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

Abstract

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.

Ultrasoft microwire neural electrodes improve chronic tissue integration

“…Surface factors include hydrophilicity [9–11,48], texture [49,50] and presence or absence of bioactive molecules [51–53]. Bulk properties include size and geometry of the device [47,48,54–56] as well as the stiffness of the implanted materials [57]. Current neural probes are fabricated with very rigid materials with a high Young’s modulus (E) such as tungsten (E = 400 GPa), silicon (E = 200 GPa), polyimide (E = 3 GPa) or parylene C (E = 2–5 GPa), while the brain tissue is very soft (E = 0.4–15 kPa) [58–61].…”

Neuroadhesive L1 coating attenuates acute microglial attachment to neural electrodes as revealed by live two-photon microscopy

“…This includes changing the footprint of the probe or the probe’s electrode sites [18,36,44,47–51,160], altering recording site materials [48,52–57], applying flexible geometries or soft materials [26,27,36,58–62,161,162], creating dissolvable insertion shuttles for softer probe materials [63], locally delivering anti-inflammatory or neuroprotective drugs [64–75], and modifying the probe’s surface chemistry [36,76–78]. …”

Recent advances in neural electrode–tissue interfaces

“…Increasing flexibility can be achieved via reducing the cross sectional area [50] or increasing the length of the device, without changing the material properties [74]. Alternatively, novel soft and/or elastic conducting materials may be developed.…”