Hybrid diamond/ carbon fiber microelectrodes enable multimodal electrical/chemical neural interfacing

Abstract

Implantable medical devices are now in regular use to treat or ameliorate medical conditions, including movement disorders, chronic pain, cardiac arrhythmias, and hearing or vision loss. Aside from offering alternatives to pharmaceuticals, one major advantage of device therapy is the potential to monitor treatment efficacy, disease progression, and perhaps begin to uncover elusive mechanisms of diseases pathology. In an ideal system, neural stimulation, neural recording, and electrochemical sensing would be conducted by the same electrode in the same anatomical region. Carbon fiber (CF) microelectrodes are the appropriate size to achieve this goal and have shown excellent performance, in vivo. Their electrochemical properties, however, are not suitable for neural stimulation and electrochemical sensing. Here, we present a method to deposit high surface area conducting diamond on CF microelectrodes. This unique hybrid microelectrode is capable of recording single-neuron action potentials, delivering effective electrical stimulation pulses, and exhibits excellent electrochemical dopamine detection. Such electrodes are needed for the next generation of miniaturized, closed-loop implants that can self-tune therapies by monitoring both electrophysiological and biochemical biomarkers.

Introduction

The cardiac pacemaker, cochlear implant, deep brain stimulator for Parkinson's disease and spinal cord stimulator for pain control are key examples of implantable devices that have progressed from basic research to commercial and clinical success. These examples represent only a small fraction of the possible clinical targets that could be addressed with “electric medicine”. There are many other approaches under development, including electrical stimulation for epilepsy, psychiatric disorders, hypertension, heart failure, gastrointestinal disorders, type II diabetes, and inflammatory disorders [1]. Additionally, recording devices are under investigation for limb prosthetics towards the promise of mobility for amputees and those suffering from paralysis [2,3]. By directly using electrical impulses to modulate the body's neural circuits, electric medicine provides a new paradigm for the treatment of disease. If devices can be miniaturized and their performance improved, electric medicine could be applied to a much broader range of clinical targets.

There is strong interest in implantable neuromodulation technologies that not only treat conditions but also record the efficacy of treatment, i.e. they could remotely inform specialists, measure their own efficacy, self-calibrate and react to the changing needs of the user. In the field, this is referred to as a closed-loop device, as illustrated in Fig. 1. Current neural implants are typically comprised of electrodes that primarily perform one function: either record from or stimulate neurons. Electrodes that perform more than one function are one way that overall device invasiveness can be minimized. Miniaturization of electrodes to microwire geometries, not only enables fabrication of smaller devices but has been shown to lead to less tissue damage and lower electrode failure, particularly when using carbon materials [4,5]. At 7–10 μm in diameter CFs are similar in diameter to the soma of individual neurons.

Therapies that employ neural stimulation hold great promise, but implantable devices face challenges in terms of safety and longevity. These considerations are governed by a range of factors including mechanical compliance, chemical biocompatibility, and electrochemical properties. CFs have been under investigation as promising neural interface electrodes because they exhibit biochemical longevity and are well tolerated in vivo due to their small diameter and flexibility, reducing the risk for infection and formation of glial scars in vivo [[6], [7], [8]]. CFs are also well established as excellent electrodes for neural recording [9] and electrochemical sensing [10,11]. They do not, however, possess sufficient electrochemical capacitance for neural stimulation within safe voltage limits. They also suffer from a relatively small “safe potential window”, the range of safe voltages within which water splitting does not occur. Electrodes that deviate beyond the water splitting water-window during stimulation can cause damage to neural tissue and are considered unsafe. Furthermore, in the case of CFs, etching of the electrode can occur at voltages higher than +1 V resulting in rapid degradation of the electrode.

The stimulation properties of CF electrodes can be improved by the addition of a high capacitance coating, leading to lower interfacial impedance and increased safe charge injection capacity (CIC) [12]. Platinum black or conductive polymers such as PEDOT:PSS have been used as the coating layer for improving the electrochemical properties of CF electrodes but polymer coatings often exhibit degraded performance after repeated stimulation either due to degradation of the coating material or lack of adhesion to the CF surface [9,[13], [14], [15], [16]].

Previously, we demonstrated that nitrogen-included ultrananocrystalline diamond (NUNCD) is an effective neural stimulation material [17]. This is a significant finding that adds an additional dimension to diamond's recognized exceptional properties in terms of chemical stability, wide water-window, and high resistance to surface fouling. Among all diamond forms, NUNCD is the only form of diamond that has been successfully used for both neural stimulation and recording [[18], [19], [20], [21]]. When an appropriate amount of nitrogen is introduced during chemical vapor deposition (CVD) and post-treated with oxygen plasma [[22], [23], [24]], NUNCD has a CIC as high as 1200 μC/cm² [25]. We have previously demonstrated that this material is well tolerated in vivo [26] and exceptionally stable, even when pushed to the limits of safe operation [17]. It has been also reported that the double-layer capacitance values for the nanostructured CNT/BDD composite electrodes are ~450 times greater than those for the equivalent flat BDD electrodes [27]. The 3D diamond-based electrodes not only used for neuroprostheses but also increase the resolution of stimulation [28].

In this work, we develop a method to grow this material on single CF microfibers and demonstrate that the resultant electrode can be used safely and effectively for neural stimulation whilst retaining excellent properties for neural recording and electrochemical detection of dopamine. The established stability and robustness of UNCD, even under extreme operating conditions, combined with the small size of CFs makes these electrodes ideal for high-resolution, single neuron neural interface electrodes for closed loop medical devices.