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Impact energy measurement in time-of-flight mass spectrometry with cryogenic microcalorimeters

Nature volume 391, pages 672–675 (1998)Cite this article

Abstract

Time-of-flight mass spectrometry—most notably matrix-assisted laser-desorption-ionization time-of-flight (MALDI-TOF) spectrometry1—is an important class of techniques for the study of proteins and other biomolecules2. Although these techniques provide excellent performance for masses up to about 20,000 daltons, there has been limited success in achieving good mass resolution at higher masses. This is because the sensitivity of the microchannel plate (MCP) detectors used in most systems decreases rapidly with increasing particle mass, limiting the utility of MCP detectors for very large masses. It has recently been proposed that cryogenic particle detectors may provide a solution to these difficulties3. Cryogenic detectors measure the thermal energy deposited by the particle impact, and thus have a sensitivity that is largely independent of particle mass. Recent experiments4,5,6 have demonstrated the sensitivity of cryogenic particle detectors to single biomolecules, a quantum efficiency several orders of magnitude larger than the MCP detectors, and sensitivity to masses as large as 750,000 daltons. Here we present results demonstrating an order of magnitude better energy resolution than previous measurements, allowing direct determination of particle charge state during acceleration7. Although application of these detectors to practical mass spectrometry will require further development of the detectors and cryogenics, these detectors can be used to elucidate the performance-limiting processes that occur in such systems.

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Figure 1: Details of experimental apparatus.
Figure 2: Experimental data obtained for the protein BSA.
Figure 3: Plot of the ratio of impact energy to kinetic energy versus kinetic energy for each ion type.
Figure 4: Time-of-flight spectrum for BSA with an acceleration voltage of 20 kV.
Figure 5: Experimental data showing additional scattering and changes in impact energy resolution due to gas phase scattering.

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Authors and Affiliations

  1. National Institute of Standards and Technology, Boulder, 80303, Colorado, USA

    G. C. Hilton, John M. Martinis, D. A. Wollman, K. D. Irwin & L. L. Dulcie

  2. Institut de Physique de l'Université Rue A.-L. Breguet 1, CH-2000 Neuchâtel, Switzerland, and GenSpec SA, case postale 120, Boudry, CH-2017, Switzerland

    Daniel Gerber & Damian Twerenbold

  3. Institute of Bioscience, Bioinformatics, and Biotechnology, George Mason University, Manassas, 22210, Virginia, USA

    Patrick M. Gillevet

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  1. G. C. Hilton
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  2. John M. Martinis
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  8. Damian Twerenbold
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Correspondence to G. C. Hilton.

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Hilton, G., Martinis, J., Wollman, D. et al. Impact energy measurement in time-of-flight mass spectrometry with cryogenic microcalorimeters. Nature 391, 672–675 (1998). https://doi.org/10.1038/35582

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