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Funder: Cambridge Trust; Id: http://dx.doi.org/10.13039/501100003343, Funder: University of Cambridge; Id: http://dx.doi.org/10.13039/501100000735, Funder: Wellcome Trust; Id: http://dx.doi.org/10.13039/100010269, Funder: University of Cambridge Borysiewicz Interdisciplinary Fellowship, Funder: Infinitus China Ltd, Silicon probes have played a key role in studying the brain. However, the stark mechanical mismatch between these probes and the brain leads to chronic damage in the surrounding neural tissue, limiting their application in research and clinical translation. Mechanically flexible probes made of thin plastic shanks offer an attractive tissue-compatible alternative but are difficult to implant into the brain and struggle to achieve the electrode density and layout necessary for the high-resolution applications their silicon counterparts excel at. Here, we present a multi-shank high-density flexible neural probe design which emulates the functionality of stiff silicon arrays for neural population recordings across multiple sites within a given region. The flexible probe is accompanied by a detachable 3D printed implanter which delivers the probe by means of hydrophobic-coated shuttles. The shuttles can then be retracted with minimal movement, and the implanter houses the electronics necessary for in vivo recording applications. Validation of the probes through extracellular recordings from multiple brain regions and histological evidence of minimal foreign body response opens the path to long-term chronic monitoring of neural ensembles

We examine the factors controlling the neuromorphic response of organic electrochemical transistors (OECTs). In these devices, the gate voltage is used to supply the pre-synaptic input, while the drain current is taken as the post-synaptic output. We analyze the behavior of devices made from polymer blends of a mixed conductor (PEDOT:PSS) and an ion conductor (PSSNa). The experimental results highlight that the post-synaptic response timescale depends on the size of ion in the electrolyte. Modeling shows that the neuromorphic response is controlled by the transient response of the ionic circuit of the OECT. These insights on device response time pave the way for a more rational design of OECT-based neuromorphic devices.

Poly(3,4-ethylenedioxythiophene) doped with polystyrene sulfonate (PEDOT:PSS) is widely used as a coating on microelectrode arrays in order to reduce impedance for both in vitro and in vivo electrophysiology. In many applications, electrode performance of months to years is desired; yet, there are few studies to date that examine the long-term stability of conducting polymers and their devices. Here, the stability of PEDOT:PSS microelectrodes is examined over a period of four months in cell culture media enriched with fetal bovine serum. The electrochemical impedance remains constant for most electrodes throughout the study, and only small changes in the structure of functional electrodes are observed at the end of the test. The results demonstrate that PEDOT:PSS electrodes show adequate stability for a variety of in vitro electrophysiology applications in toxicology, drug development, tissue engineering, and fundamental studies of electrically active cells and tissues.

Graphical abstract, Conjugated polymers have been increasingly considered for the design of conductive materials in the field of regenerative medicine. However, optimal scaffold properties addressing the complexity of the desired tissue still need to be developed. The focus of this study lies in the development and evaluation of a conductive scaffold for bone tissue engineering. In this study PEDOT:PSS scaffolds were designed and evaluated in vitro using MC3T3-E1 osteogenic precursor cells, and the cells were assessed for distinct differentiation stages and the expression of an osteogenic phenotype. Ice-templated PEDOT:PSS scaffolds presented high pore interconnectivity with a median pore diameter of 53.6 ± 5.9 µm and a total pore surface area of 7.72 ± 1.7 m2·g−1. The electrical conductivity, based on I-V curves, was measured to be 140 µS·cm−1 with a reduced, but stable conductivity of 6.1 µS·cm−1 after 28 days in cell culture media. MC3T3-E1 gene expression levels of ALPL, COL1A1 and RUNX2 were significantly enhanced after 4 weeks, in line with increased extracellular matrix mineralisation, and osteocalcin deposition. These results demonstrate that a porous material, based purely on PEDOT:PSS, is suitable as a scaffold for bone tissue engineering and thus represents a promising candidate for regenerative medicine. Statement of Significance Tissue engineering approaches have been increasingly considered for the repair of non-union fractions, craniofacial reconstruction or large bone defect replacements. The design of complex biomaterials and successful engineering of 3-dimensional tissue constructs is of paramount importance to meet this clinical need. Conductive scaffolds, based on conjugated polymers, present interesting candidates to address the piezoelectric properties of bone tissue and to induce enhanced osteogenesis upon implantation. However, conductive scaffolds have not been investigated in vitro in great measure. To this end, we have developed a highly porous, electrically conductive scaffold based on PEDOT:PSS, and provide evidence that this purely synthetic material is a promising candidate for bone tissue engineering.

Organic semiconductors can be employed as the active layer in accumulation mode organic electrochemical transistors (OECTs), where redox stability in aqueous electrolytes is important for long‐term recordings of biological events. It is observed that alkoxy‐benzo[1,2‐b:4,5‐b′]dithiophene (BDT) copolymers can be extremely unstable when they are oxidized in aqueous solutions. The redox stability of these copolymers can be improved by molecular design of the copolymer where it is observed that the electron rich comonomer 3,3′‐dimethoxy‐2,2′‐bithiophene (MeOT2) lowers the oxidation potential and also stabilizes positive charges through delocalization and resonance effects. For copolymers where the comonomers do not have the same ability to stabilize positive charges, irreversible redox reactions are observed with the formation of quinone structures, being detrimental to performance of the materials in OECTs. Charge distribution along the copolymer from density functional theory calculations is seen to be an important factor in the stability of the charged copolymer. As a result of the stabilizing effect of the comonomer, a highly stable OECT performance is observed with transconductances in the mS range. The analysis of the decomposition pathway also raises questions about the general stability of the alkoxy‐BDT unit, which is heavily used in donor–acceptor copolymers in the field of photovoltaics.

Organic electrochemical transistors (OECTs) are being intensively developed for applications in electronics and biological interfacing. These devices rely on ions injected in a polymer film from an aqueous liquid electrolyte for their operation. However, the development of solid or semi-solid electrolytes are needed for future integration of OECTs into flexible, printed or conformable bioelectronic devices. Here, we present a new polyethylene glycol hydrogel with high Na+ conductivity which is particularly suitable for OECTs. This novel hydrogel was synthesized using cost-effective photopolymerization of poly(ethylene glycol)-dimethacrylate and sodium acrylate. Due to the high water content (83% w/w) and the presence of free Na+, the hydrogel showed high ionic conductivity values at room temperature (10-2 S cm-1) as characterized by electrochemical impedance spectroscopy. OECTs made using this hydrogel as a source of ions showed performance that was equivalent to that of OECTs employing a liquid electrolyte. They also showed improved stability, with only a 3% drop in current after 6 h of operation. This hydrogel paves the way for the replacement of liquid electrolytes in high performance OECTs bringing about advantages in terms of device integration and protection.

Funder: Beijing Institute of Collaborative Innovation, Small‐fiber neuropathy (SFN), a pathology caused by severe loss of free‐endings of unmyelinated sensory nerves, is difficult to diagnose and monitor. The use of cutaneous electrical stimulation as a diagnostic tool is hampered by the fact that the injected current penetrates deep into the skin and stimulates many other receptors. Interdigitated electrodes are recently proposed to control the depth of current penetration and selectively address small‐fibers. Here, flexible and adhesive interdigitated electrodes made of Au coated with poly(3,4‐ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) are developed, that conform comfortably and reliably to human skin. It is shown that the PEDOT:PSS coating improves safety by significantly reducing the voltage required to inject current. The selectivity of the device is assessed by showing that it elicits a significantly slower reaction time than commercial cutaneous electrophysiology electrodes, as it exclusively activates unmyelinated fibers. The device is further evaluated on volunteers that undergo local capsaicin treatment to induce temporary loss of the nerve endings of small‐fibers. Pre‐ and post‐treatment electrical stimulation of the affected area with the device reveals impaired sensory detection that is not observed with commercial cutaneous electrophysiology electrodes. These results represent a significant step towards the use of electrical stimulation as a diagnostic and monitoring tool for SFN.

Organic electrochemical transistors (OECTs) have been widely used as transducers in electrophysiology and other biosensing applications. Their identifying characteristic is a transconductance that increases with channel thickness, and this provides a facile mechanism to achieve high signal amplification. However, little is known about their noise behavior. Here, we investigate noise and extract metrics for the signal-to-noise ratio and limit of detection in OECTs with different channel thicknesses. These metrics are shown to improve as the channel thickness increases, demonstrating that OECTs can be easily optimized to show not only high amplification, but also low noise., This work was funded by the European Union's Horizon 2020 research and innovation programme under Grant Agreement No. 732032 (BrainCom) the King Abdullah University of Science and Technology (KAUST) Office of sponsored Research (OSR) under Award No. OSR-2016-CRG5-3003. Authors also acknowledge funding from the 2DTecBio (FIS2017-85787-R) funded by the Spanish Ministry of Science, Innovation and Universities, the State Research Agency (AEI), and the European Regional Development Fund.

Organic electrochemical transistors (OECTs) from poly(3,4-ethylenedioxythiophene) doped with polystyrene sulfonate (PEDOT:PSS) are used as amplifying transducers for bioelectronics. Although the impact on performance of device geometry parameters such as channel area and thickness has been widely explored, the overlap between the semiconductor film and the source and drain contacts has not been considered. Here we vary this overlap and explore its impact on transconductance and noise. We show that increasing contact overlap does not alter the magnitude of the steady-state transconductance but it does decreases the cut-off frequency. Noise was found to be independent of contact overlap and to vary according to the charge noise model. The results show that high-quality contacts can be established in PEDOT:PSS OECTs with minimal overlap.

Organic electrochemical transistors (OECTs) are proving essential in bioelectronics and printed electronics applications, with their simple structure, ease of tunability, biocompatibility and suitability for different routes to fabrication. OECTs are also being explored as neuromorphic devices, where they emulate characteristics of biological neural networks through co-location of information storage and processing on the same unit, overcoming the von Neumann performance bottleneck. To achieve the long-term vision of translating to inexpensive, low-power computational devices, fabrication needs to be feasible with adaptable, scalable digital techniques. Here we show a hybrid direct-write additive manufacturing approach to fabricating OECTs. We combine 3D printing of commercially available printing filament to deliver conducting and insulating layers, with inkjet printing of a semi-conducting thin films to create OECTs. These printed OECTs show depletion mode operation paired-pulse depression behaviour and evidence of adaptation to support their translation to neuromorphic devices. These results show that a hybrid of accessible and design-flexible AM techniques can be used to rapidly fabricate devices that exhibit good OECT and neuromorphic performances., EP/L016567/1

Cochlear implants (CIs) have tremendously helped people with severe to profound hearing loss to gain access to sound and oral-verbal communication. However, the electrical stimulus in the cochlea spreads easily and widely, since the perilymph and endolymph (i.e., intracochlear fluids) are essentially electrolytes, leading to an inability to focus stimulation to discrete portions of the auditory nerve, which blurs the neural signal. Here, we characterize the complex transimpedances of human cadaveric cochleas to investigate how electrical stimulus spread is distributed from 10 Hz to 100 kHz. By using electrochemical impedance spectroscopy (EIS), both the resistive and capacitive elements of human cochleas are measured and modeled with an electrical circuit model, identifying spread-induced and spread-independent impedance components. Based on this electrical circuit model, we implement a Laplace transform to simulate the theoretical shapes of the spread signals. The model is validated by experimentally applying the simulated stimulus as a real stimulus to the cochlea and measuring the shapes of the spread signals, with relative errors of

Funder: King Abdullah University of Science and Technology; Id: http://dx.doi.org/10.13039/501100004052, Organic electrochemical transistors (OECTs) are widely used as amplifying transducers of biological signals due to their high transconductance and biocompatibility. For implantable applications that penetrate into tissue, OECTs need to be integrated onto narrow probes. The scarcity of real estate necessitates the use of small local gate electrodes and narrow interconnects. This work shows that both of these factors lead to a decrease in the maximum transconductance and an increase in gate voltage required to attain this maximum. This work further shows that coating the gate electrode with a thick conducting polymer improves performance. These findings help guide the development of efficient OECTs on implantable probes.