DOI: 10.1002/ijch.201000035 Highlights in Coupled Electrochemical Flow Cell-Mass Spectrometry, EC/MS Jenny Gun, [a] Subramanian Bharathi, [a] Vitaly Gutkin, [a] Dan Rizkov, [a] Anna Voloshenko, [a] Rimma Shelkov, [a] Sergei Sladkevich, [a] Nilar Kyi, [a] Michael Rona, [a] Yitzik Wolanov, [a] Dan Rizkov, [a] Maxmilian Koch, [a] Shaul Mizrahi, [a] Petr V. Pridkhochenko, [a] Alexander Modestov, [a] and Ovadia Lev* [a] 1. Introduction and EC/MS Early Studies Electrochemistry coupled with mass spectrometry is find- ing new applications in diverse fields of chemistry, elec- trochemistry, and mass spectrometry, but surprisingly, this is still taking place at a much slower pace compared to the enthusiasm with which the electrochemical communi- ty embraced other in-situ characterization techniques such as the vibration spectroscopies, fluorescence spec- troscopies, let alone the STM, AFM, and scanning elec- trochemical microscopy (SECM) scanning probe tech- niques. This may seem rather surprising in view of the success of mass spectrometry in so many other different research fields. The challenges in EC/MS and EC/electro- spray mass spectrometry (EC/ESI-MS) are indeed formi- dable, and different ways in which different research groups manage to overcome them are addressed here, with an emphasis on our own contributions. 1.1 Early Studies and the Rationale for Coupling Electrochemistry and Mass Spectrometry For most of the past century, electrochemistry was regard- ed to be self-contained in the sense that electroanalysis was considered to be sufficiently powerful to identify it, electrochemical products, intermediates, and byproducts. The growing complexity of electrochemical reactions, and progress in the development of fuel cells and energy stor- age devices, brought about a realization that minor quan- tities of byproducts can alter the course of electrochemi- cal reactions (e. g., by surface modification or passiva- tion). This has increasingly forced the electrochemical community to look for complementary analytical solu- tions, which initially involved ex-situ investigation, and with time also shifted to in-situ characterization methods. First, off-site analysis of the solid electrode interface, e. g., by electron microscopies, electron spectroscopy for chem- ical analysis (ESCA), vibrational spectroscopies (e.g., Raman, FTIR), and later on also secondary ion mass spectrometry (SIMS) proved useful. Soon enough, the sci- entific community came to realize that in-situ spectros- copies are invaluable for the determination of the species on the electrode, because the nature of the interface and its composition is potential-dependent. Since SIMS and electron microscopies could not provide such information, vibrational spectroscopy means as well as probe micros- copies and spectroscopies became widespread. As power- ful as these techniques are for unraveling the solid side of the interface, they cannot provide information on the so- [a] J. Gun, S. Bharathi, V. Gutkin, D. Rizkov, A. Voloshenko, R. Shelkov, S. Sladkevich, N. Kyi, M. Rona, Y. Wolanov, M. Koch, S. Mizrahi, P. V. Pridkhochenko, A. Modestov, O. Lev The Casali Institute of Applied Chemistry, The Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904, Israel phone: + 972 (0)2 6584191 fax: + 972 (0)2 6586155 e-mail: ovadia@vms.huji.ac.il Abstract : Probing electrochemical processes by mass spec- trometry (EC/MS) is a developing field that benefits from the unmatched identification power of mass spectrometry and from the rapid transfer of electrochemical cell products to the mass spectrometer. Most of the current EC/MS ef- forts are directed towards the development of differential electrochemical mass spectrometry (DEMS) using the elec- tro-ionization source for identification of volatile com- pounds, and towards the application of electrospray mass spectrometers for determination of semivolatile and nonvo- latile products. The challenges in coupling mass spectrome- try and electrochemistry are described, and different ap- proaches to using the coupled system for diverse applica- tions are reviewed, with emphasis on electrospray mass spectrometry. Reaction mechanism studies, diagnostic ap- plications, and activity imaging of electrodes are demon- strated based on approaches that were devised in our labo- ratory. Keywords: electrochemistry · electrospray · mass spectrometry · probe microscopy · scanning capillary microscopy 360  2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Isr. J. Chem. 2010, 50, 360 – 373 Review J. Gun et al.