Microspray and microflow liquid chromatography: the way forward for LC–MS bioanalysis

It is well known that the efficiency of ionization improves as the liquid flow rate to the source decreases for ESI. The improved ionization efficiency leads to better MS signal. Microflow liquid chromatography (MFLC) has also been shown to be advantageous for over 40 years. Conventional LC–MS flow rates are in the range of 250–600 µl/min with column internal diameters of 2.1 mm. Nanospray, a technique highly developed by Gary Valaskovic utilizes flow rates in the order of sub µl/min with column internal diameters of <100 µm. Microspray (also known as ‘high flow nanospray’) is a technique that typically consists of flow rates of 5–100 µl/min with column diameters from 0.25–1.0 mm. Microspray and MFLC combined, are a great means to achieve the benefits of improved MS signal from nanospray and optimal analysis times shown by conventional LC–MS flow rates.