Wireless, Battery-Free Implants for Electrochemical Catecholamine Sensing and Optogenetic Stimulation

Abstract

Neurotransmitters and neuromodulators mediate communication between neurons and other cell types; knowledge of release dynamics is critical to understanding their physiological role in normal and pathological brain function. Investigation into transient neurotransmitter dynamics has largely been hindered due to electrical and material requirements for electrochemical stimulation and recording. Current systems require complex electronics for biasing and amplification and rely on materials that offer limited sensor selectivity and sensitivity. These restrictions result in bulky, tethered, or battery-powered systems impacting behavior and that require constant care of subjects. To overcome these challenges, we demonstrate a fully implantable, wireless, and battery-free platform that enables optogenetic stimulation and electrochemical recording of catecholamine dynamics in real time. The device is nearly 1/10th the size of previously reported examples and includes a probe that relies on a multilayer electrode architecture featuring a microscale light emitting diode (μ-LED) and a carbon nanotube (CNT)-based sensor with sensitivities among the highest recorded in the literature (1264.1 nA μM–1 cm–2). High sensitivity of the probe combined with a center tapped antenna design enables the realization of miniaturized, low power circuits suitable for subdermal implantation even in small animal models such as mice. A series of in vitro and in vivo experiments highlight the sensitivity and selectivity of the platform and demonstrate its capabilities in freely moving, untethered subjects. Specifically, a demonstration of changes in dopamine concentration after optogenetic stimulation of the nucleus accumbens and real-time readout of dopamine levels after opioid and naloxone exposure in freely behaving subjects highlight the experimental paradigms enabled by the platform.

Wireless Battery-free and Fully Implantable Organ Interfaces

“…f) Electrochemical signal change showing dopamine response after morphine injection and subsequent naloxone injection. (d–f) Reproduced with permission from ref . Copyright 2023 American Chemical Society.…”

A Highly Selective Implantable Electrochemical Fiber Sensor for Real-Time Monitoring of Blood Homovanillic Acid

“…Homovanillic acid (HVA), a major metabolite of the pivotal central neurotransmitter dopamine, has the ability to cross the blood–brain barrier and enter the blood circulatory system, unlike dopamine. , Consequently, the fluctuation of blood HVA is closely related to dopamine activity in the central nervous system (CNS). − Clinically, CNS dopamine detection needs labor-intensive cerebrospinal fluid analysis or complex neurosurgery to implant the device which is prone to cause infection and permanent CNS function damage. , In contrast, blood samples are easy to collect and less invasive to implant, positioning the dynamic profile of blood HVA as a potent complement to existing methods for studying dopamine activity. , Furthermore, blood HVA is used as an indicator to assess the progression of schizophrenia and the effectiveness of related therapeutic drugs. , It has also been implicated in the pathogenesis of neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease. − Therefore, real-time monitoring of blood HVA is of great significance for the study of central dopamine activity, disease pathogenesis, and drug efficacy evaluation.…”

Battery‐Free, Wireless, Cuff‐Type, Multimodal Physical Sensor for Continuous Temperature and Strain Monitoring of Nerve

“…The battery-free operation based on a resonant magnetic inductive coupling to harvest power makes the implantable device smaller and more comfortable for subjects. [32] The wireless communication between the implantable device and an external reader allows for freedom of movement and reduces the risk of infection due to the percutaneous wire. In addition, this approach can provide capabilities for continuous in vivo nerve monitoring along with not only therapies for improving regeneration, including wireless electrical, optogenetic, and pharmacologic stimuli, [33][34][35] but also neuropathic pain treatment using local cooling.…”