Allison Marina Stiller

While intracortical microelectrode arrays (MEAs) may be useful in a variety of basic and clinical scenarios, their implementation is hindered by a variety of factors, many of which are related to the stiff material composition of the device. MEAs are often fabricated from high modulus materials such as silicon, leaving devices vulnerable to brittle fracture and thus complicating device fabrication and handling. For this reason, polymer-based devices are being heavily investigated; however, their implementation is often difficult due to mechanical instability that requires insertion aids during implantation. In this study, we design and fabricate intracortical MEAs from a shape memory polymer (SMP) substrate that remains stiff at room temperature but softens to 20 MPa after implantation, therefore allowing the device to be implanted without aids. We demonstrate chronic recordings and electrochemical measurements for 16 weeks in rat cortex and show that the devices are robust to physical deformation, therefore making them advantageous for surgical implementation.

Objective . Neural interfaces designed to stimulate or record electrical activity from peripheral nerves have applications ranging from the electrical modulation of nerve activity as a therapeutic option (e.g. epilepsy and depression) to the design of prosthetics. Currently, most peripheral nerve interfaces are either cuff-style devices that wrap around the target nerve or intraneural devices that are implanted within the nerve. While the latter option offers higher specificity and signal-to-noise ratio, penetrating devices can cause significant damage to the nerve due to the high degree of mechanical mismatch. Because of this, there is interest in developing penetrating devices fabricated from soft or softening materials (materials having a low elastic modulus). However, there is currently a lack of understanding regarding implantation forces required for successful insertion, which is a constraint for soft device design. Softer devices require robust designs to achieve a critical buckling force that is larger than forces experienced during device insertion. Approach . This study comprehensively assesses insertion force under different implantation conditions, with three variations for implantation speed, angle, and device tip angle, during insertion of silicon shanks in rat sciatic nerve. Additionally, we report compression moduli for rat sciatic nerve at different compression rates to inform computational modeling. Main results . We found that insertion speed and angle had significant effects on peak insertion force. We observed lower insertion forces (10–60 mN) when the device was implanted at higher angles relative to perpendicular insertion (80–125 mN). We also demonstrate the use of a nerve-stabilizing device to keep the nerve immobile during implantation. Additionally, we found that compression moduli were significantly different in small and large strain regions of the stress–strain curve with values between 1500–4500 Pa depending on compression rate. Significance . This study provides information imperative to the design and successful implementation of soft penetrating peripheral nerve interfaces.

Thiol-ene/acrylate-based shape memory polymers (SMPs) with tunable mechanical and thermomechanical properties are promising substrate materials for flexible electronics applications. These UV-curable polymer compositions can easily be polymerized onto pre-fabricated electronic components and can be molded into desired geometries to provide a shape-changing behavior or a tunable softness. Alternatively, SMPs may be prepared as a flat substrate, and electronic circuitry may be built directly on top by thin film processing technologies. Whichever way the final structure is produced, the operation of electronic circuits will be influenced by the electrical and mechanical properties of the underlying (and sometimes also encapsulating) SMP substrate. Here, we present electronic properties, such as permittivity and resistivity of a typical SMP composition that has a low glass transition temperature (between 40 and 60 °C dependent on the curing process) in different thermomechanical states of polymer. We fabricated parallel plate capacitors from a previously reported SMP composition (fully softening (FS)-SMP) using two different curing processes, and then we determined the electrical properties of relative permittivity and resistivity below and above the glass transition temperature. Our data shows that the curing process influenced the electrical permittivity, but not the electrical resistivity. Corona-Kelvin metrology evaluated the quality of the surface of FS-SMP spun on the wafer. Overall, FS-SMP demonstrates resistivity appropriate for use as an insulating material.

Current intracortical probe technology is limited in clinical implementation due to the short functional lifetime of implanted devices. Devices often fail several months to years post-implantation, likely due to the chronic immune response characterized by glial scarring and neuronal dieback. It has been demonstrated that this neuroinflammatory response is influenced by the mechanical mismatch between stiff devices and the soft brain tissue, spurring interest in the use of softer polymer materials for probe encapsulation. Here, we demonstrate stable recordings and electrochemical properties obtained from fully encapsulated shape memory polymer (SMP) intracortical electrodes implanted in the rat motor cortex for 13 weeks. SMPs are a class of material that exhibit modulus changes when exposed to specific conditions. The formulation used in these devices softens by an order of magnitude after implantation compared to its dry, room-temperature modulus of ~2 GPa.

Thiol-ene based shape memory polymers (SMPs) have been developed for use as intracortical microelectrode substrates. The unique chemistry provides precise control over the mechanical and thermal glass-transition properties. As a result, SMP substrates are stiff at room temperature, allowing for insertion into the brain without buckling and subsequently soften in response to body temperatures, reducing the mechanical mismatch between device and tissue. Since the surface chemistry of the materials can contribute significantly to the ultimate biocompatibility, as a first step in the characterization of our SMPs, we sought to isolate the biological response to the implanted material surface without regards to the softening mechanics. To accomplish this, we tightly controlled for bulk stiffness by comparing bare silicon ‘dummy’ devices to thickness-matched silicon devices dip-coated with SMP. The neuroinflammatory response was evaluated after devices were implanted in the rat cortex for 2 or 16 weeks. We observed no differences in the markers tested at either time point, except that astrocytic scarring was significantly reduced for the dip-coated implants at 16 weeks. The surface properties of non-softening thiol-ene SMP substrates appeared to be equally-tolerated and just as suitable as silicon for neural implant substrates for applications such as intracortical microelectrodes, laying the groundwork for future softer devices to improve upon the prototype device performance presented here.

Microelectrode arrays that consistently and reliably record and stimulate neural activity under conditions of chronic implantation have so far eluded the neural interface community due to failures attributed to both biotic and abiotic mechanisms. Arrays with transverse dimensions of 10 µm or below are thought to minimize the inflammatory response; however, the reduction of implant thickness also decreases buckling thresholds for materials with low Young’s modulus. While these issues have been overcome using stiffer, thicker materials as transport shuttles during implantation, the acute damage from the use of shuttles may generate many other biotic complications. Amorphous silicon carbide (a-SiC) provides excellent electrical insulation and a large Young’s modulus, allowing the fabrication of ultrasmall arrays with increased resistance to buckling. Prototype a-SiC intracortical implants were fabricated containing 8 - 16 single shanks which had critical thicknesses of either 4 µm or 6 µm. The 6 µm thick a-SiC shanks could penetrate rat cortex without an insertion aid. Single unit recordings from SIROF-coated arrays implanted without any structural support are presented. This work demonstrates that a-SiC can provide an excellent mechanical platform for devices that penetrate cortical tissue while maintaining a critical thickness less than 10 µm.

Neural implants offer solutions for a variety of clinical issues. While commercially available devices can record neural signals for short time periods, they fail to do so chronically, partially due to the sustained tissue response around the device. Our objective was to assess the correlation between device stiffness, a function of both material modulus and cross-sectional area, and the severity of immune response. Meta-analysis data were derived from nine previously published studies which reported device material and geometric properties, as well as histological outcomes. Device bending stiffness was calculated by treating the device shank as a cantilevered beam. Immune response was quantified through analysis of immunohistological images from each study, specifically looking at fluorescent markers for neuronal nuclei and astrocytes, to assess neuronal dieback and gliosis. Results demonstrate that the severity of the immune response, within the first 50 µm of the device, is highly correlated with device stiffness, as opposed to device modulus or cross-sectional area independently. In general, commercially available devices are around two to three orders of magnitude higher in stiffness than devices which induced a minimal tissue response. These results have implications for future device designs aiming to decrease chronic tissue response and achieve increased long-term functionality.

Mosquitos are among the deadliest insects on the planet due to their ability to transmit diseases like malaria through their bite. In order to bite, a mosquito must insert a set of micro-sized needles through the skin to reach vascular structures. The mosquito uses a combination of mechanisms including an insertion guide to enable it to bite and feed off of larger animals. Here, we report on a biomimetic strategy inspired by the mosquito insertion guide to enable the implantation of intracortical microelectrodes into the brain. Next generation microelectrode designs leveraging ultra-small dimensions and/or flexible materials offer the promise of increased performance, but present difficulties in reliable implantation. With the biomimetic guide in place, the rate of successful microprobe insertion increased from 37.5% to 100% due to the rise in the critical buckling force of the microprobes by 3.8-fold. The prototype guides presented here provide a reproducible method to augment the insertion of small, flexible devices into the brain. In the future, similar approaches may be considered and applied to the insertion of other difficult to implant medical devices.