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High-Resolution Live-Cell Imaging and Analysis by Laser Desorption/Ionization Droplet Delivery Mass Spectrometry
Stanford Univ, Dept Chem, 333 Campus Dr, Stanford, CA 94305 USA..
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Stanford Univ, Dept Chem, 333 Campus Dr, Stanford, CA 94305 USA..
Inst Basic Sci, Ctr Plant Aging Res, Daegu 42988, South Korea.;DGIST, Dept New Biol, Daegu 42988, South Korea..
Stanford Univ, Dept Chem, 333 Campus Dr, Stanford, CA 94305 USA..
2016 (English)In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 88, no 10, 5453-5461 p.Article in journal (Refereed) PublishedText
Abstract [en]

We have developed a new ambient-ionization mass spectrometric technique named laser desorption/ionization droplet delivery mass spectrometry (LDIDD-MS). LDIDD-MS permits high-resolution, high-sensitivity imaging of tissue samples as well as measurements of both single-cell apoptosis and live-cell exocytosis. A pulsed Hz) UV laser beam (266 nm) is focused on a surface covered with target analytes to trigger their desorption and ionization. A spray of liquid droplets is simultaneously directed onto the laser-focused surface region to capture the ionized analytes and deliver them to a mass spectrometer. The approach of rapid and effective capturing of molecules after laser desorption/ionization allows the limit of detection for the amino acid lysine to be as low as 2 amol under ambient ionization conditions. Two-dimensional maps of the desorbed/ionized species are recorded by moving the sample on an XY translational stage. The spatial resolution for imaging with LDIDD-MS was determined to be 2.4 mu m far an ink-printed pattern and 3 mu m for mouse brain tissue. We applied LDIDD-MS to single-cell analysis of apoptotic HEK cells. Differences were observed in the profiles of fatty acids and lipids between healthy HEK cells and those undergoing apoptosis. We observed upregulation of phosphatidylcholine (PC) with a relatively shorter carbon chain length and downregulation of PC with a relatively longer carbon chain length. We also applied LDIDD-MS for a real-time direct measurements of live-cell exocytosis. The catecholamine dopamine and trace amines (phenethylamine and tyramine) were detected from live PC12 cells without damaging them.

Place, publisher, year, edition, pages
2016. Vol. 88, no 10, 5453-5461 p.
National Category
Analytical Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-298091DOI: 10.1021/acs.analchem.6b00881ISI: 000376223500059PubMedID: 27110027OAI: oai:DiVA.org:uu-298091DiVA: diva2:944477
Funder
Swedish Research Council, 2015-00406
Available from: 2016-06-29 Created: 2016-06-29 Last updated: 2016-06-29Bibliographically approved

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