Parylene C is a promising material for constructing flexible, biocompatible and corrosion-resistant microelectromechanical systems (MEMS) devices. Historically, Parylene C has been employed as an encapsulation material for medical implants, such as stents and pacemakers, due to its strong barrier properties and biocompatibility. In the past few decades, the adaptation of planar microfabrication processes to thin film Parylene C has encouraged its use as an insulator, structural and substrate material for MEMS and other microelectronic devices. However, Parylene C presents unique challenges during microfabrication and during use with liquids, especially for flexible, thin film electronic devices. In particular, the flexibility and low thermal budget of Parylene C require modification of the fabrication techniques inherited from silicon MEMS, and poor adhesion at Parylene-Parylene and Parylene-metal interfaces causes device failure under prolonged use in wet environments. Here, we discuss in detail the promises and challenges inherent to Parylene C and present our experience in developing thin-film Parylene MEMS devices.

A novel Parylene C-based peripheral nerve interface that combines both electrodes and microfluidic channels in an adjustable cuff was designed, fabricated, and characterized. This minimally invasive interface incorporates a drug delivery system for targeted delivery of lysing agents and neurotrophic factors to the nerve surface to locally disrupt the epineurium and allow fascicular selectivity. Multiple platinum (Pt) electrodes were embedded in the microfluidic channels for neural stimulation and recording. The lyse-and-attract cuff electrode (LACE) uses a simple locking mechanism that is adjustable for close contact with nerves of varying diameters. Devices were fabricated using standard Parylene microfabrication techniques resulting in low variability and high device yield. A procedure for the implantation of the LACE was developed and successfully demonstrated in vivo around rat sciatic nerves. The adjustable locking mechanism demonstrated adequate holding strength and fit around the nerves. Benchtop electrochemical characterization of the thin-film Pt electrodes showed that the electrodes possessed high charge storage capacity (>1 mC/cm²) and low impedances (<2 kΩ at 1 kHz) suitable for neural stimulation and recording. As expected, embedded electrodes demonstrated higher impedance values. Acute neural recording from the rat sciatic nerve verified the capability of the LACE to record evoked neural activity (compound action potentials). Controlled and localized microfluidic infusions were achieved at low flow rates (<1 μL/min). Finally, infusion experiments in vivo demonstrated targeted drug delivery to the sciatic nerve fascicles. This multifunctional peripheral nerve interface has the potential to enhance implant-tissue integration in vivo and provide reliable chronic performance not available in the existing extraneural or intraneural interfaces. [2018-0192]

We present for the first time the design, fabrication, and preliminary bench-top characterization of a high-density, polymer-based penetrating microelectrode array, developed for chronic, large-scale recording in the cortices and hippocampi of behaving rats. We present two architectures for these targeted brain regions, both featuring 512 Pt recording electrodes patterned front-and-back on micromachined eight-shank arrays of thin-film Parylene C. These devices represent an order of magnitude improvement in both number and density of recording electrodes compared with prior work on polymer-based microelectrode arrays. We present enabling advances in polymer micro-machining related to lithographic resolution and a new method for back-side patterning of electrodes. In vitro electrochemical data verifies suitable electrode function and surface properties. Finally, we describe next steps toward the implementation of these arrays in chronic, large-scale recording studies in free-moving animal models.

Extraneural cuffs are among the least invasive peripheral nerve interfaces as they remain outside the nerve. However, compared with more invasive interfaces, these electrodes may suffer from lower selectivity and sensitivity since the targeted nerve fibers are more distanced from the electrodes. A lyse-and-attract cuff electrode (LACE) was enabled by microfabrication and developed to improve selectivity and sensitivity while maintaining a cuff format. Its engineering design was described in previous work. LACE is a hybrid cuff that integrates both microelectrodes and microfluidic channels. The ultimate goal is to increase fascicular selectivity and sensitivity by focal delivery via the microchannels of (1) lysing agent to remove connective tissue separating electrodes from nerve fibers, and (2) neurotrophic factors to promote axonal sprouting of the exposed nerve fibers into microfluidic channels where electrodes are embedded. Here, we focus on demonstrating in vivo function of microfluidics and microelectrodes in an acute preparation in which we evaluate the ability to focally remove connective tissue and record and stimulate with microchannel-embedded microelectrodes neural activity in rat sciatic nerves. While extraneural interfaces prioritize nerve health and intraneural interfaces prioritize functionality, LACE represents a new extraneural approach which could potentially excel at both aims. Surgical implantation demonstrate preservation of LACE function following careful and minimal handling. In vivo electrical evaluation demonstrates the ability of microelectrodes placed within microfluidic channels to successfully stimulate and record compound action potentials from rat sciatic nerve. Furthermore, collagen-rich epineurium was focally removed following infusion of collagenase via microchannels and confirmed via microscopy. The feasibility of using a cuff having integrated microelectrodes and microfluidics to stimulate, record, and deliver drug to focally lyse away the epineurium layer was demonstrated in acute experiments on rat sciatic nerve.

Electrochemical aptamer-based (EAB) sensing is a generalizable approach to monitoring a wide range of molecular targets. Selective, dynamically responsive, real-time measurements are possible in complex body fluids while using standard electrochemical methods for read out. To advance miniaturized, wearable EAB sensing formats, 17 candidate materials compatible with microfabrication into 2D and 3D microstructures were investigated as sensor substrates. Since the aptamer attachment chemistry requires a gold surface, adhesion of gold thin films was evaluated followed by compatibility with EAB surface functionalization chemistry and the electrochemical interrogation method. Sensing results for each material were benchmarked against the gold standard solid gold microwire sensor format. Finally, two microneedle-based EAB sensor formats were demonstrated at the benchtop and in vivo, by modifying commercially produced microneedles and developing a novel laser-machined polyether ether ketone (PEEK) microneedle array. Multiplexed sensing was enabled by selective functionalization of subgroups of needles within a single array.[2025-0204]