Analytical Methods View Article Online MINIREVIEW View Journal | View Issue Ambient ionization mass spectrometry: real-time, proximal sample processing and ionization Cite this: Anal. Methods,2017,9, 4896 R. Javanshad and A. R. Venter * The definition of ambient ionization is updated from “no sample preparation” to sample preparation proximal and in real time with the ionization and analysis step. We differentiate between ambient ionization methods and the direct and hyphenated techniques. Ambient ionization has been reviewed many times and we summarise some of the approaches that reviews have taken to categorize the many ambient ionization methods. Due to the large number of permutations, frequent redundancy and Received 11th April 2017 complexity of the 80+ techniques developed so far, none of the review classifications is successful in Accepted 15th May 2017 classifying all the ambient ionization methods based on the chosen scheme. Likewise our classification DOI: 10.1039/c7ay00948h based on major sample preparation method also fails at finding a good category for every method, but it rsc.li/methods does highlight the central role that real-time, proximal sample preparation plays in ambient analysis. Introduction sample processing that takes place during the analysis. In other words ambient ionization is a form of ionization where sample What ambient ionization is, and what it isn't preparation takes place in real-time and proximal to the ionization Ambient ionization methods have been revolutionary in sample and during the analysis of analytes. analysis by mass spectrometry. It is a form of ionization in A purely ambient method is one where the sample is avail- which ions are formed in an ion source outside the vacuum able for mass spectrometry analysis without any prior sample system of the mass spectrometer. While it is oen said that preparation or, in the ultimate case the mass spectrometer is ambient ionization methods do not require sample prepara- taken to the sample for analysis without disturbing the sample tion,1–4 our view is that it is more accurate to say these methods from its environment. Sample processing, introduction and frequently require no sample preparation, other than the ionization then all take place in a concerted, simultaneous manner during a single analysis step near the point of ion introduction into the vacuum system of the mass spectrometer. Published on 31 May 2017. Downloaded by Western Michigan University 8/10/2018 5:08:31 PM. Department of Chemistry, Western Michigan University, Kalamazoo, Michigan, It is the immediacy of sample preparation that differentiates the 49008-5413, USA. E-mail: [email protected] Roshan Javanshad studied Andre Venter is an associate chemistry at University of Teh- professor at Western Michigan ran (Tehran, Iran), where she University. His research group received her Bachelor of Science studies spray ionization mecha- in Chemistry in 2015. Roshan is nisms and ambient surface enrolled in the Ph.D. program at analysis mass spectrometry for the Department of Chemistry at protein analysis. Prior to coming Western Michigan University to WMU in 2008 he worked with (Kalamazoo, MI). Her eld of Prof. Graham Cooks at Purdue interest is bioanalytical chem- University. During this post-doc istry and proteomics. Her he investigated fundamentals of current research activities desorption electrospray ioniza- involve improving ambient ioni- tion mass spectrometry and zation mass spectrometry for protein detection and developing other ionization methods. He obtained his tertiary education from novel methods for the analysis and quantication of proteins. the University of Pretoria in South Africa and a Ph.D. in 2003 with Prof. Egmont Rohwer, where he developed a comprehensive multidimensional supercritical uid and gas chromatography (SFCxGC) method for petrochemical and natural product analyses. 4896 | Anal. Methods,2017,9,4896–4907 This journal is © The Royal Society of Chemistry 2017 View Article Online Minireview Analytical Methods Fig. 1 Hyphenated methods on the left frequently require offline sample preparation and online separation. Direct methods rely solely on offline sample preparation, while analysis relies on the mass spectrometer alone for separation. The ambient methods typically do the bulk of sample processing during the analysis step, and like direct methods, rely on the mass spectrometer for separation and detection. ambient analysis methods from direct mass spectrometry analysis. To better differentiate between ambient, direct and hyphenated techniques we provide Fig. 1. Direct analysis methods imply the use of offline sample preparation but without an inline sample separation step. Hyphenated chromatography-mass spectrometry fi ffl Fig. 2 (a) Flowergrams depicting classi cation of ambient ionization techniques usually include both o ine and online sample prep- methods based on ionization mechanism (Reprinted from TrAC, 27 aration prior to MS detection and analysis. Direct methods rely Venter, Nefliu, Cooks, 284–290, Copyright (2008) with permission solely on offlinesamplepreparation,whileanalysisreliesonthe from Elsevier). (b) Summary of the major classes of ambient ionization mass spectrometer alone for separation. The ambient methods methods based on traditional groupings (green), examples of methods typically do the bulk of sample processing during the analysis step, (shades of pink), and the various sample processing methods (black). The mechanism of ionization is indicated by the font color for each and like direct methods, rely on the mass spectrometer for sepa- listed example. Black indicates ESI, blue APCI, and white ambient ration and detection. sample processing without ionization. (Reprinted with permission from Venter, Douglass et al. Anal. Chem., 86, 233–249. Copyright (2014) American Chemical Society). Published on 31 May 2017. Downloaded by Western Michigan University 8/10/2018 5:08:31 PM. Reviews of reviews of ambient ionization In some instances ionization and desorption occur in a concerted fashion or no desorption step is required, while Ambient ionization has been reviewed frequently over the past others use distinct desorption and ionization processes. This 10 years. A number of excellent review articles are available on aspect of ambient ionization was captured by Huang et al. in yet the topic of ambient ionization, and the reader is kindly another classication scheme, based on basic principles of referred to those for more inclusive information on both the ionization: direct ionization methods, direct ionization/ 5 methods and their common applications. Without aiming for desorption methods, and methods based on a two-step ioniza- inclusivity we rst attempt to show the diversity, complexity and tion process.7 possible redundancies of ambient ionization by highlighting Alternatively the methods have been arranged by the the major schemes by which various reviewers have classi ed desorption mechanism, or as shown in Fig. 2b, by the major 6 the more than 80 ambient ionization techniques. processing steps of liquid extraction, spallation/laser ablation An obvious approach is for methods to be arranged primarily or thermal desorption.8 A “technique-centric” organization for by either desorption method or ionization method, although it the material has also been published based on both the is common to rst separate by one aspect and then a second. extraction/desorption technique and ionization mechanism.3 Primary categorization by ionization is frequently used as the Ambient methods are also frequently classied based on one 2 basis for categorization. An example is shown in Fig. 2a, which of the three major techniques: spray, plasma and laser ioniza- divides techniques based on electrospray ionization (ESI) and tion methods.8,9 atmospheric-pressure chemical ionization (APCI) mechanisms. There are also many reviews that focus only on a particular Table 1 similarly separates on ionization rst and then further subcategory of ambient ionization. For example the plasma ff di erentiates the methods in terms of the approach used for methods were reviewed recently,10,11 and so were electrospray sampling. A similar approach was followed by Huang et al.7 This journal is © The Royal Society of Chemistry 2017 Anal. Methods,2017,9,4896–4907 | 4897 View Article Online Analytical Methods Minireview Table 1 Ambient ionization methods arranged first by ionization method then desorption agent and indicating sample processing method Ionization Sample processing agent Desorption agent method Acronym Method name Reference None Liq–Sol Ex. SDC Spray desorption collection 65 Liq–Sol Ex. DESIa Desorption electrospray ionization 1 Liq–Liq Ex. L-DESI Liquid desorption electrospray 27 ionization Liq–Sol Ex. TM-DESI Transmission mode DESI 60 Spray desorption/ momentum transfer Liq–Sol Ex. EASI Easy ambient sonic-spray ionization 61 ESI Liq–Sol Ex. DEMI Desorption electrospray/metastable- 62 induced plasma Liq–Sol Ex. DICE Desorption ionization by charge 63 exchange Liq–Liq Ex. EESI Extractive electrospray ionization 28 Dissolution DEP Direct electrospray probe 79 Filtration PS Paper spray 29 Liq–Sol Ex. — Leaf spray 82 Dissolution PESI Probe electrospray ionization 80 None Liq–Sol Ex. LMJ-SSP Liquid microjunction surface sampling 57 probe Liq–Sol Ex. Nano-DESI Nanospray desorption electrospray 24 ionization Liq–Sol Ex. LESAa Liquid extraction surface analysis 71 Spallation LA-LMJ-SSP Laser ablation liquid microjunction 70 surface sampling probe Spallation LSII Laserspray inlet