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Voltage Switching on a Dual Nano-Electrospray/Atmospheric Pressure Chemical Ionization Platform Provides Higher Discrimination Power for Malaria Detection via Direct Infusion Mass Spectrometry.

Created on 26 Aug 2025

Authors

Riley Ferguson, Dmytro S Kulyk, Abraham K Badu-Tawiah

Published in

Analytical chemistry. Aug 26, 2025. Epub Aug 26, 2025.

Abstract

Nanoelectrospray ionization (nESI) is a powerful ion source enabling direct mass spectrometry (MS) analysis of polar compounds in small volumes. The exposure of charged microdroplets derived from nESI to nonthermal plasma discharge allows the ionization of nonpolar compounds via atmospheric pressure chemical ionization (APCI). In this work, we show that step voltage switching allows a distinctive composite spectrum to be recorded, which is richer in chemical information than the spectra derived from the pure nESI and APCI operated at constant voltages. Careful investigations revealed that the upper voltage in the switching event is not reached instantaneously. Instead, there is a gradual rise of the voltage within the set limits of the switching program, which allows different ionization mechanisms (nESI and APCI) to be activated at different times during the ramping period. We applied this step voltage approach to analyze nine malaria-infected and nine uninfected samples. We compared results to analyses achieved at constant applied voltages in nESI and APCI. Partial least-squares discriminant analysis (PLS-DA) showed that the composite spectra were achieved in voltage switching mode to provide the highest discriminatory power. Volcano plots, which analyze fold-changes in up- and down-regulated species in infected samples, confirmed the ability of the voltage switching process to enable the detection of many downregulated species. Consequently, heat maps derived from constant voltage APCI MS analysis showed the misclassification of four samples, while nESI MS analysis misclassified two samples. The composite spectra from nESI/ACPI in voltage switching mode enabled the correct classification of all 18 clinical samples.

PMID:
40855944
Bibliographic data and abstract were imported from PubMed on 26 Aug 2025.

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