A fully Integrated Monolithic Microchip Electrospray Device for Mass Spectrometry

摘要

A novel microfabricated nozzle has been developed for the electrospray of liquids from microfluidic devices for analysis by mass spectrometry. The electrospray device was fabricated from a monolithic silicon substrate using deep reactive ion etching and other standard semiconduc-tor techniques to etch nozzles from the planar surface of a silicon wafer. A channel extends through the wafer from the tip of the nozzle to a reservoir etched into the opposite planar surface of the wafer. Nozzle diameters as small as 13 pm have been fabricated using this method. The microfabricated electrospray device provides a reproduc-ible, controllable, and robust means of producing nano-electrospray of a liquid sample. The electrospray device was interfaced to an abnospheric pressure ionization lime-of-flight mass spectrometer using continuous infusion of test compounds at low nanoliter-per-minute flow rates. Nozzle-to-nozzle signal intensity reproducibility using 10 nozzles was demonstrated to be 12% with single-nozzle signal stability routinely less than 4% relative standard deviation (RSD). Solvent compositions have been elec-trosprayed ranging from 100% organic to 100% aqueous. The signal-to-noise ratio from the infusion of a 10 nM cytochrome c solution in 100% water at 100 nL./min was 450:1. Microchip electrospray nozzles were compared with pulled capillaries for overall sensitivity and signal stability for small and large molecules. The microchip electrospray nozzles showed a 1.5—3-times increase in sensitivity compared with that from a pulled capillary, and signal stability with the microchip was 2—4% RSD com-pared with 4—10% with a pulled capillary. Electrospray device lifetimes achieved thus far have exceeded 8 h of continuous operation and should be sufficient for typical microfluidic applications. The total volume of the elec-trospray device is less than 25 pL, making it suitable for combination with microfluidic separation devices.