Recent advances in single-cell MALDI mass spectrometry imaging and potential clinical impact

Abstract

Single-cell analysis is gaining popularity in the field of mass spectrometry as a method for analyzing protein and peptide content in cells. The spatial resolution of MALDI mass spectrometry (MS) imaging is by a large extent limited by the laser focal diameter and the displacement of analytes during matrix deposition. Owing to recent advancements in both laser optics and matrix deposition methods, spatial resolution on the order of a single eukaryotic cell is now achievable by MALDI MS imaging. Provided adequate instrument sensitivity, a lateral resolution of ˜10 µm is currently attainable with commercial instruments. As a result of these advances, MALDI MS imaging is poised to become a transformative clinical technology. In this article, the crucial steps needed to obtain single-cell resolution are discussed, as well as potential applications to disease research.

Keywords::

• biomarker
• clinical
• histopathology
• immunohistochemistry
• MALDI MS imaging
• mass spectrometry
• prognosis
• single cell

Acknowledgements

The authors would like to thank members of the Agar laboratory for critical reading and comments on this manuscript. The authors would also like to thank Roman Pavlyuk for initial technical work on the YFP mouse colony. We acknowledge the Brandeis University Animal Care Facility for care of transgenic mice used in this study.

Financial & competing interests disclosure

This work was supported by the Amyotrophic Lateral Sclerosis Association (grant number 1856) (to Jeffrey N Agar), and the Brain Science Foundation and the Daniel E Ponton Fund for the Neurosciences (to Nathalie YR Agar). Matrix solution fixation is the subject of a patent pending with Jeffrey N Agar and Nathalie YR Agar as inventors. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.