Fabrication of Subretinal 3D Microelectrodes with Hexagonal Arrangement

micromachines Article Fabrication of Subretinal 3D Microelectrodes with Hexagonal Arrangement Hee Won Seo , Namju Kim and Sohee Kim * Department of Robotics Engineering, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Korea; [email protected] (H.W.S.); [email protected] (N.K.) * Correspondence: [email protected]; Tel.: +82-53-785-6217 Received: 29 March 2020; Accepted: 27 April 2020; Published: 29 April 2020 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 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 kW 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. Keywords: retinal implant; subretinal stimulation; 3D electrodes; hexagonal electrodes; transparent base 1. Introduction Retinal degenerative diseases are one of the causes that impair the vision of patients. Age-related macular degeneration (AMD) and retinitis pigmentosa (RP) are the diseases caused by the degeneration of photoreceptors, which finally lead to visual loss [1–4]. Photoreceptor cells consist of rod and cone cells in the retina, and these cells convert light entering the eye into electrical signals. However, if photoreceptors are lost because of AMD and RP, these signals cannot be generated and transmitted to non-spiking neurons in the inner nuclear layer (INL) [5]. Thus, this results in no responses of the retinal ganglion cells (RGCs) that transmit the signals to the optic nerve. Hence, to restore the vision in patients with such diseases, various retinal prostheses have been developed, which can replace the function of lost photoreceptors [5–13]. The retinal prosthesis, including stimulating electrodes, can partially restore the patient’s vision by stimulating live RGCs using a variety of surgical methods [14]. Depending on the surgical procedure, there are epiretinal electrodes placed on the retinal surface to directly stimulate RGCs [6,11,15–18], subretinal electrodes implanted between the outer nuclear layer (ONL) and the retinal pigment epithelium (RPE) [7–10,19–24], and suprachoroidal electrodes implanted between the choroid and the sclera [12]. Mostly, the stimulating electrodes have been developed to stimulate retinal cells epiretinally or subretinally [6–11], which differ in their stimulation thresholds to electrically elicit the responses of Micromachines 2020, 11, 467; doi:10.3390/mi11050467 www.mdpi.com/journal/micromachines Micromachines 2020, 11, 467 2 of 12 RGCs. The stimulation threshold can vary depending on the type of pulse applied to the electrode (monophasicMicromachines or 2020 biphasic),, 11, x pulse polarity (cathodic or anodic), and pulse duration [25–29].2 Typically, of 12 the epiretinal electrodes, to elicit direct RGC responses, have low stimulation thresholds with pulses of shorterRGCs. durations The stimulation of around threshold 0.5 ms, can whereas vary depending the subretinal on the electrodes, type of pulse which applied avoid to the direct electrode activation of RGCs,(monophasic have relatively or biphasic), low pulse stimulation polarity (cathodic thresholds, or anodic), with pulses and pulse of longer duration durations [25–29]. Typically, ranging from the epiretinal electrodes, to elicit direct RGC responses, have low stimulation thresholds with pulses 1 to 10 ms [8,25,29]. For subretinal electrodes, stimulating pulses are transmitted to non-spiking of shorter durations of around 0.5 ms, whereas the subretinal electrodes, which avoid direct neurons in INL (horizontal, bipolar and amacrine cells), and due to the slow nature of these neurons, activation of RGCs, have relatively low stimulation thresholds, with pulses of longer durations stimuliranging with from moderately 1 to 10 ms long [8,25,29]. pulse For durations subretinal (1 electrodes, to 10 ms) stimulating help reduce pulses the thresholdsare transmitted [5,25 to]. non- Previously,spiking neurons we in focused INL (horizontal, on the subretinal bipolar and approach amacrine that cells), can and deliver due to su theffi slowcient nature stimulation of these to the cellsneurons, in the INL, stimuli and with demonstrated moderately along three-dimensional pulse durations (1 subretinal to 10 ms) help electrode reduce array,the thresholds based on [5,25]. a flexible and transparentPreviously, base we [30 focused], which, on the however, subretinal had approach a small that number can deliver of electrodes; sufficient upstimulation to 25 in to an the area of 2.8 mmcells in2.8 the mm INL,. Here, and demonstrated we present a a subretinal three-dimensiona electrodel subretinal array with electrode an increased array, based number on a offlexible electrodes × to anticipateand transparent better visualbase [30], acuity. which, For however, that, a had large a smal numberl number of electrodes of electrodes; need up to 25 be in accommodated an area of within2.8 the mm limited × 2.8 sizemm. ofHere, the device.we present In addition, a subretinal when electrode an electric array field with is generatedan increased by number the stimulating of electrodes to anticipate better visual acuity. For that, a large number of electrodes need to be electrodes, the arrangement of return electrodes, the electrode size and spacing should be considered accommodated within the limited size of the device. In addition, when an electric field is generated together to reduce undesired dissipation of electric currents, i.e., crosstalk [31,32]. Based on such by the stimulating electrodes, the arrangement of return electrodes, the electrode size and spacing previousshould results, be considered we aimed together to implement to reduce the undesired hexagonal dissipation return electrodes of electric surroundingcurrents, i.e., acrosstalk stimulating electrode[31,32]. in Based center, on tosuch achieve previous the results, localized we ai activationmed to implement of RGCs the on hexagonal stimulating return sites. electrodes Moreover, by adaptingsurrounding the hexagonala stimulating electrode electrode arrangement, in center, to advantages achieve the such localized as more activation correct of identification RGCs on of symbolsstimulating [33] and sites. a higher Moreover, electrode by adapting density the withinhexagonal the electrode limited devicearrangement, area [advantages34] can be such anticipated. as Finally,more we correct fabricated identification a three-dimensional of symbols [33] (3D) and microelectrodea higher electrode array density with within 98 electrodes the limited based device on the transparentarea [34] base can andbe anticipated. characterized Finally, the electrochemicalwe fabricated a three-dimensional properties of the fabricated(3D) microelectrode electrodes, array prior to in vitrowith and 98 electrodes in vivo experiments. based on the transparent base and characterized the electrochemical properties of the fabricated electrodes, prior to in vitro and in vivo experiments. 2. Materials and Methods 2. Materials and Methods 2.1. Design of Subretinal Electrode Array 2.1. Design of Subretinal Electrode Array Figure1 shows the schematic illustrations of the 3D microelectrodes for subretinal stimulation. Figure 1 shows the schematic illustrations of the 3D microelectrodes for subretinal stimulation. The microelectrodes,The microelectrodes, which which can be can combined be combined with anwith integrated an integrated circuit (IC),circuit are (IC), subretinally are subretinally implantable, as shownimplantable, in Figure as 1showna. The in electrode Figure 1a. array The consists electrode of 98array hexagonally consists of arranged98 hexagonally electrodes, arranged and the sensedelectrodes, light can and be the converted sensed light into can the be converted electrical into signal the byelectrical the photodiodes signal by the inphotodiodes the IC that in the is to be integratedIC that with is to the be electrodes.integrated with For thethe photodiodeselectrodes. For to the detect photodiodes light directly, to detect polydimethylsiloxane light directly, (PDMS)polydimethylsiloxane was used as the (PDMS) transparent was used base as of the the transparent electrodes, base as of shown the electrodes, in Figure as1 shownb. The in thickness Figure of PDMS1b. was The chosen thickness to beof 140PDMSµm. was The chosen

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