The combination of microfabricated fluidic systems (mu FAB) and electrospray mass spectrometers (ESI-MS) will provide multiplexed and integrated analytical systems for proteins and other;biomolecules, Implementation of this novel approach requires the development of robust and user-friendly mu FAB devices. Here, we present new approaches that improve the robustness, user friendliness and performance of mu FAB devices coupled to MS. First, we present the development of a convenient mount to connect a mu FAB device to the ESI-MS and the incorporation of filters in the reservoirs and exit of the mu FAB. This mount facilitates interfacing and significantly reduces the chemical noise observed by the MS. Furthermore, we demonstrate improvements in sample handling and delivery by using either a nonaqueous electrolyte or a cationic coating on the surfaces in the mu FAB device and transfer capillary. These improvements are applied to protein analysis by continuous infusion of proteolytic digests.