Ultra-flexible and Stretchable Intrafascicular Peripheral Nerve Recording Device with Axon-dimension, Cuff-less Microneedle Electrode Array

Abstract

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 (i) how to apply them to small peripheral nerves, and (ii) how to minimize chronic reactivity. We developed a flexible microneedle nerve array (MINA), which is the first high-density penetrating electrode array made with axon-sized silicon microneedles embedded in low-modulus thin silicone. We present the design, fabrication, acute recording, and chronic reactivity to an implanted MINA. Distinctive units were identified in the rat peroneal nerve. We also demonstrate a long-term, cuff-free, and suture-free fixation manner using rose bengal as a light-activated adhesive for two timepoints. The tissue response at 1-week included a sham (N=5) and MINA-implanted (N=5) group, and the response at 6-week also included a sham (N=3) and MINA-implanted (N=4) group. These conditions were quantified in the left vagus nerve of rats using histomorphometry. Micro-CT was added to visualize and quantify tissue encapsulation around the implant. MINA demonstrated 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.

A flexible protruding microelectrode array for neural interfacing in bioelectronic medicine

“…As introduced earlier, Yan et al 52 combined DRIE with silicone casting and backside alignment to fabricate a Utah-like stretchable 3D MEA. However, the process flow involves complex steps, which usually affect fabrication costs and device design.…”

“…Because the fabrication process of the USEA is based on wafer-etching, conventional 3D microelectrode arrays (3D MEAs) are based on rigid silicon as the substrate material 50 . However, Lee et al 51 and Yan et al 52 demonstrated the possibility of producing flexible Utah-like 3D MEAs with silicon pillars by combining several micromachining techniques.…”

Flexible high-density microelectrode arrays for closed-loop brain–machine interfaces: a review

“…However, the development of flexible HDMEAs with these ideal properties entails confronting both the general challenges inherent to HDMEAs and specific challenges unique to their flexible design, encompassing mechanical (Oldroyd and Malliaras, 2022), electrical (Szostak et al, 2017;Qiang et al, 2021), biological (Golabchi et al, 2019), chemical (Shepherd et al, 2021), and interconnection issues (Behfar et al, 2021). In response, researchers employ strategies spanning material exploration (Bonafe, 2022;Chik et al, 2022), flexible HDMEA design innovation, advanced fabrication strategies (Scholten et al, 2020;Shah et al, 2022;Xiang et al, 2022), engineering optimization (Chik et al, 2022;Yan et al, 2022;Yin et al, 2022), and holistic combination strategies (Eunah et al, 2022;Hong et al, 2022), aiming to enhance performance and minimize risks in flexible neural interfacing devices.…”

Advances and challenges in developing smart, multifunctional microneedles for biomedical applications

“…Additionally, the injection approach is accompanied by a risk of needle breakage and overdosing, and it eventually requires waste management of sharps (Yao et al, 2020). Microneedles (MNs) are devices with arrays of microscale needles or pins that can bypass the external barriers of tissues and achieve enhanced therapeutic delivery or biosensing in a minimally invasive manner (Byun et al, 2017; Yan et al, 2022) (Figure 1A–a,b). Various types of MNs, such as solid, hollow, or coated MNs, have been developed to increase the efficacy of MNs depending on their specific applications (Lee, Goudie, et al, 2020).…”