Building a Versatile Platform for the Detection of Protein–Protein Interactions Based on Organic Field-Effect Transistors

Detection and characterization of biomolecular interactions, such as protein–protein interactions (PPIs), are critical to a fundamental understanding of biochemical processes, thus being a driver of innovation for drug discovery, clinical diagnostics, and protein engineering. Among the many sensor types used to probe PPIs, organic field-effect transistors are particularly desirable due to their unique features, including tunability, sensitivity, low-power requirements, and multi-parameter readouts. This work describes the development of a biosensor based on organic field-effect transistors, covalently functionalized at the surface with an engineered ubiquitin variant for the specific and sensitive detection of ubiquitin-specific protease 8 (USP8). The resulting sensor was carefully characterized to reveal both electronic and solid-state properties. The sensing platform showed high sensitivity (sub-nanomolar analyte concentrations) and selectivity for USP8 and robust performance that suggests that it may be highly tunable. The sensing system introduced in this work provides a detection method for PPIs, which constitutes a promising platform for advanced biotechnology applications.