Imaging of Protein Distribution in Tissues Using Mass Spectrometry: An Interdisciplinary Challenge

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Authors

Jiaying Han1,2, Hjalmar Permentier1, Rainer Bischoff1, Geny Groothuis2, Angela Casini2,3, and Péter Horvatovich1

Organizations

  1. Analytical Biochemistry, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, the Netherlands
  2. Pharmacokinetics, Toxicology and Targeting, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, the Netherlands
  3. School of Chemistry, Cardiff University, Main Building, Park Place, CF10 3AT Cardiff, United Kingdom

Abstract

The recent development of mass spectrometry imaging (MSI) technology allowed to obtain extremely detailed images of the spatial distribution of proteins in tissue at high spatial resolution reaching cell dimensions, high target specificity and a large dynamic concentration range. This review focusses on the development of two main MSI principles, namely targeted and untargeted detection of protein distribution in tissue samples, with special emphasis on the improvements in analyzed mass range and spatial resolution over the last 10 years. Untargeted MSI of in situ digested proteins with matrix-assisted laser desorption ionization is the most widely used approach, but targeted protein MSI technologies using laser ablation inductively coupled plasma (LA-ICP) and photocleavable mass tag chemical labeling strategies are gaining momentum. Moreover, this review also provides an overview of the effect of sample preparation on image quality and the bioinformatic challenge to identify proteins and quantify their distribution in complex MSI data.

CovalX Technology Used

HM4

Discussion

This article makes reference to publications involving CovalX technologies and discusses typical mass spectrometers which are unable to analyze large proteins. However, with the use of a system such as the CovalX HM1 TOF detector, intact proteins up to 70 kDa can be analyzed with improved sensitivity on a MALDI MSI. The HM1 is discussed as being less prone to detector saturation and having a much larger charge capacity in comparison to other commercially available detectors.

Source

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Categories : Publications, HM5