Japanese Journal of AppliedPhysics

     

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Performance improvement and in vivodemonstration of a sophisticated retinal stimulatorusing smart electrodes with built-in CMOSmicrochipsTo cite this article: Toshihiko Noda et al 2018 Jpn. J. Appl. Phys. 57 1002B3

 

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Performance improvement and in vivo demonstration of a sophisticated retinal

stimulator using smart electrodes with built-in CMOS microchips

Toshihiko Noda1*, Yukari Nakano2, Yasuo Terasawa2, Makito Haruta1,Kiyotaka Sasagawa1, Takashi Tokuda1, and Jun Ohta1

1Graduate School of Science and Technology, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan2Vision Institute, NIDEK Co., Ltd., Gamagori, Aichi 433-0038, Japan

*E-mail: t-noda@ms.naist.jp

Received June 6, 2018; revised July 14, 2018; accepted July 19, 2018; published online September 12, 2018

A retinal stimulator for next-generation retinal prosthesis was fabricated and demonstrated through in vivo experiments. The most significantelement of the stimulator is a smart electrode that has built-in CMOS microchips to achieve high functionality with four bus wirings. The proposedarchitecture of the smart electrode allows large arrays such as a 1,000-electrode array, which can provide high-resolution restored vision. Thedesign of the CMOS microchip was optimized to achieve a high-yield assembly. Circular fabricated microchips were embedded in the microcavitiesof stimulus electrodes. The assembly process of smart electrodes with built-in microchips was also optimized. A floating power supply system wasproposed, and this system improved the stimulus capability of the smart electrode. To validate the functionality of the fabricated stimulator, anin vivo experiment was performed. Neural responses were successfully observed as potential peaks recorded from the visual cortex of the brain.

© 2018 The Japan Society of Applied Physics

1. Introduction

Visual prosthesis, which is classified as an input-type brain–machine interface (BMI),1,2) is an approach to restoring thesight of people suffering from vision loss. Among theexisting visual prosthesis approaches such as brain stimula-tion,3–5) optic nerve stimulation,6–8) and retinal stimulation,the retinal approach9) has attracted attention as a practicalapplication using medically approved products.10–15) Theauthors focus on suprachoroidal-transretinal stimulation(STS)16–21) and propose a retinal stimulator based on CMOStechnology22–25) as a next-generation retinal prosthesis thatprovides high-resolution restored vision by multipoint stimu-lation of the retina (i.e., over 1,000 points). CMOS micro-chips are used for realizing multipoint stimulation with alarge array of stimulus electrodes. CMOS microchips play asignificant role in achieving sophisticated functions withminimally invasive implantation such as the control of largeelectrode arrays with a few wires. As a promising candidatefor next-generation retinal prosthesis, the authors propose asmart electrode architecture with built-in CMOS micro-chips.26) Although the proposed concept was demonstratedby a proof-of-concept device,27) the device has room forimprovement. In this study, the authors present an optimizedbuilt-in microchip and its assembly process. The improve-ment in the stimulus capability is also investigated. Finally,an in vivo stimulation of the retina is performed todemonstrate the stimulus function of the fabricated device.

2. Device fabrication

In retinal prosthesis, a retinal stimulator is implanted into theeyeball to electrically stimulate the retina to evoke neuralresponses, as shown in Fig. 1. Therefore, a retinal stimulatorshould be flexible, safe, durable, and biocompatible. Theproposed stimulator, shown in Fig. 2 as a conceptual figure,meets these requirements. The basic architecture of thedevice is similar to that in the authors’ previous work.27)

Bullet-shaped stimulus electrodes are mounted on a flexiblesubstrate, and a tiny CMOS microchip is embedded into eachstimulus electrode. The microchips are fully encapsulated in

the electrodes, as shown in Fig. 3, and hence, long-termdurability can be expected. A high level of safety is alsoexpected because all the electrical components, including thewiring, are sealed or encapsulated. The details of each com-ponent are provided in the following subsections. Then, theassembly process of the components is described in Sect. 2.4.2.1 CMOS microchipA dedicated CMOS microchip embedded inside a stimuluselectrode is presented. Multiple functions such as targetelectrode selection, operation control, and stimulus currentgeneration are implemented into the microchip. Table I liststhe design specifications of the microchip. Figure 4 showsthe block diagram of the microchip. The microchip is con-trolled by an asynchronous logic circuit using two controlsignals. A 3-bit counter was used as a resistor to selectinternal operation modes. The selection of a target microchipwas possible by comparing the target ID with the chip IDwritten by laser trimming of the fuse line. A stimulus currentgenerator was operated according to the programmed currentintensity. Although the fundamental components and con-struction are based on the microchip used in the authors’previous work,27) the circuit performance and layout havebeen improved. Low-voltage cascode current mirror circuits(Fig. 5) were used in the stimulus current generator toachieve constant-current stimulation with a sufficient com-pliance voltage. The parameters of the current mirror circuitswere optimized through circuit simulation in order to achievecharge-balanced biphasic stimulation based on accurate

EyeballRetina/Choroid/Sclera

Retinal stimulator

Fig. 1. (Color online) Illustration of implantation of retinal stimulator.

Japanese Journal of Applied Physics 57, 1002B3 (2018)

https://doi.org/10.7567/JJAP.57.1002B3

STAP ARTICLEPhysics-based circuits and systems

1002B3-1 © 2018 The Japan Society of Applied Physics

control of the stimulus current intensity in anodic andcathodic stimulation. The five cross-aligned electrode padsused in the previous work27) made it difficult to design andfabricate a flexible substrate on which to mount themicrochip. As a result, the assembly process yielded poorresults because of an insufficient margin of error in theflexible substrate design. In this work, the arrangement of theelectrode pads was optimized to achieve equal clearance

among the five electrode pads. Figure 6 shows a micrographof the microchip. The five electrode pads are located on thevertices of an equilateral pentagon. The pads and other circuitcomponents are arranged inside a circle of 350 µm diameter.

The designed microchip was fabricated using standard0.35 µm CMOS technology. Seventeen unit microchips werefabricated on each die and then separated into each unitmicrochip. The separation process using deep reactive-ion

CMOS microchip

Bullet-shaped electrode

Flexible substrate

Lands

Pads

MicrocavityFlexible substrate

Stimulus electrodes

Bus wirings

Fig. 2. (Color online) Conceptual figure of structure of smart electrode with built-in CMOS microchip.

Bullet-shaped electrode

Microcavity

Flexiblesubstrate

Epoxy resin

Parylene-C film

Sub-micronAu particles

Lands

Fig. 3. (Color online) Illustration of cross section of smart electrode withbuilt-in CMOS microchip.

Table I. Specifications of the microchip.

Technology 0.35 µm standard CMOS

Supply voltage DC 5.0V

Number of pads 5 (pentagonal arrangement)

Pad size 60 × 60 µm2

Chip ID 10 bit

Stimulation mode Biphasic constant current pulse

Stimulus current ±1240 µA (40 µA step)

Layout size ϕ350 µm (circle)

Thickness 100 µm

Ctrl 1

Ctrl 2

POR

POR

Power on reset

Chip ID comparator

Current reference

POR

Cathodicstimulation

driver

Stimulus current

generator

5bit counter(Current intensity resistor)

Anodic stimulation

driver

3bit counter(Internal

mode resistor)

11bit counter

C

C

C

C

Q1Q5

Q1Q10Q11

QN

QD

POR

VDD POR

D-FF

Stimulusoutput

Fig. 4. Block diagram of the microchip.

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1002B3-2 © 2018 The Japan Society of Applied Physics

etching (deep RIE) is the same as that in the previous work.Please refer to Ref. 27 for detailed process information.2.2 Stimulus electrodesBullet-shaped stimulus electrodes have a microcavity at thebottom center for microchip embedding. The electrodes are500 µm in height and 550 µm in diameter, the same as in theformer prototype.27) The stimulus electrodes were fabricatedthrough a machining process using bulk titanium. Figure 7shows a scanning electron microscopy (SEM) image of thefabricated electrode. As described in Sect. 3.2, since thevoltage swing range of the stimulus output is limited, iridiumoxide (IrOx)28–30) was used as the high-performance electrodematerial. IrOx requires a lower voltage swing upon stimula-

tion than conventional electrode materials such as platinum.The authors focus on IrOx as a candidate stimulus electrodematerial and have investigated the optimization of the fabri-cation process.25,31–33) In this work, the surface of thestimulus electrode was coated with IrOx under optimizedreactive sputtering process conditions.32)

2.3 Flexible substrateA flexible substrate that holds the stimulus electrodes withbuilt-in CMOS microchips was designed and fabricated.The flexible substrate has four bus wirings that are used totransmit the power supply and control signals of microchipsmounted on the flexible substrate. In this study, a conven-tional flexible printed circuit (FPC) made of polyimide filmwas used. A double-sided FPC was designed and fabricatedas shown in Fig. 8. One end of the FPC is the stimulus headwith a 5 × 5 electrode array while the other end is the ex-ternal connection. Each electrode site has five lands arrangedin the shape of a pentagon for microchip connection and adoughnut-shaped land for stimulus electrode connection. Thepentagonal lands and doughnut-shaped land were formedusing the lower and upper layers of the double-sided FPC,respectively. The surface of the FPC was coated with a coverlayer except for the lands. The depths of the lands from theFPC surface are 27 and 52 µm for the doughnut-shaped landand pentagonal lands, respectively.2.4 Assembly processFigure 9 shows the flow of the smart electrode assemblyprocess. The assembly process consists of three major stages:(i) preparation of FPC lands (process steps 1–3), (ii) flip-chipbonding (process steps 4–5), and (iii) stimulus electrodemounting (process steps 6–9).

In the first stage of the assembly process, FPC lands weremodified. Lands for the microchip connection and stimuluselectrode connection were formed underneath the FPC surfaceas described in Sect. 2.3. In the previous work,27) the authorsused Au stud bumps to fill the gaps between the lands and themicrochip. However, this approach resulted in poor microchipconnection caused by insufficient reliability of the Au bondingprocess. In this work, the authors propose an alternativeapproach using submicron Au particles.34) The submicron Auparticles can be used as a slurry that can easily fill the dimpleson the lands and are bulkanized at low temperatures of below200 °C, which is allowable for the FPC. Moreover, thesubmicron Au particles can be patterned using photolithog-raphy. A 15 µm thick photoresist film (Hitachi ChemicalPhotec RY-3315EE) was placed on the FPC surface andpatterned to open the land areas by photolithography (processstep 1 in Fig. 9). A slurry of submicron Au particles (TanakaKikinzoku Kogyo AuRoFUSE) was used to fill the dimples of

VDD

Ctrl1

VSS Ctrl2

Out

Stimulus current generatorControl logic

Chip ID

Fig. 6. (Color online) Micrograph of the microchip.

Microcavity IrOx coated surface

200 μm

Fig. 7. SEM image of the stimulus electrode.

GND

W/4L

W/L

W/L

VDD

Iref Iref

16IOUT

16W/L

16W/L

8IOUT

8W/L

8W/L

4IOUT

4W/L

4W/L

2IOUT

2W/L

2W/L

1IOUT

W/L

W/L

Fig. 5. Schematic of low-voltage cascode current mirror circuit in thestimulus current generator.

130

mm

1 m100 μm

Fig. 8. (Color online) Photograph of the fabricated flexible printed circuit.

Jpn. J. Appl. Phys. 57, 1002B3 (2018) STAP ARTICLE

1002B3-3 © 2018 The Japan Society of Applied Physics

the photoresist pattern, and surplus slurry was removed bysqueegeeing the photoresist surface (process step 2). Afterbaking at 150 °C for 1 h to bulkanize the submicron Au parti-cles, the photoresist was removed (process step 3). Figure 10shows an SEM image of one electrode site after convex landformation. The height of the convex lands is 15 µm, which isthe same as the thickness of the photoresist film.

The second stage of the assembly process is the flip-chipbonding of the microchip. In process step 4, anisotropic con-ductive paste (ACP) was applied to the convex lands. ACPwith conductive polymer particles (KYOCERA TAP0403C)was used to realize stud-bump-free flip-chip bonding.Circular CMOS microchips, which were separated as shownin Sect. 2.1, were bonded to the FPC using a flip-chip bonder(HiSOL M-90). The curing conditions for the ACP were astage temperature of 70 °C, a tool temperature of 190 °C, anda bonding load of 7N. Figure 11 shows an SEM image of themicrochip after flip-chip bonding.

The last stage of the assembly is the stimulus electrodemounting. The entire FPC with the microchips was coated

with 2.5 µm thick parylene C as an insulator between the sidewall of the microchip and the inner wall of the microchamberof the stimulus electrode (process step 6). The parylene Cfilm on the doughnut-shaped convex land was removed bylaser processing, and then conductive epoxy resin (EpoxyTechnology EPO-TEK H-20E) was applied (process step 7).The stimulus electrode was mounted on the FPC, after whichthe conductive epoxy resin was cured by baking at 80 °C for3 h (process step 8). As the final step, the bottom perimeter ofthe stimulus electrode was sealed and reinforced by epoxyresin (NISSIN RESIN low viscosity epoxy resin Z-1).

Figure 12 shows a micrograph of the stimulus electrodeafter the assembly process. Because the microchip is com-pletely embedded in the stimulus electrode, optical observa-tion of the built-in microchip is difficult. Therefore, theauthors performed an inner structure analysis of the fabricatedelectrode using X-ray computed tomography. The convexlands kept their shape after the assembly process, as shown inFig. 13(a). From Fig. 13(b), the microchip is embedded in themicrocavity in accordance with the concept shown in Fig. 2.

[3] Photoresist removal[1] Photoresist patterningPhotoresist film

[2] Filling sub-micron Au particlesSub-micron Au particles

[4] Apply anisotropic conductive paste [5] Flip-chip bonding [6] Parylene-C coating

Anisotropic conductive paste MicrochipParylene-C

[7] Apply conductive epoxy resin [8] Stimulus electrode mounting [9] Apply epoxy resin

Conductiveepoxy resin

Stimulus electrode

Epoxy resin

Fig. 9. (Color online) Assembly process.

100 μm

Fig. 10. SEM image of convex lands made of submicron Au particles.

100 μm

Fig. 11. SEM image of CMOS microchip after flip-chip bonding to FPC.

Jpn. J. Appl. Phys. 57, 1002B3 (2018) STAP ARTICLE

1002B3-4 © 2018 The Japan Society of Applied Physics

3. Functional demonstration

3.1 Properties of the stimulus current generatorThe fabricated CMOS microchip was characterized to con-firm that it operates as designed. A dummy load (1 kΩresistor) was connected to the stimulus output instead ofa stimulation load of biological tissue. The output currentwas measured with the programmed current varied from 40to 1,240 µA as shown in Fig. 14. The accuracy of the outputcurrent compared with the programmed value was within3%. The transient response of the stimulus current generatorwas also evaluated. Figure 15 shows the waveform of theoutput current during pulse operation of the stimulus currentgenerator. The rectangular waveform of the stimulus pulsecurrent with 200 µs pulse duration was confirmed, which is2.5 times shorter than the 500 µs used in retinal stimulation,which will be described in Sect. 3.3. Complementary anodic=cathodic pulses, which were necessary to perform charge-balanced biphasic stimulation, were confirmed. From theevaluation results of the fundamental electrical properties ofthe stimulus current generator, the generator is shown to be

applicable to retinal stimulation with an acceptable marginof error.3.2 Power supply systemAs shown in Table I, the power supply voltage of themicrochip is 5V. One approach to conducting charge-balanced stimulation is to use the biphasic stimulus currentas a split power supply system (SPSS), which powers themicrochip by a ±2.5V split supply (5V total), as shown inFig. 16.24,25,27) In this case, the potential of the counter elec-trode in the stimulation, which is implanted in a vitreousbody, is fixed to the middle potential 0V— the same as theground level of the living body. Although the system con-figuration is simple, the voltage swing range of the stimuluselectrode is limited to ±1.8V if the voltage drop of thestimulus current generator is 0.7V. This compliance voltageis insufficient for strong stimulation; for instance, over 500µA is required for the STS method. As a result, constant-current stimulation is impossible. The waveform of thestimulus current is an exponential charging curve that resultsfrom the constant–voltage charging of the electric bilayercapacity between the electrodes and electrolyte (refer toFig. 16 in Ref. 27).

One solution to the problem is to use a high-voltageCMOS process instead of the standard CMOS process. Thehigh-voltage CMOS process allows a high power supplyvoltage, such as over 15V. As a result, the voltage swingrange of the stimulus electrode, i.e., the compliance voltagefor constant-current stimulation, can be extended althoughthe circuit configuration is the same. However, for the high-voltage CMOS process, the layout area of the circuit, i.e., themicrochip size, is larger than that for the standard CMOSprocess. Therefore, the high-voltage CMOS process is

200 μm

Fig. 12. (Color online) Micrograph of the stimulus electrode after theassembly process.

500 μmSub-micron Au particles

Stimulus electrode

(a)

500 μm

Microcavity

Stimulus electrode

Microchip

(b)

Fig. 13. Radiolucent images of fabricated electrode: (a) oblique view(b) cross-sectional view.

Fig. 14. Output linearity of stimulus current generator.

Fig. 15. Waveform of pulse operation of stimulus current generator.

Jpn. J. Appl. Phys. 57, 1002B3 (2018) STAP ARTICLE

1002B3-5 © 2018 The Japan Society of Applied Physics

unsuitable for the retinal prosthesis approach, which requiresmicrochip implantation.

In this work, the authors propose alternative approachesfor the voltage swing range of the stimulus electrode usingstandard CMOS. Figure 17 shows a schematic of theproposed approach called a floating power supply system(FPSS). The counter electrode is connected to a voltagesupply of VDD or VSS, which are the maximum and minimumpotentials of the microchip, respectively, through switches ina control box. In the case of anodic stimulation, switches arecontrolled as shown in Fig. 18(a). Anodic stimulus currentflows from the stimulus electrode to the counter electrode,whose potential is VSS. Conversely, cathodic stimulus currentflows as shown in Fig. 18(b). The potential of the counterelectrode is VDD. The potential of the living body is the sameas the counter electrode potential and is as stable as thebiological ground (earth) level. This means that the absolutepotential of the microchip is actively controlled.

The stimulus capability of the fabricated electrode wasevaluated. The fabricated electrode was driven by the con-ventional SPSS and proposed FPSS. The programmed valueof the stimulus intensity was 800 µA. The dummy load, whichwas connected between the stimulus electrode and counterelectrode, was varied from 510Ω to 9.7 kΩ. Figure 19 showsthe measurement results of the output properties of thefabricated electrode. The output current was standardizedby the programmed stimulus intensity. Here, the limit loadwas defined as the maximum resistance that the electrodecan generate with over 0.8 arb. unit of stimulus current. Thelimit loads were 5.4 and 2.4 kΩ for the proposed FPSS andconventional SPSS, respectively. The stimulus capability ofthe FPSS was improved by 225% compared with that of theconventional SPSS. This result means that constant-current

stimulation also becomes possible in the electrode impedancerange of 2.4–5.4 kΩ.3.3 In vivo demonstrationAs a functional demonstration of retinal stimulation with thefabricated electrode, an in vivo experiment was performed.All animal experiments were regulated by the guidelinesof NIDEK Co., Ltd. The basic configuration of the in vivoexperiment was based on that in the authors’ previouswork.25) The fabricated electrode and counter electrode wereimplanted into an anesthetized rabbit. An intrascleral pocketwas made in the eyeball, and the stimulus head of thefabricated device was inserted into the pocket. The counterelectrode was implanted into the vitreous body. The stimulusresponse was recorded from the visual cortex of the brain.A screw electrode was placed on the skull of the visual area,and electrically evoked potentials (EEPs) were recorded.

2.5 VStimulus electrode

Counter electrode

Eyeball

Cathodic

Anodic

Microchip

2.5 V

VDD

VSS

5.0 V

Intra-bodyControl box

Fig. 16. (Color online) Schematic of split power supply system.

Stimulus electrode

Counter electrode

Eyeball

Cathodic

Anodic

MicrochipVDD

VSS

Intra-bodyControl box

Anodic

Cathodic

Fig. 17. (Color online) Schematic of floating power supply system.

Stimulus electrode

Counter electrodeCathodic

Anodic

MicrochipVDD

VSS

Intra-bodyControl box

Anodic

Cathodic

Eyeball

(a)

Stimulus electrode

Counter electrodeCathodic

Anodic

MicrochipVDD

VSS

Intra-bodyControl box

Anodic

Cathodic

Eyeball

(b)

Fig. 18. (Color online) Current path of the stimulation in floating powersupply system: (a) anodic stimulation, (b) cathodic stimulation.

Fig. 19. (Color online) Output property of fabricated electrode.

Jpn. J. Appl. Phys. 57, 1002B3 (2018) STAP ARTICLE

1002B3-6 © 2018 The Japan Society of Applied Physics

Current-controlled stimulation with a cathodic-first bipha-sic pulse was performed using the conventional SPSS andthe proposed FPSS. Figure 20 shows the waveform of thestimulus current. In the case of the SPSS, a constant-currentpulse was observed for 400 µA stimulation, as shown inFig. 20(a). However, the waveforms were not rectangularpulses in the case of 800 and 1200 µA stimulation, whichindicates that the electrode potential reached the compliancevoltage of the stimulus current generator. On the other hand,for the FPSS, a rectangular pulse current was observed for400, 800, and 1200 µA stimulation, as shown in Fig. 20(b).Thus, the improvement of the stimulus performance wasclearly demonstrated.

The neural response evoked by the fabricated stimulatorwas evaluated. The stimulator was driven by the FPSS. Thepulse parameters of the stimulation were a pulse duration of500 µs for each phase, an interpulse duration of 200 µs, arepetition frequency of 2Hz, and a stimulus intensity of 100–1200 µA. The pulse duration was the same as that employedin clinical trials that use a retinal prosthesis system with anSTS configuration having a similar-size stimulus electrode18)

as the fabricated electrode in this study. The stimulus inten-sity range sufficiently covered the stimulus intensity used inour previous in vivo trial.24,25) Evoking a retinal response andthe discussion of the stimulus threshold intensity were madepossible by the stimulus intensity range. The EEPs wererecorded in synchrony (or simultaneously) with the stim-ulation. A thousand stimulations were performed per trial,and the recorded EEPs were averaged. A stimulus repetitionfrequency of 2Hz was used as the interval between each

stimulation in order to record individual responses to eachstimulation. To confirm the stimulus artifact, an EEPrecording with 0 µA stimulus intensity was performed. TheEEP was then recorded with 1200 µA stimulus intensity aftersacrifice. Figure 21 shows the recorded EEPs. The large andsharp responses at the stimulation timing are the stimulusartifacts. Some specific response peaks that have the samelatency after stimulation were observed. Here, the authorsfocused on the response peaks with 15ms latency. As shownin Fig. 22, the height of the response peaks, which wasdefined as the difference between the top of the peak and therecording baseline, changed according to stimulus intensity.Using extrapolation to find the point where the peak heightbecomes zero, the authors estimated the stimulus threshold asapproximately 200–300 µA.35) These results show that the

(a)

(b)

Fig. 20. (Color online) Waveform of stimulus current during in vivoretinal stimulation: (a) split power supply system, (b) floating power supplysystem.

Fig. 21. (Color online) Electrically evoked potentials.

Fig. 22. Height of response peak versus stimulus intensity.

Jpn. J. Appl. Phys. 57, 1002B3 (2018) STAP ARTICLE

1002B3-7 © 2018 The Japan Society of Applied Physics

fabricated stimulator has the ability to evoke neural responsesvia stimulation, and the strength of the response can becontrolled via the stimulus intensity. The stimulus function ofthe stimulator was successfully demonstrated through thein vivo experiment.

4. Conclusions

In this work, a sophisticated=advanced retinal stimulator wasfabricated and demonstrated. By using smart electrodes witha built-in CMOS microchip, large electrode arrays with over1,000 electrodes can be controlled with four bus wirings. Thelayout of the microchip, especially the arrangement of elec-trode pads, was optimized to achieve high yield assembly.The FPC design was also optimized and submicron Auparticles were introduced to form convex lands on the FPC.The patterning process of the submicron Au particles wasdiscussed and applied to fabricate a prototype device. Thepower supply system of the fabricated device was consideredto improve the stimulus capability, and an FPSS wasproposed. The FPSS made high-current stimulation possiblewithout a special CMOS process or significant changes in thestimulus circuit. The improvement of the stimulus capabilitywith the FPSS was evaluated quantitatively and comparedwith that of conventional SPSS. The stimulus function of thefabricated device was demonstrated through an in vivo trial.The rectangular waveform of the stimulus pulse current,which indicates constant-current stimulation, was confirmedeven at a high stimulus intensity. Moreover, the neuralresponse of the visual cortex as a result of successful retinalstimulation was clearly observed. Through the in vivoexperiment, the stimulus function and the capabilities of thefabricated device were demonstrated clearly.

In this study, the stimulus function of the fabricated devicewas demonstrated on the basis of single-point stimulation.Switching of the functions of electrodes in the 5 × 5 array forstimulus target selection should be confirmed, which is theauthors’ next goal. Furthermore, in the case of larger arraysof electrodes, the one-by-one assembly of CMOS-embeddedelectrodes is not realistic. One solution being considered isthe batch assembly of smart electrodes. A CMOS die thatincludes a multiple-unit microchip can be flip-chip bonded toa flexible substrate, and then microchip separation using deepRIE might be possible. A jig for the simultaneous pick-up ofmultiple stimulus electrodes can be introduced to achieve thebatch mounting of stimulus electrodes. Larger arrays of smartelectrodes can be achieved through the implementationprocess described above.

Shrinking the size of the smart electrode is also importantin order to achieve high-resolution restored vision by densestimulus electrodes. From the results of spatial profile meas-urement of the retinal response by STS,36,37) the authors areconsidering the target dimensions for next-generation elec-trodes as 300 µm in diameter and 450 µm in pitch. The built-in CMOS microchip can be shrunk using a fine CMOS proc-ess, such as a 0.18 µm process, instead of the mature CMOSprocess used in this study. The implementation processdescribed above is also suitable for achieving miniaturizedsmart electrodes.

Acknowledgments

This work was partially supported by a Grant-in-Aid

for Scientific Research (C), No. 18K04265, from the JapanSociety for the Promotion of Science (JSPS) and a researchgrant from Murata Science Foundation, Japan. The designof the microchip was supported by the VLSI Design andEducation Center (VDEC), The University of Tokyo, incollaboration with Cadence Corporation.

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Toshihiko Noda received the B.E. and M.E. degreesin electrical and electronic engineering in 2001,2003, respectively, and Ph.D. degree in engineeringin 2006, all from Toyohashi University of Technol-ogy (TUT), Aichi, Japan. He was a Post-Doctoralresearcher of Venture Business Laboratory in TUTfrom 2006 to 2007. He joined the faculty ofIntelligent Sensing System Research Center in TUTfrom 2008 as assistant professor. Since 2009, he hasbeen an assistant professor in Nara Institute of

Science and Technology (NAIST), Nara, Japan. His current research interestsfocus on retinal prosthesis devices and bio-imaging with CMOS imagesensors.

Yukari Nakano received her B.S. degree inchemical engineering from Shizuoka University,Shizuoka, Japan, in 2009. In 2009, she joined NidekCo., Ltd., Aichi, Japan. Since 2012, she has been aninvestigator at the Artificial Vision Institute of NidekCo., Ltd. In 2018, she received her Ph.D. degree inmaterials science from Nara Institute of Science andTechnology (NAIST), Nara, Japan. Her researchincludes the development of active implantabledevices for blind people, electrophysiological eval-

uation, and statistical analysis of electrophysiological evaluation.

Yasuo Terasawa received his B.S. degree inapplied physics and M.S. degree in informationscience from Tohoku University, Miyagi, Japan in1996 and 1998, respectively. He joined NomuraResearch Institute in 1998. Since 2001, he has beenan investigator in the Vision Institute of NidekCo., Ltd., Aichi, Japan. He received his Ph.D. degreein materials science in 2009 from Nara Institute ofScience and Technology (NAIST), Nara, Japan.Since 2009, he has been both a research fellow in

NAIST and an investigator in Nidek. Since 2016, he has been a manager ofthe Artificial Vision Institute of Nidek. His research includes electrodetechnology, microfabrication, neural interface, and implantable electronics.

Makito Haruta received B.E. in bioscience andbiotechnology from Okayama University, Okayama,Japan in 2009, M.S. in biological science from NaraInstitute of Science and Technology (NAIST), Nara,Japan in 2011, and Dr. Eng. in material science fromNAIST in 2014. In 2014, he joined Graduate Schoolof Materials Science, NAIST, as Postdoctoral fellow.His research interest is brain imaging devices forunderstanding brain functions related to animalbehaviors.

Kiyotaka Sasagawa received the B.S. degree fromKyoto University, Kyoto, Japan, in 1999, and theM.E. and Ph.D. degrees in materials science from theNara Institute of Science and Technology, Nara,Japan, in 2001 and 2004, respectively. From 2004 to2008, he was a Researcher with the National Instituteof Information and Communications Technology,Tokyo, Japan. In 2008, he joined the Nara Instituteof Science and Technology, Nara, Japan, where heis currently an assistant professor. His research

interests involve bioimaging, bio-sensing, and electromagnetic fieldmeasurement.

Takashi Tokuda received his B.E. and M.E.degrees in Electronic Engineering from KyotoUniversity, Kyoto, Japan, in 1993 and 1995,respectively. He received his Ph.D. degree inMaterials Engineering from Kyoto University in1998. He had been an assistant professor since 1999and has been working as an associate professor since2008 at the Graduate School of Materials Science,Nara Institute of Science and Technology (NAIST).His research interests include CMOS image sensors,

retinal prosthesis devices, bioimaging sensors, and bio-sensing devices.

Jun Ohta received the B.E., M.E., and Dr. Eng.degrees in applied physics, all from the University ofTokyo, Japan, in 1981, 1983, and 1992, respectively.In 1983, he joined Mitsubishi Electric Corporation,Hyogo, Japan. In 1998, he joined Graduate School ofMaterials Science, Nara Institute of Science andTechnology, Nara, Japan as Associate Professor.He was appointed as Professor in 2004. His currentresearch interests are smart CMOS image sensorsfor biomedical applications and retinal prosthetic

devices. He is a Fellow of the Japan Society of Applied Physics and theInstitute of Image, Information, and Television Engineers, and a SeniorMember of IEEE.

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1002B3-9 © 2018 The Japan Society of Applied Physics