Recent advances in dynamic single-molecule analysis platforms for diagnostics: Advantages over bulk assays and miniaturization approaches

Single-molecule science is a unique technique for unraveling molecular biophysical processes. Sensitivity to single molecules provides the capacity for the early diagnosis of low biomarker amounts. Furthermore, the miniaturization of instruments for portable diagnostic tools toward point-of-care testing (POCT) is a crucial development in this field. Herein, we discuss recent developments in single-molecule sensing platforms and their advantages for diagnostics over bulk measurements including molecular size measurements, interaction dynamics, and fast biomarker sensing and sequencing at low concentrations. We highlight the capabilities of dynamic optical and electrical sensing platforms for single-biomolecule and single-vesicle monitoring associated with neurodegenerative disorders, viral diseases, cancers, and more. Current approaches to instrument miniaturization have brought technology closer to portable diagnostics settings via smartphone-based devices, multifunctional portable microscopes, handheld electrical circuit devices, and remote single-molecule assays. Finally, we provide an overview of the clinical applications of single-molecule sensors in POCT assays. Altogether, single-molecule analyses platforms exhibit significant potential for the development of novel portable healthcare devices.