Two fundamental approaches for the coupling of microfabricated devices to e
lectrospray mass spectrometry (ESI-MS) have been developed and evaluated. T
he microdevices, designed for electrophoretic separation, were constructed
from glass by standard photolithographic/wet chemical etching techniques. B
oth approaches integrated sample inlet ports, preconcentration sample loops
, the separation channel, and a port for ESI coupling. In one design, a mod
ular, reusable microdevice was coupled to an external subatmospheric electr
ospray interface using a liquid junction and a fused silica transfer capill
ary. The transfer capillary allowed the use of an independent electrospray
interface as well as fiber optic UV detection. In the second design, a mini
aturized pneumatic nebulizer was fabricated as an integral part of the chip
, resulting in a very simple device, The on-chip pneumatic nebulizer provid
ed control of the flow of the electrosprayed liquid and minimized the dead
volume associated with droplet formation at the electrospray exit port. Thu
s, the microdevice substituted for a capillary electrophoresis instrument a
nd an electrospray interface-traditionally two independent components. This
type of microdevice is simple to fabricate and may thus be developed eithe
r as a part of a reusable system or as a disposable cartridge, Both devices
were tested on CE separations of angiotensin peptides and a cytochrome c t
ryptic digest. Several electrolyte systems including a transient isotachoph
oretic preconcentration step were tested for separation and analysis by an
ion trap mass spectrometer.