Stable chronic functionality of intracortical probes is of utmost importance toward realizing clinical application of brain-machine interfaces. Sustained immune response from the brain tissue to the neural probes is one of the major challenges that hinder stable chronic functionality. There is a growing body of evidence in the literature that highly compliant neural probes with sub-cellular dimensions may significantly reduce the foreign-body response, thereby enhancing long term stability of intracortical recordings. Since the prevailing commercial probes are considerably larger than neurons and of high stiffness, new approaches are needed for developing miniature probes with high compliance. In this paper, we present design, fabrication, and in vitro evaluation of ultra-miniature (2.7 μm x 10 μm cross section), ultra-compliant (1.4 × 10 μN/μm in the axial direction, and 2.6 × 10 μN/μm and 1.8 × 10 μN/μm in the lateral directions) neural probes and associated probe-encasing biodissolvable delivery needles toward addressing the aforementioned challenges. The high compliance of the probes is obtained by micron-scale cross-section and meandered shape of the parylene-C insulated platinum wiring. Finite-element analysis is performed to compare the strains within the tissue during micromotion when using the ultra-compliant meandered probes with that when using stiff silicon probes. The standard batch microfabrication techniques are used for creating the probes. A dissolvable delivery needle that encases the probe facilitates failure-free insertion and precise placement of the ultra-compliant probes. Upon completion of implantation, the needle gradually dissolves, leaving behind the ultra-compliant neural probe. A spin-casting based micromolding approach is used for the fabrication of the needle. To demonstrate the versatility of the process, needles from different biodissolvable materials, as well as two-dimensional needle arrays with different geometries and dimensions, are fabricated. Further, needles incorporating anti-inflammatory drugs are created to show the co-delivery potential of the needles. An automated insertion device is developed for repeatable and precise implantation of needle-encased probes into brain tissue. Insertion of the needles without mechanical failure, and their subsequent dissolution are demonstrated. It is concluded that ultra-miniature, ultra-compliant probes and associated biodissolvable delivery needles can be successfully fabricated, and the use of the ultra-compliant meandered probes results in drastic reduction in strains imposed in the tissue as compared to stiff probes, thereby showing promise toward chronic applications.
Structural analysis of explanted and Utah microelectrode arrays (MEA) was performed using scanning electron microscopy (SEM) and energy dispersive x-ray spectroscopy (EDS) to determine the impact of prolonged exposure to the IN VIVO environment. The MEAs, one designed for recording and one designed for stimulation, had been implanted in the pre-and postcentral gyri, respectively, of a rhesus macaque for 362 days, prior to explantation. Possible processing, handling or implantation damage was observed on individual electrodes on each MEA. Metal degradation/delamination was observed on the stimulating MEA while residual carbon-based matter on the electrode sites and small fissures in the insulation were observed on the recording MEA. The electrode area of the recording MEA had a 5.0x range and the stimulating MEA had a 7.6x range, which did not appear to be related to long-term exposure to tissue.
A fully-dry, flip-chip fabrication technology was developed for the integration of high fill factor, silicon-on-insulator (SOI) structures and CMOS-MEMS actuators. An SOI mirror array with a fill factor of 95% and radius of curvature >1.3 m was fabricated on CMOS-MEMS electrothermal actuators using this technology. The unloaded actuators achieved an optical scan range of >92º. Following flip-chip bonding with high temperature epoxy, the structures were released using deep reactive ion etching (DRIE). Aspect ratio dependent etching (ARDE) modulated local structural silicon thickness on the CMOS-MEMS actuators and reduced notching and microtrenching on the posts of the SOI mirrors.
Ultra-compliant neural probes implanted into tissue using a molded, biodissolvable sodium carboxymethyl cellulose (Na-CMC)-saccharide composite needle delivery vehicle are subjected to fluid-structure interactions that can displace the recording site of the probe with respect to its designed implant location. We applied particle velocimetry to analyze the behavior of ultra-compliant structures under different implantation conditions for a range of CMC-based materials and identified a fluid management protocol that resulted in the successful targeted depth placement of the recording sites.
A time-multiplexed, anisotropic, inductively coupled plasma Si deep reactive ion etch process is characterized in terms of the Si macroload, cross-wafer spatial variation, local pattern density, and feature size. The process regime is established as neutral flux limited, in which material transport occurs in the molecular flow to transition flow regimes. For this process regime, a semiempirical, unified analytic model and a numeric model are developed using the Dushman and Clausing vacuum conductance correction factors, respectively, in the Coburn and Winters model of aspect ratio dependent etching. The experimental reaction probability for etching of Si by F was found to be 0.24 for Dushman’s factor and 0.22 for Clausing’s factor. Each model is validated to ±10% against experimental depth data for microdonut and trench test structures and match each other to within 10% for depths of up to 160 μm. The observed depth range is 64 μm at a depth of 160 μm.
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