Microelectrode Arrays Insertion System Using Ultrasonic Vibration to Improve Insertion Mechanics and Reduce Tissue Dimpling and Trauma in the Cortex
NN TIRKO, RS CLEMENT, JK GREASER, AS ALSUBHI, EM STEFFAN, RB BAGWELL, ML MULVIHILL
Actuated Med. Inc., Bellefonte, PA
S LEE, HJ KIM, MF AGHA
University of North Carolina, Chapel Hill, NC
Intracortical Electrode Arrays (IEAs) provide direct access to extracellular neural signals in the brain with high temporal and spatial resolution. Unfortunately, chronically implanted IEAs have limited functional lifespans that impede significant clinical translation. The host tissue reaction is a major contributor to neural interface failure, causing formation of glial scars and loss of neurons at electrode sites. Studies suggest that the initial insertion trauma alone is responsible for significant damage. The forces applied to the cortical tissue during insertion can deform tissue, causing strain and membrane disruptions in underlying neurons and vasculature. While insertion is a technical hurdle common to all IEA types, high-density multi-shank arrays have uniquely significant insertion challenges. Following insertion, the IEA chronic interface can be degraded due to mechanical mismatch between the IEA and the cortical tissue. Superior tissue response and device longevity has been demonstrated with ultra-fine microwire (<15 µm diameter) and flexible (e.g., polyimide) arrays. However, given their tendency to buckle/break during insertion they struggle to penetrate meningeal layers and temporary support structures, shuttles, or dissolvable stiffeners are often necessary for mechanical reinforcement during insertion. This increases the complexity and time of the surgery and insertion process, and may limit reliable electrode performance and adaptation of these arrays.
Ultrasonic vibration of IEAs represents a promising approach to reduce frictional and penetration forces associated with insertion. We have demonstrated that this approach has implantation capability of both rigid, multi-shank arrays and mechanically soft microwire or polymer-based arrays. In the case of rigid arrays (i.e. silicon shanks from NeuroNexus, Blackrock and microwires from MicroProbes, Tucker Davis Technologies) vibration-assisted insertion reduces insertion force 61-82% relative to standard insertion via stereotaxic equipment when using an agar model (0.5% base, 1.5% top layer). In vivo studies demonstrated a significant (p<0.01) reduction in cortical surface dimpling/compression with vibration during insertion of silicon arrays (NeuroNexus H-series) into rat cortex, as well as successful insertion through the dura. Electrodes inserted with vibration have no detriment to electrophysiology signal quality.
In the case of flexible arrays, vibration-assisted insertion both reduces insertion force and improves insertion trajectory. Polyimide thin-film single-shanks probes were inserted in rat nucleus accumbens without vibration (n=6), with vibration through pia (n=10) and with vibration through dura (n=5). Using T2-weighted MRI, insertion accuracy was measured; targeting success was improved with vibration (through pia: 70%, through dura: 83%) as compared to Control (50%; p>0.05 due to limited sample size). Ten days after surgery, neuromodulation outcomes (evoked response patterns, as measured through fMRI) were increased with the vibration-inserted electrodes (through pia: 100%, through dura: 80%) versus Control (66%). Additionally, histological evaluation of the implantation site (4 weeks post-op) revealed that the intensity of glial scaring (visualized via glial fibrillary acidic protein immunohistochemistry) was significantly reduced when electrodes were inserted with vibration (p<0.05) relative to Control. Together, these benchtop insertion studies in agar and ex vivo tissue models, as well as in vivo insertion studies support the potential of vibrated insertion for improved outcomes for studies using IEAs, specifically for flexible electrodes.