title: 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 × 10-2μN/μm in the axial direction, and 2.6 × 10-5μN/μm and 1.8 × 10-6μN/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.
authors: Department of Mechanical Engineering, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA, 15213, USA.
authors: Rakesh
authors: R
authors: Khilwani
authors: Department of Electrical and Computer Engineering, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA, 15213, USA.
authors: Peter J
authors: PJ
authors: Gilgunn
authors: Department of Bioengineering, University of Pittsburgh, 4200 Fifth Avenue, Pittsburgh, PA, 15260, USA.|Center for the Neural Basis of Cognition, University of Pittsburgh, 4400 Fifth Ave, Pittsburgh, PA, 15213, USA.|McGowan Institute of Regenerative Medicine, University of Pittsburgh, 450 Technology Dr, Ste 300, Pittsburgh, PA, 15219, USA.|NeuroTech Center, University of Pittsburgh Brain Institute, University of Pittsburgh, 3501 Fifth Avenue, Pittsburgh, PA, 15261, USA.
authors: Takashi D Y
authors: TD
authors: Kozai
authors: Department of Electrical and Computer Engineering, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA, 15213, USA.
authors: Xiao Chuan
authors: XC
authors: Ong
authors: Department of Mechanical Engineering, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA, 15213, USA.
authors: Emrullah
authors: E
authors: Korkmaz
authors: Department of Biomedical Engineering, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA, 15213, USA.
authors: Pallavi K
authors: PK
authors: Gunalan
authors: Department of Bioengineering, University of Pittsburgh, 4200 Fifth Avenue, Pittsburgh, PA, 15260, USA.|Center for the Neural Basis of Cognition, University of Pittsburgh, 4400 Fifth Ave, Pittsburgh, PA, 15213, USA.|McGowan Institute of Regenerative Medicine, University of Pittsburgh, 450 Technology Dr, Ste 300, Pittsburgh, PA, 15219, USA.
authors: X Tracy
authors: XT
authors: Cui
authors: Department of Mechanical Engineering, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA, 15213, USA.|Department of Electrical and Computer Engineering, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA, 15213, USA.|Department of Biomedical Engineering, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA, 15213, USA.|The Robotics Institute, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA, 15213, USA.
authors: Gary K
authors: GK
authors: Fedder
authors: Department of Mechanical Engineering, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA, 15213, USA. ozdoganlar@cmu.edu.|Department of Biomedical Engineering, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA, 15213, USA. ozdoganlar@cmu.edu.|Department of Materials Science and Engineering, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA, 15213, USA. ozdoganlar@cmu.edu.
authors: O Burak
authors: OB
authors: Ozdoganlar
mesh_terms: D062207:Brain-Computer Interfaces; D055119:Elastic Modulus; D004567:Electrodes, Implanted; D004867:Equipment Design; D055595:Mechanical Phenomena; D055616:Microtechnology / Q000295:instrumentation*; D008954:Models, Biological; D009339:Needles
keywords: Brain-computer interfaces; Dissolvable polymer microneedles; Flexible probes; Microelectrode; Micromolding; Micromotion; Neural probes