Closed-loop Hydrogel Electronics for Intelligent Neurotreatment

Description

Closed-loop strategies featuring adaptive pharmaceutical intervention of pathological activities lead to an advanced therapeutic promise with intelligent disease management. In such an intelligent therapeutic system, medication could be delicately controlled for optimal treatment over prolonged periods. This concept features a dose-adaptive and time-sensitive pharmaceutical intervention on an as-needed basis, achieving better effectiveness and more assessable outcome with external intervention. Accordingly, closed-loop strategies comprising of continuous signal monitoring and feedback-based modulation offers on-demand and precise management of chronic and acute pathological conditions, such as seizure, diabetes mellitus, Parkinson’s disease, and arrhythmia, etc. The looped feedback signal could trigger immediate response to sudden deterioration conditions, or even preventive measures based on subtle pathological indications.However, very limited closed-loop systems are currently available for treating brain diseases. Using anti-epilepsy therapy as an example, the first and only clinically available closed-loop treatment uses an electrical recording and stimulation system for treating adults with drug-resistant focal epilepsy, which is applicable to only a small fraction of epilepsy patient population. The lack of success with closed-loop controlled pharmacological interventions shows the urgent needs for a rational approach that combines electrical and pharmacological intervention to achieve superior efficacy.In this project, we aims to develop a hydrogel-based, single-component, organic electronic device for closed-loop neurotreatment. The device will be made of conductive hydrogels and fabricated as a flexible array of microneedle electrodes, each of which can be individually addressed for electrical recording and chemical releasing with sophisticated spatial and temporal control in vivo. The recorded neural spiking signal acts as a closed-loop feedback to trigger a voltage-driven drug release in detected pathological conditions, where seizure occurrence is predicted by real-time electrophysiology analysis. When implanted into epileptic animals, the device will enable autonomous and preventative anti-seizure management, in which the dosing of anti-epileptic drug will be intelligently controlled in a time-sensitive, region-selective and dose-adaptive manner. In this way, sporadic seizure outburst can be successfully managed by just-necessary drug doses, exemplifying a smart pharmaceutical intervention that can be extended to treat a broad range of diseases. We believe that success in this project will open new paths towards the development of novel closed-loop neurotreatment strategy and technique by employing organic electronics and artificial intelligence, which can also be further extended to develop precise and autonomous pharmaceutical administration in a broad range of chronic diseases or medical conditions to achieve smart health management.