Two capillary approach for a multifunctional nanoflow sheath liquid interface for capillary electrophoresis‐mass spectrometry

Abstract

CE hyphenated to ESI‐MS (CE‐ESI‐MS) is a well‐established technique to analyze charged analytes in complex samples. Although various interfaces for CE‐MS coupling are commercially available, the development of alternatives which combine sensitivity, simplicity, and robustness remains a topic of research. In this work, a nanoflow sheath liquid CE‐MS interface with two movable capillaries inside a glass emitter is described. The setup enables a separation mode and a conditioning mode to guide the separation capillary effluent either into the electrospray or to the waste, respectively. This enables to exclude parts of the analysis from MS detection and unwanted matrix components reaching the mass spectrometer, comparable to divert valves in LC‐MS coupling. Also, this function improves the overall robustness of the system by reduction of particles blocking the emitter. Preconditioning with electrospray interfering substances and even the application of coating materials for every analysis is enabled, even while the separation capillary is built into the interface with running electrospray. The functionality is demonstrated by analyses of heavy matrix bioreactor samples. Overall, this innovation offers a more convenient installation of the interface, improved handling with an extended lifetime of the emitter tips and additional functions compared to previous approaches, while keeping the higher sensitivity of nanoflow CE‐MS‐coupling.

nanoCEasy: An Easy, Flexible, and Robust Nanoflow Sheath Liquid Capillary Electrophoresis-Mass Spectrometry Interface Based on 3D Printed Parts

“…The nanoCEasy interface is designed to improve mounting and handling based on our recently described nanoflow SL interface with the two capillary approach . The two capillary approach provides several benefits compared to the conventional approach of using a single capillary in an electrospray emitter.…”

“…FS capillaries (50 μm ID) with a length of 65–70 cm were used for separation. Separation capillaries were etched at one end with hydrofluoric acid over a length of 10 mm to reduce the outer diameter (<150 μm) as reported previously , ( safety consideration: wear appropriate protective gear and perform handling under a fume hood ). Capillaries were initially conditioned by flushing with methanol (10 min), 1 M sodium hydroxide (15 min), UPW (5 min), and finally BGE (10 min).…”

“…Our group recently developed an in-house built nanoflow SL interface which was already successfully used for the quantification and screening of anionic compounds in drinking water and the analysis CE­(SDS)-separated monoclonal antibody fragments . Moreover, we were able to overcome some of the aforementioned problems by introducing a two capillary approach …”

A Hypothesis From Metabolomics Analysis of Diabetic Retinopathy: Arginine-Creatine Metabolic Pathway May Be a New Treatment Strategy for Diabetic Retinopathy

“…Capillary electrophoresis (CE) has a long history of use. Its application is mainly limited by its poor sensitivity, which has been greatly improved by the introduction of the CE-ESI interface ( 71 , 72 ).…”

A Mini Review on Capillary Isoelectric Focusing-Mass Spectrometry for Top-Down Proteomics

“…Both the two sheath-flow interfaces have been successfully applied to cIEF-MS characterization of intact proteins (Zhong et al, 2011a,b;Zhu et al, 2017). More recently, several other sheathflow CE-MS interfaces with nL/min flow rates of sheath liquid have been developed (Choi et al, 2016;Fang et al, 2018;Krenkova et al, 2019;Höcker et al, 2020). However, based on our best knowledge, there are still no literature reports about using these new CE-MS interfaces for cIEF-MS.…”