Lowering the threshold for bioelectronics

A high-speed, high-gain enhancement-mode ion-gated transistor shows promise for low-power chronically implanted bioelectronic systems.

Bioelectronic applications aim to link the biological environment with conventional electronic systems. But due to the vastly different nature of both worlds (hard versus soft, electrons/holes versus ions, dielectrics versus liquids), finding optimal materials has proven difficult and has been the focus of the field of bioelectronics for many years. Recently, organic electrochemical transistors — or ion-gated transistors — based on soft and biocompatible materials have been developed to bridge this gap. These devices convert ionic currents from biological media to electronic signals and at the same time reduce the mechanical mismatch with biological tissues. There have been significant demonstrations of IGTs for biosensing and electrophysiological recordings1, yet they are still limited by their relatively slow speeds (about 1–10 kHz) and high power consumption. Now, writing in Nature Materials, Claudia Cea, George Spyropoulos and colleagues have found a straightforward way to modify an ion-gated transitor material to connect electronic devices with biological environments in a fast, stable and low-power manner2.

Poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) has been the basis for a wide variety of applications and is generally considered the most ubiquitous mixed ionic/electronic conducting polymer blend, resulting from its wide commercial availability, biocompatibility and straightforward processing. However, when implemented in ion-gated transistors, PEDOT:PSS has two key drawbacks. First, it is intrinsically doped with positive charges (holes) due to the negatively charged PSS backbone. As a result, transistors based on this material operate by default in the ON state unless they are switched to the OFF state with an applied gate potential VG (this is the so-called depletion-mode operation of a transistor, whose transfer characteristic is shown in Fig. 1b, red curve). A default ON state leads to both relatively high power consumption as well as device-to-device crosstalk due to the transmission of signals when VG = 0 V. Second, the high areal capacitance of PEDOT:PSS leads to slow charging times, limiting the operating speed of the transistors.

Fig. 1: High-performance rectifying circuits based on enhancement and depletion mode internal ion-gated transistors (e-IGT and d-IGT, respectively).

a, Schematic showing the gate structure of an IGT, where the metallic gate contact (G) is coated with a ion membrane interfacing the device channel made of PEDOT:PSS (dark green spheres represent the negative charges of the PSS backbone, light green spheres represent positive ions). By applying a negative VG, holes (represented by white +) injected from the source contact (S) induce ions to move rapidly towards the gate due to the short drift distance (Dion) travelled compared to an IGT without ions in the channel. Fast response of the IGT is thus due to fast ion transport through the channel as well as its low gate capacitance (CEDL), resulting from the formation of an electronic double layer (EDL) at the metal–electrolyte interface. b, Comparison of transfer characteristics of e-IGT (green curve) and d-IGT (red curve) highlighting for each device the subthreshold region that is optimal for amplification of electrophysiological signals. c, Combining both devices, circuits can be designed that amplify voltages near 0 V (green area in b) as well as higher potentials (red area in b). d, These circuits are used to process electrophysiological recordings in implanted bioelectronic systems. Scale bars 5 s, 0.5 µA. Figure adapted with permission from ref. 2, Springer Nature Ltd (a,c).

The authors have overcome both problems by combining an internal ion-gated organic electrochemical transistor (IGT) architecture, based on previous work3, with a common de-doping reagent for PEDOT:PSS, polyethylene-imine. The IGT architecture results in a faster device response due to the inclusion of the electrolyte in the device channel to avoid diffusion-limited ionic transport, as well as the use of a low-capacitance gate that reduces the total RC charging time of the device (Fig. 1a). The de-doping reagent lowers the threshold potential to effectively tune the device to its OFF state when no gate voltage is applied — the device thus operates in enhancement mode, and its transfer characteristic is shifted with respect to VG (as shown in Fig. 1b, green curve). This means that the IGT channel has high intrinsic resistance when VG = 0 V, ensuring that stray signals are blocked from the surrounding circuitry.

Modifying the doping state to optimize the properties of PEDOT:PSS according to the application targeted has already proven to be successful in solar cells4, batteries5 and neuromorphic devices6. Now, this same technique improves the performance of PEDOT:PSS-based IGTs too; importantly, the biocompatibility of the dopant chosen, polyethylene-imine, enables the use of these devices for high-fidelity electrophysiological recordings and in situ signal filtering. In fact, Cea and colleagues showed that their IGTs were fast and sensitive enough to record action potentials from single neurons when implanted in rats’ brains. Moreover, they combined enhancement-mode and depletion-mode IGTs to realize implantable electrical filters working in a wide voltage range (Fig. 1b–d). Each of the IGTs have a different optimal operating voltage range given by the subthreshold region of their transfer curves (Fig. 1b). Interestingly, by combining the two devices in a rectifying amplification circuit (Fig. 1c), both small (near 0 V) and large voltage signals in hippocampal recordings are rectified efficiently by the enhancement-mode and depletion-mode IGTs, respectively (Fig. 1d). By efficiently detecting both small and large amplitude hippocampal activity, the demonstrated circuit could be used to accurately detect epileptic discharges, outperforming traditional signal filtering approaches.

Modification of bioelectronic device properties can thus open up further applications by building systems that can sense and locally process complex electrophysiological signals, and even diagnose health problems. Local computation at the point of recording is in itself particularly interesting as it reduces the need for high-bandwidth data communication in and out of the biological system (for instance, the brain). Adaptable circuits could be trained to identify a particular seizure and react to it by releasing drugs to supress epileptic activity7. Other exciting applications can be envisioned, such as advanced prosthetics in which signalling from the biological environment can be used to modify the electrical or chemical properties of the material to dynamically tune and close a feedback loop. The tuning of electrical properties of IGTs is therefore an essential step forward in the field of adaptable, chronically implanted bioelectronic interfaces.

Yet, despite the great performance already demonstrated by doped organic electronic materials, the electronic and structural effects of doping and de-doping are still poorly understood. Better understanding of the mechanism behind modification of the doping state will further enhance the design and manufacturability of specific materials and allow for a larger range of tunability and optimization. At present, most organic devices used in bioelectronics employ positively charged polymers (p-type) like PEDOT:PSS, yet progress is being made to develop negatively charged (n-type) materials8, where the electronic carriers are electrons rather than holes, compatible with these applications. Combining p- and n-type transistors can enable more advanced complementary circuits, which are the basis for almost all conventional computational circuits.

The results presented by Cea, Spyropoulos and co-workers provide a compelling demonstration of how biocompatible additives can be used straightforwardly to tune the properties of bioelectronic devices. This will certainly encourage further work to tune doping in wider ranges and will possibly suggest strategies to realize stable n-type devices with similar tunability. High-performance-integrated complementary logic circuits embedded in flexible and implantable bioelectronic systems may be within reach soon.


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Correspondence to Yoeri van de Burgt.

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Keene, S., van de Burgt, Y. Lowering the threshold for bioelectronics. Nat. Mater. 19, 584–586 (2020).

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