Dynamic Spray Mass Spectrometry for Direct Analysis of Complex Mixtures

The analysis of small volumes of complex mixtures is important for biological, medicinal, toxicological, and forensic applications. Herein, we report the development of a single-step method using nanoelectrospray ionization (nESI), capable of atmospheric pressure chemical ionization (APCI) for mass spectrometry (MS) analysis of polar and nonpolar compounds. This capability was enabled by creating a novel dynamic power supply, which allowed spray voltage to be applied in a linear sweep, thus generating a composite mass spectrum over the specified ramp period. At lower voltages, polar analytes are ionized via electrospray. Upon reaching a higher voltage (>4 kV) in the ramp process, APCI is activated from the same nESI emitter, allowing the ionization of nonpolar analytes, typically undetectable via nESI. Collectively, the advantages associated with the dynamic spray process include (i) increased matrix tolerance, (ii) autocorrection of spray voltage based on analyte type and emitter tip size/shape, and (iii) simultaneous quantification of different compounds from a single mixture. The broad applicability of this strategy was demonstrated via the analysis of proteins, nucleic acids, steroids, illicit drugs, lipids, and fatty acids. Importantly, the method was applied to diagnose malaria by analyzing whole blood, without any sample pretreatment. The method provided good sensitivity, accuracy, and precision. These results encourage future developments where the simple platform discussed here can be utilized as an alternative to conventional MS methods for analyzing biofluids.