Characterization of a nanoflow sheath liquid interface and comparison to a sheath liquid and a sheathless porous-tip interface for CE-ESI-MS in positive and negative ionization

Coupling of capillary electrophoresis to electrospray mass spectrometry still remains challenging and a topic of research to find the best interface regarding sensitivity, robustness, and ease of use. Here, a nanoflow sheath liquid interface for CE-ESI-MS is presented and compared to both a standard triple-tube sheath liquid and a porous-tip sheathless interface for three groups of analytes. The nanoflow sheath liquid interface with a separation capillary inserted into a glass emitter was initially characterized to facilitate optimization and method development. Implementation of a shut-off valve, syringe pump, and inline filter enabled easy handling and fast analyses, repeatable both in positive and negative modes (intra-day RSD of 6.6 to 12.0%). The same setup was used for sheathless interfacing by exchanging the emitter and using a porous etched tip separation capillary. Both nanoflow interfaces showed similar performance. Average peak areas using the nanoflow sheath liquid interface were a factor of 38 for 6 organic acids in negative mode, 114 and 36 for the light and heavy chain of a monoclonal antibody, and 13 higher for peptides in positive mode compared to the triple-tube interface. This first direct comparison of the three most common interfaces exhibits a strong improvement in sensitivity to the same extent for both nanoflow interfaces, where sheath liquid interfaces offer full flexibility in method development.