Column switching is still the main coupling approach for the setup of miniaturized SP-LC systems, and the degradation of separation efficiency caused by dead volume is more serious than conventional online systems. In this case, the volumes in transfer lines and fittings should be minimized. The “zero dead volume column connection” has been proven important to enhance the sample processing capability, separation efficiency and extraction/elution characteristics of the SPE-nanoLC systems [177]. Chip-based online systems integrate the enrichment column, analytical column, connecting
capillaries and nanospray emitter directly onto a chip device, which can enhance chromatographic performance and
further analytical sensitivity. The online coupling on a chip can be realized by a “chip-rotor interface”, where the chip can be sandwiched between the stator and the rotor of a two-position HPLC rotary switching valve [178,179]. Another online coupling approach is to fabricate the chips employing an integrated injector/ splitter structure, which allows the devices to be interfaced with a standard LC pump. According to this strategy, monolithic trap column can be photopolymerized ahead of the separation channel (column), allowing sample cleanup/enrichment and gradient LC separation to be performed on the same microchip.