Selective Chemical Reactivity of Non‐Fullerene Acceptor for Photoelectrochemical Bioassay of Urease Activity

Abstract Non‐fullerene acceptors (NFAs) are a crucial component of organic photovoltaics, and they have gained significant attention due to their outstanding photoelectric conversion efficiency. However, the recognition reactions of specific building blocks in NFAs are largely overlooked in the construction of photoelectrochemical (PEC) biosensing platforms. In this study, the potential of Y6, a prototype NFA, is explored to construct a sensitive PEC biosensor for monitoring urease activity due to the selective chemical reactivity of its organic building blocks. The resultant biosensor relies on the urease‐mediated enzymatic reaction, which produces OH⁻ anions that act as a nucleophilic reagent for the linkage of C═C in the Y6 moiety. This results in the formation of Y6‐OH, which exhibits a depressive photoelectric response due to the destroyed conjugated structure and intramolecular charge transfer. As expected, a linear relationship is observed between the recession of photoelectric performance and the concentration of urease, with good sensitivity and selectivity. Furthermore, urease activity detection is also successfully realized in human saliva samples, suggesting the promising potential of NFA‐based PEC biosensors for clinical applications even in the absence of common biological recognition units.