Versatile, modular 3D microelectrode arrays for neuronal ensemble recordings: from design to fabrication, assembly, and functional validation in non-human primates

OBJECTIVE Application-specific designs of electrode arrays offer an improved effectiveness for providing access to targeted brain regions in neuroscientific research and brain machine interfaces. The simultaneous and stable recording of neuronal ensembles is the main goal in the design of advanced neural interfaces. Here, we describe the development and assembly of highly customizable 3D microelectrode arrays and demonstrate their recording performance in chronic applications in non-human primates. APPROACH System assembly relies on a microfabricated stacking component that is combined with Michigan-style silicon-based electrode arrays interfacing highly flexible polyimide cables. Based on the novel stacking component, the lead time for implementing prototypes with altered electrode pitches is minimal. Once the fabrication and assembly accuracy of the stacked probes have been characterized, their recording performance is assessed during in vivo chronic experiments in awake rhesus macaques (Macaca mulatta) trained to execute reaching-grasping motor tasks. MAIN RESULTS Using a single set of fabrication tools, we implemented three variants of the stacking component for electrode distances of 250, 300 and 350 µm in the stacking direction. We assembled neural probes with up to 96 channels and an electrode density of 98 electrodes mm-2. Furthermore, we demonstrate that the shank alignment is accurate to a few µm at an angular alignment better than 1°. Three 64-channel probes were chronically implanted in two monkeys providing single-unit activity on more than 60% of all channels and excellent recording stability. Histological tissue sections, obtained 52 d after implantation from one of the monkeys, showed minimal tissue damage, in accordance with the high quality and stability of the recorded neural activity. SIGNIFICANCE The versatility of our fabrication and assembly approach should significantly support the development of ideal interface geometries for a broad spectrum of applications. With the demonstrated performance, these probes are suitable for both semi-chronic and chronic applications.

[1]  Patrick Ruther,et al.  Application of floating silicon-based linear multielectrode arrays for acute recording of single neuron activity in awake behaving monkeys , 2014, Biomedizinische Technik. Biomedical engineering.

[2]  R. Normann,et al.  A Novel Method of Fabricating Convoluted Shaped Electrode Arrays for Neural and Retinal Prosthesis , 2007, TRANSDUCERS 2007 - 2007 International Solid-State Sensors, Actuators and Microsystems Conference.

[3]  J.P. Donoghue,et al.  Reliability of signals from a chronically implanted, silicon-based electrode array in non-human primate primary motor cortex , 2005, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[4]  Patrick Ruther,et al.  Novel method for the assembly and electrical contacting of out-of-plane microstructures , 2010, 2010 IEEE 23rd International Conference on Micro Electro Mechanical Systems (MEMS).

[5]  G. Rizzolatti,et al.  Architecture of superior and mesial area 6 and the adjacent cingulate cortex in the macaque monkey , 1991, The Journal of comparative neurology.

[6]  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 .

[7]  P. Tresco,et al.  A new high-density (25 electrodes/mm2) penetrating microelectrode array for recording and stimulating sub-millimeter neuroanatomical structures , 2013, Journal of neural engineering.

[8]  Arjun K. Bansal,et al.  Decoding 3D reach and grasp from hybrid signals in motor and premotor cortices: spikes, multiunit activity, and local field potentials. , 2012, Journal of neurophysiology.

[9]  G. Rizzolatti,et al.  Extending the Cortical Grasping Network: Pre-supplementary Motor Neuron Activity During Vision and Grasping of Objects , 2016, Cerebral cortex.

[10]  Thomas Lenarz,et al.  Investigation of a New Electrode Array Technology for a Central Auditory Prosthesis , 2013, PloS one.

[11]  N. Shimizu,et al.  Novel wafer dicing and chip thinning technologies realizing high chip strength , 2006, 56th Electronic Components and Technology Conference 2006.

[12]  Maurits Ortmanns,et al.  A 232-channel retinal vision prosthesis with a miniaturized hermetic package , 2012, 2012 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[13]  Patrick Ruther,et al.  A Novel Assembly Method for Silicon-Based Neural Devices , 2009 .

[14]  Alessandro Livi,et al.  Space-Dependent Representation of Objects and Other's Action in Monkey Ventral Premotor Grasping Neurons , 2014, The Journal of Neuroscience.

[15]  T. Stieglitz,et al.  CMOS-Based High-Density Silicon Microprobe Array for Electronic Depth Control in Neural Recording , 2009, 2009 IEEE 22nd International Conference on Micro Electro Mechanical Systems.

[16]  Richard A Normann,et al.  Technology Insight: future neuroprosthetic therapies for disorders of the nervous system , 2007, Nature Clinical Practice Neurology.

[17]  Patrick Ruther,et al.  Modular assembly concept for 3D neural probe prototypes offering high freedom of design and alignment precision , 2014, 2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[18]  R. Oostenveld,et al.  A MEMS-based flexible multichannel ECoG-electrode array , 2009, Journal of neural engineering.

[19]  Robert Puers,et al.  An interconnect for out-of-plane assembled biomedical probe arrays , 2008 .

[20]  István Ulbert,et al.  A novel multisite silicon probe for laminar neural recordings , 2011, FET.

[21]  Marzio Gerbella,et al.  Multimodal architectonic subdivision of the rostral part (area F5) of the macaque ventral premotor cortex , 2009, The Journal of comparative neurology.

[22]  Chih-Wei Chang,et al.  A Wireless and Batteryless Microsystem with Implantable Grid Electrode/3-Dimensional Probe Array for ECoG and Extracellular Neural Recording in Rats , 2013, 2011 16th International Solid-State Sensors, Actuators and Microsystems Conference.

[23]  Nicholas V. Annetta,et al.  Restoring cortical control of functional movement in a human with quadriplegia , 2016, Nature.

[24]  R. Andersen,et al.  A floating metal microelectrode array for chronic implantation , 2007, Journal of Neuroscience Methods.

[25]  R. Stein,et al.  Selective stimulation of cat sciatic nerve using an array of varying-length microelectrodes. , 2001, Journal of neurophysiology.

[26]  Ming-Yuan Cheng,et al.  3D probe array integrated with a front-end 100-channel neural recording ASIC , 2014 .

[27]  Justin C. Williams,et al.  Chronic neural recording using silicon-substrate microelectrode arrays implanted in cerebral cortex , 2004, IEEE Transactions on Biomedical Engineering.

[28]  Alessandro Livi,et al.  Mirror Neuron Activation Prior to Action Observation in a Predictable Context , 2014, The Journal of Neuroscience.

[29]  P. Donaldson,et al.  The essential role played by adhesion in the technology of neurological prostheses , 1996 .

[30]  Patrick Ruther,et al.  Novel technology for the in-plane to out-of-plane transfer of multiple interconnection lines in 3D neural probes , 2013, 2013 Transducers & Eurosensors XXVII: The 17th International Conference on Solid-State Sensors, Actuators and Microsystems (TRANSDUCERS & EUROSENSORS XXVII).

[31]  K. Horch,et al.  A silicon-based, three-dimensional neural interface: manufacturing processes for an intracortical electrode array , 1991, IEEE Transactions on Biomedical Engineering.

[32]  Patrick Ruther,et al.  Large-scale recording of thalamocortical circuits: in vivo electrophysiology with the two-dimensional electronic depth control silicon probe. , 2016, Journal of neurophysiology.

[33]  Rajmohan Bhandari,et al.  Long-term reliability of Al2O3 and Parylene C bilayer encapsulated Utah electrode array based neural interfaces for chronic implantation , 2014, Journal of neural engineering.

[34]  Sundman Bo.,et al.  エレクトロウェッティングディスプレイの油脱ぬれパターンの観測と光学的意味 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター , 2008 .

[35]  Kensall D. Wise,et al.  A compact architecture for three-dimensional neural microelectrode arrays , 2008, 2008 30th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[36]  Rafael Yuste,et al.  Nanotools for neuroscience and brain activity mapping. , 2013, ACS nano.

[37]  K. Wise,et al.  An integrated-circuit approach to extracellular microelectrodes. , 1970, IEEE transactions on bio-medical engineering.

[38]  O. Paul,et al.  Out-of-plane assembly of 3D neural probe arrays using a platform with SU-8-based thermal actuators , 2011, 2011 16th International Solid-State Sensors, Actuators and Microsystems Conference.

[39]  Patrick Ruther,et al.  Fabrication technology for silicon-based microprobe arrays used in acute and sub-chronic neural recording , 2009 .

[40]  Onnop Srivannavit,et al.  A 3-D 160-Site Microelectrode Array for Cochlear Nucleus Mapping , 2011, IEEE Transactions on Biomedical Engineering.

[41]  O. Paul,et al.  Ultrathin Silicon Chips of Arbitrary Shape by Etching Before Grinding , 2011, Journal of Microelectromechanical Systems.

[42]  Patrick Ruther,et al.  Recent Progress in Neural Probes Using Silicon MEMS Technology , 2010 .

[43]  M. M. H. Shandhi,et al.  A novel method of fabricating high channel density neural array for large neuronal mapping , 2015, 2015 Transducers - 2015 18th International Conference on Solid-State Sensors, Actuators and Microsystems (TRANSDUCERS).

[44]  K. E. Jones,et al.  A glass/silicon composite intracortical electrode array , 2006, Annals of Biomedical Engineering.

[45]  Refet Firat Yazicioglu,et al.  Time multiplexed active neural probe with 678 parallel recording sites , 2016, 2016 46th European Solid-State Device Research Conference (ESSDERC).