Long-term stability of intracortical recordings using perforated and arrayed Parylene sheath electrodes

OBJECTIVE Acquisition of reliable and robust neural recordings with intracortical neural probes is a persistent challenge in the field of neuroprosthetics. We developed a multielectrode array technology to address chronic intracortical recording reliability and present in vivo recording results. APPROACH The 2 × 2 Parylene sheath electrode array (PSEA) was microfabricated and constructed from only Parylene C and platinum. The probe includes a novel three-dimensional sheath structure, perforations, and bioactive coatings that improve tissue integration and manage immune response. Coatings were applied using a sequential dip-coating method that provided coverage over the entire probe surface and interior of the sheath structure. A sharp probe tip taper facilitated insertion with minimal trauma. Fabricated probes were subject to examination by optical and electron microscopy and electrochemical testing prior to implantation. MAIN RESULTS 1 × 2 arrays were successfully fabricated on wafer and then packaged together to produce 2 × 2 arrays. Then, probes having electrode sites with adequate electrochemical properties were selected. A subset of arrays was treated with bioactive coatings to encourage neuronal growth and suppress inflammation and another subset of arrays was implanted in conjunction with a virally mediated expression of Caveolin-1. Arrays were attached to a custom-made insertion shuttle to facilitate precise insertion into the rat motor cortex. Stable electrophysiological recordings were obtained during the period of implantation up to 12 months. Immunohistochemical evaluation of cortical tissue around individual probes indicated a strong correlation between the electrophysiological performance of the probes and histologically observable proximity of neurons and dendritic sprouting. SIGNIFICANCE The PSEA demonstrates the scalability of sheath electrode technology and provides higher electrode count and density to access a greater volume for recording. This study provided support for the importance of creating a supportive biological environment around the probes to promote the long-term electrophysiological performance of flexible probes in the cerebral cortex. In particular, we demonstrated beneficial effects of the Matrigel coating and the long-term expression of Caveolin-1. Furthermore, we provided support to an idea of using an artificial acellular tissue compartment as a way to counteract the walling-off effect of the astrocytic scar formation around the probes as a means of establishing a more intimate and stable neural interface.

[1]  Arati Sridharan,et al.  Long-term changes in the material properties of brain tissue at the implant–tissue interface , 2013, Journal of neural engineering.

[2]  D. Kipke,et al.  Insertion shuttle with carboxyl terminated self-assembled monolayer coatings for implanting flexible polymer neural probes in the brain , 2009, Journal of Neuroscience Methods.

[3]  김성준,et al.  Neural stimulation and recording electrode array and method of manufacturing the same , 2012 .

[4]  Xiliang Luo,et al.  Carbon nanotube nanoreservior for controlled release of anti-inflammatory dexamethasone. , 2011, Biomaterials.

[5]  S. Retterer,et al.  Controlling cellular reactive responses around neural prosthetic devices using peripheral and local intervention strategies , 2003, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[6]  A. Michael,et al.  Brain Tissue Responses to Neural Implants Impact Signal Sensitivity and Intervention Strategies , 2014, ACS chemical neuroscience.

[7]  Diana George,et al.  Removable silicon insertion stiffeners for neural probes using polyethylene glycol as a biodissolvable adhesive , 2012, 2012 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[8]  R. Wm A Molecular Perspective on Understanding and Modulating the Performance of Chronic Central Nervous System (CNS) Recording Electrodes -- Indwelling Neural Implants: Strategies for Contending with the In Vivo Environment , 2008 .

[9]  P. Insel,et al.  Neuron-targeted Caveolin-1 Protein Enhances Signaling and Promotes Arborization of Primary Neurons* , 2011, The Journal of Biological Chemistry.

[10]  Patrick A Tresco,et al.  The brain tissue response to implanted silicon microelectrode arrays is increased when the device is tethered to the skull. , 2007, Journal of biomedical materials research. Part A.

[11]  Thomas Stieglitz,et al.  Micromachined devices for interfacing neurons , 1998, Smart Structures.

[12]  David C. Martin,et al.  Sustained release of dexamethasone from hydrophilic matrices using PLGA nanoparticles for neural drug delivery. , 2006, Biomaterials.

[13]  P. Tresco,et al.  Response of brain tissue to chronically implanted neural electrodes , 2005, Journal of Neuroscience Methods.

[14]  Michael L. Roukes,et al.  Iop Publishing Journal of Micromechanics and Microengineering Dual-side and Three-dimensional Microelectrode Arrays Fabricated from Ultra-thin Silicon Substrates , 2022 .

[15]  L. Carin,et al.  Relationship between intracortical electrode design and chronic recording function. , 2013, Biomaterials.

[16]  D. Johnston,et al.  16-METHYLATED STEROIDS. II. 16α-METHYL ANALOGS OF CORTISONE, A NEW GROUP OF ANTI-INFLAMMATORY STEROIDS. 9α-HALO DERIVATIVES , 1958 .

[17]  Dejan Markovic,et al.  Technology-Aware Algorithm Design for Neural Spike Detection, Feature Extraction, and Dimensionality Reduction , 2010, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[18]  P. Kennedy,et al.  Neurotrophic electrode: Method of assembly and implantation into human motor speech cortex , 2008, Journal of Neuroscience Methods.

[19]  S. Yen,et al.  Ultra-thin flexible polyimide neural probe embedded in a dissolvable maltose-coated microneedle , 2014 .

[20]  D. Johnston,et al.  16-METHYLATED STEROIDS. I. 16α-METHYLATED ANALOGS OF CORTISONE, A NEW GROUP OF ANTI-INFLAMMATORY STEROIDS , 1958 .

[21]  Stuart J. Rowan,et al.  Mechanically adaptive nanocomposites for neural interfacing , 2012 .

[22]  R. Bellamkonda,et al.  A Novel Dexamethasone-releasing, Anti-inflammatory Coating for Neural Implants , 2005, Conference Proceedings. 2nd International IEEE EMBS Conference on Neural Engineering, 2005..

[23]  P. Kennedy,et al.  The cone electrode: Ultrastructural studies following long-term recording in rat and monkey cortex , 1992, Neuroscience Letters.

[24]  O. B. Ozdoganlar,et al.  An ultra-compliant, scalable neural probe with molded biodissolvable delivery vehicle , 2012, 2012 IEEE 25th International Conference on Micro Electro Mechanical Systems (MEMS).

[25]  Ravi V. Bellamkonda,et al.  Dexamethasone-coated neural probes elicit attenuated inflammatory response and neuronal loss compared to uncoated neural probes , 2007, Brain Research.

[26]  G. Gabriel,et al.  SU-8 based microprobes with integrated planar electrodes for enhanced neural depth recording. , 2012, Biosensors & bioelectronics.

[27]  R. Jensen,et al.  Tissue Engineering Applied to the Retinal Prosthesis: Neurotrophin-Eluting Polymeric Hydrogel Coatings. , 2008, Materials science & engineering. C, Materials for biological applications.

[28]  S. Cogan,et al.  Neurotrophin-eluting hydrogel coatings for neural stimulating electrodes. , 2007, Journal of biomedical materials research. Part B, Applied biomaterials.

[29]  James D. Weiland,et al.  Electrodeposition and Characterization of Thin-Film Platinum-Iridium Alloys for Biological Interfaces , 2011 .

[30]  D J Weber,et al.  In vivo effects of L1 coating on inflammation and neuronal health at the electrode-tissue interface in rat spinal cord and dorsal root ganglion. , 2012, Acta biomaterialia.

[31]  Andrés J. García,et al.  Host response to microgel coatings on neural electrodes implanted in the brain. , 2014, Journal of biomedical materials research. Part A.

[32]  Ellis Meng,et al.  Formation of three-dimensional Parylene C structures via thermoforming , 2014 .

[33]  X Tracy Cui,et al.  Effects of caspase-1 knockout on chronic neural recording quality and longevity: insight into cellular and molecular mechanisms of the reactive tissue response. , 2014, Biomaterials.

[34]  D. Higgins,et al.  Laminin and a basement membrane extract have different effects on axonal and dendritic outgrowth from embryonic rat sympathetic neurons in vitro. , 1989, Developmental biology.

[35]  Ellis Meng,et al.  An Electrochemical Investigation of the Impact of Microfabrication Techniques on Polymer-Based Microelectrode Neural Interfaces , 2015, Journal of Microelectromechanical Systems.

[36]  P. Kennedy The cone electrode: a long-term electrode that records from neurites grown onto its recording surface , 1989, Journal of Neuroscience Methods.

[37]  Brian J. Kim,et al.  Novel flexible Parylene neural probe with 3D sheath structure for enhancing tissue integration. , 2013, Lab on a chip.

[38]  J. Muthuswamy,et al.  Brain micromotion around implants in the rodent somatosensory cortex , 2006, Journal of neural engineering.

[39]  Robert Puers,et al.  Determining the Young's modulus and creep effects in three different photo definable epoxies for MEMS applications , 2009 .

[40]  Justin C. Williams,et al.  Flexible polyimide-based intracortical electrode arrays with bioactive capability , 2001, IEEE Transactions on Biomedical Engineering.

[41]  Victor Pikov,et al.  Matrigel coatings for Parylene sheath neural probes. , 2016, Journal of biomedical materials research. Part B, Applied biomaterials.

[42]  Kunihiko Mabuchi,et al.  Preliminary Study of Multichannel Flexible Neural Probes Coated with Hybrid Biodegradable Polymer , 2006, 2006 International Conference of the IEEE Engineering in Medicine and Biology Society.

[43]  Frank H. Guenther,et al.  Brain-computer interfaces for speech communication , 2010, Speech Commun..

[44]  R. Bellamkonda,et al.  The effect of inflammatory cell-derived MCP-1 loss on neuronal survival during chronic neuroinflammation. , 2014, Biomaterials.

[45]  André Mercanzini,et al.  Controlled release nanoparticle-embedded coatings reduce the tissue reaction to neuroprostheses. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[46]  D. Kipke,et al.  Neural probe design for reduced tissue encapsulation in CNS. , 2007, Biomaterials.

[47]  G. Gillies,et al.  A realistic brain tissue phantom for intraparenchymal infusion studies. , 2004, Journal of neurosurgery.

[48]  K. Mabuchi,et al.  Parylene flexible neural probes integrated with microfluidic channels. , 2005, Lab on a chip.

[49]  S. Senturia,et al.  Stress in Polyimide Coatings , 1994 .

[50]  David C. Martin,et al.  A finite-element model of the mechanical effects of implantable microelectrodes in the cerebral cortex , 2005, Journal of neural engineering.

[51]  Erdrin Azemi,et al.  Seeding neural progenitor cells on silicon-based neural probes. , 2010, Journal of neurosurgery.

[52]  Jessica K. Nguyen,et al.  Mechanically-compliant intracortical implants reduce the neuroinflammatory response , 2014, Journal of neural engineering.

[53]  F. Pervin,et al.  Mechanically Similar Gel Simulants for Brain Tissues , 2011 .

[54]  Stephen O'Leary,et al.  Delivery of Neurotrophin-3 to the Cochlea using Alginate Beads , 2005, Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology.

[55]  Patrick A Tresco,et al.  Directed nerve outgrowth is enhanced by engineered glial substrates , 2003, Experimental Neurology.

[56]  Patrick A Tresco,et al.  Reducing surface area while maintaining implant penetrating profile lowers the brain foreign body response to chronically implanted planar silicon microelectrode arrays. , 2011, Progress in brain research.

[57]  Brian J. Kim,et al.  3D Parylene sheath neural probe for chronic recordings , 2013, Journal of neural engineering.

[58]  A. Bertsch,et al.  Controlled Release Drug Coatings on Flexible Neural Probes , 2007, 2007 29th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[59]  Garrett B Stanley,et al.  The impact of chronic blood-brain barrier breach on intracortical electrode function. , 2013, Biomaterials.

[60]  C. Bergaud,et al.  Parylene-based flexible neural probes with PEDOT coated surface for brain stimulation and recording. , 2015, Biosensors & bioelectronics.