Organic bioelectronics involves the connection of organic semiconductors with living organisms, organs, tissues, cells, membranes, proteins, and even small molecules. In recent years, this field has received great interest due to the development of all kinds of devices architectures, enabling the detection of several relevant biomarkers, the stimulation and sensing of cells and tissues, and the recording of electrophysiological signals, among others. In this review, we discuss recent functionalization approaches for PEDOT and PEDOT:PSS films with the aim of integrating biomolecules for the fabrication of bioelectronics platforms. As the choice of the strategy is determined by the conducting polymer synthesis method, initially PEDOT and PEDOT:PSS films preparation methods are presented. Later, a wide variety of PEDOT functionalization approaches are discussed, together with bioconjugation techniques to develop efficient organic-biological interfaces. Finally, and by making use of these approaches, the fabrication of different platforms towards organic bioelectronics devices is reviewed.

"Clickable" organic electrochemical transistors (OECTs) allow the reliable and straightforward functionalization of electronic devices through the well-known click chemistry toolbox. In this work, we study various aspects of the click chemistry-based interface engineering of "clickable" OECTs. First, different channel architectures are investigated, showing that PEDOT-N₃ films can properly work as a channel of the transistors. Furthermore, the Cu(I)-catalyzed click reaction of ethynyl-ferrocene is studied under different reaction conditions, endowing the spatial control of the functionalization. The strain-promoted and catalyst-free cycloaddition of a dibenzocyclooctyne-derivatized poly-l-lysine (PLL-DBCO) is also performed on the OECTs and validated by a fiber optic (FO)-SPR setup. The further immobilization of an azido-modified HD22 aptamer yields OECT-based biosensors that are employed for the recognition of thrombin. Finally, their performance is evaluated against previously reported architectures, showing higher density of the immobilized HD22 aptamer, and originating similar K_D values and higher maximum signal change upon analyte recognition.

We introduce a new approach for glucose oxidase (GOx) immobilization on graphene field-effect transistors (gFETs) to fabricate highly sensitive glucose sensors. The strategy relies on the electropolymerization of a layer of the copolymer poly(3-amino-benzylamine-co-aniline) (PABA) on graphene-based transistors. The synthesized polymer film provides the suitable electrostatic charge and non-denaturing environment for enzyme immobilization without the need of any chemical primer. Then, the local pH changes triggered by the enzyme-catalyzed oxidation produce a shift in the Dirac potential of the gFETs to more negative values, which is evidenced by the differences in the graphene channel conductivity and constitutes the signal transduction mechanism of the sensing devices. The assembled biosensors revealed a low LOD of 4.1 μM and were capable of detecting glucose in the range from 10 to 1000 μM in a flow configuration. Moreover, they showed sensitivity of −24.9 μA per decade of glucose concentration and a fast response time, with an average value of 190 seconds, while allowing the operation at small gate-source and drain-source voltages. Finally, the biosensors were able to successfully monitor the analyte in urine samples, showing their potential towards the fabrication of point-of-care glucose testing devices.

Interfacing the surface of an organic semiconductor with biological elements is a central quest when it comes to the development of efficient organic bioelectronic devices. Here, we present the first example of "clickable" organic electrochemical transistors (OECTs). The synthesis and characterization of an azide-derivatized EDOT monomer (azidomethyl-EDOT, EDOT-N₃) are reported, as well as its deposition on Au-interdigitated electrodes through electropolymerization to yield PEDOT-N₃-OECTs. The electropolymerization protocol allows for a straightforward and reliable tuning of the characteristics of the OECTs, yielding transistors with lower threshold voltages than PEDOT-based state-of-the-art devices and maximum transconductance voltage values close to 0 V, a key feature for the development of efficient organic bioelectronic devices. Subsequently, the azide moieties are employed to click alkyne-bearing molecules such as redox probes and biorecognition elements. The clicking of an alkyne-modified PEG₄-biotin allows for the use of the avidin-biotin interactions to efficiently generate bioconstructs with proteins and enzymes. In addition, a dibenzocyclooctyne-modified thrombin-specific HD22 aptamer is clicked on the PEDOT-N₃-OECTs, showing the application of the devices toward the development of organic transistors-based biosensors. Finally, the clicked OECTs preserve their electronic features after the different clicking procedures, demonstrating the stability and robustness of the fabricated transistors.

In this work, we present the ultra-sensitive detection of acetylcholine (Ach) using enzymatic nanofluidic biosensors in which the ionic signal is generated via local chemical amplification of enzymatic processes.