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

Abstract

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.

Asymmetric side-chain engineering in semiconducting polymers: a platform for greener processing and post-functionalization of organic electronics

“…Moreover, a-P(iIT)-OH, due to its asymmetric design, can maintain a good solubility in common organic solvent without sacrificing regioregularity, which is not always possible in more traditional symmetric designs. This novel post-functionalization technique has a lot of potential for designing sensing materials and devices specific analytes and/or receptor-ligand interactions, particularly for biosensing applications, [51][52][53][54] including but not limited to the detection and determination of DNA concentrations, and printable immunosensors for point-of-care biosensor applications. 55,56 To evaluate the new asymmetric design for facile solid-state post-functionalization, a-P(iIT)-OH was reacted with fluorescein isocyanate (FITC) to afford the functionalized a-P(iIT)-O-C(S)-NH-Fluo (Fig.…”

Review of recent advances and sensing mechanisms in solid-state organic thin-film transistor (OTFT) sensors

“…3C). 72 Devices with covalently-bound bait protein continued to demonstrate field-effect behaviour and I SD increased proportionally to increasing concentration of prey protein binding to the device. The LOD of the device was 0.22 nM (0.01 μg mL −1 ) and demonstrated a novel and robust sensing platform for the detection of protein–protein interactions.…”

Healthcare Monitoring Sensors Based on Organic Transistors: Surface/Interface Strategy and Performance

“…Functionalizing the surface of the gate electrode presents another convenient approach, primarily thanks to the extensive research conducted on metal modifications in the electrochemical field, as well as surface self-assembly techniques on metal surfaces like the widely used thiol-gold chemistry. [203,207,[209][210][211][223][224][225][226][227][228][229][230] Regarding the case of the con-OFETs or ion-gel gated OFETs, an extend gate structured was commonly employed to separate the sensing area from the transistor's operation region. The functionalization was processed on the extended gate region where the analyte solution was located.…”