Capillary Electrophoresis Mass Spectrometry Interfacing via Multifunctional Vibrating Sharp Edge Ionization Spray for the Simultaneous Delivery of an Auxiliary Flow, Analyte Mixing, and Fluid Nebulization

A new method of connecting capillary electrophoresis (CE) to mass spectrometry (MS) is introduced in which a vibrating sharp edge spray ionization (VSSI) probe is adapted to deliver a secondary fluid directly at the capillary electrophoresis surface. In VSSI, acoustic streaming at a sharp edge converts solutions into an aerosol. Consequently, a superimposed electric field is not required to nebulize fluid as is the case for electrospray ionization. In this report, a directed VSSI auxiliary flow assists in analyte transfer to the MS, making it amenable to electrophoretic separations that have a low electroosmotic bulk flow. Unlike a coaxial sheath, a directed auxiliary flow can be used with nonconductive liquids because the superimposed fluid is not integral to the process of electrophoresis grounding. An order of magnitude improvement in analyte signal is realized when deionized water is used for the supplementary liquid. In addition to the multifunctional role of VSSI for delivery of fluid, mixing with analyte, and nebulization, a self-aligning grounding cap is described for use with standard fused silica separation capillaries that have a blunt cut at the end. These features enable coupling to a commercial CE instrument. The direct CE-VSSI-MS interface is compatible with background electrolytes maintained at acidic or neutral pH and even composed of 200 mM ammonium acetate. Separations are demonstrated with cationic beta-blockers, amino acids, peptide standards, a peptide mixture from a chymotrypsin digestion of transferrin, and a 17-residue peptide monomer and homodimer derived from Huntington's protein that is implicated in protein aggregation.