Preserving single cells in space and time for analytical assays

Analytical assays performed within clinical laboratories influence roughly 70% of all medical decisions by facilitating disease detection, diagnosis, and management. Both in clinical and academic research laboratories, single-cell assays permit measurement of cell diversity and identification of rare cells, both of which are important in the understanding of disease pathogenesis. For clinical utility, the single-cell assays must be compatible with the clinical workflow steps of sample collection, sample transportation, pre-analysis processing, and single-cell assay; therefore, it is paramount to preserve cells in a state that resembles that in vivo rather than measuring signaling behaviors initiated in response to stressors such as sample collection and processing. To address these challenges, novel cell fixation (and more broadly, cell preservation) techniques incorporate programmable fixation times, reversible bond formation and cleavage, chemoselective reactions, and improved analyte recovery. These technologies will further the development of individualized, precision therapies for patients to yield improved clinical outcomes. •Single-cell analyses will be an important addition to the suite of technologies used for personalized medicine.•Living cells can individually alter their physiology in response to subtle changes in the microenvironment.•Analytes within cells must reflect that of the living state for accurate single-cell assays.•Current cell preservation strategies yield accurate readouts for many single-cell assays but are inadequate for others.•Novel sample preparation strategies will enable improved understanding of the role of single cells in patient disease.