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Detecting Low-Abundance Molecules at Single-Cell Level by Repeated Ion Accumulation in Ion Trap Mass Spectrometer

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Download Hi-Res ImageDownload to MS-PowerPointCite This:Anal. Chem. 2017, 89, 4, 2275-2281
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    Detecting Low-Abundance Molecules at Single-Cell Level by Repeated Ion Accumulation in Ion Trap Mass Spectrometer
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    Beijing Key Laboratory for Microanalytical Methods, Instrumentation, Department of Chemistry, Tsinghua University, Beijing 100084, People’s Republic of China
    *E-mail [email protected] (X.F.).
    *E-mail [email protected] (X.Z.).
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    Analytical Chemistry

    Cite this: Anal. Chem. 2017, 89, 4, 2275–2281
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    https://doi.org/10.1021/acs.analchem.6b03390
    Published January 17, 2017
    Copyright © 2017 American Chemical Society
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    Abstract

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    Low-abundance metabolites or proteins in single-cell samples are usually undetectable by mass spectrometry (MS) due to the limited amount of substances in single cells. This limitation inspired us to further enhance the sensitivity of commercial mass spectrometers. Herein, we developed a technique named repeated ion accumulation by ion trap MS, which is capable of enhancing the sensitivity by selectively and repeatedly accumulating ions in a linear ion trap for up to 25 cycles. The increase in MS sensitivity was positively correlated with the number of repeated cycles. When ions were repeatedly accumulated for 25 cycles, the sensitivity of adenosine triphosphate detection was increased by 22-fold within 1.8 s. Our technique could stably detect low-abundance ions, especially MSn ions, at the single-cell level, such as 5-methylcytosine hydrolyzed from sample equivalent to ∼0.2 MCF7 cell. The strategy presented in this study offers the possibility to aid single-cell analysis by enhancing MS detection sensitivity.

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    Supporting Information

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.analchem.6b03390.

    • Twelve figures showing homemade sample loop, user interface of software, optimization of ion injection time for 5mCyt, relationship between MS intensity and number of cycles for reserpine and 5mCyt, MS2 spectra of 5mCyt for high-concentration standard solution, MS and MS2 spectra of angiotensin II, MS, MS2, and MS3 spectra of caffeine, MS and MS2 spectra of malic acid and ATP, EIC curves of low-concentration ATP and of adenine and 5mCyt; four tables listing optimized ion injection time, NCE, and activation Q of different ions and components and detected scans of low-concentration caffeine and ATP (PDF)

    • Available software used for modifying the MS scan function and corresponding step-by-step user instructions (ZIP)

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    Cited By

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    This article is cited by 16 publications.

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    Analytical Chemistry

    Cite this: Anal. Chem. 2017, 89, 4, 2275–2281
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.analchem.6b03390
    Published January 17, 2017
    Copyright © 2017 American Chemical Society
    Request reuse permissions

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