Insulation of thin-film parylene-C/platinum probes in saline solution through encapsulation in multilayer ALD ceramic films.

The long-term electrical leakage performance of parylene-C/platinum/parylene-C (Px/Pt/Px) interconnect in saline is evaluated using electrochemical impedance spectroscopy (EIS). Three kinds of additional ceramic encapsulation layers between the metal and Px are characterized: 50 nm-thick alumina (Al2O3), 50 nm-thick titania (TiO2), and 80 nm-thick Al2O3-TiO2 nanolaminate (NL). The Al2O3 and TiO2 encapsulation layers worsen the overall insulation properties. The NL encapsulation layer improves the insulation when combined with a TiO2 outer layer to promote adhesion to the Px. Experiments are performed with various insulation promotion treatments: A-174 silane (A174) treatment before Px deposition (to promote adhesion); SF6 plasma treatment (F) after Px deposition (to increase hydrophobicity); and ion-milling descum (IM) after Px deposition (to prevent parylene oxidation). A174 and F treatments do not have a significant impact, while IM leads to worse insulation performance. A circuit model elucidates the insulation characteristics of Px-ceramic-Pt-ceramic-Px interconnect. These studies provide a foundation for processing ultra-compliant neural probes with long-term chronic utility.

Ultra-miniature ultra-compliant neural probes with dissolvable delivery needles: design, fabrication and characterization.

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 × 10-2 µN/µm in the axial direction, and 2.6 × 10-5 µN/µm and 1.8 × 10-6 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.

Dissolvable microneedle arrays for intradermal delivery of biologics: fabrication and application.

PURPOSE: Design and evaluate a new micro-machining based approach for fabricating dissolvable microneedle arrays (MNAs) with diverse geometries and from different materials for dry delivery to skin microenvironments. The aims are to describe the new fabrication method, to evaluate geometric and material capability as well as reproducibility of the method, and to demonstrate the effectiveness of fabricated MNAs in delivering bioactive molecules. METHODS: Precise master molds were created using micromilling. Micromolding was used to create elastomer production molds from master molds. The dissolvable MNAs were then fabricated using the spin-casting method. Fabricated MNAs with different geometries were evaluated for reproducibility. MNAs from different materials were fabricated to show material capability. MNAs with embedded bioactive components were tested for functionality on human and mice skin. RESULTS: MNAs with different geometries and from carboxymethyl cellulose, polyvinyl pyrrolidone and maltodextrin were created reproducibly using our method. MNAs successfully pierce the skin, precisely deliver their bioactive cargo to skin and induce specific immunity in mice. CONCLUSIONS: We demonstrated that the new fabrication approach enables creating dissolvable MNAs with diverse geometries and from different materials reproducibly. We also demonstrated the application of MNAs for precise and specific delivery of biomolecules to skin microenvironments in vitro and in vivo.

Chronic tissue response to carboxymethyl cellulose based dissolvable insertion needle for ultra-small neural probes.

Implantable neural electrodes must drastically improve chronic recording stability before they can be translated into long-term human clinical prosthetics. Previous studies suggest that sub-cellular sized and mechanically compliant probes may result in improved tissue integration and recording longevity. However, currently these design features are restricted by the opposing mechanical requirements needed for minimally damaging insertions. We designed a non-cytotoxic, carboxymethylcellulose (CMC) based dissolvable delivery vehicle (shuttle) to provide the mechanical support for insertion of ultra-small, ultra-compliant microfabricated neural probes. Stiff CMC-based shuttles rapidly soften immediately after being placed ∼1 mm above an open craniotomy as they absorb vapors from the brain. To address this, we developed a sophisticated targeting, high speed insertion (∼80 mm/s), and release system to implant these shuttles. After implantation, the goal is for the shuttle to dissolve away leaving only the electrodes behind. Here we show the histology of chronically implanted shuttles of large (300 µm × 125 µm) and small (100 µm × 125 µm) size at discrete time points over 12 weeks. Early time points show the CMC shuttle expanded after insertion as it absorbed moisture from the brain and slowly dissolved. At later time points neuronal cell bodies populate regions within the original shuttle tract. The large CMC shuttles show that the CMC expansion can cause extended secondary damage. On the other hand, the smaller CMC shuttles show limited secondary damage, wound closure by 4 weeks, absence of activated microglia at 12 weeks, as well as evidence suggesting neural regeneration at the implant site. This shuttle, therefore, shows great promise facilitating the implantation of nontraditional ultra-small, and ultra-compliant probes.