Structure-switching biosensors: inspired by Nature

Chemosensing in nature relies on biomolecular switches, biomolecules that undergo binding-induced changes in conformation or oligomerization to transduce chemical information into specific biochemical outputs. Motivated by the impressive performance of these natural ‘biosensors,’ which support continuous, real-time detection in highly complex environments, significant efforts have gone into the adaptation of such switches into artificial chemical sensors. Ongoing advances in the fields of protein and nucleic acid engineering (e.g. computational protein design, directed evolution, selection strategies and labeling chemistries) have greatly enhanced our ability to design new structure-switching sensors. Coupled with the development of advanced optical readout mechanisms, including genetically encoded fluorophores, and electrochemical readouts supporting detection directly in highly complex sample matrices, switch-based sensors have already seen deployment in applications ranging from real time, in vivo imaging to the continuous monitoring of drugs in blood serum.