Nanoelectrospray infusion

Tandem mass spectrometric methods have demonstrated superb specificity because of their ability to isolate analytes selectively in the presence of endogenous interferences. Attempts to further increase sample throughput led to the idea of using LC/MS/MS without the LC. Traditional chromatographic separations were replaced with flow injection analysis (FLA) or nanoelectrospray infusion techniques. The MS-based columnless methods attracted a lot of attention because of their inherent fast cycle times and no need for LC method development. 

Dethy, J. M., Ackermann, B. L., Delatour, C., Henion, J. D., and Schultz, G. A. (2003a). Demonstration of direct bioanalysis of drugs in plasma using nanoelectrospray infusion from a silicon chip coupled with tandem mass spectrometry. Anal. Chem. 75 805-811. 

Dethy, J.M. Ackermann, B.L. Delatour, C. Henion, J.D. Schultz, G.A. "Demonstration of Direct Bioanalysis of Drugs in Plasma Using Nanoelectrospray Infusion from a Silicon Chip Coupled with Tandem Mass Spectrometry, Anal. Chem. 75, 805-811 (2003). 

Figure 3.6 Pipette tip aligned and sealed around the inlet to a nozzle of the ESI Chip using the NanoMate system that automates nanoelectrospray infusion. Spray voltage and backing pressure are optimized based on the solution solvent composition to obtain a stable spray. The NanoMate system loads a new sample into a new pipette tip and automatically positions it to a new nozzle. The chip is automatically moved to the optimized spray position.

Very low flow electrospray is called nanoelectrospray [26] where the samples are infused into the mass spectrometer at the nanoliter flow rate range. The infusion of a few microliters will result in a stable signal for more then 30 min, using pulled capillaries or chip-based emitters [27]. With infusion, signal averaging allows to improve the limit of detection in tandem mass spectrometry. Nanoelectrospray is particularly important in combination with nanoflow liquid chromatography or chip-based infusion for the analysis of peptides and proteins. 

Erve, J. C. L., DeMaio, W., and Talaat, R. E. (2008). Rapid metabolite identification with sub parts-per million mass accuracy from biological matrices by direct infusion nanoelectrospray ionization after clean-up on a ZipTip and LTQ/Orbitrap mass spectrometry. Rapid... 

Ackermann, B. L., and Dethy, J. M. (2005). Understanding the role and potential of infusion nanoelectrospray ionization for pharmaceutical hioanalysis. In Using Mass Spectrometry for Drug Metabolism Studies (Korfmacher, W. A., Ed.). CRC Press, Boca Raton, pp. 329-356. 

Kapron, J. T., Pace, E., Van Pelt, C. K., and Henion, J. (2003). Quantitation of midazolam in human plasma by automated chip-based infusion nanoelectrospray tandem mass spectrometry. Rapid Common. Mass Spectrom. 17 2019-2026. 

Extensions of the ESI interface led to miniaturized formats, microelectrospray (Emmett and Caprioli, 1994) and nanoelectrospray (Wilm and Mann, 1996), applied specifically for peptide mapping. Microelectrospray was developed for use with capillary chromatography formats or direct infusion at flow rates 200-700nL/min. Nanoelectrospray formats are operated at 20-70nL/min and the flow is caused solely by the ESI voltage. 

The group of Mann [2-3] pioneered in nanoelectrospray (nano-ESI), enabling the identification of proteins separated by two-dimensional gel electrophoresis (2D-GE), digested with trypsin, and infused by nano-ESI-MS-MS. 

A Unal example of direct bioanalysis was recently published by Dethy et al. and involves the appUcation of infusion nanoelectrospray (nano-ESI) from a silicon chip [110]. In this example, supernatant obtained from protein precipitation was directly infused with an automated pipette-tip delivery system. Individual, conductive pipette tips that contain sample were sequentially introduced to the backplane of a silicon chip for analysis. The front plane of the chip that consisted of 100 individual nano-ESI nozzles, was positioned near the API orifice of a TQMS for direct serial analysis. Quantitation of verapamil and its metaboUte norverapamil occurred in human plasma over a range of 5-1000 ng/mL. It is possible to achieve analysis times of less than 1 minute per sample with this technology. An important advantage, demonstrated by this work, is the unique abiUty to avoid system carryover with this device [110]. 

Kapron, J.T. Pace, E. Van Pelt, C.K. Henion, J. Quantitation of Midazolam in Human Plasma by Automated Chip-Based Infusion Nanoelectrospray... 

Southam, A.D. Payne, T.G. Cooper, H.J. Arvanitis, T.N. Viant, M.R. Dynamic range and mass accuracy of wide-scan direct infusion nanoelectrospray FT-ICR mass spectrometry-based metabolomics increased by the spectral stitching method. Anal. Chem. 2007, 79,4595-4602. 

Zhang, S. Chblius, D. Characterization of protein glycosylation using chip-based infusion nanoelectrospray linear ion trap. J. Biomol. Techniques 2004, 15, 120-133. 

---