A matrix-assisted laser desorption/ionization time of flight/time of flight tandem mass spectrometer (MALDI TOF/TOF) has been used for high-speed precursor/fragment ion transition image acquisition. High-throughput analysis is facilitated by an Nd: YLF solid state laser capable of pulse repetition rates up to 5 kHz, a high digitizer acquisition rate (up to 50pixels/s), and continuous laser raster sampling. MS/MS experiments are enabled through the use of a precision timed ion selector, second source acceleration, and a dedicated collision cell. Continuous raster sampling is shown here to facilitate rapid MS/MS ion image acquisition from thin tissue sections for the drug rifampicin and for a common kidney lipid, SM4s(d18:1/24:1). The ability to confirm the structural identity of an analyte as part of the MS/MS imaging experiment is an essential part of the analysis. Additionally, the increase in sensitivity and specificity afforded by an MS/MS approach is highly advantageous, especially when interrogating complex chemical environments such as those in biological tissues. Herein, we report continuous laser raster sampling TOF/TOF imaging methodologies which demonstrate 8 to 14-fold increases in throughput compared with existing MS/MS instrumentation, an important advantage when imaging large areas on tissues. Copyright (C) 2015 John Wiley & Sons, Ltd.
机构:
Leiden Univ, Med Ctr, Dept Parasitol, Biomol Mass Spectrometry Unit, NL-2333 ZA Leiden, NetherlandsLeiden Univ, Med Ctr, Dept Parasitol, Biomol Mass Spectrometry Unit, NL-2333 ZA Leiden, Netherlands
McDonnell, Liam A.
van Remoortere, Alexandra
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Leiden Univ, Med Ctr, Dept Parasitol, Biomol Mass Spectrometry Unit, NL-2333 ZA Leiden, NetherlandsLeiden Univ, Med Ctr, Dept Parasitol, Biomol Mass Spectrometry Unit, NL-2333 ZA Leiden, Netherlands
van Remoortere, Alexandra
van Zeijl, Rene J. M.
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Leiden Univ, Med Ctr, Dept Parasitol, Biomol Mass Spectrometry Unit, NL-2333 ZA Leiden, NetherlandsLeiden Univ, Med Ctr, Dept Parasitol, Biomol Mass Spectrometry Unit, NL-2333 ZA Leiden, Netherlands
van Zeijl, Rene J. M.
Dalebout, Hans
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Leiden Univ, Med Ctr, Dept Parasitol, Biomol Mass Spectrometry Unit, NL-2333 ZA Leiden, NetherlandsLeiden Univ, Med Ctr, Dept Parasitol, Biomol Mass Spectrometry Unit, NL-2333 ZA Leiden, Netherlands
Dalebout, Hans
Bladergroen, Marco R.
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Leiden Univ, Med Ctr, Dept Parasitol, Biomol Mass Spectrometry Unit, NL-2333 ZA Leiden, NetherlandsLeiden Univ, Med Ctr, Dept Parasitol, Biomol Mass Spectrometry Unit, NL-2333 ZA Leiden, Netherlands
Bladergroen, Marco R.
Deelder, Andre M.
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Leiden Univ, Med Ctr, Dept Parasitol, Biomol Mass Spectrometry Unit, NL-2333 ZA Leiden, NetherlandsLeiden Univ, Med Ctr, Dept Parasitol, Biomol Mass Spectrometry Unit, NL-2333 ZA Leiden, Netherlands
机构:
Vanderbilt Univ, Med Ctr, Mass Spectrometry Res Ctr, Nashville, TN 37235 USA
Vanderbilt Univ, Med Ctr, Dept Biochem Chem Pharmacol & Med, Nashville, TN USAVanderbilt Univ, Med Ctr, Mass Spectrometry Res Ctr, Nashville, TN 37235 USA
Spraggins, Jeffrey M.
Caprioli, Richard M.
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Vanderbilt Univ, Med Ctr, Mass Spectrometry Res Ctr, Nashville, TN 37235 USA
Vanderbilt Univ, Med Ctr, Dept Biochem Chem Pharmacol & Med, Nashville, TN USA
Vanderbilt Univ, Sch Med, Nashville, TN 37232 USAVanderbilt Univ, Med Ctr, Mass Spectrometry Res Ctr, Nashville, TN 37235 USA
机构:
Genentech Inc, Dept Drug Metab & Pharmacokinet, San Francisco, CA 94080 USAGenentech Inc, Dept Drug Metab & Pharmacokinet, San Francisco, CA 94080 USA
Jones, E. Ellen
Zhang, Wujuan
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Cincinnati Childrens Hosp Med Ctr, Div Pathol & Lab Med, Cincinnati, OH 45229 USAGenentech Inc, Dept Drug Metab & Pharmacokinet, San Francisco, CA 94080 USA
Zhang, Wujuan
Zhao, Xueheng
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Cincinnati Childrens Hosp Med Ctr, Div Pathol & Lab Med, Cincinnati, OH 45229 USAGenentech Inc, Dept Drug Metab & Pharmacokinet, San Francisco, CA 94080 USA
Zhao, Xueheng
Quiason, Cristine
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Genentech Inc, Dept Drug Metab & Pharmacokinet, San Francisco, CA 94080 USAGenentech Inc, Dept Drug Metab & Pharmacokinet, San Francisco, CA 94080 USA
Quiason, Cristine
Dale, Stephanie
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Genentech Inc, Dept Drug Metab & Pharmacokinet, San Francisco, CA 94080 USAGenentech Inc, Dept Drug Metab & Pharmacokinet, San Francisco, CA 94080 USA
Dale, Stephanie
Shahidi-Latham, Sheerin
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Genentech Inc, Dept Drug Metab & Pharmacokinet, San Francisco, CA 94080 USAGenentech Inc, Dept Drug Metab & Pharmacokinet, San Francisco, CA 94080 USA
Shahidi-Latham, Sheerin
Grabowski, Gregory A.
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Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Med Ctr, Div Human Genet, Cincinnati, OH USA
Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USAGenentech Inc, Dept Drug Metab & Pharmacokinet, San Francisco, CA 94080 USA
Grabowski, Gregory A.
Setchell, Kenneth D. R.
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Cincinnati Childrens Hosp Med Ctr, Div Pathol & Lab Med, Cincinnati, OH 45229 USAGenentech Inc, Dept Drug Metab & Pharmacokinet, San Francisco, CA 94080 USA
Setchell, Kenneth D. R.
Drake, Richard R.
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Med Univ South Carolina, Dept Cell & Mol Pharmacol, Charleston, SC 29425 USA
Med Univ South Carolina, Prote Ctr, Charleston, SC 29425 USAGenentech Inc, Dept Drug Metab & Pharmacokinet, San Francisco, CA 94080 USA
Drake, Richard R.
Sun, Ying
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Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Med Ctr, Div Human Genet, Cincinnati, OH USA
Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USAGenentech Inc, Dept Drug Metab & Pharmacokinet, San Francisco, CA 94080 USA