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Imaging mass spectrometry increased resolution using 2-mercaptobenzothiazole and 2,5-diaminonaphtalene matrices: application to lipid distribution in human colon

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Abstract

Imaging mass spectrometry is becoming a reference technique in the field of lipidomics, due to its ability to map the distribution of hundreds of species in a single run, along a tissue section. The next frontier is now achieving increasing resolution powers to offer cellular (or even sub-cellular) resolution. Thus, the new spectrometers are equipped with sophisticated optical systems to decrease the laser spot to <30 μm. Here, we demonstrate that by using the correct matrix (i.e., a matrix that maximizes ion detection and forms small crystals) and a careful preparation, it is possible to achieve resolutions of ∼5–10 μm, even with spectrometers equipped with non-optimal optics, which produces laser spots of 50 μm or even larger. As a proof of concept, we present images of distributions of lipids, both in positive and negative ion mode, over human colon endoscopic sections, recorded using 2-mercaptobenzothiazole for positive ion mode and 2,5-diaminonaphtalene for negative ion mode and an LTQ-Orbitrap XL, equipped with a matrix-assisted laser desorption ionization (MALDI) source that produces astigmatic laser spots.

Imaging mass spectrometry is becoming an invaluable technique to complement traditional histology, but still higher resolutions are required. Here we deal with such issue

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Abbreviations

Cer:

Ceramide

Cer-PE:

Ceramide phosphatidylethanolamine

DAG:

Diacylglycerol

DAG-O:

Diacylglycerol ether

DAN:

2,5-diaminonaphtalene

MBT:

2-mercaptobenzothiazole

PA:

Glycerophosphatidic acid

PC:

Glycerophophatidylcholine

PE:

Glycerophosphatidyl ethanolamine

PI:

Glycerophosphatidylinositol

PS:

Glycerophosphatidylserine

S/N:

Signal-to-noise ratio

SFT:

Sulfatide

SM:

Sphingomyelin

TAG:

Triacylglycerol

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Acknowledgments

We are greatly thankful to the nurses and medical doctors of the Gastroenterology Unit of the Hospital Universitari de Son Espases (Palma, Spain) and of the Hospital Comarcal de Inca (Inca, Spain) for their participation during patient’s enrolment and sample acquisition. This study was partially supported by the Institute of Health Carlos III (Ministerio de Economía y Competitividad) and the EC (European Regional Development Fund, ERDF) (CP12/03338), by UPV/EHU (UFI 11/23), and by the Basque Government (SAIOTEK, consolidated groups). GBC and RRM’s contract were supported by the Miguel Servet program of the Institute of Health Carlos III. Technical and human support provided by the Servicio de Lipidómica of the SGIKER (UPV/EHU, MICINN, GV/EJ, ESF) is gratefully acknowledged.

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Correspondence to Gwendolyn Barceló-Coblijn or José A. Fernández.

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Garate, J., Fernández, R., Lage, S. et al. Imaging mass spectrometry increased resolution using 2-mercaptobenzothiazole and 2,5-diaminonaphtalene matrices: application to lipid distribution in human colon. Anal Bioanal Chem 407, 4697–4708 (2015). https://doi.org/10.1007/s00216-015-8673-7

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