to one SFC higher efficiency little frightening for some… instrument could be of interest. R5 -. ,5)&/'(5, ! ( ,.#)(5 R5 Ļ 5#&#.35.)5/- 5-'&& ,5*,.#& -5 Of course. It is always important for On my thesis manuscript, 25 years ago, or longer columns scientists to take the time to evaluate I used this quote: R5 &. ,(.#0 65),.")!)(&5**,)" -5 new analytical approaches. Those “When I believe I understand to standard RPLC and GC setups who were disappointed by SFC in the something, I note the day, the hour, R5 Ļ 5!, (5-* .651"#"5#-5 ,.#(&35 past because of its lack of robustness the longitude, the latitude. Then I take a consideration at preparative scale or sensitivity compared with RPLC one step to the side and ask myself should give it a second chance using again what I have understood.” – Yves Despite the fact that many state-of-the-art instrumentation. Simon (translated). chromatographers have recognized the The potential of SFC is real – it has

the Analytical Scientist Feature 43

Final words?

SFC has a lot to offer. I would highly used because it is a mass flow-dependent opportunity to work today with such recommend analytical laboratories to device and offers better sensitivity at powerful separation science. Now, we have get in touch with an instrument vendor high mobile phase flow rates. However, the responsibility to show how this versatile to discuss applications and take SFC ESI has been adapted for a wider range and unified chromatographic method for a test drive. Think not of SFC as a of compounds and often provides better can be used to separate terpene isomers, panacea for all your analytical challenges, sensitivity than APCI, so providers have polymers, enantiomers, sunscreens, anti- but rather as an additional tool alongside developed several SFC interfaces to oxidants, sugars, lipids, pigments, and so your RPLC system – it might bring you simplify coupling. Using an appropriate many other compounds. solutions faster, more efficiently and in a interface, analyte precipitation during SFC is what I have been involved in for more sustainable way: a win, win, win. carbon dioxide decompression can be the last 25 years – and I will fight with the avoided, while sensitivity and robustness last of my strength to give it the position What about mass spectrometry? Just like are drastically improved for routine use of it deserves! RPLC, SFC can easily be coupled with SFC-ESI MS. MS with either electrospray ionization For a longer discussion on system (ESI) or atmospheric-pressure chemical The pioneers who invented SFC and performance, method development and ionization (APCI) sources. In the past, demonstrated its potential – Terry Berger, column dimensions, and more, please check when SFC was predominantly used for Larry Taylor, Pat Sandra, David Pinckston out the online version of this article at: apolar compound analysis, APCI was – should be thanked for giving us the theanalyticalscientist.com/issues/0813/402. 2013 NEC, Birmingham 6 & 7 November 2013 Discovering innovation at the heart of the laboratory industries

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Safe toxic waste disposal and its subsequent monitoring pose significant challenges. In the developing world, where access to qualified staff and adequate facilities are often lacking, creative solutions are required. This one is time-efficient, financially viable, and suitable for use in developing economies.

By Jayne de Vos and Peter Gorst-Allman

The Problem for the extraction, sample clean-up The entrenchment of gas chromato- and determination of persistent organic graphy-high resolution mass spectro- pollutants (POPs) is frequently not in implementation, fast turn-around, metry (GC-HRMS) as the tool of place. Consequently, there is a lack of reliability at EPA Method 1613 levels, choice for quantitation of chlorinated coordinated routine capability. and cost effectiveness. dioxins and furans has left some For twenty years now, the quantitation Notably, in the study below, GC- countries without access to adequate of chlorinated dioxins and furans has HRMS comparative analysis was analytical infrastructure. How can been governed internationally by US performed overseas after threshold advances in instrumentation and Environmental Protection Agency screening. A process that was not only technology be leveraged to the benefit of (EPA) Method 1613 or methods derived extremely costly but also impractical, low-economy nations? from it. This has led to the entrenchment giving rise to delays that would be of HRMS as the analytical option of unacceptable in critical projects, for Background choice. For quantitation at concentration example, assessing bird population The disposal of toxic waste is a matter of levels under parts per billion (ppb), decline (1) or large-scale crocodile deaths enormous concern globally. The problem selected ion monitoring (SIM) is used. in Kruger National Park (2). is most acute in the developing world, In South Africa, there is no established where legislation is often in place but not facility capable of routine dioxin The Solution adequately regulated or enforced, opening measurement using GC-HRMS. While We chose to combine two screening the door to unscrupulous operators. GC-HRMS was the only available techniques: the H4IIE-luc bioassay Despite the potential risks, many poor technique that could reach the low and comprehensive GC-time-of-flight countries are driven to import toxic levels required by EPA 1613 at the time MS (GC×GC-TOFMS). The former waste for disposal as a means of raising of its publication, the advancement of is fast, user-friendly and inexpensive; revenue. The result? Waste disposal that instrument technology over the last the latter is unique in its ability to detect is at best careless and at worst criminally twenty years has given rise to alternative all compounds in complex samples at negligent. To exacerbate the problem, the approaches. There is a clear need the levels needed for priority pollutant facilities and instrumentation required for methodology that offers simple determination in a single analysis, can

the Analytical Scientist Solutions 45

provide quantitative data, and is capable acceptable quantitation at the mandated The System of reaching the levels stipulated in EPA levels of detection (4,5). Method 1613. Positive samples can also GC×GC-TOFMS: LECO Pegasus be sent for quantitative analysis using the South African Soil and Sediment Analysis 4D (Agilent GC and autosampler, reference GC-HRMS technique, which Fresh soil and sediment samples were a secondary oven, and a dual stage removes the costs associated in analyzing taken from diverse regions of South modulator). Liquid nitrogen cooling negative samples. Africa to represent different land- was used for the cold jets; synthetic During quantitative method uses and anthropogenic impacts. The air for the hot jets. Primary and development, we compared the results of samples were first analyzed for dioxins secondary columns were connected GC×GC-TOFMS with those obtained and furans by GC-HRMS and then using a press-tight connector. for the same sample set using GC-HRMS by GC×GC-TOFMS. The excellent A GC multi-step temperature to confirm validity, making it the most agreement between GC-HRMS and program was developed to facilitate comprehensive environmental screening GC×GC-TOFMS for the total sample separation and quantification of the and dioxin determination study to date in toxicity results (total toxic equivalents, maximum number of POPs that South Africa using GC×GC-TOFMS. TEQ) confirms the reliability of the new could be present in environmental method (data available in online article). samples in a single analysis, thus fully H4IIE-luc Bioassay The extraction and clean-up procedure benefitting from the added selectivity In this bioassay, dioxin-like chemicals for the H4IIE-luc bioassay and GC×GC- of GC×GC and the full range mass bind the aryl-hydrocarbon receptor TOFMS samples is similar. Samples spectra generated by TOFMS. (AhR), initiating transcription of the are air dried and homogenized. A 40 g Tuning: The less conventional reporter gene, luciferase. Luciferase portion is mixed with sodium sulfate 414 ion was used in an attempt to activity, proportional to the amount before accelerated solvent extraction improve the signal intensity in the of dioxin-like chemical present, is using dichloromethane and hexane. The higher mass range (3). measured using a microplate-scanning extracts are treated with activated copper Software: All instrument functions luminometer. This provides information to remove sulfur, and cleaned by gel and data processing were managed on the cumulative biological effects of permeation chromatography (GPC) and with LECO ChromaTOF software, the sample, and allows samples to be acid digestion. The samples for GC×GC- including the manual review of all ranked according to their toxic potential. TOFMS analysis are spiked at appropriate peak identifications and integrations. It is not compound specific, however, levels using the internal standards for Searches were performed using a reacting with any chemical that can bind the 17 toxic dioxin and furan congeners dioxin/ furan user library compiled to the AhR receptor; it therefore provides recommended by EPA 1613. from the 17 toxic dioxin and furans no information on the concentration of The bioassay detected dioxin-like congener standards. individual compounds. activity in 22 percent of the sediment samples (BEQ20; n=96) and 58 percent GC×GC-TOFMS of the soil samples (BEQ20; n=66). generally present at levels an order of GC×GC-TOFMS perfectly complements BEQ20 indicates a sample extract that magnitude higher than the dioxins/ the bioassay with the necessary gave a 20 percent response to the dioxin furans, and this is most likely the cause of selectivity (through the added peak (TCDD) positive control. the many false positive results. capacity of GC×GC), and sensitivity All samples that tested positive and A prime consideration in method (through the focusing effect of the six samples that tested negative in the development is the accurate modulator). The instrumentation is bioassay analysis were then analyzed determination of low concentrations more affordable and more user friendly by GC×GC-TOFMS for dioxins and of 2,3,7,8-Tetrachlorodibenzo-p-dioxin than GC-HRMS. And, because it is not furans. Of these, 23 percent of positive (TCDD). Using the EPA-1613 a target molecule technique, GC×GC- soil samples and 41 percent of positive standard calibration set (0.5 - 200 pg/ TOFMS can provide a comprehensive sediment samples were found to be false μl), a calibration curve was constructed snapshot of total sample toxic potential positives (the bioassay is not dioxin/furan for the seventeen congeners. The 2,3,7,8- in one run (3). Furthermore, it meets the specific). In South Africa, polynuclear TCDD calibration curve obtained was requirements of EPA 1613 by providing aromatic hydrocarbons (PAHs) are linear (R2 = 0.9996); and an average January 27, 2014

response factor of 1.06 was obtained. not alone. We hope we have emphasized The quantitation capability was further a real need to develop local analytical investigated using the low-level standard capability that employs regionally relevant (0.5 pg/μl) to calculate a signal/noise methods to generate internationally (S/N) ratio for the ion of mass to charge acceptable results. Our end result is a January 28-30, 2014 ratio (m/z) 322 for 2,3,7,8-TCDD. The method that is time-efficient, financially resulting S/N of 20 is well above that set viable, and suitable for use in developing by EPA Method 1613 (>10). economies where instrumental availability, To confirm the limit of detection skills and finances are often limited. (LOD) in soils, two 10 g confirmed blank Please view the online version of this Renaissance soil samples were spiked with native article for additional data table and dioxins at concentrations of 0.5 pg/μl and figures: tas.txp.to/0913-dioxin Mayﬂower Hotel 200 pg/μl for 2,3,7,8-TCDD. After the addition of labeled material, extraction, Jayne de Vos is Director of Chemistry Washington, D.C. clean-up (GPC) and concentration, at NMISA, Pretoria, South Africa it was possible to calculate LODs for ([email protected]) and Peter Gorst- 2,3,7,8-TCDD of 322 fg and 353 fg Allman is Director, Applications at respectively. These calculations were made LECO Africa, Kempton Park, South by determining the S/N for the ion of m/z Africa ([email protected]). 322 and extrapolating linearly to an S/N of 3:1. Results were consistent with the LOD References determined from the lowest calibration 1. POPs, PAHs, and elemental levels in sediment, fish standard, thus providing assurance that the and wild bird eggs in the Orange-Senqu River basin. method has the sensitivity necessary for Report 002/2013, prepared by H. Bouwman, R. low-level dioxin determination. Pieters, B. Genthe and J. Chamier for ORASECOM, Pretoria. Beyond the Solution 2. R. Dixon et al., Crocodile Deaths in the Kruger We now have a combined method for the National Park (http://tas.txp.to/901-Kruger) analysis of dioxins and furans in soil and 3. J. de Vos et al., “Comprehensive two-dimensional sediment samples. It uses the H4IIE- gas chromatography time of flight mass spectrometry luc bioassay as a preliminary screening (GCxGC-TOFMS) for environmental tool, reducing the need for unnecessary investigations in developing countries”, instrumental analysis and driving down Chemosphere, 82, 1230 (2011) the cost per sample. Analysis of positive 4. J. de Vos, P. Gorst-Allman, and E. Rohwer, samples is conducted using GC×GC- “Establishing an alternative method for the TOFMS, which provides dioxin sensitivity quantitative analysis of polychlorinated dibenzo- Abstract Submission at the required levels. In addition, since p-dioxins and polychlorinated dibenzofurans by Deadline: this is not a target compound technique comprehensive two-dimensional gas it is capable of providing information on chromatography-time-of-flight mass spectrometry December 14, 2013 multiple compound classes present in the for developing countries”, Journal of for poster consideration sample in one run, giving a comprehensive Chromatography A, 1218, 3282 (2011). picture of sample toxic potential. 5. E. Hoh, K. Mastovska, and S. Lehotay, A lack of access to certain analytical “Optimization of separation and detection resources means that South Africa is not conditions for comprehensive two-dimensional SCAN always able to quickly assess and respond to gas chromatography–time-of-flight mass to browse POP emergencies, which could negatively spectrometry analysis of polychlorinated dibenzo-p- CASSS affect human and environmental health, as dioxins and dibenzofurans”, Journal of for forum updates at casss.org well as trade and industry. South Africa is Chromatography A, 1145, 210 (2007).

Organized by CASSS An International Separation Science Society Application Note 47

High resolution separation of related compounds of Erythromycin using the new VWR-Hitachi ChromasterUltra Rs and LaChromUltra II C18 column with dimensions 250 x 3 (1.9 μm particle size)

Synthetic impurities as well as of ten asymmetric carbon atoms. degradation products are becoming Therefore, there is an increased probability increasingly important in today’s of structurally similar impurities being analytical laboratories. Over the past present in the final product. There are few years there have been steps made a number of publications of methods References by The International Conference involving high end mass spectroscopy 1. http://www.ich.org/fileadmin/Public_Web_Site/ on Harmonisation of Technical for the analysis of related substances, ICH_Products/Guidelines/Multidisciplinary/ Requirements for Registration of however, these methods are not suitable M7/M7_Step_2.pdf Pharmaceuticals for Human Use (ICH) for the tight budgets of small and medium 2. Pal S (2006). “A journey across the sequential to produce a consensus guideline on sized pharmaceutical companies. development of macrolides and ketolides related to the assessment and control of DNA erythromycin”. Tetrahedron 62 (14): 3171–3200. reactive (mutagenic) impurities in Column temperature: 50 °C 3. A. Deubel, A.S. Fandiño, F. Sörgel, U. Holzgrabe, pharmaceuticals to limit potential Eluent: 20 mmol/L Phosphate Buffer/ “Determination of erythromycin and related carcinogenic risk. In this current M7 CH3CN/CH3OH = 45/40/15 (pre- substances in commercial samples using liquid step 2 draft document lower thresholds mixed) chromatography/ion trap mass spectrometry”, of impurities are mentioned. It therefore Wavelength: 210 nm Journal of Chromatography A, Volume 1136, appears that there will be a need in the Column Type: LaChromUltra II C18 Issue 1, 8 December 2006, Pages 39-47. near future for HPLC with improved Max Pressure: 1350 bar (Coupled sensitivity and resolution. columns) It is proposed that the ChromasterUltra Rs together with the LaChrom Ultra Sample: Erythromaycin A: Wako pure II high resolution column is able to chemicals fulfill some of these future needs. The 056-07361 DCH57893 ChromasterUltra Rs is equipped with Liquid Beat Technology (LBT), which is the automatic continual adjustment of Figure 1: Zoom of the piston stroke using four independent main peak (Poor pressure sensors in order to compensate separation between for the change in compressibility of the main peak and solvent as the mobile phase composition suspect impurity and the back pressure changes over time. peak) Flow rate: LBT, along with the new double cork 1.000 mL/min. Inj. mixing technology, allows exceptional Vol.: 20 μL Column: baseline stability. The ChromasterUltra 4.6 x 150 x 5μm Rs DAD has an optional 65 mm capillary flow cell. These key features help to Figure 2: Flow rate: deliver the excellent sensitivity and 0.50 mL/min. Inj. resolution required for more stringent Vol.: 10 μL. Two requirements of impurity and related columns coupled (3.0 compound testing. mm x 250+250, 1.9 Erythromycin is a widely prescribed μm). Showing excel- antibiotic manufactured using either lent separation of the fungal fermentation or a highly complex suspected impurities. chemical synthesis, owing to the presence

For more information: [email protected] 48 Application Note

Sophisticated antibody analysis by GPC/SEC

Monoclonal antibodies (mAB) are increasingly growing in importance for the diagnosis and therapy of various diseases, including cancer as well as autoimmune and inflammatory disorders. One essential parameter to define their quality is the content of aggregates (dimers, trimers and higher aggregates). These aggregates can be formed during processing and purification or are the result of long-term storage. Due to the aggregation antibodies lose their pharmaceutical efficacy and can facilitate an immune response.

Antibody fragments, which lack the Fc phosphate pH 6.7 + shown in Figure 2. The light scattering region, can be used for the treatment of 0.25 M NaCl signal shows improved sensitivity for high diseases. Also, they can be the result of Flow-rate: 1.0 mL/min aggregates compared to the other signals. degradation of full length antibodies. Temperature: 25 °C Therefore, a GPC method that offers Detection: Refractive index Conclusion the opportunity to analyse antibodies increment (RI), UV at The GPC/SEC method including and their aggregates as well as antibody Ȝ=280 nm, PSS UV, RI and RALS can be used for fragments simultaneously with superior SLD1000 (RALS) at the simultaneous determination of resolution is worthwhile, in addition to Ȝ=488 nm aggregate content of monoclonal offering highly sensitive detection. Calibration: Light scattering antibodies and antibody fragments. Injected mass: 60 to 80 μg The column combination used covers Experimental: Data acquisition, the separation range for all three GPC/SEC analysis was performed on a Calibration and types but nonetheless provides a high PSS SECcurity GPC System, equipped Evaluation: PSS WinGPC resolution for the determination of the with a PSS SECcurity SLD1000 light UniChrom 8.1 dimer content. Due to its molecular scattering detector, using the following weight dependency, the PSS SLD1000 conditions: Results RALS detector offers high sensitivity Figure 1 shows an overlay of elugrams for small quantities of high aggregates Columns: PSS PROTEEMA, obtained for a full length antibody and and also allows the determination 5 μm, antibody fragments analysed on one set of the absolute molecular weight of 2x300 Å (8x300 mm of columns. the antibodies. each) + precolumn All three detector signals for the Solvent: 100 mM sodium analysis of a monoclonal antibody are

Fig 1. Separation range of the column combination. Red curve shows the UV Fig 2. Sensitive analysis of antibody aggregates. The light scattering signal signal of a full length antibody and its dimers plotted against the elution volume. for the dimer is relatively high compared to that of the mABs due to molar The blue curve is the elugram of antibody fragments and their high mass dependency and provides improved sensitivity for the detection of level aggregates. high aggregates (inset).

www.pss-polymer.com Application Note 49

Analysis of Synthetic Oligomers and Polymers

New roles and applications in the areas of science and technology are continuously being found for synthetic polymers. As the applications of synthetic polymers increase, there is a need for methods to accurately and precisely characterize these materials. Here, we summarize two GPC applications developed on the all-in-one EcoSEC® GPC System. The system was used to monitor the synthesis and to quantify the oligomeric content of two PEGylated synthetic polymers and to measure the molar mass of an isocyanate modifiedpolyurethane prepolymer in less than one hour.

The utility of size exclusiondistribution between the two PEGylated System with a refractive index detector chromatography (SEC or gel permeation samples. Additionally, based on the peak- using a column bank consisting of chromatography, GPC) for synthesis average molar masses Mp the oligomeric two TSKgel® SuperH3000 columns monitoring and oligomeric analysis makes content of the two PEGylated polymers and tetrahydrofuran (THF) as mobile it an invaluable tool for characterizing were shown to differ, with PEG-A phase. The low dead volume of the synthetic polymeric material for use containing mainly oligomeric species and EcoSEC GPC System combined with in medicine, as these materials require PEG-B containing both low- and high- the use of semi-micro GPC columns thorough characterization. The synthesis molar mass species. allowed for an efficient separation and of two PEGylated synthetic polymers Isocyanates are both highly reactive characterization of the prepolymer intended for use in medical applications and highly toxic low molar mass sample in less than 1 hour. The molar was monitored and the oligomeric content chemicals. One common technique used mass averages and polydispersity index of was analyzed on an EcoSEC GPC to take advantage of isocyanate reactivity the IMPP sample was determined using a System equipped with a column bank while eliminating safety concerns is to polystyrene relative calibration curve. The consisting of two 6.0 mm ID × 15 cm, synthesize polyurethane prepolymers chromatogram of the IMPP displayed 3 μm TSKgel® SuperH3000 columns. for use in subsequent polymerizations. twelve distinctive peaks. Peaks 1 through The synthesis process was analyzed by The physical properties of the resultant 5 were determined to be the urethane comparing the SEC chromatograms of polymer are influenced to a large degree prepolymer component of the IMPP. the two PEGylated polymers with that by the size of the polyol chains in the The sample was analyzed at two different of one of the starting materials. From this prepolymer. Harder polymers are chromatographic flow rates, 0.3 and 0.6 comparison it was concluded that starting formed with larger polyol chains and mL/min. The flow rate of 0.6 mL/min material remained in one of the PEGylated softer polymers are formed with smaller (Figure 2) compared to that of 0.3 mL/ samples, PEG-A, and was absent in polyol chains. The molar mass and molar min resulted in a decrease in analysis time the other PEGylated sample, PEG-B mass averages of an isocyanate modified from 45 minutes to 22 minutes. (Figure 1). The SEC chromatograms of polyurethane prepolymer (IMPP) with the PEGylated polymers also provided residual dimethyl sulfoxide (DMSO) References: Amandaa K. Brewer, Ph.D., Tosoh indication of differences in the molar mass were measured with an EcoSEC GPC Bioscience LLC; A13I15A & A13I14A

Figure 1: Synthesis monitoring of PEGylated polymers Figure 2: GPC elution profile of IMPP sample Elution profile of PEG-A (red), PEG-B (blue), and starting material C (green) Monitored by refractive index detection at 0.6 mL/min in THF at 35 °C. monitored by refractive Index detection at 0.3 mL/min in THF at 35°C

More GPC applications can be found in the application database at www.ecosec.eu A Sense of (Historical) Perspective Sitting Down With Mike Grayson, Archivist at the American Society for Mass Spectrometry

the Analytical Scientist Sitting Down With 51

What does a science archivist would have required access to a major, the tone for the things that you publish. actually do? physical library. As an example, 2013 is, I have argued, The primary functions are to collect I am drawn to controversies. Certain the centenary of mass spectrometry information that would otherwise be ideas have been dismissed out of hand as an analytical tool. In 1913, lost and to provide a repository for items as impossible, useless or meaningless, J. J. Thomson published both his book, that are of historical value. There is not a which, later on, have opened new vistas. “Rays of Positive Electricity and their fixed set of criteria for what to archive; Let me give two examples. The original Application to Chemical Analysis,” everything is judged on individual merit. study submitted by Frank Field and and his concept of the atom; and it was Burnaby Munson to JACS on chemical the year that an x-ray tube sufficiently What are your functions as ASMS ionization got scathing reviews. They powerful to x-ray something other archivist? stuck with it and when it was eventually than a human being was developed. There are several. I preserve the papers published it kick-started gas-phase These were essential developments that from ASMS Board meetings. Some of ionization chemistry. I’d love to know should be celebrated. it can seem a bit mundane, for example, who the reviewers were. Another is deliberations on whether posters should John Fenn’s work on electrospray, which Should scientists make a personal be allowed at the annual meeting, but was rejected on a number of occasions archive of their work? it also provides a useful record to help before it became a powerful tool for the Yes, even if it is for no other reason determine when important events ionization of proteins. Both instances than your own interest in retirement occurred and how they were perceived by reflected the ‘old boys club’. Field and and your children and grandchildren’s the community. I also run an oral history Munson worked for a small oil company interest. A lot of it can be done by project: these are in-depth interviews called Humble Oil; and Fenn, while he filing away daily work and notebooks. I with two or three key contributors had a reputation in supersonic expansion have a miniature archive that captures to mass spectroscopy every year. And nozzles, was an outsider in mass spec. contributions from my career. However, I represent ASMS to the Chemical don’t expect an archive to take it; they Heritage Foundation (CHF), where we You enjoyed a long career in the lab, have limited space for Frank Field’s have pursued the collection of mass spec were you interested in history then? papers but not for mine. instrumentation. But that can be a little No, it was a subsequent development. rough because of the sheer size of the At the lab bench, I was focused Which two historic figures would you instruments, some of which take up an on the research and day-to-day most like to have had dinner with, entire room. instrumentation, although the history and why? interest group of ASMS did intrigue J. J. Thomson would be one. He has Is there any way around this? me. What really got me involved was not been adequately recognized One idea is to record instrument history the sense that some classical instruments for his contributions, although the via video. Rather than collecting the should be preserved. Then, when I was mass spectrometry community now instrument itself, this involves someone involved in running a local mass spec appreciates him. Before him, the concept using the instrument and talking about discussion group we invited Al Neer of the atom was a philosophical one; its application and idiosyncrasies. from Minnesota to give a talk about after him, it was physically available for his career and his research. That was examination and experimentation, a Are you also an historian of science? when the oral history project got up and paradigm shift for atoms and elements. I do not consider myself a historian as running – I wrote up a proposal to spend I’d be fascinated by Thomson’s reaction I lack the formal training, but it does the weekend interviewing Neer. From to how we do mass spectrometry today, really interest to me. Obviously, the then on, I had the bug. would it be beyond what he could have interpretation (history) is more fun than imagined? The other would be Werner cataloging (archiving). These days the Why should lab scientists take note of Heisenberg. I’d like to discuss his opportunity to do historical research the history? decision to use heavy water for fission is there: you can dig quite deeply into Apart from its intrinsic fascination, reactions in the 1940’s, specifically if he the primary source literature using the having a historical perspective can help had non-scientific reasons for doing it. Internet where twenty years ago you you become a better scientist; it helps set It’s something I’m really curious about.