Mei-Chun Tseng Yet-Ran Chen Guor-Rong Her Department of Chemistry, National Taiwan University, Taipei, Taiwan, R.O.C A beveled tip sheath liquid interface for capillary electrophoresis-electrospray ionization-mass spectrometry A simple and durable sheath liquid interface for capillary zone electrophoresis-electro- spray ionization-mass spectrometry (CZE-ESI-MS) has been developed. This interface utilized a beveled tip emitter and was found to be more sensitive than the conventional sheath liquid interface. The use of a beveled tip reduces the optimal flow rate and therefore decreases sample dilution. The interface utilized a 380 mm inner diameter and 400 mm outer diameter beveled tapered tip. Because of the large inner diameter and outer diameter of the tip, the interface is robust and can be easily implemented. The performance of this interface for CZE-ESI-MS and micelle electrokinetic capillary electrophoresis-electrospray-mass spectrometry, as demonstrated by the analysis of synthetic drugs and triazine mixtures, was significantly better than results obtained using a conventional sheath liquid interface. Keywords: Capillary zone electrophoresis / Low-flow interface / Mass spectrometry / Micellar electrokinetic chromatography DOI 10.1002/elps.200305907 1 Introduction The combination of liquid-based separation systems and mass spectrometry (MS) has great potential, because it combines efficient separation with selective mass identi- fication [1]. Due to its ability to provide fast, highly efficient separations using extremely small sample quantities, the coupling of electrospray ionization mass-spectrometry (ESI-MS) with capillary electrophoresis (CE) represents one of the most powerful on-line combinations involving chromatography and MS detection. While several inter- facing methods have been reported for CE-ESI-MS, two interface types, sheath liquid and sheathless, have gained general acceptance [2, 3]. The sheath liquid is the most widely used interface because of its relative ease of im- plementation and versatility [4]. The interface is config- ured with a fused-silica separation capillary inside a co- axial liquid sheath tube or needle, which often resides within a second coaxial tube supplying sheath gas. The sheath liquid provides electrical contact with the outlet end of the separation capillary [5]. More importantly, the mixing of the running buffer with the sheath liquid before electrospray allows CE-ESI-MS operation using a wide range of buffer conditions [6]. The major disadvantage of using a sheath liquid is the reduction in sensitivity due to dilution of the sample as it elutes from the capillary. It is a well-known phenomenon that the optimal flow rate in ESI depends on the ID of the emitter [7, 8]. Above the opti- mal flow rate, the ESI emitter behaves as a concentration- sensitive detector. The ID of the conventional sheath liquid emitter is about 400 mm and the optimal flow rate is about 4–5 mL/min. This flow rate is much higher than the flow rate of the CE separation column (about 50– 300 nL/min). Thus, the analyte is diluted considerably by the sheath liquid. In the sheathless interface, several approaches have been proposed to maintain the electrical continuity of the electrophoresis circuit, including the application of a con- ductive coating, connecting to a stainless steel tip and the use of a liquid junction [8–15]. An important consequence of the sheathless design is that the sample bands are not diluted. Thus, significant gains in sensitivity (25–50-fold) have been reported [16]. However, this interface has sev- eral disadvantages, e.g., the limitation in the selection of running buffer. In sheathless operation, it is often difficult to find a buffer solution optimized for both CE separation and ESI efficiency. Furthermore, as mentioned earlier, the optimal flow rate in ESI depends on the ID of the sprayer. Therefore, to accommodate the flow rate of conventional CZE (about 50–300 nL/min), the size at one end of the CE capillary is often reduced to about 10–25 mm [8–11, 13–15]. In addition to the difficulty of emitter fabrication, the susceptibility to breaking or clogging of the tapered tip during coating or cleaning represents another problem of the sheathless interface. Correspondence: Dr. Guor-Rong Her, Department of Chemistry, NationalTaiwan University, Taipei, Taiwan, R.O.C E-mail: grher@ntu.edu.tw Fax: 1886-2-23638058 2084 Electrophoresis 2004, 25, 2084–2089  2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim