Pocket-Size Wireless Nanoelectrospray Ionization Mass Spectrometry for Metabolic Analysis of Salty Biofluids and Single Cells

Abstract

Analysis of volume-limited biological samples such as single cells and biofluids not only benefits clinical purposes but also promotes fundamental research in life sciences. Detection of these samples, however, imposes strict requirements on measurement performance because of the minimal volume and concentrated salts of the samples. Herein, we developed a self-cleaning nanoelectrospray ionization device powered by a pocket-size "MasSpec Pointer" (MSP-nanoESI) for metabolic analysis of salty biological samples with limited volume. The self-cleaning effect induced by Maxwell−Wagner electric stress helps with keeping the borosilicate glass capillary tip free from clogging and thus increasing salt tolerance. This device possesses a high sample economy (about 0.1 μL per test) due to its pulsed high voltage supply, sampling method (dipping the nanoESI tip into analyte solution), and contact-free electrospray ionization (ESI) (the electrode does not touch the analyte solution during ESI). High repeatable results could be acquired by the device with a relative standard deviation (RSD) of 1.02% for voltage output and 12.94% for MS signals of caffeine standard. Single MCF-7 cells were metabolically analyzed directly from phosphate buffered saline, and two types of untreated cerebrospinal fluid from hydrocephalus patients were distinguished with 84% accuracy. MSP-nanoESI gets rid of the bulky apparatus and could be held in hand or put into one's pocket for transportation, and it could operate for more than 4 h without recharge. We believe this device will boost scientific research and clinical usage of volume-limited biological samples with high-concentration salts in a low-cost, convenient, and rapid manner.

Pulsed Direct Current Arc-Induced Nanoelectrospray Ionization Mass Spectrometry

“…Owing to its high voltage and temperature, the AC arc can directly ionize organic compounds by leveraging the array of active species it generates. Based on its high electric field and active species, arc plasma has been developed as various ambient ion sources. − Conversely, because it is a cold arc, the DC arc cannot directly ionize compounds (no spectra and data shown). Nonetheless, it generates abundant background ions in positive and negative ion modes (Figure D,E), holding potential for MS analysis.…”

“…Traditional nano-ESI sources are susceptible to unforeseen electrochemical reactions, resulting in capillary blockages and substantial signal interference. Conversely, DCAI-nano-ESI mass spectra exhibit enhanced clarity and are devoid of sodium or potassium adduct peaks during analyte detection because of the absence of Maxwell–Wagner electric stress behavior , and (H 2 O) n H + produced by DC arc plasma (Figure D), ensuring precise interpretation of mass spectra. Notably, the active species produced by the arc may contribute to the enhanced protonation capability of DCAI-nano-ESI, facilitating the ionization analysis of low-polarity compounds, as exemplified by cholesterol and anthracene (Figure S2).…”

Surface charge-induced electrospray for high-throughput analysis of complex samples and electrochemical reaction intermediates using mass spectrometry

“…The nano ESI technique also takes advantage of the suppression of matrix effects. 3 Despite this, the limited suppression effect of nano ESI has prompted tremendous efforts to develop various strategies, including direct/alternating current (DC/AC) voltageinduced, [3][4][5][6][7][8][9][10] solvent-assisted, 11 self-cleaning, 12 step-voltage, 13 and analyte migration 14 or slug-ow microextraction. 15 Among these protocols, DC/AC voltage-induced nano ESI 3,4 is promising for high-throughput analysis of complex samples due to its simple conguration and no contact between the metal electrode and sample solution, whereas the tip of the nano ESI emitter is easily clogged and fragile, 16 and induced ionization sources require additional power supplies, complicating the components of commercial mass spectrometers.…”

A Microfluidic-Fabricated Rod Sprayer for Nanoelectrospray Mass Spectrometry

“…First, biological samples with limited amount and large abundance difference require nanoESI to have high ionization efficiency and broad dynamic range . Second, buffer solutions with high salt concentration are usually essential for protein stabilization and resolution, which demands nanoESI to operate steadily in a complex matrix environment . Third, nanoLC-ESI-MS analysis for omics research is typically time-consuming, which makes it necessary for nanoESI to maintain a good stability during prolonged operation periods, and in the case of nanoESI degradation or failure, the device should be rapidly replaced with low cost while maintaining a consistent electrospray performance.…”