Quasi-Simultaneous Identification of Polar and Neutral Lipids in Mass Spectrometry by kHz Switching of Electrospray...

The identification of polar and neutral lipid species as biomarkers in complex biological samples is a key task in clinical and life sciences. Electrospray and plasma-based ionization techniques are necessary to cover the full range of lipidomes, owing to their limited molecular polarity ranges. However, combining both to generate hybrid spectra is difficult without averaging spectra, as electrospray and plasma sources operate under vastly different conditions. Their electric fields also interfere, resulting in a mutual destabilization of the ionization processes. Herein, a heated nanoelectrospray is combined with a flexible microtube plasma using a rapid (kHz range) switching process (heated nESI-sFμTP) to generate quasi-simultaneous ionization. This approach loads the ion trap with polar and less-polar ions during each injection cycle, generating hybrid spectra without averaging it. The performance of the quasi-simultaneous approach is investigated in positive ion mode, comparing it with conventional ion sources through the analysis of complex lipid liver and heart samples. While no improvements are observed in negative ion mode, the novel quasi-simultaneous approach shows great potential for analyzing complex samples in positive ion mode. The combined heated nESI-sFμTP exceeds the molecular polarity range of individual sources, offering excellent ionization efficiency and MS² capabilities.