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Micromachines
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Neural Microelectrodes: Design and Applications
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Neural Microelectrodes: Design and Applications

A special issue of Micromachines (ISSN 2072-666X). This special issue belongs to the section "B：Biology and Biomedicine".

Deadline for manuscript submissions: closed (31 July 2018) | Viewed by 126973

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Prof. Dr. Joseph Pancrazio

E-Mail Website
Guest Editor
Department of Bioengineering, University of Texas at Dallas, Richardson, TX 75080, USA
Interests: neural interface devices; neural stimulation and recording; implantable microelectrode arrays; neuronal networks
Prof. Dr. Stuart Cogan

E-Mail Website
Guest Editor
Department of Bioengineering, University of Texas at Dallas, Richardson, TX 75080, USA
Interests: neural stimulation and recording; thin-film optical switching devices; chronic implants; multielectrode devices; implantable encapsulation

Special Issue Information

Dear Colleagues,

Neural electrodes enable the recording and stimulation of bioelectrical activity from the nervous system. This technology provides neuroscientists with the means to probe the functionality of neural circuitry in both health and disease. In addition, neural electrodes can deliver therapeutic stimulation for the relief of debilitating symptoms associated with neurological disorders such as Parkinson’s Disease and may serve as the basis for the restoration of sensory perception through peripheral nerve and brain regions after disease or injury. Lastly, microscale neural electrodes recording signals associated with volitional movement in paralyzed individuals can be decoded for controlling external devices, prosthetic limbs, or driving the stimulation of paralyzed muscles for functional movements. In spite of the promise of neural electrodes for a range of applications, chronic performance remains a goal for long term basic science studies as well as clinical applications. New perspectives and opportunities from fields including tissue biomechanics, material science, and biological mechanisms of inflammation and neurodegeneration are critical to advances in neural electrode technology. This Special Issue will address the state-of-the-art knowledge and emerging opportunities for the development and demonstration of advanced neural electrodes.

Prof. Dr. Joseph Pancrazio
Prof. Dr. Stuart Cogan
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Micromachines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • neural interface devices
  • neural stimulation and recording
  • neuronal networks
  • neural electrodes
  • neural implants

Published Papers (24 papers)

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Editorial

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6 pages, 175 KiB  
Editorial
Editorial for the Special Issue on Neural Electrodes: Design and Applications
by Joseph J. Pancrazio and Stuart F. Cogan
Micromachines 2019, 10(7), 466; https://doi.org/10.3390/mi10070466 - 12 Jul 2019
Cited by 3 | Viewed by 2416
Abstract
Neural electrodes enable the recording and stimulation of bioelectrical activity from the nervous system [...] Full article
(This article belongs to the Special Issue Neural Microelectrodes: Design and Applications)

Research

Jump to: Editorial, Review, Other

15 pages, 3563 KiB  
Article
Dextran as a Resorbable Coating Material for Flexible Neural Probes
by Dries Kil, Marta Bovet Carmona, Frederik Ceyssens, Marjolijn Deprez, Luigi Brancato, Bart Nuttin, Detlef Balschun and Robert Puers
Micromachines 2019, 10(1), 61; https://doi.org/10.3390/mi10010061 - 17 Jan 2019
Cited by 22 | Viewed by 4930
Abstract
In the quest for chronically reliable and bio-tolerable brain interfaces there has been a steady evolution towards the use of highly flexible, polymer-based electrode arrays. The reduced mechanical mismatch between implant and brain tissue has shown to reduce the evoked immune response, which [...] Read more.
In the quest for chronically reliable and bio-tolerable brain interfaces there has been a steady evolution towards the use of highly flexible, polymer-based electrode arrays. The reduced mechanical mismatch between implant and brain tissue has shown to reduce the evoked immune response, which in turn has a positive effect on signal stability and noise. Unfortunately, the low stiffness of the implants also has practical repercussions, making surgical insertion extremely difficult. In this work we explore the use of dextran as a coating material that temporarily stiffens the implant, preventing buckling during insertion. The mechanical properties of dextran coated neural probes are characterized, as well as the different parameters which influence the dissolution rate. Tuning parameters, such as coating thickness and molecular weight of the used dextran, allows customization of the stiffness and dissolution time to precisely match the user’s needs. Finally, the immunological response to the coated electrodes was analyzed by performing a histological examination after four months of in vivo testing. The results indicated that a very limited amount of glial scar tissue was formed. Neurons have also infiltrated the area that was initially occupied by the dissolving dextran coating. There was no noticeable drop in neuron density around the site of implantation, confirming the suitability of the coating as a temporary aid during implantation of highly flexible polymer-based neural probes. Full article
(This article belongs to the Special Issue Neural Microelectrodes: Design and Applications)
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18 pages, 5870 KiB  
Article
Remote Stimulation of Sciatic Nerve Using Cuff Electrodes and Implanted Diodes
by Arati Sridharan, Sanchit Chirania, Bruce C. Towe and Jit Muthuswamy
Micromachines 2018, 9(11), 595; https://doi.org/10.3390/mi9110595 - 14 Nov 2018
Cited by 6 | Viewed by 6243
Abstract
We demonstrate a method of neurostimulation using implanted, free-floating, inter-neural diodes. They are activated by volume-conducted, high frequency, alternating current (AC) fields and address the issue of instability caused by interconnect wires in chronic nerve stimulation. The aim of this study is to [...] Read more.
We demonstrate a method of neurostimulation using implanted, free-floating, inter-neural diodes. They are activated by volume-conducted, high frequency, alternating current (AC) fields and address the issue of instability caused by interconnect wires in chronic nerve stimulation. The aim of this study is to optimize the set of AC electrical parameters and the diode features to achieve wireless neurostimulation. Three different packaged Schottky diodes (1.5 mm, 500 µm and 220 µm feature sizes) were tested in vivo (n = 17 rats). A careful assessment of sciatic nerve activation as a function of diode–dipole lengths and relative position of the diode was conducted. Subsequently, free-floating Schottky microdiodes were implanted in the nerve (n = 3 rats) and stimulated wirelessly. Thresholds for muscle twitch responses increased non-linearly with frequency. Currents through implanted diodes within the nerve suffer large attenuations (~100 fold) requiring 1–2 mA drive currents for thresholds at 17 µA. The muscle recruitment response using electromyograms (EMGs) is intrinsically steep for subepineurial implants and becomes steeper as diode is implanted at increasing depths away from external AC stimulating electrodes. The study demonstrates the feasibility of activating remote, untethered, implanted microscale diodes using external AC fields and achieving neurostimulation. Full article
(This article belongs to the Special Issue Neural Microelectrodes: Design and Applications)
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21 pages, 4762 KiB  
Article
Characterizing Longitudinal Changes in the Impedance Spectra of In-Vivo Peripheral Nerve Electrodes
by Malgorzata M. Straka, Benjamin Shafer, Srikanth Vasudevan, Cristin Welle and Loren Rieth
Micromachines 2018, 9(11), 587; https://doi.org/10.3390/mi9110587 - 12 Nov 2018
Cited by 26 | Viewed by 4271
Abstract
Characterizing the aging processes of electrodes in vivo is essential in order to elucidate the changes of the electrode–tissue interface and the device. However, commonly used impedance measurements at 1 kHz are insufficient for determining electrode viability, with measurements being prone to false [...] Read more.
Characterizing the aging processes of electrodes in vivo is essential in order to elucidate the changes of the electrode–tissue interface and the device. However, commonly used impedance measurements at 1 kHz are insufficient for determining electrode viability, with measurements being prone to false positives. We implanted cohorts of five iridium oxide (IrOx) and six platinum (Pt) Utah arrays into the sciatic nerve of rats, and collected the electrochemical impedance spectroscopy (EIS) up to 12 weeks or until array failure. We developed a method to classify the shapes of the magnitude and phase spectra, and correlated the classifications to circuit models and electrochemical processes at the interface likely responsible. We found categories of EIS characteristic of iridium oxide tip metallization, platinum tip metallization, tip metal degradation, encapsulation degradation, and wire breakage in the lead. We also fitted the impedance spectra as features to a fine-Gaussian support vector machine (SVM) algorithm for both IrOx and Pt tipped arrays, with a prediction accuracy for categories of 95% and 99%, respectively. Together, this suggests that these simple and computationally efficient algorithms are sufficient to explain the majority of variance across a wide range of EIS data describing Utah arrays. These categories were assessed over time, providing insights into the degradation and failure mechanisms for both the electrode–tissue interface and wire bundle. Methods developed in this study will allow for a better understanding of how EIS can characterize the physical changes to electrodes in vivo. Full article
(This article belongs to the Special Issue Neural Microelectrodes: Design and Applications)
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16 pages, 3306 KiB  
Article
A Mechanically-Adaptive Polymer Nanocomposite-Based Intracortical Probe and Package for Chronic Neural Recording
by Allison Hess-Dunning and Dustin J. Tyler
Micromachines 2018, 9(11), 583; https://doi.org/10.3390/mi9110583 - 08 Nov 2018
Cited by 22 | Viewed by 3670
Abstract
Mechanical, materials, and biological causes of intracortical probe failure have hampered their utility in basic science and clinical applications. By anticipating causes of failure, we can design a system that will prevent the known causes of failure. The neural probe design was centered [...] Read more.
Mechanical, materials, and biological causes of intracortical probe failure have hampered their utility in basic science and clinical applications. By anticipating causes of failure, we can design a system that will prevent the known causes of failure. The neural probe design was centered around a bio-inspired, mechanically-softening polymer nanocomposite. The polymer nanocomposite was functionalized with recording microelectrodes using a microfabrication process designed for chemical and thermal process compatibility. A custom package based upon a ribbon cable, printed circuit board, and a 3D-printed housing was designed to enable connection to external electronics. Probes were implanted into the primary motor cortex of Sprague-Dawley rats for 16 weeks, during which regular recording and electrochemical impedance spectroscopy measurement sessions took place. The implanted mechanically-softening probes had stable electrochemical impedance spectra across the 16 weeks and single units were recorded out to 16 weeks. The demonstration of chronic neural recording with the mechanically-softening probe suggests that probe architecture, custom package, and general design strategy are appropriate for long-term studies in rodents. Full article
(This article belongs to the Special Issue Neural Microelectrodes: Design and Applications)
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15 pages, 3395 KiB  
Article
Integrity Assessment of a Hybrid DBS Probe that Enables Neurotransmitter Detection Simultaneously to Electrical Stimulation and Recording
by Danesh Ashouri Vajari, Maria Vomero, Johannes B. Erhardt, Ali Sadr, Juan S. Ordonez, Volker A. Coenen and Thomas Stieglitz
Micromachines 2018, 9(10), 510; https://doi.org/10.3390/mi9100510 - 10 Oct 2018
Cited by 13 | Viewed by 6269
Abstract
Deep brain stimulation (DBS) is a successful medical therapy for many treatment resistant neuropsychiatric disorders such as movement disorders; e.g., Parkinson’s disease, Tremor, and dystonia. Moreover, DBS is becoming more and more appealing for a rapidly growing number of patients with other neuropsychiatric [...] Read more.
Deep brain stimulation (DBS) is a successful medical therapy for many treatment resistant neuropsychiatric disorders such as movement disorders; e.g., Parkinson’s disease, Tremor, and dystonia. Moreover, DBS is becoming more and more appealing for a rapidly growing number of patients with other neuropsychiatric diseases such as depression and obsessive compulsive disorder. In spite of the promising outcomes, the current clinical hardware used in DBS does not match the technological standards of other medical applications and as a result could possibly lead to side effects such as high energy consumption and others. By implementing more advanced DBS devices, in fact, many of these limitations could be overcome. For example, a higher channels count and smaller electrode sites could allow more focal and tailored stimulation. In addition, new materials, like carbon for example, could be incorporated into the probes to enable adaptive stimulation protocols by biosensing neurotransmitters in the brain. Updating the current clinical DBS technology adequately requires combining the most recent technological advances in the field of neural engineering. Here, a novel hybrid multimodal DBS probe with glassy carbon microelectrodes on a polyimide thin-film device assembled on a silicon rubber tubing is introduced. The glassy carbon interface enables neurotransmitter detection using fast scan cyclic voltammetry and electrophysiological recordings while simultaneously performing electrical stimulation. Additionally, the presented DBS technology shows no imaging artefacts in magnetic resonance imaging. Thus, we present a promising new tool that might lead to a better fundamental understanding of the underlying mechanism of DBS while simultaneously paving our way towards better treatments. Full article
(This article belongs to the Special Issue Neural Microelectrodes: Design and Applications)
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14 pages, 6071 KiB  
Article
Chronic Intracortical Recording and Electrochemical Stability of Thiol-ene/Acrylate Shape Memory Polymer Electrode Arrays
by Allison M. Stiller, Joshua Usoro, Christopher L. Frewin, Vindhya R. Danda, Melanie Ecker, Alexandra Joshi-Imre, Kate C. Musselman, Walter Voit, Romil Modi, Joseph J. Pancrazio and Bryan J. Black
Micromachines 2018, 9(10), 500; https://doi.org/10.3390/mi9100500 - 29 Sep 2018
Cited by 45 | Viewed by 5622
Abstract
Current intracortical probe technology is limited in clinical implementation due to the short functional lifetime of implanted devices. Devices often fail several months to years post-implantation, likely due to the chronic immune response characterized by glial scarring and neuronal dieback. It has been [...] Read more.
Current intracortical probe technology is limited in clinical implementation due to the short functional lifetime of implanted devices. Devices often fail several months to years post-implantation, likely due to the chronic immune response characterized by glial scarring and neuronal dieback. It has been demonstrated that this neuroinflammatory response is influenced by the mechanical mismatch between stiff devices and the soft brain tissue, spurring interest in the use of softer polymer materials for probe encapsulation. Here, we demonstrate stable recordings and electrochemical properties obtained from fully encapsulated shape memory polymer (SMP) intracortical electrodes implanted in the rat motor cortex for 13 weeks. SMPs are a class of material that exhibit modulus changes when exposed to specific conditions. The formulation used in these devices softens by an order of magnitude after implantation compared to its dry, room-temperature modulus of ~2 GPa. Full article
(This article belongs to the Special Issue Neural Microelectrodes: Design and Applications)
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18 pages, 3890 KiB  
Communication
Design Choices for Next-Generation Neurotechnology Can Impact Motion Artifact in Electrophysiological and Fast-Scan Cyclic Voltammetry Measurements
by Evan N. Nicolai, Nicholas J. Michelson, Megan L. Settell, Seth A. Hara, James K. Trevathan, Anders J. Asp, Kaylene C. Stocking, J. Luis Lujan, Takashi D.Y. Kozai and Kip A. Ludwig
Micromachines 2018, 9(10), 494; https://doi.org/10.3390/mi9100494 - 27 Sep 2018
Cited by 13 | Viewed by 5334
Abstract
Implantable devices to measure neurochemical or electrical activity from the brain are mainstays of neuroscience research and have become increasingly utilized as enabling components of clinical therapies. In order to increase the number of recording channels on these devices while minimizing the immune [...] Read more.
Implantable devices to measure neurochemical or electrical activity from the brain are mainstays of neuroscience research and have become increasingly utilized as enabling components of clinical therapies. In order to increase the number of recording channels on these devices while minimizing the immune response, flexible electrodes under 10 µm in diameter have been proposed as ideal next-generation neural interfaces. However, the representation of motion artifact during neurochemical or electrophysiological recordings using ultra-small, flexible electrodes remains unexplored. In this short communication, we characterize motion artifact generated by the movement of 7 µm diameter carbon fiber electrodes during electrophysiological recordings and fast-scan cyclic voltammetry (FSCV) measurements of electroactive neurochemicals. Through in vitro and in vivo experiments, we demonstrate that artifact induced by motion can be problematic to distinguish from the characteristic signals associated with recorded action potentials or neurochemical measurements. These results underscore that new electrode materials and recording paradigms can alter the representation of common sources of artifact in vivo and therefore must be carefully characterized. Full article
(This article belongs to the Special Issue Neural Microelectrodes: Design and Applications)
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18 pages, 3727 KiB  
Article
Characterization of the Neuroinflammatory Response to Thiol-ene Shape Memory Polymer Coated Intracortical Microelectrodes
by Andrew J. Shoffstall, Melanie Ecker, Vindhya Danda, Alexandra Joshi-Imre, Allison Stiller, Marina Yu, Jennifer E. Paiz, Elizabeth Mancuso, Hillary W. Bedell, Walter E. Voit, Joseph J. Pancrazio and Jeffrey R. Capadona
Micromachines 2018, 9(10), 486; https://doi.org/10.3390/mi9100486 - 24 Sep 2018
Cited by 24 | Viewed by 4569
Abstract
Thiol-ene based shape memory polymers (SMPs) have been developed for use as intracortical microelectrode substrates. The unique chemistry provides precise control over the mechanical and thermal glass-transition properties. As a result, SMP substrates are stiff at room temperature, allowing for insertion into the [...] Read more.
Thiol-ene based shape memory polymers (SMPs) have been developed for use as intracortical microelectrode substrates. The unique chemistry provides precise control over the mechanical and thermal glass-transition properties. As a result, SMP substrates are stiff at room temperature, allowing for insertion into the brain without buckling and subsequently soften in response to body temperatures, reducing the mechanical mismatch between device and tissue. Since the surface chemistry of the materials can contribute significantly to the ultimate biocompatibility, as a first step in the characterization of our SMPs, we sought to isolate the biological response to the implanted material surface without regards to the softening mechanics. To accomplish this, we tightly controlled for bulk stiffness by comparing bare silicon ‘dummy’ devices to thickness-matched silicon devices dip-coated with SMP. The neuroinflammatory response was evaluated after devices were implanted in the rat cortex for 2 or 16 weeks. We observed no differences in the markers tested at either time point, except that astrocytic scarring was significantly reduced for the dip-coated implants at 16 weeks. The surface properties of non-softening thiol-ene SMP substrates appeared to be equally-tolerated and just as suitable as silicon for neural implant substrates for applications such as intracortical microelectrodes, laying the groundwork for future softer devices to improve upon the prototype device performance presented here. Full article
(This article belongs to the Special Issue Neural Microelectrodes: Design and Applications)
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14 pages, 2422 KiB  
Article
Amorphous Silicon Carbide Platform for Next Generation Penetrating Neural Interface Designs
by Felix Deku, Christopher L. Frewin, Allison Stiller, Yarden Cohen, Saher Aqeel, Alexandra Joshi-Imre, Bryan Black, Timothy J. Gardner, Joseph J. Pancrazio and Stuart F. Cogan
Micromachines 2018, 9(10), 480; https://doi.org/10.3390/mi9100480 - 20 Sep 2018
Cited by 22 | Viewed by 4480
Abstract
Microelectrode arrays that consistently and reliably record and stimulate neural activity under conditions of chronic implantation have so far eluded the neural interface community due to failures attributed to both biotic and abiotic mechanisms. Arrays with transverse dimensions of 10 µm or below [...] Read more.
Microelectrode arrays that consistently and reliably record and stimulate neural activity under conditions of chronic implantation have so far eluded the neural interface community due to failures attributed to both biotic and abiotic mechanisms. Arrays with transverse dimensions of 10 µm or below are thought to minimize the inflammatory response; however, the reduction of implant thickness also decreases buckling thresholds for materials with low Young’s modulus. While these issues have been overcome using stiffer, thicker materials as transport shuttles during implantation, the acute damage from the use of shuttles may generate many other biotic complications. Amorphous silicon carbide (a-SiC) provides excellent electrical insulation and a large Young’s modulus, allowing the fabrication of ultrasmall arrays with increased resistance to buckling. Prototype a-SiC intracortical implants were fabricated containing 8 - 16 single shanks which had critical thicknesses of either 4 µm or 6 µm. The 6 µm thick a-SiC shanks could penetrate rat cortex without an insertion aid. Single unit recordings from SIROF-coated arrays implanted without any structural support are presented. This work demonstrates that a-SiC can provide an excellent mechanical platform for devices that penetrate cortical tissue while maintaining a critical thickness less than 10 µm. Full article
(This article belongs to the Special Issue Neural Microelectrodes: Design and Applications)
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22 pages, 6027 KiB  
Article
Acquisition of Neural Action Potentials Using Rapid Multiplexing Directly at the Electrodes
by Mohit Sharma, Avery Tye Gardner, Hunter J. Strathman, David J. Warren, Jason Silver and Ross M. Walker
Micromachines 2018, 9(10), 477; https://doi.org/10.3390/mi9100477 - 20 Sep 2018
Cited by 34 | Viewed by 6353
Abstract
Neural recording systems that interface with implanted microelectrodes are used extensively in experimental neuroscience and neural engineering research. Interface electronics that are needed to amplify, filter, and digitize signals from multichannel electrode arrays are a critical bottleneck to scaling such systems. This paper [...] Read more.
Neural recording systems that interface with implanted microelectrodes are used extensively in experimental neuroscience and neural engineering research. Interface electronics that are needed to amplify, filter, and digitize signals from multichannel electrode arrays are a critical bottleneck to scaling such systems. This paper presents the design and testing of an electronic architecture for intracortical neural recording that drastically reduces the size per channel by rapidly multiplexing many electrodes to a single circuit. The architecture utilizes mixed-signal feedback to cancel electrode offsets, windowed integration sampling to reduce aliased high-frequency noise, and a successive approximation analog-to-digital converter with small capacitance and asynchronous control. Results are presented from a 180 nm CMOS integrated circuit prototype verified using in vivo experiments with a tungsten microwire array implanted in rodent cortex. The integrated circuit prototype achieves <0.004 mm2 area per channel, 7 µW power dissipation per channel, 5.6 µVrms input referred noise, 50 dB common mode rejection ratio, and generates 9-bit samples at 30 kHz per channel by multiplexing at 600 kHz. General considerations are discussed for rapid time domain multiplexing of high-impedance microelectrodes. Overall, this work describes a promising path forward for scaling neural recording systems to numbers of electrodes that are orders of magnitude larger. Full article
(This article belongs to the Special Issue Neural Microelectrodes: Design and Applications)
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12 pages, 3951 KiB  
Communication
Genetic Modulation at the Neural Microelectrode Interface: Methods and Applications
by Bailey M. Winter, Samuel R. Daniels, Joseph W. Salatino and Erin K. Purcell
Micromachines 2018, 9(10), 476; https://doi.org/10.3390/mi9100476 - 20 Sep 2018
Cited by 7 | Viewed by 3535
Abstract
The use of implanted microelectrode arrays (MEAs), in the brain, has enabled a greater understanding of neural function, and new treatments for neurodegenerative diseases and psychiatric disorders. Glial encapsulation of the device and the loss of neurons at the device-tissue interface are widely [...] Read more.
The use of implanted microelectrode arrays (MEAs), in the brain, has enabled a greater understanding of neural function, and new treatments for neurodegenerative diseases and psychiatric disorders. Glial encapsulation of the device and the loss of neurons at the device-tissue interface are widely believed to reduce recording quality and limit the functional device-lifetime. The integration of microfluidic channels within MEAs enables the perturbation of the cellular pathways, through defined vector delivery. This provides new approaches to shed light on the underlying mechanisms of the reactive response and its contribution to device performance. In chronic settings, however, tissue ingrowth and biofouling can obstruct or damage the channel, preventing vector delivery. In this study, we describe methods of delivering vectors through chronically implanted, single-shank, “Michigan”-style microfluidic devices, 1–3 weeks, post-implantation. We explored and validated three different approaches for modifying gene expression at the device-tissue interface: viral-mediated overexpression, siRNA-enabled knockdown, and cre-dependent conditional expression. We observed a successful delivery of the vectors along the length of the MEA, where the observed expression varied, depending on the depth of the injury. The methods described are intended to enable vector delivery through microfluidic devices for a variety of potential applications; likewise, future design considerations are suggested for further improvements on the approach. Full article
(This article belongs to the Special Issue Neural Microelectrodes: Design and Applications)
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14 pages, 6091 KiB  
Article
LED Optrode with Integrated Temperature Sensing for Optogenetics
by S. Beatriz Goncalves, José M. Palha, Helena C. Fernandes, Márcio R. Souto, Sara Pimenta, Tao Dong, Zhaochu Yang, João F. Ribeiro and José H. Correia
Micromachines 2018, 9(9), 473; https://doi.org/10.3390/mi9090473 - 17 Sep 2018
Cited by 18 | Viewed by 6860
Abstract
In optogenetic studies, the brain is exposed to high-power light sources and inadequate power density or exposure time can cause cell damage from overheating (typically temperature increasing of 2 ∘ C). In order to overcome overheating issues in optogenetics, this paper presents a [...] Read more.
In optogenetic studies, the brain is exposed to high-power light sources and inadequate power density or exposure time can cause cell damage from overheating (typically temperature increasing of 2 ∘ C). In order to overcome overheating issues in optogenetics, this paper presents a neural tool capable of assessing tissue temperature over time, combined with the capability of electrical recording and optical stimulation. A silicon-based 8 mm long probe was manufactured to reach deep neural structures. The final proof-of-concept device comprises a double-sided function: on one side, an optrode with LED-based stimulation and platinum (Pt) recording points; and, on the opposite side, a Pt-based thin-film thermoresistance (RTD) for temperature assessing in the photostimulation site surroundings. Pt thin-films for tissue interface were chosen due to its biocompatibility and thermal linearity. A single-shaft probe is demonstrated for integration in a 3D probe array. A 3D probe array will reduce the distance between the thermal sensor and the heating source. Results show good recording and optical features, with average impedance magnitude of 371 k Ω , at 1 kHz, and optical power of 1.2 mW·mm − 2 (at 470 nm), respectively. The manufactured RTD showed resolution of 0.2 ∘ C at 37 ∘ C (normal body temperature). Overall, the results show a device capable of meeting the requirements of a neural interface for recording/stimulating of neural activity and monitoring temperature profile of the photostimulation site surroundings, which suggests a promising tool for neuroscience research filed. Full article
(This article belongs to the Special Issue Neural Microelectrodes: Design and Applications)
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9 pages, 1589 KiB  
Article
A Meta-Analysis of Intracortical Device Stiffness and Its Correlation with Histological Outcomes
by Allison M. Stiller, Bryan J. Black, Christopher Kung, Aashika Ashok, Stuart F. Cogan, Victor D. Varner and Joseph J. Pancrazio
Micromachines 2018, 9(9), 443; https://doi.org/10.3390/mi9090443 - 06 Sep 2018
Cited by 41 | Viewed by 4640
Abstract
Neural implants offer solutions for a variety of clinical issues. While commercially available devices can record neural signals for short time periods, they fail to do so chronically, partially due to the sustained tissue response around the device. Our objective was to assess [...] Read more.
Neural implants offer solutions for a variety of clinical issues. While commercially available devices can record neural signals for short time periods, they fail to do so chronically, partially due to the sustained tissue response around the device. Our objective was to assess the correlation between device stiffness, a function of both material modulus and cross-sectional area, and the severity of immune response. Meta-analysis data were derived from nine previously published studies which reported device material and geometric properties, as well as histological outcomes. Device bending stiffness was calculated by treating the device shank as a cantilevered beam. Immune response was quantified through analysis of immunohistological images from each study, specifically looking at fluorescent markers for neuronal nuclei and astrocytes, to assess neuronal dieback and gliosis. Results demonstrate that the severity of the immune response, within the first 50 µm of the device, is highly correlated with device stiffness, as opposed to device modulus or cross-sectional area independently. In general, commercially available devices are around two to three orders of magnitude higher in stiffness than devices which induced a minimal tissue response. These results have implications for future device designs aiming to decrease chronic tissue response and achieve increased long-term functionality. Full article
(This article belongs to the Special Issue Neural Microelectrodes: Design and Applications)
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21 pages, 3796 KiB  
Article
Scalable, Modular Three-Dimensional Silicon Microelectrode Assembly via Electroless Plating
by Jörg Scholvin, Anthony Zorzos, Justin Kinney, Jacob Bernstein, Caroline Moore-Kochlacs, Nancy Kopell, Clifton Fonstad and Edward S. Boyden
Micromachines 2018, 9(9), 436; https://doi.org/10.3390/mi9090436 - 30 Aug 2018
Cited by 4 | Viewed by 5681
Abstract
We devised a scalable, modular strategy for microfabricated 3-D neural probe synthesis. We constructed a 3-D probe out of individual 2-D components (arrays of shanks bearing close-packed electrodes) using mechanical self-locking and self-aligning techniques, followed by electroless nickel plating to establish electrical contact [...] Read more.
We devised a scalable, modular strategy for microfabricated 3-D neural probe synthesis. We constructed a 3-D probe out of individual 2-D components (arrays of shanks bearing close-packed electrodes) using mechanical self-locking and self-aligning techniques, followed by electroless nickel plating to establish electrical contact between the individual parts. We detail the fabrication and assembly process and demonstrate different 3-D probe designs bearing thousands of electrode sites. We find typical self-alignment accuracy between shanks of <0.2° and demonstrate orthogonal electrical connections of 40 µm pitch, with thousands of connections formed electrochemically in parallel. The fabrication methods introduced allow the design of scalable, modular electrodes for high-density 3-D neural recording. The combination of scalable 3-D design and close-packed recording sites may support a variety of large-scale neural recording strategies for the mammalian brain. Full article
(This article belongs to the Special Issue Neural Microelectrodes: Design and Applications)
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20 pages, 5266 KiB  
Article
Development, Modeling, Fabrication, and Characterization of a Magnetic, Micro-Spring-Suspended System for the Safe Electrical Interconnection of Neural Implants
by Katharina Hoch, Frederick Pothof, Felix Becker, Oliver Paul and Patrick Ruther
Micromachines 2018, 9(9), 424; https://doi.org/10.3390/mi9090424 - 23 Aug 2018
Cited by 3 | Viewed by 4410
Abstract
The development of innovative tools for neuroscientific research is based on in vivo tests typically applied to small animals. Most often, the interfacing of neural probes relies on commercially available connector systems which are difficult to handle during connection, particularly when freely behaving [...] Read more.
The development of innovative tools for neuroscientific research is based on in vivo tests typically applied to small animals. Most often, the interfacing of neural probes relies on commercially available connector systems which are difficult to handle during connection, particularly when freely behaving animals are involved. Furthermore, the connectors often exert high mechanical forces during plugging and unplugging, potentially damaging the fragile bone structure. In order to facilitate connector usage and increase the safety of laboratory animals, we developed a new magnetic connector system circumventing the drawbacks of existing tools. The connector system uses multiple magnet pairs and spring-suspended electrical contact pads realized using micro-electromechanical systems (MEMS) technologies. While the contact pad suspension increases the system tolerance in view of geometrical variations, we achieved a reliable self-alignment of the connector parts at ±50 µm provided by the specifically oriented magnet pairs and without the need of alignment pins. While connection forces are negligible, we can adjust the forces during connector release by modifying the magnet distance. With the connector test structures developed here, we achieved an electrical connection yield of 100%. Based on these findings, we expect that in vivo experiments with freely behaving animals will be facilitated with improved animal safety. Full article
(This article belongs to the Special Issue Neural Microelectrodes: Design and Applications)
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12 pages, 2151 KiB  
Article
Liquid Crystal Elastomer-Based Microelectrode Array for In Vitro Neuronal Recordings
by Rashed T. Rihani, Hyun Kim, Bryan J. Black, Rahul Atmaramani, Mohand O. Saed, Joseph J. Pancrazio and Taylor H. Ware
Micromachines 2018, 9(8), 416; https://doi.org/10.3390/mi9080416 - 20 Aug 2018
Cited by 26 | Viewed by 6294
Abstract
Polymer-based biomedical electronics provide a tunable platform to interact with nervous tissue both in vitro and in vivo. Ultimately, the ability to control functional properties of neural interfaces may provide important advantages to study the nervous system or to restore function in patients [...] Read more.
Polymer-based biomedical electronics provide a tunable platform to interact with nervous tissue both in vitro and in vivo. Ultimately, the ability to control functional properties of neural interfaces may provide important advantages to study the nervous system or to restore function in patients with neurodegenerative disorders. Liquid crystal elastomers (LCEs) are a class of smart materials that reversibly change shape when exposed to a variety of stimuli. Our interest in LCEs is based on leveraging this shape change to deploy electrode sites beyond the tissue regions exhibiting inflammation associated with chronic implantation. As a first step, we demonstrate that LCEs are cellular compatible materials that can be used as substrates for fabricating microelectrode arrays (MEAs) capable of recording single unit activity in vitro. Extracts from LCEs are non-cytotoxic (>70% normalized percent viability), as determined in accordance to ISO protocol 10993-5 using fibroblasts and primary murine cortical neurons. LCEs are also not functionally neurotoxic as determined by exposing cortical neurons cultured on conventional microelectrode arrays to LCE extract for 48 h. Microelectrode arrays fabricated on LCEs are stable, as determined by electrochemical impedance spectroscopy. Examination of the impedance and phase at 1 kHz, a frequency associated with single unit recording, showed results well within range of electrophysiological recordings over 30 days of monitoring in phosphate-buffered saline (PBS). Moreover, the LCE arrays are shown to support viable cortical neuronal cultures over 27 days in vitro and to enable recording of prominent extracellular biopotentials comparable to those achieved with conventional commercially-available microelectrode arrays. Full article
(This article belongs to the Special Issue Neural Microelectrodes: Design and Applications)
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18 pages, 1718 KiB  
Article
Demonstration of a Robust All-Silicon-Carbide Intracortical Neural Interface
by Evans K. Bernardin, Christopher L. Frewin, Richard Everly, Jawad Ul Hassan and Stephen E. Saddow
Micromachines 2018, 9(8), 412; https://doi.org/10.3390/mi9080412 - 18 Aug 2018
Cited by 22 | Viewed by 4859 | Correction
Abstract
Intracortical neural interfaces (INI) have made impressive progress in recent years but still display questionable long-term reliability. Here, we report on the development and characterization of highly resilient monolithic silicon carbide (SiC) neural devices. SiC is a physically robust, biocompatible, and chemically inert [...] Read more.
Intracortical neural interfaces (INI) have made impressive progress in recent years but still display questionable long-term reliability. Here, we report on the development and characterization of highly resilient monolithic silicon carbide (SiC) neural devices. SiC is a physically robust, biocompatible, and chemically inert semiconductor. The device support was micromachined from p-type SiC with conductors created from n-type SiC, simultaneously providing electrical isolation through the resulting p-n junction. Electrodes possessed geometric surface area (GSA) varying from 496 to 500 K μm2. Electrical characterization showed high-performance p-n diode behavior, with typical turn-on voltages of ~2.3 V and reverse bias leakage below 1 nArms. Current leakage between adjacent electrodes was ~7.5 nArms over a voltage range of −50 V to 50 V. The devices interacted electrochemically with a purely capacitive relationship at frequencies less than 10 kHz. Electrode impedance ranged from 675 ± 130 kΩ (GSA = 496 µm2) to 46.5 ± 4.80 kΩ (GSA = 500 K µm2). Since the all-SiC devices rely on the integration of only robust and highly compatible SiC material, they offer a promising solution to probe delamination and biological rejection associated with the use of multiple materials used in many current INI devices. Full article
(This article belongs to the Special Issue Neural Microelectrodes: Design and Applications)
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Review

Jump to: Editorial, Research, Other

19 pages, 1635 KiB  
Review
Progress in the Field of Micro-Electrocorticography
by Mehdi Shokoueinejad, Dong-Wook Park, Yei Hwan Jung, Sarah K. Brodnick, Joseph Novello, Aaron Dingle, Kyle I. Swanson, Dong-Hyun Baek, Aaron J. Suminski, Wendell B. Lake, Zhenqiang Ma and Justin Williams
Micromachines 2019, 10(1), 62; https://doi.org/10.3390/mi10010062 - 17 Jan 2019
Cited by 32 | Viewed by 8548
Abstract
Since the 1940s electrocorticography (ECoG) devices and, more recently, in the last decade, micro-electrocorticography (µECoG) cortical electrode arrays were used for a wide set of experimental and clinical applications, such as epilepsy localization and brain–computer interface (BCI) technologies. Miniaturized implantable µECoG devices have [...] Read more.
Since the 1940s electrocorticography (ECoG) devices and, more recently, in the last decade, micro-electrocorticography (µECoG) cortical electrode arrays were used for a wide set of experimental and clinical applications, such as epilepsy localization and brain–computer interface (BCI) technologies. Miniaturized implantable µECoG devices have the advantage of providing greater-density neural signal acquisition and stimulation capabilities in a minimally invasive fashion. An increased spatial resolution of the µECoG array will be useful for greater specificity diagnosis and treatment of neuronal diseases and the advancement of basic neuroscience and BCI research. In this review, recent achievements of ECoG and µECoG are discussed. The electrode configurations and varying material choices used to design µECoG arrays are discussed, including advantages and disadvantages of µECoG technology compared to electroencephalography (EEG), ECoG, and intracortical electrode arrays. Electrode materials that are the primary focus include platinum, iridium oxide, poly(3,4-ethylenedioxythiophene) (PEDOT), indium tin oxide (ITO), and graphene. We discuss the biological immune response to µECoG devices compared to other electrode array types, the role of µECoG in clinical pathology, and brain–computer interface technology. The information presented in this review will be helpful to understand the current status, organize available knowledge, and guide future clinical and research applications of µECoG technologies. Full article
(This article belongs to the Special Issue Neural Microelectrodes: Design and Applications)
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14 pages, 2746 KiB  
Review
A Bidirectional Neuromodulation Technology for Nerve Recording and Stimulation
by Jian Xu, Hongsun Guo, Anh Tuan Nguyen, Hubert Lim and Zhi Yang
Micromachines 2018, 9(11), 538; https://doi.org/10.3390/mi9110538 - 23 Oct 2018
Cited by 18 | Viewed by 5370
Abstract
Electrical nerve recording and stimulation technologies are critically needed to monitor and modulate nerve activity to treat a variety of neurological diseases. However, current neuromodulation technologies presented in the literature or commercially available products cannot support simultaneous recording and stimulation on the same [...] Read more.
Electrical nerve recording and stimulation technologies are critically needed to monitor and modulate nerve activity to treat a variety of neurological diseases. However, current neuromodulation technologies presented in the literature or commercially available products cannot support simultaneous recording and stimulation on the same nerve. To solve this problem, a new bidirectional neuromodulation system-on-chip (SoC) is proposed in this paper, which includes a frequency-shaping neural recorder and a fully integrated neural stimulator with charge balancing capability. In addition, auxiliary circuits consisting of power management and data transmission circuits are designed to provide the necessary power supply for the SoC and the bidirectional data communication between the SoC and an external computer via a universal serial bus (USB) interface, respectively. To achieve sufficient low input noise for sensing nerve activity at a sub-10 μ V range, several noise reduction techniques are developed in the neural recorder. The designed SoC was fabricated in a 0.18 μ m high-voltage Bipolar CMOS DMOS (BCD) process technology that was described in a previous publication and it has been recently tested in animal experiments that demonstrate the proposed SoC is capable of achieving reliable and simultaneous electrical stimulation and recording on the same nerve. Full article
(This article belongs to the Special Issue Neural Microelectrodes: Design and Applications)
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14 pages, 1797 KiB  
Review
Chronically Implanted Intracranial Electrodes: Tissue Reaction and Electrical Changes
by Andrew Campbell and Chengyuan Wu
Micromachines 2018, 9(9), 430; https://doi.org/10.3390/mi9090430 - 25 Aug 2018
Cited by 82 | Viewed by 8174
Abstract
The brain-electrode interface is arguably one of the most important areas of study in neuroscience today. A stronger foundation in this topic will allow us to probe the architecture of the brain in unprecedented functional detail and augment our ability to intervene in [...] Read more.
The brain-electrode interface is arguably one of the most important areas of study in neuroscience today. A stronger foundation in this topic will allow us to probe the architecture of the brain in unprecedented functional detail and augment our ability to intervene in disease states. Over many years, significant progress has been made in this field, but some obstacles have remained elusive—notably preventing glial encapsulation and electrode degradation. In this review, we discuss the tissue response to electrode implantation on acute and chronic timescales, the electrical changes that occur in electrode systems over time, and strategies that are being investigated in order to minimize the tissue response to implantation and maximize functional electrode longevity. We also highlight the current and future clinical applications and relevance of electrode technology. Full article
(This article belongs to the Special Issue Neural Microelectrodes: Design and Applications)
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19 pages, 1018 KiB  
Review
Opportunities and Challenges for Single-Unit Recordings from Enteric Neurons in Awake Animals
by Bradley B. Barth, Hsin-I Huang, Gianna E. Hammer and Xiling Shen
Micromachines 2018, 9(9), 428; https://doi.org/10.3390/mi9090428 - 25 Aug 2018
Cited by 5 | Viewed by 4579
Abstract
Advanced electrode designs have made single-unit neural recordings commonplace in modern neuroscience research. However, single-unit resolution remains out of reach for the intrinsic neurons of the gastrointestinal system. Single-unit recordings of the enteric (gut) nervous system have been conducted in anesthetized animal models [...] Read more.
Advanced electrode designs have made single-unit neural recordings commonplace in modern neuroscience research. However, single-unit resolution remains out of reach for the intrinsic neurons of the gastrointestinal system. Single-unit recordings of the enteric (gut) nervous system have been conducted in anesthetized animal models and excised tissue, but there is a large physiological gap between awake and anesthetized animals, particularly for the enteric nervous system. Here, we describe the opportunity for advancing enteric neuroscience offered by single-unit recording capabilities in awake animals. We highlight the primary challenges to microelectrodes in the gastrointestinal system including structural, physiological, and signal quality challenges, and we provide design criteria recommendations for enteric microelectrodes. Full article
(This article belongs to the Special Issue Neural Microelectrodes: Design and Applications)
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1 pages, 155 KiB  
Correction
Correction: Bernardin E.K.; et al. Demonstration of a Robust All-Silicon-Carbide Intracortical Neural Interface. Micromachines, 2018, 9, 412
by Evans K. Bernardin, Christopher L. Frewin, Richard Everly, Jawad Ul Hassan and Stephen E. Saddow
Micromachines 2018, 9(9), 451; https://doi.org/10.3390/mi9090451 - 10 Sep 2018
Cited by 6 | Viewed by 2258
Abstract
The authors would like to indicate the following financial support they received to the Acknowledgement Section of their published paper [...] Full article
(This article belongs to the Special Issue Neural Microelectrodes: Design and Applications)
17 pages, 1881 KiB  
Perspective
The History and Horizons of Microscale Neural Interfaces
by Takashi D. Y. Kozai
Micromachines 2018, 9(9), 445; https://doi.org/10.3390/mi9090445 - 06 Sep 2018
Cited by 14 | Viewed by 6134
Abstract
Microscale neural technologies interface with the nervous system to record and stimulate brain tissue with high spatial and temporal resolution. These devices are being developed to understand the mechanisms that govern brain function, plasticity and cognitive learning, treat neurological diseases, or monitor and [...] Read more.
Microscale neural technologies interface with the nervous system to record and stimulate brain tissue with high spatial and temporal resolution. These devices are being developed to understand the mechanisms that govern brain function, plasticity and cognitive learning, treat neurological diseases, or monitor and restore functions over the lifetime of the patient. Despite decades of use in basic research over days to months, and the growing prevalence of neuromodulation therapies, in many cases the lack of knowledge regarding the fundamental mechanisms driving activation has dramatically limited our ability to interpret data or fine-tune design parameters to improve long-term performance. While advances in materials, microfabrication techniques, packaging, and understanding of the nervous system has enabled tremendous innovation in the field of neural engineering, many challenges and opportunities remain at the frontiers of the neural interface in terms of both neurobiology and engineering. In this short-communication, we explore critical needs in the neural engineering field to overcome these challenges. Disentangling the complexities involved in the chronic neural interface problem requires simultaneous proficiency in multiple scientific and engineering disciplines. The critical component of advancing neural interface knowledge is to prepare the next wave of investigators who have simultaneous multi-disciplinary proficiencies with a diverse set of perspectives necessary to solve the chronic neural interface challenge. Full article
(This article belongs to the Special Issue Neural Microelectrodes: Design and Applications)
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