Developments in Interfacing Designs for CE–MS: Towards Enabling Tools for Proteomics and Metabolomics

Capillary electrophoresis–electrospray ionization-mass spectrometry (CE-ESI-MS) has emerged as a powerful tool for the analysis of charged compounds in biological samples [1–3]. CE–MS can be used for the characterization of a wide variety of analytes, e.g., metabolites, peptides, glycans and intact proteins [4–6]. So far, the co-axial sheath–liquid interface has been primarily used for the coupling of CE to MS [7, 8]. In this design, the sheath–liquid is provided co-axially to the end of the CE capillary as a terminal electrolyte reservoir, thereby providing a closed electrical contact (see “Advancements in CE–MS Interface Designs” for details). For many applications, this interfacing technique provided an acceptable performance and robustness [9–12]. However, a limitation of the use of the sheath liquid is that it dilutes the CE effluent [13], thereby compromising the achievable concentration sensitivity. This may have been one of the reasons why CE–MS lagged behind LC–MS in the field of proteomics (apart from intact protein analysis), glycomics and metabolomics. The low loadability (nL injection volumes) of CE is also mentioned as an obstacle to obtain improved concentration sensitivities and/or low concentration detection limits. In order to overcome this issue, various chromatographicand electrophoretic-based preconcentration techniques have been developed to enhance the concentration sensitivity of CE–MS. The reader is referred Abstract Capillary electrophoresis–mass spectrometry (CE–MS) can be considered a useful analytical technique for the analysis of charged compounds in the fields of proteomics and metabolomics. Currently, the commercially available co-axial sheath–liquid interface is generally employed for coupling CE to MS in most application areas. Although it has proven to be rather robust for various proteomics, glycomics and metabolomics studies, the intrinsically low-flow separation property of CE is not effectively utilized in this set-up. In this type of interfacing the sheath– liquid (typical flow-rate between 1 and 10 μL/min) dilutes the CE effluent (flow-rate between 20 and 100 nL/min), thereby reducing the detection sensitivity. Over the past few years some significant developments that aim to overcome this limitation have been made in interfacing techniques for CE–MS, which resulted in an increased interest of CE–MS for proteomics and metabolomics. This paper provides an overview of these developments and the utility of CE–MS employing the new interfacing techniques is demonstrated