Electrospray device for coupling microscale separations and other miniaturized devices with electrospray mass spectrometry

A miniaturized ion sprayer device is described which is suitable for coupli ng with chip-based analytical separation devices, multiwell plates, or surf aces containing residues of prepared samples. Two versions of a similar dev ice are described. A "microsprayer" device suitable for coupling to the ter minal edge of a capillary electrophoresis (CE) chip is constructed from mod ified 1/(16)-in. HPLC fittings. This microsprayer employs a free-standing l iquid junction formed via continuous delivery of a now (2-6 muL/min) of sui table solvent which carries the CE effluent through a pneumatically assiste d electrospray lion spray) needle positioned in front of an atmospheric pre ssure ionization (API) mass spectrometer. A related but larger "minisprayer " device is also described which employs the same features as the microspra yer, but with an extended sampling capillary tube which can reach into the depths of 96-, 384-, and 1536-multiwell plates containing either sample sol utions or dried sample residues. The minisprayer may be positioned in front of an API ion sampling orifice and the multiwell plate positioned stepwise from sample to sample for analysis of trace samples contained in the wells . The resulting infusion-ion spray mass spectrometric analyses can provide sequential analysis of previously prepared biological samples containing sm all drug compounds, proteins, and related compounds. This same device is al so shown to be useful for sampling from a surface containing trace level co mpounds of biological interest. Results are shown that demonstrate microsca le separations and selected ion monitoring (SIM) capillary electrophoresis/ mass spectrometry (CE/MS) detection of berberine and palmatine using the mi crosprayer. SIM ion spray determination of a 2 ng/muL solution of berberine contained as a dry residue in the bottom of a 384-well plate as well as fu ll-scan electrospray mass spectra for low-picomole levels of cytochrome c c ontained in a 1536-well microtiter plate are shown. The respective micro- a nd minisprayer devices provide a simple yet effective means of transferring trace-level samples either from a microscale or chip-based separation devi ce as well as samples contained in multiwell plates which are increasingly employed in high-throughput applications in the pharmaceutical industry.