The functioning principles of electronic sensors based on organic semiconductor field-effect transistors (OFETs) are presented. The focus is on biological sensors but also chemical ones are reviewed to address general features. The field-induced electronic transport and the chemical and biological interactions for the sensing, each occurring at the relevant functional interface, are separately introduced. Once these key learning points have been acquired, the combined picture for the FET electronic sensing is proposed. The perspective use of such devices in point-of-care is introduced, after some basics on analytical biosensing systems are provided as well. This tutorial review includes also a necessary overview of the OFET sensing structures, but the focus will be on electronic rather than electrochemical detection. The differences among the structures are highlighted along with the implications on the performance level in terms of key analytical figures of merit such as: repeatability, sensitivity and selectivity.

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.

Organic bioelectronic sensors are gaining momentum as they can combine high-performance sensing level with flexible large-area processable materials. This opens to potentially highly powerful sensing systems for point-of-care health monitoring and diagnostics at low cost. Prominent to detect biochemical recognition events, are electrolyte-gated organic field-effect transistors (EGOFETs) and organic electrochemical transistors (OECTs) as they are easily fabricated and operated. EGOFETs are recently shown to be capable of labelfree single-molecule detections, even in serum. This progress report aims to provide a critical perspective through a selected overview of the literature on both EGOFET and OECT biosensors. Attention is paid to correctly attribute them to the potentiometric and amperometric biosensor categories, which is important to set the right conditions for quantification purposes. Moreover, to deepen the understanding of the sensing mechanisms, with the support of unpublished data, focus is put on two among the most critical aspects, namely, the capacitance interplay and the role of Faradaic currents. The final aim is to provide a rationale of the functional mechanisms encompassing both EGOFET and OECT sensors, to improve materials and devices' designs taking advantage of the processes that enhance the sensing response enabling the extremely highperformance level resulting in ultimate sensitivity, selectivity, and fast response.