Special Issue "Micro/Nanofabrication for Retinal Implants"

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 August 2020).

Special Issue Editor

Prof. Dr. Maesoon Im
E-Mail Website
Guest Editor
Division of Bio-Medical Science & Technology, University of Science & Technology, Seoul 02792, Republic of Korea
Interests: neural engineering with a specific focus on retinal prosthesis; MEMS/NEMS (Micro-/Nano-Electro Mechanical System); electric stimulation; retinal neurobiology; electrophysiology; visual neuroscience

Special Issue Information

Dear Colleagues,

For a long time, many people have dreamed of restoring sight to blind individuals. For those blinded by outer retinal degenerative diseases (e.g., age-related macular degeneration and retinitis pigmentosa), retinal implants can evoke visual percepts by stimulating the inner retinal neurons that survive the diseases. Indeed, when microelectronic retinal prosthetic devices demonstrated promising clinical outcomes, it seemed like the dream had been realized. Unfortunately, the best visual performance restored by the prostheses is still far removed from the normal vision. For a significantly enhanced quality of restored vision, retinal implants require breakthroughs in their electrode designs, dimensions, materials, and so on, which would heavily rely on micro-/nano-fabrication technologies. Also, because of the nature of biomedical devices aiming for physiological function restoration, multidisciplinary endeavors are crucial; for example, a physiological and/or anatomical rationale would be ideal for new designs. This Special Issue invites original research papers and short communications reporting novel micro-/nano-fabrication techniques for an improved performance of retinal implants. The Special Issue also welcomes review articles summarizing the state-of-the-art technologies and offering insights for future research directions in the retinal prosthetic community.

Dr. Maesoon Im
Guest Editor

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 papers will be 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.

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 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

  • retinal prosthesis
  • retinal implant
  • retinal stimulation
  • implantable device
  • neuromodulation

Published Papers (8 papers)

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Editorial

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Editorial
Editorial for the Special Issue on Micro/Nanofabrication for Retinal Implants
Micromachines 2020, 11(11), 1005; https://doi.org/10.3390/mi11111005 - 14 Nov 2020
Viewed by 489
Abstract
The retinal prosthetic community has witnessed tremendous technological advances during the last two decades since the emergence of pioneering work [...] Full article
(This article belongs to the Special Issue Micro/Nanofabrication for Retinal Implants)

Research

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Article
Micro-Fabrication of Components for a High-Density Sub-Retinal Visual Prosthesis
Micromachines 2020, 11(10), 944; https://doi.org/10.3390/mi11100944 - 19 Oct 2020
Cited by 1 | Viewed by 919
Abstract
We present a retrospective of unique micro-fabrication problems and solutions that were encountered through over 10 years of retinal prosthesis product development, first for the Boston Retinal Implant Project initiated at the Massachusetts Institute of Technology and at Harvard Medical School’s teaching hospital, [...] Read more.
We present a retrospective of unique micro-fabrication problems and solutions that were encountered through over 10 years of retinal prosthesis product development, first for the Boston Retinal Implant Project initiated at the Massachusetts Institute of Technology and at Harvard Medical School’s teaching hospital, the Massachusetts Eye and Ear—and later at the startup company Bionic Eye Technologies, by some of the same personnel. These efforts culminated in the fabrication and assembly of 256+ channel visual prosthesis devices having flexible multi-electrode arrays that were successfully implanted sub-retinally in mini-pig animal models as part of our pre-clinical testing program. We report on the processing of the flexible multi-layered, planar and penetrating high-density electrode arrays, surgical tools for sub-retinal implantation, and other parts such as coil supports that facilitated the implantation of the peri-ocular device components. We begin with an overview of the implantable portion of our visual prosthesis system design, and describe in detail the micro-fabrication methods for creating the parts of our system that were assembled outside of our hermetically-sealed electronics package. We also note the unique surgical challenges that sub-retinal implantation of our micro-fabricated components presented, and how some of those issues were addressed through design, materials selection, and fabrication approaches. Full article
(This article belongs to the Special Issue Micro/Nanofabrication for Retinal Implants)
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Article
The Roles of an Aluminum Underlayer in the Biocompatibility and Mechanical Integrity of Vertically Aligned Carbon Nanotubes for Interfacing with Retinal Neurons
Micromachines 2020, 11(6), 546; https://doi.org/10.3390/mi11060546 - 28 May 2020
Cited by 2 | Viewed by 819
Abstract
Retinal implant devices are becoming an increasingly realizable way to improve the vision of patients blinded by photoreceptor degeneration. As an electrode material that can improve restored visual acuity, carbon nanotubes (CNTs) excel due to their nanoscale topography, flexibility, surface chemistry, and double-layer [...] Read more.
Retinal implant devices are becoming an increasingly realizable way to improve the vision of patients blinded by photoreceptor degeneration. As an electrode material that can improve restored visual acuity, carbon nanotubes (CNTs) excel due to their nanoscale topography, flexibility, surface chemistry, and double-layer capacitance. If vertically aligned carbon nanotubes (VACNTs) are biocompatible with retinal neurons and mechanically robust, they can further improve visual acuity—most notably in subretinal implants—because they can be patterned into high-aspect-ratio, micrometer-size electrodes. We investigated the role of an aluminum (Al) underlayer beneath an iron (Fe) catalyst layer used in the growth of VACNTs by chemical vapor deposition (CVD). In particular, we cultured dissociated retinal cells for three days in vitro (DIV) on unfunctionalized and oxygen plasma functionalized VACNTs grown from a Fe catalyst (Fe and Fe+Pl preparations, where Pl signifies the plasma functionalization) and an Fe catalyst with an Al underlayer (Al/Fe and Al/Fe+Pl preparations). The addition of the Al layer increased the mechanical integrity of the VACNT interface and enhanced retinal neurite outgrowth over the Fe preparation. Unexpectedly, the extent of neurite outgrowth was significantly greater in the Al/Fe than in the Al/Fe+Pl preparation, suggesting plasma functionalization can negatively impact biocompatibility for some VACNT preparations. Additionally, we show our VACNT growth process for the Al/Fe preparation can support neurite outgrowth for up to 7 DIV. By demonstrating the retinal neuron biocompatibility, mechanical integrity, and pattern control of our VACNTs, this work offers VACNT electrodes as a solution for improving the restored visual acuity provided by modern retinal implants. Full article
(This article belongs to the Special Issue Micro/Nanofabrication for Retinal Implants)
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Article
Hemispherical Microelectrode Array for Ex Vivo Retinal Neural Recording
Micromachines 2020, 11(5), 538; https://doi.org/10.3390/mi11050538 - 25 May 2020
Cited by 2 | Viewed by 1080 | Correction
Abstract
To investigate the neuronal visual encoding process in the retina, researchers have performed in vitro and ex vivo electrophysiological experiments using animal retinal tissues. The microelectrode array (MEA) has become a key component in retinal experiments because it enables simultaneous neural recording from [...] Read more.
To investigate the neuronal visual encoding process in the retina, researchers have performed in vitro and ex vivo electrophysiological experiments using animal retinal tissues. The microelectrode array (MEA) has become a key component in retinal experiments because it enables simultaneous neural recording from a population of retinal neurons. However, in most retinal experiments, it is inevitable that the retinal tissue is flattened on the planar MEA, becoming deformed from the original hemispherical shape. During the tissue deforming process, the retina is subjected to mechanical stress, which can induce abnormal physiological conditions. To overcome this problem, in this study, we propose a hemispherical MEA with a curvature that allows retinal tissues to adhere closely to electrodes without tissue deformation. The electrode array is fabricated by stretching a thin, flexible polydimethylsiloxane (PDMS) electrode layer onto a hemispherical substrate. To form micro patterns of electrodes, laser processing is employed instead of conventional thin-film microfabrication processes. The feasibility for neural recording from retinal tissues using this array is shown by conducting ex vivo retinal experiments. We anticipate that the proposed techniques for hemispherical MEAs can be utilized not only for ex vivo retinal studies but also for various flexible electronics. Full article
(This article belongs to the Special Issue Micro/Nanofabrication for Retinal Implants)
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Article
Fabrication of Subretinal 3D Microelectrodes with Hexagonal Arrangement
Micromachines 2020, 11(5), 467; https://doi.org/10.3390/mi11050467 - 29 Apr 2020
Cited by 3 | Viewed by 967
Abstract
This study presents the fabrication of three-dimensional (3D) microelectrodes for subretinal stimulation, to accommodate adjacent return electrodes surrounding a stimulating electrode. For retinal prosthetic devices, the arrangement of return electrodes, the electrode size and spacing should be considered together, to reduce the undesired [...] Read more.
This study presents the fabrication of three-dimensional (3D) microelectrodes for subretinal stimulation, to accommodate adjacent return electrodes surrounding a stimulating electrode. For retinal prosthetic devices, the arrangement of return electrodes, the electrode size and spacing should be considered together, to reduce the undesired dissipation of electric currents. Here, we applied the hexagonal arrangement to the microelectrode array for the localized activation of retinal cells and better visual acuity. To provide stimuli more efficiently to non-spiking neurons, a 3D structure was created through a customized pressing process, utilizing the elastic property of the materials used in the fabrication processes. The diameter and pitch of the Pt-coated electrodes were 150 μm and 350 μm, respectively, and the height of the protruded electrodes was around 20 μm. The array consisted of 98 hexagonally arranged electrodes, supported by a flexible and transparent polydimethylsiloxane (PDMS) base, with a thickness of 140 μm. Also, the array was coated with 2 μm-thick parylene-C, except the active electrode sites, for more focused stimulation. Finally, the electrochemical properties of the fabricated microelectrodes were characterized, resulting in the mean impedance of 384.87 kΩ at 1 kHz and the charge storage capacity (CSC) of 2.83 mC·cm−2. The fabricated microelectrodes are to be combined with an integrated circuit (IC) for additional in vitro and in vivo experiments. Full article
(This article belongs to the Special Issue Micro/Nanofabrication for Retinal Implants)
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Article
Shape Morphable Hydrogel/Elastomer Bilayer for Implanted Retinal Electronics
Micromachines 2020, 11(4), 392; https://doi.org/10.3390/mi11040392 - 09 Apr 2020
Cited by 2 | Viewed by 1201
Abstract
Direct fabrication of a three-dimensional (3D) structure using soft materials has been challenging. The hybrid bilayer is a promising approach to address this challenge because of its programable shape-transformation ability when responding to various stimuli. The goals of this study are to experimentally [...] Read more.
Direct fabrication of a three-dimensional (3D) structure using soft materials has been challenging. The hybrid bilayer is a promising approach to address this challenge because of its programable shape-transformation ability when responding to various stimuli. The goals of this study are to experimentally and theoretically establish a rational design principle of a hydrogel/elastomer bilayer system and further optimize the programed 3D structures that can serve as substrates for multi-electrode arrays. The hydrogel/elastomer bilayer consists of a hygroscopic polyacrylamide (PAAm) layer cofacially laminated with a water-insensitive polydimethylsiloxane (PDMS) layer. The asymmetric volume change in the PAAm hydrogel can bend the bilayer into a curvature. We manipulate the initial monomer concentrations of the pre-gel solutions of PAAm to experimentally and theoretically investigate the effect of intrinsic mechanical properties of the hydrogel on the resulting curvature. By using the obtained results as a design guideline, we demonstrated stimuli-responsive transformation of a PAAm/PDMS flower-shaped bilayer from a flat bilayer film to a curved 3D structure that can serve as a substrate for a wide-field retinal electrode array. Full article
(This article belongs to the Special Issue Micro/Nanofabrication for Retinal Implants)
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Review

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Review
Ultrasonic Retinal Neuromodulation and Acoustic Retinal Prosthesis
Micromachines 2020, 11(10), 929; https://doi.org/10.3390/mi11100929 - 13 Oct 2020
Cited by 2 | Viewed by 1104
Abstract
Ultrasound is an emerging method for non-invasive neuromodulation. Studies in the past have demonstrated that ultrasound can reversibly activate and inhibit neural activities in the brain. Recent research shows the possibility of using ultrasound ranging from 0.5 to 43 MHz in acoustic frequency [...] Read more.
Ultrasound is an emerging method for non-invasive neuromodulation. Studies in the past have demonstrated that ultrasound can reversibly activate and inhibit neural activities in the brain. Recent research shows the possibility of using ultrasound ranging from 0.5 to 43 MHz in acoustic frequency to activate the retinal neurons without causing detectable damages to the cells. This review recapitulates pilot studies that explored retinal responses to the ultrasound exposure, discusses the advantages and limitations of the ultrasonic stimulation, and offers an overview of engineering perspectives in developing an acoustic retinal prosthesis. For comparison, this article also presents studies in the ultrasonic stimulation of the visual cortex. Despite that, the summarized research is still in an early stage; ultrasonic retinal stimulation appears to be a viable technology that exhibits enormous therapeutic potential for non-invasive vision restoration. Full article
(This article belongs to the Special Issue Micro/Nanofabrication for Retinal Implants)
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Review
Retinal Prosthetic Approaches to Enhance Visual Perception for Blind Patients
Micromachines 2020, 11(5), 535; https://doi.org/10.3390/mi11050535 - 24 May 2020
Cited by 3 | Viewed by 1408
Abstract
Retinal prostheses are implantable devices that aim to restore the vision of blind patients suffering from retinal degeneration, mainly by artificially stimulating the remaining retinal neurons. Some retinal prostheses have successfully reached the stage of clinical trials; however, these devices can only restore [...] Read more.
Retinal prostheses are implantable devices that aim to restore the vision of blind patients suffering from retinal degeneration, mainly by artificially stimulating the remaining retinal neurons. Some retinal prostheses have successfully reached the stage of clinical trials; however, these devices can only restore vision partially and remain insufficient to enable patients to conduct everyday life independently. The visual acuity of the artificial vision is limited by various factors from both engineering and physiological perspectives. To overcome those issues and further enhance the visual resolution of retinal prostheses, a variety of retinal prosthetic approaches have been proposed, based on optimization of the geometries of electrode arrays and stimulation pulse parameters. Other retinal stimulation modalities such as optics, ultrasound, and magnetics have also been utilized to address the limitations in conventional electrical stimulation. Although none of these approaches have been clinically proven to fully restore the function of a degenerated retina, the extensive efforts made in this field have demonstrated a series of encouraging findings for the next generation of retinal prostheses, and these could potentially enhance the visual acuity of retinal prostheses. In this article, a comprehensive and up-to-date overview of retinal prosthetic strategies is provided, with a specific focus on a quantitative assessment of visual acuity results from various retinal stimulation technologies. The aim is to highlight future directions toward high-resolution retinal prostheses. Full article
(This article belongs to the Special Issue Micro/Nanofabrication for Retinal Implants)
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