Graphene Nanosensor for the Detection of Small Organic Compounds Using an Insect Olfactory Receptor

Insect olfactory receptors have evolved to detect a wide range of chemicals and biomolecules, offering a promising foundation for next-generation chemical sensors. We report the first direct integration of the odorant receptor MhOR5 from Machilis hrabei onto a graphene field-effect transistor (gFET) for selective, label-free detection of small organic compounds (SOCs). Large scale production of MhOR5 was achieved for the first time, yielding a stable tetrameric protein (80% purity) with up to 3-month stability. High-quality gFETs were fabricated at the wafer scale and quality controlled before utilization, demonstrating highly reproducible chips. The MhOR5-functionalized gFETs were tested against sixteen chemically diverse SOCs, including eugenol, DEET, hexanol, and octanol, across a concentration range of 200 nm to 10 mm. Each analyte induced a concentration-dependent response in the sensor. Binding analysis within the tested SOCs revealed the strongest affinity for acetophenone (logK_D = 0.28), and the weakest for sulcatone (logK_D = 4.4). Notably, the sensor distinguished eugenol from its structural isomer, isoeugenol, an achievement difficult to detect using conventional sensors. This work establishes a modular biosensing platform that couples the molecular selectivity of insect olfactory receptors with the exceptional sensitivity of graphene-based sensors. The MhOR5-gFET biosensor demonstrates significant potential for applications in biotechnology, diagnostics, and biosurveillance.