# 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

## TL;DR

A new method connects capillary electrophoresis to mass spectrometry using a vibrating sharp edge spray that improves signal and works with various fluids.

## Contribution

The VSSI probe enables fluid delivery, mixing, and nebulization without requiring an electric field for ionization.

## Key findings

- VSSI improves analyte signal by an order of magnitude when using deionized water.
- The interface works with nonconductive liquids and standard capillaries.
- Successful separations were demonstrated with peptides and proteins relevant to Huntington’s disease.

## Abstract

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.