The present invention relates to electrospray ionization (ESI) at atmospheric pressure coupled with a mass spectrometer, in particular to a special kind of micro-electrospray with liquid flows in the range of 0.1 to 100 microliters per minute. The invention describes the use of an off-axis pre-entrance channel in an ESI ion source to prevent particulate matter with higher inertia than the (charged) gas molecules, such as droplets, from entering the mass spectrometer. The elimination of the particulate matter improves the quantitative precision of an LC/MS bioassay, minimizes the contamination of the mass spectrometer and improves the robustness for high throughput assays.