Synchronized Inductive Desorption Electrospray Ionization Mass Spectrometry

Abstract

Mass spectrometry (MS) plays an important role in chemical analysis which is currently being enhanced by the increasing demand for rapid trace analysis in the areas of public safety, forensics, food safety, and pharmaceutical quality assurance, amongst others. These demands constitute an impetus to simplify MS instrumentation and methodologies. This in turn has resulted in the development of miniaturized instrumentation [1][2][3] and the invention of ambient ionization methods in which samples are examined without preparation in their native state. [4][5][6][7][8][9][10][11][12] The ambient ionization methods include spray-based, [13][14][15][16][17][18][19][20] plasma-based, [21,22] and laser-assisted methods. [23][24][25][26][27] Like other ambient methods, desorption electrospray ionization (DESI) [14] has the advantages of simple instrumentation, rapid and sensitive analysis, and broad applicability. In situ mass spectrometry requires both portable instruments and simple ionization/sampling methods. In our laboratory, this requirement has been met by fitting the small ion trap based Mini 10 and 11 instruments [1] with ambient ionization sources. The performance of the combined system is limited by the low pumping speed of small mass spectrometers and the large nebulizing gas and solvent volumes that must be handled. This problem was addressed by the development of the discontinuous atmospheric pressure interface (DAPI). [28,29] The DAPI interface is opened briefly to admit a bolus of ions, solvent vapor and gas, then closed while the neutrals are pumped away before the trapped ions are mass analyzed. The system operates well in spite of a duty cycle of just 1 %. [28,29] Further improvement should be achievable by synchronization of the experiment (Figure 1) which requires the use of an inductive method to charge the primary microdroplets. This allows droplet creation to be synchronized with the opening of the sample introduction system (and also with the pulsing of the nebulizing gas). Synchronized inductive DESI shows good performance: 1) over 100-fold improvement in sensitivity (Figure 1c and 1d) while still using the 1:100 DAPI duty cycle, 2) reduced solvent spray flow rate from ca. 5 mL min À1 to 0.5 mL min À1 , 3) reduced nebulizing gas usage from ca. 2 L min À1 to 0.2 L min À1, 4) improved sampling efficiency by a factor of 100, and 5) quasi-simultaneous recording of positive and negative ion spectra using a pulsed monopolar ion source. These capabilities are based on accurate control of charged droplet creation by placing an electrode near a spray emitter (typically 2-5 mm distant) and pulsing it repetitively to high positive potentials (5-7 kV, 50-3000 Hz, pulse width 0.2-2 ms). The pulsed positive voltage was applied to a metal tube (inner diameter (i.d.) 250 mm), covering an inner silica capillary which served as the spray emitter tip (i.d. 50 mm). Electromagnetic induction produces high electrical fields in the DESI source that result in bursts of charged droplets. Precise synchronization with the ...

High‐Throughput Bioassays using “Dip‐and‐Go” Multiplexed Electrospray Mass Spectrometry

“…[10] Nevertheless,t he outstanding analytical performance of nESI has not been exploited for HTS analysis because the sample introduction step in nESI has only been done manually.I nr ecent years,o ur group has developed inductive nESI which enables the ionization of liquid samples using ar emote electrode. [13] Inductive nESI, better termed inductive picoelectrospray (pL min À1 flowrate of spray solvent, pESI) can perform reliable analysis from small confined volumes including droplets [14] and single cells [13c] with sensitivity down to the zeptomole level. [13b] When either as tatic [13c,15] or alternating electrical field [13b] is applied to initiate inductive nESI, the polarization of the liquid causes the spatial separation of ions, [13c, 16] allowing in situ micro-electrophoresis.T his effect becomes particularly significant when:a)sample amounts are at the nanoliter level and b) the electrical field applied to initiate inductive nESI is also used to effect micro-electrophoresis.Wehypothesize that the combination of inductive nESI with high performance micro-electrophoresis could constitute ap romising approach for HTS bioassays.…”

Recent Advances of In‐Source Electrochemical Mass Spectrometry

“…It should also be noted that the in-source electrochemical property is not always wanted. Methods of alleviating or avoiding electrochemistry in ion sources include fast polarity switching" [110] flow splitting, [111] and inductive [112][113][114] and extractive ESI. [115] With further instrumentation development in the future, our expectations include i) EC-MS with ultra-low delay time to probe transient species with half-lives of pico-to nanoseconds; ii) rapid and high-throughput screening of electrochemical reactions and condition optimization to guide electrosynthesis; iii) increasing studies on electroreduction and extensive applications to hardly ionizable compounds.…”

“…Specifically, SIMS imaging illustrated possible changes on the electrode surface dependent upon the electrolyte composition, visualizing the status of the electrochemical processes. The same group further investigated the electro‐oxidation mechanism of ascorbic acid at the electrode‐electrolyte interface, [110] where transient radical intermediates were probed directly for the first time.…”

Mechanistic study of CBT-Cys click reaction and its application for identifying bioactive N-terminal cysteine peptides in amniotic fluid

“…Inspired by the pioneering studies above, in this work, we firstly aim to investigate the mechanism of CBT-Cys click reaction by using induced nano-electrospray ionization mass spectrometry (InESI-MS), a new emerging MS technique which has shown good performance in matrix tolerance and thus facilitated the direct identification of intermediates in raw reaction mixtures. 38 – 40 Using a 15 N-labeled Cys as one reactant and InESI-MS, we firstly validated that the N-atom in the second thiazole ring of Aminoluciferin originated from Cys but not from cyano group of CBT ( Scheme 1 ). Then, we assembled a micro-reactor for InESI-MS analysis and successfully intercepted the crucial Intermediate 2 , with which the mechanism of this CBT-Cys click reaction was satisfactorily interpreted, as shown in Scheme 3 .…”