Ambient Sampling/Ionization & Imaging MS

The first wide-spread attention to the concept of ambient ionization/sampling prior to MS analysis was the introduction of desorption electrospray ionization (DESI) by Cooks and coworkers in 2004 [1]. This article presented an exciting new perspective on performing both qualitative and quantitative chemical analysis by MS.  The central idea was that the surface of real-life objects such as a piece of leather, a nitrile glove, a plant seed cut in half, an intact tomato, the tip of a finger, etc. could be directly examined by MS without extraction of the molecules of interest or pretreatment of the object itself.

The excitement about the new opportunities offered by the field of ambient sampling/ionization has triggered a renaissance in the development of new ion generation approaches, and their application to real-life analytical and diagnostic challenges. My group at Georgia Tech has been at the sharp end of this renaissance since 2005 and is considered one of the leaders in this field. Our first ambient MS paper appeared in 2006 and described the first coupling of DESI to FTICR [2], and was followed by the first application of both DESI and DART to counterfeit drug detection [3]. We currently have 38 publications in the field and 6 in the area of counterfeit drug ambient MS detection methods. Our first review article [4] has been cited over 178 times and our 2011 Anal. Chem. review article[5] has already received more than 300 citations. We have recently published a massive review article describing developments in the last two years which made the cover of Chemical Reviews[6]. Our ambient MS work has been on the covers of the Journal of the American Society for Mass Spectrometry[7], Analytical and Bioanalytical Chemistry[8], PLoS Medicine [9], Lancet Infectious Diseases[10], and the Journal of Chemical Ecology[11]. Our work on the application of Direct Analysis in Real Time (DART) and DESI MS to counterfeit drug detection has been covered by Scientific American, the BBC, The Guardian, Oxford Science Blog, ABC News, NBC Learn, Science News, SciDev, EurekaAlert, C&EN, Analytical Chemistry, J-WAVE (Tokyo), CNN International, Voice of America, NPR, ACS, RSC, Nature, Science, New Scientist, Reuters, The Mirror, The National Post and CBC (Canada). Moreover, our ambient MS work was featured on the cover of the International Herald Tribune and the NY Times. A replica ambient ionization mass spectrometer simulating the one used in the investigation of fake antimalarials by my group was displayed at the “Medicine Now” exhibit housed by the Wellcome Trust Collection, in London, and was labeled as “the most sobering item” in the exhibit, by the Media Watch section of the Lancet Inf. Dis., 7(9), 2007.

Our most salient contributions to the field of ambient MS include fundamental studies on DART ion suppression[12], DART internal energy deposition[13], DART fluid dynamics[14], the first transmission mode DART interface[15], first DART-drift tube ion mobility spectrometry (DTIMS) coupling[16], first laser ablation-DART ion source for ambient imaging[17], first ovarian cancer DART test [18], first DART profiling of bacteria[19], first DART/DESI hybrid ion source[20], first DESI quantitation approach based on ligand competition[21], first DESI imaging of chemical defenses on algae [22], and organics on minerals[23], first open access software for DESI imaging[24], and the first hybrid DESI-differential mobility-MS instrument[25].


(1)        Z. Takats, J. M. Wiseman, B. Gologan, R. G. Cooks; "Mass spectrometry sampling under ambient conditions with desorption electrospray ionization". Science 306, 471-473 (2004).doi: 10.1126/science.1104404

(2)        M. S. Bereman, L. Nyadong, F. M. Fernandez, D. C. Muddiman; "Direct high resolution peptide and protein analysis by desorption electrospray ionization (desi) fourier transform ion cyclotron resonance mass spectrometry". Rapid Communications in Mass Spectrometry 20, 3409-3411 (2006).

(3)        F. M. Fernandez, R. B. Cody, M. Green, C. Y. Hampton, R. McGready, S. Sengaloundeth, N. J. White, P. N. Newton; "Characterization of solid counterfeit drug samples by desorption electrospray ionization and direct-analysis-in-real-time coupled to time-of-flight mass spectrometry". ChemMedChem 1, 702-705 (2006).doi: 10.1002/cmdc.200600041

(4)        G. A. Harris, L. Nyadong, F. M. Fernandez; "Recent developments in ambient ionization techniques for analytical mass spectrometry". The Analyst 133, 1297-1301 (2008).doi: 10.1039/b806810k

(5)        G. A. Harris, A. S. Galhena, F. M. Fernandez; "Ambient sampling/ionization mass spectrometry: Applications and current trends". Analytical Chemistry 83, 4508-4538 (2011).doi: 10.1021/ac200918u

(6)        M. E. Monge, G. A. Harris, P. Dwivedi, F. M. Fernandez; "Mass spectrometry: Recent advances in direct open air surface sampling/ionization". Chemical reviews 113, 2269-2308 (2013).doi: 10.1021/cr300309q

(7)        L. Nyadong, S. Late, M. D. Green, A. Banga, F. M. Fernandez; "Direct quantitation of active ingredients in solid artesunate antimalarials by noncovalent complex forming reactive desorption electrospray ionization mass spectrometry". Journal of the American Society for Mass Spectrometry 19, 380-388 (2008).doi: 10.1016/j.jasms.2007.11.016

(8)        C. Ricci, L. Nyadong, F. M. Fernandez, P. N. Newton, S. G. Kazarian; "Combined fourier-transform infrared imaging and desorption electrospray-ionization linear ion-trap mass spectrometry for analysis of counterfeit antimalarial tablets". Analytical and bioanalytical chemistry 387, 551-559 (2007).doi: 10.1007/s00216-006-0950-z

(9)        P. N. Newton, F. M. Fernandez, A. Plancon, D. C. Mildenhall, M. D. Green, L. Ziyong, E. M. Christophel, S. Phanouvong, S. Howells, E. McIntosh, P. Laurin, N. Blum, C. Y. Hampton, K. Faure, L. Nyadong, C. W. Soong, B. Santoso, W. Zhiguang, J. Newton, K. Palmer; "A collaborative epidemiological investigation into the criminal fake artesunate trade in south east Asia". PLoS medicine 5, e32 (2008).doi: 10.1371/journal.pmed.0050032

(10)      P. N. Newton, M. D. Green, F. M. Fernandez, N. P. Day, N. J. White; "Counterfeit anti-infective drugs". Lancet Infect Dis 6, 602-613 (2006).doi: S1473-3099(06)70581-3 [pii]


(11)      T. D. Andras, T. S. Alexander, A. Gahlena, R. M. Parry, F. M. Fernandez, J. Kubanek, M. D. Wang, M. E. Hay; "Seaweed allelopathy against coral: Surface distribution of a seaweed secondary metabolite by imaging mass spectrometry". Journal of chemical ecology 38, 1203-1214 (2012).doi: 10.1007/s10886-012-0204-9

(12)      G. A. Harris, C. E. Falcone, F. M. Fernandez; "Sensitivity "hot spots" in the direct analysis in real time mass spectrometry of nerve agent simulants". Journal of the American Society for Mass Spectrometry 23, 153-161 (2012).doi: 10.1007/s13361-011-0276-8

(13)      G. A. Harris, D. M. Hostetler, C. Y. Hampton, F. M. Fernandez; "Comparison of the internal energy deposition of direct analysis in real time and electrospray ionization time-of-flight mass spectrometry". Journal of the American Society for Mass Spectrometry 21, 855-863 (2010).doi: 10.1016/j.jasms.2010.01.019

(14)      G. A. Harris, F. M. Fernandez; "Simulations and experimental investigation of atmospheric transport in an ambient metastable-induced chemical ionization source". Analytical Chemistry 81, 322-329 (2009).doi: 10.1021/ac802117u

(15)      J. J. Perez, G. A. Harris, J. E. Chipuk, J. S. Brodbelt, M. D. Green, C. Y. Hampton, F. M. Fernandez; "Transmission-mode direct analysis in real time and desorption electrospray ionization mass spectrometry of insecticide-treated bednets for malaria control". The Analyst 135, 712-719 (2010).doi: 10.1039/B924533b

(16)      G. A. Harris, M. Kwasnik, F. M. Fernandez; "Direct analysis in real time coupled to multiplexed drift tube ion mobility spectrometry for detecting toxic chemicals". Analytical Chemistry 83, 1908-1915 (2011).doi: 10.1021/ac102246h

(17)      A. S. Galhena, G. A. Harris, L. Nyadong, K. K. Murray, F. M. Fernandez; "Small molecule ambient mass spectrometry imaging by infrared laser ablation metastable-induced chemical ionization". Analytical Chemistry 82, 2178-2181 (2010).doi: 10.1021/ac902905v

(18)      M. Zhou, W. Guan, L. D. Walker, R. Mezencev, B. B. Benigno, A. Gray, F. M. Fernandez, J. F. McDonald; "Rapid mass spectrometric metabolic profiling of blood sera detects ovarian cancer with high accuracy". Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 19, 2262-2271 (2010).doi: 10.1158/1055-9965.EPI-10-0126

(19)      C. Y. Pierce, J. R. Barr, R. B. Cody, R. F. Massung, A. R. Woolfitt, H. Moura, H. A. Thompson, F. M. Fernandez; "Ambient generation of fatty acid methyl ester ions from bacterial whole cells by direct analysis in real time (DART) mass spectrometry". Chemical Communications 807-809 (2007).doi: Doi 10.1039/B613200f

(20)      L. Nyadong, A. S. Galhena, F. M. Fernandez; "Desorption electrospray/metastable-induced ionization: A flexible multimode ambient ion generation technique". Analytical Chemistry 81, 7788-7794 (2009).doi: 10.1021/Ac9014098

(21)      L. Nyadong, E. G. Hohenstein, K. Johnson, C. D. Sherrill, M. D. Green, F. M. Fernandez; "Desorption electrospray ionization reactions between host crown ethers and the influenza neuraminidase inhibitor oseltamivir for the rapid screening of Tamiflu (r)". The Analyst 133, 1513-1522 (2008).doi: Doi 10.1039/B809471c

(22)      A. L. Lane, L. Nyadong, A. S. Galhena, T. L. Shearer, E. P. Stout, R. M. Parry, M. Kwasnik, M. D. Wang, M. E. Hay, F. M. Fernandez, J. Kubanek; "Desorption electrospray ionization mass spectrometry reveals surface-mediated antifungal chemical defense of a tropical seaweed". Proceedings of the National Academy of Sciences of the United States of America 106, 7314-7319 (2009).doi: 10.1073/pnas.0812020106

(23)      R. V. Bennett, H. J. Cleaves, 2nd, J. M. Davis, D. A. Sokolov, T. M. Orlando, J. L. Bada, F. M. Fernandez; "Desorption electrospray ionization imaging mass spectrometry as a tool for investigating model prebiotic reactions on mineral surfaces". Anal Chem 85, 1276-1279 (2013).doi: 10.1021/ac303202n

(24)      R. M. Parry, A. S. Galhena, C. M. Gamage, R. V. Bennett, M. D. Wang, F. M. Fernandez; "Omnispect: An open matlab-based tool for visualization and analysis of matrix-assisted laser desorption/ionization and desorption electrospray ionization mass spectrometry images". J Am Soc Mass Spectrom 24, 646-649 (2013).doi: 10.1007/s13361-012-0572-y

(25)      A. S. Galhena, G. A. Harris, M. Kwasnik, F. M. Fernandez; "Enhanced direct ambient analysis by differential mobility-filtered desorption electrospray ionization-mass spectrometry". Analytical Chemistry 82, 9159-9163 (2010).doi: 10.1021/ac102340h