Capillary electrophoresis (CE) offers fast and high‐resolution separation of charged analytes from small injection volumes. Coupled to mass spectrometry (MS), it represents a powerful analytical technique providing (exact) mass information and enables molecular characterization based on fragmentation. Although hyphenation of CE and MS is not straightforward, much emphasis has been placed on enabling efficient ionization and user‐friendly coupling. Though several interfaces are now commercially available, research on more efficient and robust interfacing with nano‐electrospray ionization (ESI), matrix‐assisted laser desorption/ionization (MALDI) and inductively coupled plasma mass spectrometry (ICP) continues with considerable results. At the same time, CE‐MS has been used in many fields, predominantly for the analysis of proteins, peptides and metabolites. This review belongs to a series of regularly published articles, summarizing 248 articles covering the time between June 2016 and May 2018. Latest developments on hyphenation of CE with MS as well as instrumental developments such as two‐dimensional separation systems with MS detection are mentioned. Furthermore, applications of various CE‐modes including capillary zone electrophoresis (CZE), nonaqueous capillary electrophoresis (NACE), capillary gel electrophoresis (CGE) and capillary isoelectric focusing (CIEF) coupled to MS in biological, pharmaceutical and environmental research are summarized.

Capillary electrophoresis-mass spectrometry (CE-MS) is a powerful tool in various fields including proteomics, metabolomics, and biopharmaceutical and environmental analysis. Nanoflow sheath liquid (SL) CE-MS interfaces provide sensitive ionization, required in these fields, but are still limited to a few research laboratories as handling is difficult and expertise is necessary. Here, we introduce nanoCEasy, a novel nanoflow SL interface based on 3D printed parts, including our previously reported two capillary approach. The customized plug-and-play design enables the introduction of capillaries and an emitter without any fittings in less than a minute. The transparency of the polymer enables visual inspection of the liquid flow inside the interface. Robust operation was systematically demonstrated regarding the electrospray voltage, the distance between the emitter and MS orifice, the distance between the separation capillary and emitter tip, and different individual emitters of the same type. For the first time, we evaluated the influence of high electroosmotic flow (EOF) separation conditions on a nanoflow SL interface. A high flow from the separation capillary can be outbalanced by increasing the electrospray voltage, leading to an overall increased electrospray flow, which enables stable operation under high-EOF conditions. Overall, the nanoCEasy interface allows easy, sensitive, and robust coupling of CE-MS. We aspire the use of this sensitive, easy-to-use interface in large-scale studies and by nonexperts.

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