Fully Implantable, Ion-Gated, Organic Integrated-Circuits for Chronic, Closed-Loop Epileptic Interventions

Bioelectronic devices are increasingly required to not only acquire biologic signals, but also to process them in real-time. For a subset of patients with epilepsy, responsive neurostimulation in the form of implanted devices are promising form of treatment. However, the only components capable of performing these functions at present are silicon-based, non-biocompatible, bulky, and need rigid encapsulation in physiologic environments. Here, we demonstrate a fully implantable, soft, biocompatible, neural acquisition and processing device based on complementary internal ion-gated organic electrochemical transistors (IGTs). A key function of these responsive neurostimulation devices is accurate detection of epileptic discharges. This detection can be challenging due to the variable amplitude of the neural potentials based on the location of the recording electrode with respect to local dipoles and the reference electrode. We combined a depletion and enhancement mode IGTs to create a non-linear rectification circuit that can be chronically implanted to recorded and detect epileptiform inter-ictal discharges (IEDs). This device was used to process signals acquired from the hippocampus of a freely moving epileptic rat. The IGT-based non-linear rectification circuit accurately detected epileptic discharges, with receiver operating characteristics that surpassed traditional filter thresholding methods. Therefore, IGTs and their ability to efficiently integrate enhancement and depletion mode devices within individual circuits can improve real-time processing of disease-relevant neurophysiological signals and have the potential to form fully implantable, conformable acquisition and processing units for bioelectronic devices. Overall, we have shown that e-IGTs can serve as reliable components for bioelectronic devices, with the potential to improve our ability to transduce and modulate physiologic signals. E-IGTs are also suitable for translation to use in humans, offering a safe, reliable, and high-performance building block for chronically implanted bioelectronics.