This paper describes a novel emitter tip having the shape of a nib and based on an open structure for nano-electrospray ionization mass spectrometry (nanoESI-MS). The nib structure is fabricated with standard lithography techniques using SU-8, an epoxy-based negative photoresist. The tip is comprised of a reservoir, a capillary slot and a point-like feature, and is fabricated on a silicon wafer. We present here a novel scheme for interfacing such nib tips to MS by applying the ionization voltage directly onto the semi-conductor support. The silicon support is in direct contact with the liquid to be analyzed at the reservoir and microchannel level, thus allowing easy use in ESI-MS. This scheme is especially advantageous for automated analysis as the manual step of positioning a metallic wire into the reservoir is avoided. In addition, the analysis performance was enhanced compared with the former scheme, as demonstrated by the tests of standard peptides (gramicidin S, Glu-fibrinopeptide B). The limit of detection was determined to be lower than 10 Ϫ 2 M. Due to their enhanced performance, these microfabricated sources might be of great interest for analysis requiring very high sensitivity, such as proteomics analysis using nanoESI-MS. Proteomics studies are carried out on small amounts of sample and, thereby, need highly sensitive analysis techniques. ESI-MS matches this sensitivity criterion [2]. It also enables species identification using their precise molecular weights and provides fragment sequences using the MS/MS mode [1,3]. Therefore, ESI-MS is one of the best techniques for use in proteomics.Nanospraying is usually performed using glass or fused-silica-based capillary tips [2], and the spray is obtained by applying the ionization voltage to the electrical conductive tip or through the sample solution. However, capillary sources present a number of weaknesses: (1) a poorly controlled fabrication route resulting in a low reproducibility of the sources, (2) an irregular profile of the aperture after source opening, (3) easy clogging due to the small i.d., (4) signal suppression caused by air bubbles, and (5) deterioration of the conductive coating [4,5] upon operation.Different improvements regarding the quality of the emitter tip are proposed in the literature. Reproducible dimensions can be achieved using an enhanced fabrication route based on laser-micromachining [6,7]. More stable coatings have also been reported [8 -10]. Most of these improvements, however, do not solve the basic problems of clogging and the lack of reproducibility that affect the analysis conditions. Using microtechnology techniques, reproducible and ready-to-use high-quality nanospray tips can be produced in large batches. The tip geometry can be chosen to allow on-chip integration together with other microfluidic components, e.g., a chromatography column, and also to be compatible with the use of standard robots. Microfabrication of ESI emitter tips follows two main approaches: (1) a "needle-like" ap- Our approach is to design an em...