A robust and extendable sheath flow interface with minimal dead volume for coupling CE with ESI-MS

In this paper, we describe a robust sheath flow-based CE-MS interface with minimal interface dead volume based on an extended pattern. A 20 Ism i.d. x 90 mu m o.d. fused-silica capillary with a chemically-etched thin-wall tip (30 mu m o.d.) was used as the separation capillary as well as electrospray emitter, and a 200 mu m i.d. x 375 pm o.d. capillary with a tapered tip (40 mu m o.d.) was used as the sheath flow capillary. An extendable sheath-flow interface mode was adopted by decreasing the thickness of separation capillary tip and extending the separation capillary tip out from the sheath flow capillary tip, and allowing the sheath flow to be transferred to the separation capillary tip along its outer surface, forming a surface sheath flow to mix with sample flow at the separation capillary tip. Such a strategy could significantly reduce the interface dead volume and thus improve the CE separation efficiency and detection sensitivity, as well as evidently enhance the working reliability of the CE-MS interface. We investigated various factors affecting the interface performance, including capillary extending distance, emitter diameters, sheath flow capillary shape, and sheath flow rate. Under the optimized conditions, a minimal interface dead volume of ca. 4 pL was obtained which is the smallest one compared with previously-reported sheath flow-based CE-MS interfaces. The feasibility and applicability of the present CE-MS interface were demonstrated in the separation of a peptide mixture with high separation efficiency of 2.07-3.38 mu m plate heights and good repeatabilities (< 6.1% RSD, n = 5). We except such a simple and robust interface could provide a possible solution for the development of commercial CE-MS interfaces differing from the currently-used ones, and has the potentials to be applied in routine analytical laboratories for various studies such as proteomics, metabolomics, or single cell analysis.