A micromachining process is described for fabricating a mass spectrometry e
lectrospray source on a silicon chip. The process utilizes polymer (parylen
e) layers to form a system of chambers, filters, channels, and hollow needl
e structures (electrospray emitters) that extend more than a millimeter bey
ond the edge of the silicon substrate. The use of photoresist as the sacrif
icial layer facilitates the creation of long channels. Access to the channe
l structures on the chip is through a port etched through the silicon subst
rate that also serves as a sample reservoir. A reusable chip holder consist
ing of two plastic plates and an elastomer gasket provides the means to mou
nt the chip in front of the mass spectrometer inlet and make electrical and
gas connections. The electrospray emitters have tapered tips with 5 mu m x
10 mu m rectangular openings. The shape of the tip can be varied depending
on the shape of the mask used to protect the parylene structures during th
e final plasma etch. The parylene emitters are physically robust and requir
e only a high electric field to achieve stable electrospray operation over
a period of a few hours. Direct comparisons with conventional glass or fuse
d silica emitters indicated very similar performance with respect to signal
strength and stability, spectral quality, and endurance. The automated MS/
MS analysis of a mixture of tryptic peptides was no more difficult and yiel
ded nearly identical results as the analysis of the same sample using a con
ventional nanospray device. This work demonstrates that an efficient electr
ospray interface to mass spectrometry can be integrated with other on-chip
structures and mass-produced using a batch process.