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

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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 × 10-2 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.

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Acknowledgments

The authors would like to thank Prof. Shawn Lister and Pratiti Mandal for assistance with Xradia UltraXRM-L200 for nano-CT images. This work was supported in part by the Defense Advanced Research Projects Agency (DARPA) Biological Technologies Office (BTO) Electrical Prescriptions (ElectRx) program under the auspices of Dr. Douglas J. Weber through the Space and Naval Warfare Systems Center (SPAWAR) – Pacific, Cooperative Agreement No. HR0011-15-2-0009 and Microsystems Technology Office (MTO) under the auspices of Dr. Jack Judy through the SPAWAR, Pacific Award No. N66001-11-1-4025. Any opinions, findings, and conclusions or recommendations expressed in this publication are those of the authors and do not necessarily reflect the views of SPAWAR or DARPA.

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Authors and Affiliations

  1. Department of Mechanical Engineering, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA, 15213, USA

    Rakesh Khilwani, Emrullah Korkmaz, Gary K. Fedder & O. Burak Ozdoganlar

  2. Department of Electrical and Computer Engineering, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA, 15213, USA

    Peter J. Gilgunn, Xiao Chuan Ong & Gary K. Fedder

  3. Department of Bioengineering, University of Pittsburgh, 4200 Fifth Avenue, Pittsburgh, PA, 15260, USA

    Takashi D. Y. Kozai & X. Tracy Cui

  4. Center for the Neural Basis of Cognition, University of Pittsburgh, 4400 Fifth Ave, Pittsburgh, PA, 15213, USA

    Takashi D. Y. Kozai & X. Tracy Cui

  5. McGowan Institute of Regenerative Medicine, University of Pittsburgh, 450 Technology Dr, Ste 300, Pittsburgh, PA, 15219, USA

    Takashi D. Y. Kozai & X. Tracy Cui

  6. NeuroTech Center, University of Pittsburgh Brain Institute, University of Pittsburgh, 3501 Fifth Avenue, Pittsburgh, PA, 15261, USA

    Takashi D. Y. Kozai

  7. Department of Biomedical Engineering, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA, 15213, USA

    Pallavi K. Gunalan, Gary K. Fedder & O. Burak Ozdoganlar

  8. The Robotics Institute, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA, 15213, USA

    Gary K. Fedder

  9. Department of Materials Science and Engineering, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA, 15213, USA

    O. Burak Ozdoganlar

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  1. Rakesh Khilwani
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Khilwani, R., Gilgunn, P.J., Kozai, T.D.Y. et al. Ultra-miniature ultra-compliant neural probes with dissolvable delivery needles: design, fabrication and characterization. Biomed Microdevices 18, 97 (2016). https://doi.org/10.1007/s10544-016-0125-4

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