Microfabrication of heated nebulizer chips for mass spectrometry

Abstract

Microfabrication technologies originating from the semiconductor industry were applied to the instrumentation of analytical chemistry. Heated nebulizer (HN) chips made of silicon and glass were developed. The HN chips are used to vaporize a sample prior to detection by a mass spectrometer. The chips can be used with both liquid and gaseous samples and they are compatible with multiple atmospheric pressure ionization techniques, which enables wide applicability with different separation methods and various types of analytes. Better sensitivity, flexibility and operation with a lower sample and nebulizer gas flow rates was achieved by the miniaturization of the heated nebulizer. The chips can operate with 50 nL min-1 to 5 µL min-1 sample flow rates typical of microfluidic separation systems. Silicon and glass microfabrication methods - etching, wafer bonding and thin film technology - were developed and applied to the fabrication of the HN chips in 40 different layout and process variations. The thermal behaviour of the chips and the shape of the gaseous jet produced by the chips was studied. A method was developed for measuring the temperature distribution of a gaseous jet using a miniature thermocouple attached to a computer controlled xyz stage. Different methods for making capillary tube and electrical interconnections to the chips were also studied. Liquid chromatography (LC) column chips were developed resulting in an integrated chip having both an LC column and a heated nebulizer on a single chip. At the end of the LC column there is a high aspect ratio micropillar frit which enables packing the column with particles. The novel chips developed in this work extend the available ionization methods and the range of suitable analytes compared to the previously presented chips for mass spectrometry.