Hyphenation of Capillary Chromatography and Electromigration Techniques with Mass Spectrometry: overcoming miniaturized challenges in Analytical Chemistry.

The use of capillary separation systems and the resulting flow of mobile phase or background electrolyte in the order of nanoliters per minute are two main features of these methodologies. Although the reduced mobile phase consumption, stationary phase and sample, as well as the high efficiency and short analysis times, are known advantages, sensitivity remains a challenge in their application for spectrophotometric detection. The coupling of Nano-LC, CE, and CEC with mass spectrometry (MS), which possesses high selectivity and sensitivity, makes them powerful tools for investigating pharmaceutical, environmental, agri-food, forensic, and biological fields. Through the use of a soft ionization technique called electrospray (ESI), which is sensitive, robust, and easy to implement, a variety of atmospheric pressure interfaces (API). Both commercial and lab-made APIs have been developed, allowing for easy transfer of analytes from the liquid phase of the separation system to the gas phase of the mass spectrometer. Reducing dead volumes, ensuring effective transfer in chromatographic or electrophoretic separations, increasing sensitivity, and improving robustness are the fundamental criteria in designing a novel MS interface. In particular, in CEC and CE separations, where the driving force is electroosmotic flow, MS interfaces must also meet the essential requirement of simultaneous closure of two ohmic circuits: the analytical and ESI source one. "Sheath flow," "nano-spray," and "liquid-junction" are just a few examples of interfaces that enable easy coupling of miniaturized separation techniques to mass spectrometry, resulting in enhanced sensitivity. This communication is an overview concerning the coupling of CE, CEC and CLC/nano-LC with MS and describes each MS interface in its operating principles, advantages, and limitations. In addition, several examples of the potential of these combined techniques in analytical chemistry will also be reported.