Microdroplet Impact-Induced Spray Ionization Mass Spectrometry (MISI MS) for Online Reaction Monitoring and Bacteria Discrimination

Abstract

Microdroplet impact-induced spray ionization (MISI) is demonstrated involving the impact of microdroplets produced from a paper and their impact on another, leading to the ionization of analytes deposited on the latter. This cascaded process is more advantageous in comparison to standard spray ionization as it performs reactions and ionization simultaneously in the absence of high voltage directly applied on the sample. In MISI, we apply direct current (DC) potential only to the terminal paper, used as the primary ion source. Charge transfer due to microdroplet/ion deposition on the flowing analyte solution on the second surface generates secondary charged microdroplets from it carrying the analytes, which ionize and get detected by a mass spectrometer. In this way, up to three cascaded spray sources could be assembled in series. We show the detection of small molecules and proteins in such ionization events. MISI provides a method to understand chemical reactions by droplet impact. The C–C bond formation reactions catalyzed by palladium and alkali metal ion encapsulation using crown ether were studied as our model reactions. To demonstrate the application of our ion source in a bioanalytical context, we studied the noninvasive in situ discrimination of bacteria samples under ambient conditions.

Toward nanofluidics‐based mass spectrometry for exploring the unknown complex and heterogeneous subcellular worlds

“…For instance, Basuri et al developed a new ambient ionization technique, microdroplet impact-induced spray ionization mass spectrometry, which allowed to construct a sequential ionization method (Figure 3B). 71 Digital microfluidics is an innovative liquid-handling technique that uses electrodes to individually control F I G U R E 3 Current state of microfluidic-based mass spectrometry. (A) Capillary-based microfluidic platform for investigating the biocatalytic conversion of substrates into products at the single-cell level by electrospray-ionization mass spectrometry used to obtain product formation rates for individual Saccharomyces cerevisiae cells.…”

“…developed a new ambient ionization technique, microdroplet impact‐induced spray ionization mass spectrometry, which allowed to construct a sequential ionization method (Figure 3B). 71 …”

“…(B) Microdroplet impact‐induced spray ionization mass spectrometry with a mass spectrum of lysozyme, and chronogram of the primary ion source in on/off conditions. Reproduced with permission 70 Copyright 2020, American Chemical Society (C) Digital microfluidics via a chip‐integrated microspray hole with mass spectrometric monitoring of a chemical reaction followed by transportation to the microhole to monitor the progression of the reaction with mass spectrometry. Reproduced with permission 73 Copyright 2022, Publisher American Chemical Society (D) Coupling chip electrophoresis to mass spectrometry with a Y‐shaped structure as two supporting channels (SC) using an ion‐permeable membrane to stabilize the high‐voltage supply.…”