Although several interfaces for CE‐MS hyphenation are commercially available, the development of new versatile, simple and yet efficient and sensitive alternatives remains an important field of research. In a previous work, a simple low sheath‐flo...
Although several interfaces for CE‐MS hyphenation are commercially available, the development of new versatile, simple and yet efficient and sensitive alternatives remains an important field of research. In a previous work, a simple low sheath‐flow interface was developed from inexpensive parts. This interface features a design easy to build, maintain, and adapt to particular needs. The present work introduces an improved design of the previous interface. By reducing the diameter of the separation capillary and the emitter, a smaller Taylor cone is spontaneously formed, minimizing the zone dispersion while the analytes go through the interface and leading to less peak broadening associated to the ESI process. Numerical modeling allowed studying the mixing and diffusion processes taking place in the Taylor cone. The analytical performance of this new interface was tested with pharmaceutically relevant molecules and endogenous metabolites. The interface was eventually applied to the analysis of neural cell culture samples, allowing the identification of a panel of neurotransmission‐related molecules. An excellent migration time repeatability was obtained (intra‐day RSD <0.5% for most compounds, and <3.0% for inter‐day precision). Most metabolites showed S/N ratios >10 with an injected volume of 6.7 nL of biological extract.