Capillary electrophoresis-mass spectrometry (CE-MS) is a powerful tool in various fields including proteomics, metabolomics, biopharmaceutical and environmental analysis. Sensitive ionisation is of utmost importance in these areas and is specifically pivotal in CE-MS to outbalance the generally low sample loadability. Nanoflow sheath liquid interfaces have been a central element of recent research. Despite the impressive results that were obtained, these interfaces remain limited to expert users as handling is difficult and expertise is necessary.<br/>Here, we present the development of a novel nanoflow sheath liquid interface, based on 3D-printed parts using a recently reported two-capillary approach [1]. The customised design allows easy setup and robust operation. The transparency of the polymer enables visual inspection of the liquid flow inside of the interface.<br/>We thoroughly characterized the interface regarding sensitivity, robustness, flow rates and EOF handling by analysis of amino acids and BSA digest and intact protein analysis.<br/>Evaluation of emitters with different tip size resulted in 20 µm as optimum tip ID regarding sensitivity. We calculated the total electrospray flow rate during operation which was between 300 nL/min and about 1 µL/min, influenced mainly by the electrospray voltage. Consequently, increasing the electrospray voltage enables the operation of the interface with high electroosmotic flows. Robustness of the interface was demonstrated regarding the electrospray voltage, the distance between emitter and MS orifice, the distance between separation capillary and emitter tip, and different individual emitters of the same type by analysis of variance. The flexibility of the interface was shown by applications with two different capillary coatings for intact protein analysis.<br/>The 3D printed interface enables sensitive, easy, and robust coupling of CE-MS. In combination with our previously reported two-capillary approach [1], easy and contamination-free conditioning and coating is enabled. Conclusively, the characteristics of the interface regarding ease-of-use, flexibility and broad applicability enable the interface to be used by non-experts and in large-scale studies.

3D-printed device as 2-capillary nanoflow sheath liquid interface for CE-MS

ACS Fall 2021

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