Organic field-effect transistors (OFETs) have emerged as powerful platforms for chemical and biological sensing due to their compatibility with flexible substrates, low-cost fabrication, and tunable electronic properties. A key advantage lies in the ability to integrate selective receptors—such as DNA, enzymes, antibodies, or synthetic ligands—directly into the transistor architecture. These receptors enable specific recognition of target analytes, while the OFET transduces the binding event into a measurable electrical signal. The resulting sensors exhibit high sensitivity, rapid response times, and potential for miniaturization, making them suitable for applications ranging from point-of-care diagnostics to environmental surveillance.

The operational principle of OFET-based sensors relies on modulation of the charge transport within the organic semiconductor layer upon interaction with the target molecule. The semiconductor material, often a conjugated polymer or small molecule, forms a thin film between the source and drain electrodes. A gate electrode controls the conductivity of this channel. When a receptor-functionalized OFET encounters the target analyte, several transduction mechanisms come into play. The most common include electrostatic gating, charge transfer, or conformational changes in the semiconductor or receptor layer, all of which alter the drain current or threshold voltage. For instance, glucose oxidase immobilized on the OFET surface catalyzes the oxidation of glucose, producing hydrogen peroxide that dopes the semiconductor and shifts the electrical characteristics. Similarly, DNA probes hybridizing with complementary strands induce dipole moments that perturb charge transport.

Selectivity in OFET sensors is achieved through careful design of the receptor layer. Enzymes like urease or acetylcholine esterase provide specificity for urea and acetylcholine detection, respectively, while aptamers or molecularly imprinted polymers offer synthetic alternatives for targets lacking natural binders. The immobilization strategy—covalent bonding, physical adsorption, or entrapment in a matrix—also influences sensor performance. Covalent attachment ensures stability but may reduce receptor activity, whereas physical adsorption is simpler but prone to leaching. Recent advances exploit bio-orthogonal chemistry or supramolecular host-guest interactions to optimize receptor orientation and accessibility.

In healthcare, OFET sensors demonstrate remarkable potential for continuous, non-invasive monitoring. Glucose sensors based on glucose oxidase-coupled OFETs achieve detection limits below 0.1 mM, covering the physiological range of 4-7 mM in blood. pH-sensitive OFETs utilize proton-responsive organic semiconductors or polyaniline gate dielectrics, providing real-time wound or sweat pH monitoring for infection detection. For neurodegenerative disease biomarkers, OFETs functionalized with antibodies detect amyloid-beta or alpha-synuclein at picomolar concentrations. Another promising direction is electrolyte sensing; OFETs with ion-selective membranes measure potassium, sodium, or calcium levels in saliva or interstitial fluid, enabling wearable kidney function monitors.

Environmental monitoring applications leverage OFETs for detecting gases, heavy metals, or organic pollutants. Ammonia sensors incorporate polyaniline or phthalocyanine semiconductors that undergo conductivity changes upon NH3 binding, with sensitivities reaching sub-ppm levels for air quality assessment. Heavy metal detection employs receptors like glutathione or crown ethers that chelate lead, mercury, or cadmium ions. The resulting charge redistribution in the OFET channel allows quantification at parts-per-billion concentrations, critical for water safety compliance. Pesticide sensors exploit acetylcholinesterase inhibition by organophosphates, where the decrease in enzymatic activity correlates with the pollutant concentration.

The choice of organic semiconductor significantly impacts sensor performance. For gas sensing, materials with high crystallinity and extended pi-conjugation, such as pentacene or C60, enhance charge mobility and response to electron-withdrawing or donating analytes. In aqueous environments, hydrophobic semiconductors like poly(3-hexylthiophene) prevent water-induced doping while allowing analyte diffusion to the receptor layer. Recent work explores donor-acceptor copolymers that amplify signal transduction through intramolecular charge transfer upon analyte binding.

Device architecture further refines sensitivity and specificity. Dual-gate OFETs separate the sensing gate from the control gate, enabling baseline compensation and drift reduction. Floating-gate configurations store analyte-induced charges, permitting time-delayed readout for portable applications. Nanostructured channels—nanowires, porous films, or graphene-organic hybrids—increase the surface-to-volume ratio, improving detection limits. For example, OFETs with porous semiconductor films exhibit 10-fold higher responses to volatile organic compounds due to enhanced adsorption sites.

Challenges remain in achieving long-term stability and reproducibility. Organic semiconductors degrade under prolonged exposure to light, oxygen, or humidity, necessitating encapsulation strategies like atomic layer deposition of alumina. Receptor denaturation over time limits sensor shelf life, prompting investigations into synthetic mimics or stabilization via trehalose coatings. Cross-sensitivity to interferents—such as humidity in gas sensors or ascorbic acid in glucose sensors—requires multivariate data analysis or differential measurement setups.

Future directions focus on integration with emerging technologies. OFETs combined with microfluidics enable lab-on-chip systems for multiplexed biomarker detection. Wireless readout via near-field communication tags facilitates deployment in smart packaging for food spoilage monitoring. Machine learning algorithms analyze complex response patterns from sensor arrays, distinguishing closely related analytes like methane and ethanol. Biodegradable OFETs using natural semiconductors or edible receptors address electronic waste concerns in disposable sensors.

The versatility of OFET-based sensors continues to expand with advances in materials science and fabrication techniques. From implantable glucose monitors to distributed networks for pollution mapping, these devices bridge the gap between high-performance sensing and scalable manufacturing. As receptor engineering and signal processing mature, OFETs will increasingly complement conventional analytical methods, offering real-time, decentralized chemical and biological monitoring.