Label-free single-molecule detection has been achieved so far by funnelling a large number of ligands into a sequence of single-binding events with few recognition elements host on nanometric transducers. Such approaches are inherently unable to sense a cue in a bulk milieu. Conceptualizing cells’ ability to sense at the physical limit by means of highly-packed recognition elements, a millimetric sized field-effect-transistor is used to detect a single molecule. To this end, the gate is bio-functionalized with a self-assembled-monolayer of 1012 capturing anti-Immunoglobulin-G and is endowed with a hydrogen-bonding network enabling cooperative interactions. The selective and label-free single molecule IgG detection is strikingly demonstrated in diluted saliva while 15 IgGs are assayed in whole serum. The suggested sensing mechanism, triggered by the affinity binding event, involves a work-function change that is assumed to propagate in the gating-field through the electrostatic hydrogen-bonding network. The proposed immunoassay platform is general and can revolutionize the current approach to protein detection.

The detection of protein biomarkers is of great importance in the early diagnosis of severe pathological states. Although in the last decade many approaches to achieve ultra-sensitive protein detection have been developed, most of them require complicated assay set-ups, hindering their adoption in point-of-care applications and on-spot diagnosis. Here we show an organic electrochemical transistor (OECT) biosensor printed on plastic substrates that can selectively detect Immunoglobulin G (IgG) with unprecedented attomolar detection limit. The OECT is used as a transducer of the biorecognition event taking place at the gate electrode. The measured concentrations are well below the detectable limits of the leading clinical diagnostic ELISA assay, and comparable to the ones gathered with the label-needing single molecule arrays (SiMoA) platform. Our work benchmarks the role of plastic OECT-based biosensors as a powerful tool in simple, low-cost, yet non-invasive, ultra-sensitive, and widely applicable immunoassay technology.

Ions dissolved in aqueous media play a fundamental role in plants, animals, and humans. Therefore, the in situ quantification of the ion concentration in aqueous media is gathering relevant interest in several fields including biomedical diagnostics, environmental monitoring, healthcare products, water and food test and control, agriculture industry and security. The fundamental limitation of the state-of-art transistor-based approaches is the intrinsic trade-off between sensitivity, ion concentration range and operating voltage. Here we show a current-driven configuration based on organic electrochemical transistors that overcomes this fundamental limit. The measured ion sensitivity exceeds by one order of magnitude the Nernst limit at an operating voltage of few hundred millivolts. The ion sensitivity normalized to the supply voltage is larger than 1200 mV V−1 dec−1, which is the largest value ever reported for ion-sensitive transistors. The proposed approach is general and can be extended to any transistor technology, thus opening opportunities for high-performance bioelectronics.