Single‐Cell Mass Spectrometry

Abstract

Over the past few decades, the chemical characterization of single cells has improved immensely. In particular, mass spectrometry (MS) has pioneered direct analysis of metabolites, lipids, and peptides from single cells. This progress has been enabled by new and improved strategies for ionization and sampling, where a multitude of techniques for single‐cell MS has contributed unique insights to many different disciplines. Here, an overview of the main three techniques secondary ion mass spectrometry (SIMS), matrix‐assisted laser desorption ionization (MALDI), and ambient ionization for direct single‐cell MS analysis are presented, including some example studies detailing the use of single‐cell MS.

Advances in mass spectrometry based single-cell metabolomics

“…Additionally, the matrix needs to form small enough crystals to maintain single-cell resolution. 29 Recent studies using MALDI-MS for single-cell metabolomics can be divided into two categories: (i) MS imaging experiments performed at single-cell resolution, where the whole surface is systematically sampled; and (ii) single-cell profiling experiments, where laser pulses are directed towards cell specific coordinates.…”

“…For readers interested in a more comprehensive view of single-cell MS, including techniques for larger biomolecules and subcellular imaging, there are several recent and nicely written review articles to explore. [6][7][8][9][10][11][12][13] Single-cell metabolomics A single cell can be regarded as the smallest functional biological unit and its chemical activities can provide unique insights into biological processes. Different biological processes continuously occur in single cells as they move, divide, communicate, and respond to their individual chemical microenvironments.…”

Mass spectrometry imaging to explore molecular heterogeneity in cell culture

“…In particular, the combination of chromatography and electrospray ionization (ESI) is a routine tool for deciphering the lipid composition from a pool of cells and occasionally even at the single-cell level ( 19 , 20 ). However, because of the limited sample volumes, single-cell metabolomics/lipidomics remains challenging ( 21 ). A typical eukaryotic cell, for example, contains only 4.2 pL of volume, and even highly abundant lipids such as cholesterol are then present at low-femtomole levels only ( 22 ).…”