Single‐Cell Mass Spectrometry Approaches to Explore Cellular Heterogeneity

Abstract

Compositional diversity is a fundamental property in cell populations. Single-cell analysis promises new insight into this cellular heterogeneity on the genomic, transcriptomic, proteomic, and metabolomic levels. Mass spectrometry (MS) is a label-free technique that enables the multiplexed analysis of proteins, peptides, lipids, and metabolites in individual cells. The abundances of these molecular classes are correlated with the physiological states and environmental responses of the cells. In this Minireview, we discuss recent advances in single-cell MS techniques with an emphasis on sampling and ionization methods developed for volume-limited samples. Strategies for sample treatment, separation methods, and data analysis require special considerations for single cells. Ongoing analytical challenges include subcellular heterogeneity, non-normal statistical distributions of cellular properties, and the need for high-throughput, high molecular coverage and minimal perturbation.

Guiding Drugs to Target‐Harboring Organelles: Stretching Drug‐Delivery to a Higher Level of Resolution

“…[16,17] While constantly improving,resolution remains the main limitation in the application of MS for determination of am olecules subcellular distribution. [20] Al eap forward in the resolution of mass spectrometry was very recently made by the Nolan group who determined the subcellular localization of the chemotherapy drug cisplatin at alateral resolution of approximately 30 nm by applying superresolution ion-beam imaging. [18,19] This level of resolution is sufficient to map the subcellular distribution of ac ompound in mammalian cells that have an average diameter of 10-100 mm.…”

Intracellular Electrochemical Sensing

“…However, most microfluidic approaches do not provide the spatiotemporal information on the intracellular contents because the collection methods are based on complete cell lysis. To study the dynamics of intracellular transportation or localization of cytoplasmic content , techniques for extracting subcellular cytoplasm are needed. In this section, we focused on recent electrical techniques of collecting subcellular cytoplasm (Figure ).…”

“…or localization of cytoplasmic content [12][13][14][15][16][17][18], techniques for extracting subcellular cytoplasm are needed. In this section, we focused on recent electrical techniques of collecting subcellular cytoplasm (Figure 1).…”

Erforschung der fundamentalen Strukturen des Lebens: Nicht zielgerichtete chemische Analyse von Einzelzellen und subzellulären Strukturen

“…B. der Neurometabolomik. [8,14] biologische Systeme mit beispielloser Auflçsung bietet, schließen wir unsere Ausführungen mit Perspektiven der nicht zielgerichteten SCMP und ihren Anwendungen in der biologischen Forschung ab.…”