The combination of microfabricated fluidic systems (muFAB) 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 muFAB devices. Here, we present new approaches that improve the robustness, user friendliness and performance of muFAB devices coupled to MS. First, we present the development of a convenient mount to connect a muFAB device to the ESI-MS and the incorporation of filters in the reservoirs and exit of the muFAB. 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 muFAB device and transfer capillary. These improvements are applied to protein analysis by continuous infusion of proteolytic digests.