Bioelectric medicine treatments target disorders of the nervous system unresponsive to pharmacological methods. While current stimulation paradigms effectively treat many disorders, the underlying mechanisms are relatively unknown, and current neuroscience recording electrodes are often limited in their specificity to gross averages across many neurons or axons. Here, we develop a novel, durable carbon fiber electrode array adaptable to many neural structures for precise neural recording. Carbon fibers (6.8 µm diameter) were sharpened using a reproducible blowtorch method that uses the reflection of fibers against the surface of a water bath. The arrays were developed by partially embedding carbon fibers in medical-grade silicone to improve durability. We recorded acute spontaneous electrophysiology from the rat cervical vagus nerve (CVN), feline dorsal root ganglia (DRG), and rat brain. Blowtorching resulted in fibers of 72.3 ± 33.5-degree tip angle with 146.8 ± 17.7 µm exposed carbon. Observable neural clusters were recorded using sharpened carbon fiber electrodes from rat CVN (41.8 µVpp), feline DRG (101.1 µVpp), and rat brain (80.7 µVpp). Recordings from the feline DRG included physiologically relevant signals from increased bladder pressure and cutaneous brushing. These results suggest that this carbon fiber array is a uniquely durable and adaptable neural recording device. In the future, this device may be useful as a bioelectric medicine tool for diagnosis and closedloop neural control of therapeutic treatments and monitoring systems.

Autonomic nerves convey essential neural signals that regulate vital body functions. Recording clearly distinctive physiological neural signals from autonomic nerves will help develop new treatments for restoring regulatory functions. However, this is very challenging due to the small nature of autonomic nerves and the low-amplitude signals from their small axons. We developed a multi-channel, high-density, intraneural carbon fiber microelectrode array (CFMA) with ultra-small electrodes (8–9 µm in diameter, 150–250 µm in length) for recording physiological action potentials from small autonomic nerves. In this study, we inserted CFMA with up to 16 recording carbon fibers in the cervical vagus nerve of 22 isoflurane-anesthetized rats. We recorded action potentials with peak-to-peak amplitudes of 15.1–91.7 µV and signal-to-noise ratios of 2.0–8.3 on multiple carbon fibers per experiment, determined conduction velocities of some vagal signals in the afferent (0.7–4.4 m/s) and efferent (0.7–8.8 m/s) directions, and monitored firing rate changes in breathing and blood glucose modulated conditions. Overall, these experiments demonstrated that CFMA is a novel interface for in-vivo intraneural action potential recordings. This work is considerable progress towards the comprehensive understanding of physiological neural signaling in vital regulatory functions controlled by autonomic nerves.

Peripheral nerve mapping tools with higher spatial resolution are needed to advance systems neuroscience, and potentially provide a closed‐loop biomarker in neuromodulation applications. Two critical challenges of microscale neural interfaces are 1) how to apply them to small peripheral nerves, and 2) how to minimize chronic reactivity. A flexible microneedle nerve array (MINA) is developed, which is the first high‐density penetrating electrode array made with axon‐sized silicon microneedles embedded in low‐modulus thin silicone. The design, fabrication, acute recording, and chronic reactivity to an implanted MINA, are presented. Distinctive units are identified in the rat peroneal nerve. The authors also demonstrate a long‐term, cuff‐free, and suture‐free fixation manner using rose bengal as a light‐activated adhesive for two time‐points. The tissue response is investigated at 1‐week and 6‐week time‐points, including two sham groups and two MINA‐implanted groups. These conditions are quantified in the left vagus nerve of rats using histomorphometry. Micro computed tomography (micro‐CT) is added to visualize and quantify tissue encapsulation around the implant. MINA demonstrates a reduction in encapsulation thickness over previously quantified interfascicular methods. Future challenges include techniques for precise insertion of the microneedle electrodes and demonstrating long‐term recording.

This protocol is for obtaining physiological action potential recordings in rat vagus nerves using carbon fiber microelectrode arrays (CFMAs) in spontaneous and blood glucose and breathing modulated conditions. The rats were anesthetized with isoflurane, which maintained consistent and stable depth of anesthesia for recording vagal nerve activity with ultra-small carbon fibers. Blood glucose levels were modulated by intraperitoneal (IP) injection of glucose, insulin, or 2-deoxy-D-glucose (2-DG). Breathing was modulated by increasing anesthesia depth. Carbon fiber microelectrode arrays are available through the Multimodal Integrated Neural Technologies (MINT) technology hub (https://mint.engin.umich.edu/), which is supported by the National Science Foundation (Award 1707316). This research was also supported by the National Institute of Health SPARC Program (Award OT2OD024907).

ObjectiveBioelectric medicine offers therapeutic diagnoses and treatments for disorders of the nervous system unresponsive to pharmacological treatments. While current neural interfaces effectively treat many disorders with stimulation, recording specificity is often limited to gross averages across many neurons or axons. Here, we develop and describe a novel, robust carbon fiber electrode array adaptable to many neural structures for precise neural recording.ApproachCarbon fibers were sharpened using a blowtorch method made reproducible by using the reflection of fibers against the surface of a water bath. Arrays of carbon fibers were developed by partially embedding carbon fibers in medical-grade silicone to improve robustness to fracture. Acute spontaneous electrophysiology was recorded from the rat cervical vagus nerve, feline dorsal root ganglia, and rat brain. Acute brushing and bladder pressure electrophysiology was recorded from feline dorsal root ganglia as well.Main resultsBlowtorching resulted in fibers of 72.3 ± 33.5 degree tip angle with 146.8 ± 17.7 μm exposed carbon. Silicone-embedded carbon fiber arrays were robust to bending (87.5% of fibers remained unbroken, 50,000 passes). Observable neural clusters were recorded using sharpened carbon fiber electrodes from rat cervical vagus nerve (41.8 μVpp, N=3 electrodes), feline dorsal root ganglia (101.1 μVpp, N=32 electrodes), and rat brain (80.7 μVpp, N=7 electrodes). Recordings from the feline dorsal root ganglia included physiologically-relevant signals from increased bladder pressure and cutaneous brushing.SignificanceThese results suggest that this carbon fiber array is a uniquely robust and adaptable neural recording device, useful for specific electrophysiology measurements. In the future, this device may be useful as a bioelectric medicine tool for diagnosis and closed-loop neural control of therapeutic treatments and monitoring systems.