Anal. Chem. 1999, 71, 3627-3631
Accelerated Articles
Subattomole-Sensitivity Microchip Nanoelectrospray Source with Time-of-Flight Mass Spectrometry Detection Iulia M. Lazar,† Roswitha S. Ramsey,† Steven Sundberg,‡ and J. Michael Ramsey*,†
Chemical and Analytical Sciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831-6365, and Caliper Technologies Corporation, Mountain View, California 94043-2234
A microfabricated microfluidic device coupled with a nanospray tip for electrospray ionization of dilute solutions is described. The device has been interfaced with a time-of-flight mass spectrometer and evaluated for sensitive, high-speed detection of peptides and proteins. The electrospray voltage was applied through the microchip to the nanospray capillary that was attached at the end of a microfabricated channel. Fluid delivery rates were 2030 nL min-1 through the hybridized structure without any pressure assistance. On-line microchip electrophoresis has been demonstrated and the effect of the capillarychip junction on band broadening examined. Full mass spectra are acquired within 10-20 ms at 50-100 spectra s-1 storage rates. Detection of subattomole levels of sample from a 100 nM solution is demonstrated for infusion experiments.
The introduction (1994) and development of the nanoelectrospray ionization (nano-ESI) source1-7 has enabled high-sensitivity * To whom correspondence should be addressed (phone) (423) 574-5662; (fax) (423) 574-8363. † Oak Ridge National Laboratory. ‡ Caliper Technologies Corp. (1) Wilm, M. S.; Mann, M. Int. J. Mass Spectrom. Ion Processes 1994, 136, 167-180. (2) Andren, P. E.; Emmett, M. A.; Caprioli, R. M. J. Am. Soc. Mass Spectrom. 1994, 5, 867-869. (3) Valaskovic, G. A.; Kelleher, N. L.; Little, D. P.; Aaserud, D. J.; McLafferty, F. W. Anal. Chem. 1995, 67, 3802-3805. (4) Wilm, M. S.; Mann, M. Anal. Chem. 1996, 68, 1-8. (5) Valaskovic, G. A.; McLafferty, F. W. J. Am. Soc. Mass Spectrom. 1996, 7, 1270-1272. (6) Hannis, J. C.; Muddiman, D. C. Rapid Commun. Mass Spectrom. 1998, 12, 443-448. (7) Geromanos, S.; Philip, J.; Freckleton, G.; Tempst, P. Rapid Commun. Mass Spectrom. 1998, 12, 551-556. 10.1021/ac990373m CCC: $18.00 Published on Web 07/24/1999
© 1999 American Chemical Society
mass spectrometry (MS) analysis on extremely limited sample volumes (
