Biodissolvable Delivery Vehicles for Ultra-Miniature Ultra-Compliant Neural Probes: Fabrication, Characterization, and Insertion Force Analysis

Brain-Machine Interfaces (BMIs) have emerged as a viable technology for interacting with central nervous system (CNS) to facilitate understanding different functions of healthy brains and basis of neurological disorders. Neural probes are a fundamental component of BMIs. Stable chronic functionality of neural probes is of utmost importance towards realizing clinical application of BMIs. However, sustained immune response from the brain tissue to the prevailing large and stiff 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 can significantly reduce the foreign-body response, thereby enhancing long-term stability of intracortical recordings. However, a trade-off of reducing the probe size and increasing flexibility of the probe is failure prone insertion of the probes into targeted brain regions. The subcellular-sized and highly-compliant neural probes commonly lack the mechanical strength to penetrate the brain tissue. As such, there is a need for plausible delivery strategies to successfully implant flexible neural probes with sub-cellular dimensions. One of the most promising approach is to use a delivery vehicle in the form of a micro-scale needle made from dissolvable and biocompatible materials. During penetration/placement of the probe, the needle provides sufficient strength and stiffness, and subsequently dissolves away, leaving behind only the ultra-compliant, ultra-miniature neural probe. As such, a short-term placement of the delivery needle considerably reduces the chronic damage to the brain tissue with respect to permanent placement of a similarly-sized probe. Although biodissolvable delivery vehicles offer attractive advantages, significant further advances are needed to address critical challenges for their design, fabrication, and application. These challenges involve (1) design, including selection of needle geometry and materials; (2) fabrication, including accurate and reproducible manufacturing approaches; and (3) characterization, including analyses on both their geometric and mechanical properties, as well as on the relationship between insertion forces and design/insertion parameters. In this doctoral research, we propose a novel biodissolvable neural probe delivery vehicle concept for effective, precise, and reproducible delivery of ultra-miniature and ultra-compliant probes to targeted brain regions. The overarching objectives of this doctoral research are to devise and evaluate a new manufacturing strategy for accurate and reproducible fabrication of biodissolvable delivery vehicles with desired geometries; and to understand the relationship between the needle design and insertion conditions towards identifying favorable insertion and design parameters. To address these objectives, we developed novel fabrication techniques for accurate and reproducible manufacturing of biodissolvable delivery vehicles (for ultra-miniature and ultra-compliant probes) with diverse geometries and from different biocompatible and dissolvable materials. We then studied the effects of design parameters and insertion speeds on insertion forces for non-dissolvable and biodissolvable delivery vehicles towards gaining a comprehensive understanding on the tissue-needle interaction.