Aperture-controllable nano-electrospray emitter and its application in cardiac proteome analysis

The emitter clogging is the most common hardware failure of nano-electrospray ionization, to improve the durability and electrospray stability of fused silica emitters, we demonstrate a means of fabricating nano-electrospray emitters with controllable aperture size and gradually-narrowed channel on the tip. We simulated the fluid morphologies in the emitter channels by computational fluid dynamics and found more stable flow on aperture-controllable nano-electrospray emitter. Besides, we found the unstable flow sections of commercial emitters match the actual clogging sections very well, indicating the main cause of emitter clogging is unstable flow. We further tested the emitters by nano-LC-MS based proteome analysis. Compared with the commercial emitter, aperture-controllable nano-electrospray emitters promoted the total ion chromatogram intensity by 25%, the number of identified proteins by 6.58%, and the number of identified peptides by 7.87%. In total, 989 proteins were identified from 1 μg of extracted mouse cardiac proteins. After the optimization by using mouse samples, we analyzed clinical auricular dextral tissues from patients undergoing cardiac surgery and found 16 proteins related to atrial fibrillation. Overall, aperture-controllable nano-electrospray emitter exhibits better sensitivity and reproducibility in the application of nano-LC-MS cardiac proteome analysis.