Achieving Stable Electrospray Ionization Mass Spectrometry Detection from Microfluidic Chips.

The past two decades have witnessed remarkable advances in the development of microfluidic devices as bioanalytical platforms for the analysis of biological molecules. The implementation of mass spectrometry (MS) detection systems on these devices has become inevitable, and various chip-MS ionization interfaces have been developed. As electrospray ionization (ESI) is particularly relevant for the analysis of large biological molecules such as proteins or peptides, efforts have focused on advancing interfaces that meet the demands of nano-separation techniques that are typically used prior to MS detection. Achieving stable ESI conditions that enable sensitive MS detection is, however, not trivial, especially when the spray is generated from a microfabricated platform. This chapter is aimed at providing a step-by-step protocol for producing stable and efficient electrospray sample ionization from microfluidic chips that are used for capillary electrophoresis (CE) separations.