Advances in nano/microscale electrochemical sensors and biosensors for analysis of single vesicles, a key nanoscale organelle in cellular communication

The study of subcellular targets and biochemical processes within a living cell is valuable for biological and medical research. Secretory vesicles, one such important intracellular target, are nanoscale lipid structures that are capable of storage, transport, and secretion of, for example, neurotransmitters, hormones, proteins or waste products. Vesicles play an essential role in intercellular communication systems, as they facilitate the release of chemical messaging agents. If deregulated, these communication processes can be a central part in the pathogenesis of some neurodegenerative diseases or diabetes. Generally, due to their nanometer size and intracellular location, the analysis of single vesicles and their content is a great challenge. It requires sensitive techniques, micro/nanoscale tools and sensitive instruments with extreme spatio-temporal resolution. This review focuses on electrochemical sensors to study the biochemistry and quantification of messenger molecules and other species (e.g., reactive oxygen and nitrogen species) stored in organelles, providing new trends and developments in this field. Furthermore, we review the effect of the chemical environment of single cells (e.g., treatment with chemicals, drugs, lipids, and ions) on regulation of the physical and chemical properties of vesicles. Finally, unsolved challenges of and perspectives on vesicle electroanalysis are discussed. •Nano/micro sensors to measure the contents of organelles are reviewed.•Vesicle chemistry measured both ex situ and in situ in living cells.•Vesicle storage, transport, and secretion of (non) redox-active chemical messengers.•Vesicle cargo in neurodegenerative diseases, and diabetes.•Effects of the chemical environment on the properties of single vesicles.