Glassy carbon microelectrode arrays enable voltage-peak separated simultaneous detection of dopamine and serotonin using fast scan cyclic voltammetry.

Progress in real-time, simultaneous in vivo detection of multiple neurotransmitters will help accelerate advances in neuroscience research. The need for development of probes capable of stable electrochemical detection of rapid neurotransmitter fluctuations with high sensitivity and selectivity and sub-second temporal resolution has, therefore, become compelling. Additionally, a higher spatial resolution multi-channel capability is required to capture the complex neurotransmission dynamics across different brain regions. These research needs have inspired the introduction of glassy carbon (GC) microelectrode arrays on flexible polymer substrates through carbon MEMS (C-MEMS) microfabrication process followed by a novel pattern transfer technique. These implantable GC microelectrodes provide unique advantages in electrochemical detection of electroactive neurotransmitters through the presence of active carboxyl, carbonyl, and hydroxyl functional groups. In addition, they offer fast electron transfer kinetics, capacitive electrochemical behavior, and wide electrochemical window. Here, we combine the use of these GC microelectrodes with the fast scan cyclic voltammetry (FSCV) technique to optimize the co-detection of dopamine (DA) and serotonin (5-HT) in vitro and in vivo. We demonstrate that using optimized FSCV triangular waveform at scan rates ≤700 V s-1 and holding and switching at potentials of 0.4 and 1 V respectively, it is possible to discriminate voltage reduction and oxidation peaks of DA and 5-HT, with 5-HT contributing distinct multiple oxidation peaks. Taken together, our results present a compelling case for a carbon-based MEA platform rich with active functional groups that allows for repeatable and stable detection of electroactive multiple neurotransmitters at concentrations as low as 1.1 nM.

Carbon-based neural electrodes: promises and challenges.

Neural electrodes are primary functional elements of neuroelectronic devices designed to record neural activity based on electrochemical signals. These electrodes may also be utilized for electrically stimulating the neural cells, such that their response can be simultaneously recorded. In addition to being medically safe, the electrode material should be electrically conductive and electrochemically stable under harsh biological environments. Mechanical flexibility and conformability, resistance to crack formation and compatibility with common microfabrication techniques are equally desirable properties. Traditionally, (noble) metals have been the preferred for neural electrode applications due to their proven biosafety and a relatively high electrical conductivity. Carbon is a recent addition to this list, which is far superior in terms of its electrochemical stability and corrosion resistance. Carbon has also enabled 3D electrode fabrication as opposed to the thin-film based 2D structures. One of carbon's peculiar aspects is its availability in a wide range of allotropes with specialized properties that render it highly versatile. These variations, however, also make it difficult to understand carbon itself as a unique material, and thus, each allotrope is often regarded independently. Some carbon types have already shown promising results in bioelectronic medicine, while many others remain potential candidates. In this topical review, we first provide a broad overview of the neuroelectronic devices and the basic requirements of an electrode material. We subsequently discuss the carbon family of materials and their properties that are useful in neural applications. Examples of devices fabricated using bulk and nano carbon materials are reviewed and critically compared. We then summarize the challenges, future prospects and next-generation carbon technology that can be helpful in the field of neural sciences. The article aims at providing a common platform to neuroscientists, electrochemists, biologists, microsystems engineers and carbon scientists to enable active and comprehensive efforts directed towards carbon-based neuroelectronic device fabrication.