A Modular Chip-Based Interface for Sheathless Capillary Electrophoresis-Mass Spectrometry

We present a novel sheathless chip-based interfacing module suitable for the plug-and-play hyphenation of capillary electrophoresis (CE) with mass spectrometry (MS). Chip fabrication was achieved via selective laser-induced etching (SLE), enabling rapid customization and high reproducibility while using inert, optically transparent fused silica as the substrate material. The three-dimensionally structured chips combine a seamless, pressure-tight connection technology for effortless replacement of CE capillaries with an optimized tapered emitter geometry featuring an orifice diameter of less than 25 μm. Additionally, sheathless electrical contacting via a nanochannel enables undiluted transfer of analytes to the MS inlet through nano-electrospray ionization (nanoESI), enabling highly sensitive analyses and improving signal-to-noise ratios by up to 19-fold compared to conventional CE-MS sheath liquid interfaces. Despite its compact dimensions at the millimeter scale, the presented interface module is highly user-friendly, offers robust operation and mechanical stability, while providing a novel microfluidic tool for the hyphenation of liquid-phase platforms to ESI-MS.