Significant increase in the efficiency of electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) sources in tandem mass spectrometry (MS/MS) will have a profound impact on single cell MS-based analysis and the entire analytical field of characterization of proteins, lipids, and metabolites. Almost 100% ionization efficiency of nanoflow ESI (APCI) sources makes it a unique analytical tool specifically applicable to the MS-based analysis of zeptomole amounts of chemical and biological substances. We plan to build a platform combining subatmospheric nanoflow ESI and APCI sources and very efficient ion collector to drastically improve sensitivity and speed of MS-based identification of miniscule amount of biomaterials harvested from single cells.
A platform combining an ultralow flow liquid chromatography separation platform with nanoflow electrospray ionization source and high mass resolution mass spectrometer will be successfully used in the analysis of complex protein mixtures harvested from single cells. The platform will provide reliable protein MS-based identification from samples that contain zeptomole amounts of these proteins. We plan to develop a novel sub atmospheric interface providing highly efficient collection of ions produced by sub atmospheric pressure ion (sAPI) sources that can be straightforwardly combined with gas-phase separation methods. This will drastically improve detection limits and accelerate characterization of proteins and metabolites from single cells using high-resolution tandem mass spectrometry. The platform can be easily incorporated into a design of a variety of commercial tandem mass spectrometers.