Fabrication of Iridium Oxide/Platinum Composite Film on Titanium Substrate for High-Performance Neurostimulation Electrodes

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Article Fabrication of Iridium Oxide/Platinum Composite Film on Titanium Substrate for High-Performance Neurostimulation Electrodes

Tsai-Wei Chung 1, Chih-Ning Huang 1, Po-Chun Chen 1,*, Toshihiko Noda 2, Takashi Tokuda 2 and Jun Ohta 2 1 Department of Materials & Mineral Resources Engineering, National Taipei University of Technology, Taipei 106, Taiwan; [email protected] (T.-W.C.); [email protected] (C.-N.H.) 2 Graduate School of Materials Science, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan; [email protected] (T.N.); [email protected] (T.T.); [email protected] (J.O.) * Correspondence: [email protected]; Tel.: +886-2-2771-2171

Received: 16 October 2018; Accepted: 22 November 2018; Published: 23 November 2018

Abstract: Electrode materials for neural stimulation have been widely investigated for implantable devices. Among them, iridium and iridium oxide are attractive materials for bio-interface applications due to their desirable stability, electrochemical performance, and biocompatibility. In this study, iridium oxide/platinum (IrOx/Pt) composite films were successfully fabricated on titanium substrates by chemical bath deposition and these films are expected to be used as biocompatible stimulation electrodes. We modified the film compositions to optimize the performances. In addition, these IrOx/Pt composite films were characterized before and after annealing by SEM and XRD. We also identified the hydrophilicity of these iridium oxide/platinum composite films by measuring contact angles. Finally, the charge storage capacities of these iridium oxide/platinum composite films were evaluated by an electrochemical workstation. As a result, the charge storage capacities of the iridium oxide/platinum composite films are largely increased, and this leads to a very efficient neurostimulation electrode. Additionally, we successfully demonstrated the chemical bath deposition of IrOx film on the surface of the bullet-shaped titanium microelectrode.

Keywords: IrOx/Pt composite ﬁlm; stimulation electrodes; biocompatible thin ﬁlm; bullet-shaped microelectrode

1. Introduction The importance of biomedical engineering has raised considerable attention recently, especially on implantable neural-interacting prosthesis [1]. Titanium and its alloys have been conﬁrmed as effective groups of traditional biomaterials [2]. Titanium has exceptional corrosion resistance in the physiological environment, therefore, is the chosen material for many structural implantable devices [3]. For instance, Noda et al. reported the development of an implantable neurostimulation system based on structural titanium microelectrodes [4]. A major limiting factor is the lack of stimulation electrodes with both reasonable performance, stability, and safety [5]. The development of stimulation electrodes requires the ability to inject electrical charges to produce a response without any tissue damage at the stimulation site. The electrode materials must be chosen and examined carefully. Safe neural stimulation requires a reversible charge injection process which can be achieved either by a capacitive process or by a faradaic reversible reaction. The capacitive stimulation electrodes allow signal transmitting to neural tissues by a dielectric ﬁlm [6]. However, only a limited amount of charge can be stored across the electrode interface. In general, electrostimulation with reversible faradaic reactions brings better charge injection performance than that with capacitive

Coatings 2018, 8, 420; doi:10.3390/coatings8120420 www.mdpi.com/journal/coatings Coatings 2018, 8, 420 2 of 8 charge storage. Stimulation electrode materials operating in a faradaic mechanism include platinum, platinum/iridium alloy, iridium oxide, and poly(3,4-ethylenedioxythiophene) (PEDOT) [1,7,8]. Among them, iridium oxide can sufficiently provide necessary charge for stimulation without damaging surrounding tissues by electrochemical reduction and oxidation reactions at the electrode interface [9]. Additionally, advantages such as high charge injection capability, desirable stability, and requisite biocompatibility render iridium oxide to become the most promising material for implantable neurostimulation electrodes. Iridium oxide has received substantial attention in recent years because of its unique ability to inject electric charge and its resistance to corrosion [10]. Iridium oxide is formed with ionic bonds and the hybridized s orbitals are fully occupied with electrons, which lead to notable thermal and chemical stability [11]. Several deposition techniques have been developed, including thermal decomposition, reactive sputtering, electrochemical activation, and electrodeposition [7,9,12–15]. However, some limitations for the processes listed above have been revealed. For instance, curved titanium substrates are not suitable for physical vapor deposition (PVD). Please define if appropriate. processes such as sputtering which causes cracking due to poor adhesion at the edge. Furthermore, titanium substrates are not suitable working electrodes for electrodeposition in most scenarios [4]. Therefore, an alternative solution for the iridium oxide synthesis is chemical bath deposition (CIROF) [16,17]. In chemical bath deposition, the precursor of Ir-ions undergoes oxidation reactions and forms film on the substrates initiated by selective oxidizers. This approach does not require an externally-imposed current/voltage and thus an insulator can be used as the substrate for film growth. Titanium substrates coated with iridium oxide by the wet synthesis process can overcome the difficulty of electrodeposition. A neurostimulation electrode plays a critical role in determining the performance of the bioelectronics [18]. In this study, we developed iridium oxide/platinum composite films on titanium substrates by a multi-step chemical bath deposition and these films are expected to be used as biocompatible stimulation electrodes. We modified the film composition in order to optimize the performance of the iridium oxide/platinum composite films on titanium substrates for neurostimulation devices [19]. Additionally, we employed the chemical bath deposition of IrOx on the surface of a bullet-shape titanium microelectrode to validate the process we developed in this study on a practical device.

2. Materials and Methods Based on previous results, a chemical bath deposition has been developed to fabricate high-quality iridium oxide films with thicknesses in the range from 50 to 1000 nm [16,17]. Therefore, a multi-step method can be used to meet the required film thickness. In this study, titanium sheets (1 × 3 cm2) were cleaned and granulated for increasing adhesion of the following coatings by a dilute HF solution (10%) for 1 min at room temperature [20]. Different compositions of IrOx/Pt composite films were prepared by the chemical bath deposition of iridium oxide on sputtered platinum film on the granulated titanium sheets. The plating bath of iridium oxide contained 0.01 M of sodium hexachloroiridate (III) hydrate (Na3IrCl6·xH2O, Sigma-Aldrich, St. Louis, MO, USA), 0.15 M of sodium hypochlorite (NaClO, SHOWA, Gyoda, Japan), 0.03 M of sodium hydroxide (NaOH, Mallinchrodt Pharmaceuticals, Dublin, Ireland), and 0.01 M of sodium nitrite (NaNO2, SHOWA, Gyoda, Japan). Subsequently, the Ti and Pt-coated Ti sheets underwent a chemical bath deposition of iridium oxide at 25 ◦C for 4 h. The ratios of the IrOx/Pt composite films are 0 to 100 nm, 100 to 200 nm, 200 to 100 nm, and 300 to 0 nm. After ◦ the IrOx/Pt composite films were formed, a heat treatment was conducted at 450 C for 2 h in air. In addition, we performed the same chemical bath deposition of IrOx on a bullet-shape titanium electrode which is 0.5 mm in diameter. The surface morphologies of our samples were analyzed using a scanning electron microscope (FESEM; Hitachi SU-8010, Hitachi, Ltd., Tokyo, Japan) with a 15 keV operating voltage. An X-ray diffractometer (XRD; Bruker D8 Discover, Bruker, Billerica, MA, USA) with a 1.54 Å Cu Kα target was employed to identify the characteristic peaks; the scan rate was 0.05◦/s from 20◦ to 80◦. Coatings 2018, 8, x FOR PEER REVIEW 3 of 8 Coatings 2018, 8, 420 3 of 8

The charge storage capacity (CSC) was determined by integration of the cathodic current in a potentialThe charge window storage for IrO capacityx and (CSC)Pt between was determined −0.6 to 0.8 by V. integration It has become of the common cathodic current practice in to a characterizepotential window the stimulation for IrOx and electrodes Pt between by− their0.6 to CSC0.8 V. values. It has become The CSC common is calculated practice from to characterize the time integralthe stimulation of the cathodic electrodes current by their in a CSCslow values.-sweep- Therate CSCcyclic is voltammetry calculated from over the a potential time integral range of that the iscathodic just within current the in water a slow-sweep-rate electrolysis window cyclic voltammetry (−0.6–0.8 V over for a IrO potentialx and Pt). range An that electrochemical is just within workstationthe water electrolysis (CHI 614E window, CH Instruments, (−0.6–0.8 V Inc. for, IrOAustin,x and TXPt)., USA An electrochemical) was employed workstation to obtain those (CHI electrical614E, CH properties. Instruments, The Inc., geometric Austin, TX,surface USA) area was was employed 0.386 cm to2 obtain. Cyclic those voltammetry electrical was properties. taken as The a sweepgeometric rate surface of 50 mV/s area from was 0.386 −0.6 cmto 0.82. Cyclic V. All voltammetrythe experiments was were taken taken as a sweep in phosphate rate of 50 buffer mV/s saline from (PBS)−0.6. to 0.8 V. All the experiments were taken in phosphate buffer saline (PBS). TheThe biocompatibility biocompatibility of the IrO x/Pt/Pt composited composited films ﬁlms was was evaluated evaluated by by a a sulforhodamine sulforhodamine B B (SRB) (SRB) assay.assay. MDA MDA-MB-231-MB-231 cells cells were seeded on differentdifferent surfacessurfaces atat aa densitydensity ofof 10001000 cells/cmcells/cm2.. After After 7 7 days,days, surfaces surfaces w wereere washed washed twice twice with with an an excess excess of of phosphate phosphate buffered buffered saline saline (PBS) (PBS) to to remove remove any any deaddead cells cells or or debris. Cells Cells were were then then fixed ﬁxed by by immersing immersing surfaces surfaces in in 10% 10% trichloroacetic trichloroacetic acid acid (TCA) (TCA) overnovernightight at at 4 4 °C.◦C. The The next next day, day, cells were washed 5 times with double distilled water (DDW) (DDW) and and allowedallowed to air air dry. dry. Cells were then stained for 1 1 h h with with 0.4% 0.4% SRB SRB (prepared (prepared in in 1% 1% acetic acetic acid). acid). Samples Samples were washed 4 times with 1% 1% acetic acetic acid acid and and air air dried. dried. Sampl Sampleses were were then then immersed immersed in in a a 10 10 mM mM Tris Tris basebase for 30 min. Optical Optical density density (OD) (OD) was was recorded recorded at 540 nm using an ELISA reader.

3.3. Results Results and and Discussion Discussion TheThe adhesion of of the the first first coated layer plays plays a a key factor in the stability of the film film synthesized byby multimulti-step-step chemical bath deposition. Platinum, Platinum, especially, especially, has has been been reported reported that that its adhesion issueissue causes causes peeling peeling of of the the deposited deposited film film [21] [21].. The The granulated granulated titanium titanium can can sufficiently sufficiently increase increase the the adhesionadhesion of of sputtered sputtered platinum platinum film film on on the titanium surface. Figure Figure 11 showsshows thethe opticaloptical microscopemicroscope imagesimages of of titanium titanium surface surface before before and and after surface granulating process. The The treated treated titanium titanium shown shown inin Figure Figure 11bb,, presentspresents moremore andand finerfiner grainsgrains compared to the raw titanium sheet shown in Figure 11a.a. TTherefore,herefore, t thehe adhesion of the IrOx/Pt composite composite films films on on titanium titanium substrate substrate can can be be increased increased..

FigureFigure 1 1.. OpticalOptical microscope microscope images images of of ( (aa)) untreated untreated Ti Ti foil; foil; and and ( (b) granulated Ti foil.foil.

FigureFigure 22 showsshows SEMSEM imagesimages ofof thethe IrOIrOxx/Pt composite composite films. films. Figure Figure 22aa is the sputtered platinumplatinum onon titanium substrate;substrate; somesome particles particles can can be be observed observed on on its its surface. surface. Figure Figure2b–d 2b,c show,d show top-view top- SEMview SEMimages images of 100/200 of 100/ nm,200 200/100 nm, 200 nm,/100 and nm, 300/0 and 300 nm/0 of nm IrO ofx/Pt IrO compositex/Pt composite films, films, respectively. respectively. As shown As shownin Figure in 2Figb–d,ure the 2b,c,d, Ti substrates the Ti substrates were fully were covered fully covered by a dense by layera dense of layer IrO x ofand IrO IrOx andx particles IrOx particles on the onsurfaces. the surfaces. More particles More particles appeared appeared on the 200/100 on the nm200/100 of IrO nmx/Pt of compositeIrOx/Pt composite film, as shown film, as in shown Figure 2inc, Figurethan that 2c, on than the that 300/0 on nm the composite 300/0 nm film, composite as shown film in, Figureas shown2d. Althoughin Figure thicker2d. Although IrO x films thicker generally IrOx filmshave moregenerally particles have bymore chemical particles bath by deposition, chemical bath the sputtereddeposition, platinum the sputtered provides platinum more nucleation provides moresites comparednucleation to sites the purecompar titaniumed to the substrate. pure titanium The contact substrat anglese. The also contact altered angles with the also composition altered with of thethe composition coated films asof listedthe coated in Table films1. Aas negative listed in correlationTable 1. A cannegative be found correlation between can the be thickness found between of IrO x thefilms thickness and measured of IrOx fi contactlms and angles. measured It implies contact that angles composite. It implies films that become composite more films hydrophilic become alongmore hydrophilicwith the increasing along with thickness the increasing of IrOx film. thickness The result of matches IrOx film. the The relationship result matches between the thickness relationship and betweenhydrophilicity thickness reported and hydrophilicity by Miyashita etreported al. [22]. by The Miyashita thicker IrO etx al.film [22] by. chemical The thicker bath IrO depositionx film by chemicalpresented bath more deposit hydrophilicity,ion presented which is more a desirable hydrophilicity property, which for an implantable is a desirable material. property for an implantable material.

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Figure 2. Top-view SEM images of annealed IrOx-Pt composite films on Ti substrate; (a) sputtered Pt, (b) 100 nm/200 nm of IrOx/Pt, (c) 200 nm/100 nm of IrOx/Pt, and (d) 300 nm/0 nm of IrOx. Figure 2.2. TopTop-view-view SEM images of annealed IrO x--PtPt composite composite films ﬁlms on on Ti Ti substrate; ( (a)) sputtered sputtered Pt, Pt,

(b)) 100 nm/200nm/200 nm nm of of IrO IrOxx/Pt,/Pt, (c ()c 200) 200 nm/100 nm/100 nm nm of ofIrO IrOx/Pt,x/Pt, and and (d) (300d) 300 nm/0 nm/0 nm nmof IrO of IrOx. x. Table 1. A summary of relations between IrOx/Pt ratio and contact angle. Table 1. A summary of relations between IrOx/Pt ratio and contact angle. Table 1. A summaryIrO ofx/Pt relations Ratio betweenContact IrOx /PtAngle ratio and contact angle. IrOx/Pt0/100 Ratio 59.44 Contact Angle IrOx/Pt Ratio Contact Angle 100/200 24.48 0/1000/100 59.44 59.44 100/200200/100 12.2224.48 100/200 24.48 200/100300/0 5.58 12.22 300/0200/100 12.22 5.58 300/0 5.58 The crystallinity of the CIROF was improved by annealing the as-deposited film at 450 °C for 2 ◦ h in air.The Figure crystallinity 3 provides of the the CIROF XRD patterns was improved of the byannealed annealing IrO thex/Pt as-depositedcomposite films. film The at 450 as-Cdeposited for 2 h in The crystallinity of the CIROF was improved by annealing the as-deposited film at 450 °C for 2 filmair. Figure was amorphous3 provides the but XRD after patterns annealing, of the the annealed crystalline IrO x /Pt rutile composite phase of films. IrO The2 was as-deposited confirmed film by h in air. Figure 3 provides the XRD patterns of the annealed IrOx/Pt composite films. The as-deposited comparingwas amorphous with the but standard after annealing, IrO2 pattern the crystalline (ICDD 00- rutile043-1019), phase Pt of pattern IrO2 was (ICDD confirmed 00-001- by1194), comparing and Ti film was amorphous but after annealing, the crystalline rutile phase of IrO2 was confirmed by Patternwith the (ICDD standard 01-089 IrO-5009).2 pattern The (ICDDcrystalline 00-043-1019), film is expected Pt pattern to reduce (ICDD defects 00-001-1194), and improve and Ti the Pattern film comparing with the standard IrO2 pattern (ICDD 00-043-1019), Pt pattern (ICDD 00-001-1194), and Ti stability.(ICDD 01-089-5009). We can determine The crystalline the charge film storage is expected capacity to reduce(CSC) of defects the films and by improve performing the film the stability. cyclic Pattern (ICDD 01-089-5009). The crystalline film is expected to reduce defects and improve the film voltammetryWe can determine tests thein PBS charge solution. storage It capacity has become (CSC) common of the films practice by performing to characterize the cyclic the voltammetrystimulation stability. We can determine the charge storage capacity (CSC) of the films by performing the cyclic electrodestests in PBS by solution. their CSC, It has which become is essentially common practicea measurement to characterize of the to thetal stimulation amount of electrodes charge ava byilable their voltammetry tests in PBS solution. It has become common practice to characterize the stimulation forCSC, a stimulation which is essentially pulse. a measurement of the total amount of charge available for a stimulation pulse. electrodes by their CSC, which is essentially a measurement of the total amount of charge available for a stimulation pulse.

Figure 3. XRD patterns of different compositions of IrO -Pt composite ﬁlms on Ti substrates with Figure 3. XRD patterns of different compositions of IrOx-xPt composite films on Ti substrates with IrOIrOx/Ptx/Pt ratio ratio of of (a ()a 300/0,) 300/0, (b) ( b200/100,) 200/100, (c) (100/200,c) 100/200, and and (d) (ICDDd) ICDD standards standards of IrO of IrO2, Ti,2, and Ti, and Pt. Pt. Figure 3. XRD patterns of different compositions of IrOx-Pt composite films on Ti substrates with

IrOx/Pt ratio of (a) 300/0, (b) 200/100, (c) 100/200, and (d) ICDD standards of IrO2, Ti, and Pt.

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The cyclic voltammograms (CV) shown in Figure 4 are the as-deposited and annealed IrOx/Pt compositeThe cyclic films, voltammograms respectively. The (CV) high shown CSC value in Figure shows4 are that the the as-deposited IrOx/Pt composite and annealed films may IrO xhave/Pt compositehigh charge films,-injection respectively. capacity The and high have CSC a potential value shows to stimulate that the IrOcellsx/Pt at a composite lower voltage. films mayFigure have 4a highpresents charge-injection the CV curves capacity for various and composition have a potential of IrO tox/Pt stimulate composite cells films. at a The lower CSC voltage. values decreased Figure4a presentsafter the the annealing CV curves process for various due composition to the effect of of IrO crystallinityx/Pt composite [12,23] films.. The The heat CSC treatment values decreased process afterefficiently the annealing crystallized process the due composite to the effect films, of crystallinityand the CSC [ 12values,23]. Thechanged heat treatment accordingly. process Furthermore, efficiently crystallizedthe 200/100 thenm compositeof IrOx/Pt films,composite and thefilm CSC presented values changedthe largest accordingly. CSC value Furthermore, of 46.28 mC/cm the2 200/100because 2 nmthe ofsputtered IrOx/Pt compositeplatinum increases film presented the surface the largest roughness CSC value of the of composite 46.28 mC/cm film.because Figure the4b shows sputtered the platinumcomparison increases of the theCV surfacecurves roughnessof as-deposit of theed and composite annealed film. IrO Figurex film4 (300/0b shows nm) the a comparisons well as annealed of the CVPt (0/100 curves nm) of as-deposited, and the CSC and values annealed were IrO35.22,x film 24.19, (300/0 and nm)1.07 asmC/cm well as2, respectively. annealed Pt(0/100 IrOx can nm), largely and 2 theincrease CSC valuesthe CSC were value 35.22, compared 24.19, and to the 1.07 traditional mC/cm , commercial respectively. electrode IrOx can material largely increase of Pt. Therefore, the CSC valuewe can compared expect to IrO thex traditionalto becom commerciale the next electrodegeneration material biocompatible of Pt. Therefore, electrode we can for expect implantable IrOx to becomeneurostimulation the next generation devices [24,25] biocompatible. electrode for implantable neurostimulation devices [24,25].

FigureFigure 4.4. CyclicCyclic voltammogramsvoltammograms of (a) as-depositedas-deposited IrO x/Pt/Pt composite composite films ﬁlms with with IrO IrOx/Ptx/Pt ratio ratio of of(i)

(i)300/0, 300/0, (ii) (ii)200/100, 200/100, (iii) (iii)100/200 100/200;; and andannealed annealed IrOx/Pt IrO compositex/Pt composite films ﬁlmswith withIrOx/Pt IrO ratiox/Pt of ratio (iv) of300/0, (iv)

300/0,(v) 200/100, (v) 200/100, (vi) 100/200; (vi) 100/200; (b) charge (b) chargestorage storage capacity capacity (CSC) (CSC) comparison comparison of (i) ofas- (i)deposit as-depositeded IrOx IrOfilmx,

film,(ii) annealed (ii) annealed IrOx IrOfilmx, film,and (iii) and Pt (iii) film Pt. film.

WeWe furtherfurther employedemployed thethe chemicalchemical bathbath depositiondeposition ofof iridiumiridium oxideoxide onon aa bullet-shapedbullet-shaped titaniumtitanium microelectrodemicroelectrode (0.5(0.5 mmmm inin diameter).diameter). NodaNoda etet al.al. reportedreported thatthat theythey developeddeveloped aa retinalretinal prosthesisprosthesis usingusing thethe curvedcurved titanium titanium microelectrodes microelectrodes [4 [4]]. Figure. Figure5a 5 displaysa displays the the optical optical microscopy microscopy (OM) (OM) image image of the bullet-shaped titanium microelectrode. IrOx film was deposited on the surface of the bullet-shaped of the bullet-shaped titanium microelectrode. IrOx film was deposited on the surface of the bullet- titaniumshaped titanium microelectrode microelect by chemicalrode by chemical bath deposition bath deposition developed developed in this study. in this As shownstudy. As in Figureshown5 a,in theFigure surface 5a, the of thesurface bullet-shaped of the bullet titanium-shapedmicroelectrode titanium microelect wasr uniformlyode was uniformly covered bycovered a thin by layer a thin of IrOx film. Figure5b displays the CV curve of the fifth cycle of the IrO x-coated bullet-shaped titanium layer of IrOx film. Figure 5b displays the CV curve of the fifth cycle of the IrOx-coated bullet-shaped · −1 microelectrodetitanium microelectrode at 50 mV ats 50. ThemV· oxidation/reductions−1. The oxidation/reduction peaks that peaks appeared that appeared in the CSCin the profile CSC profile of the IrOx-coated bullet-shaped titanium microelectrode were identical to the CSC profiles of the IrOx-coated of the IrOx-coated bullet-shaped titanium microelectrode were identical to the CSC profiles of the titanium and IrOx/Pt-coated titanium shown in Figure4. Consequently, we successfully implemented IrOx-coated titanium and IrOx/Pt-coated titanium shown in Figure 4. Consequently, we successfully chemicalimplemented bath deposition chemical bath to replace deposition deposition to replace techniques deposition such as technique sputtering.s such In addition, as sputtering. the CSC In 2 value of the IrOx-coated bullet-shaped titanium microelectrode was 30.12 mC/cm correlated to the addition, the CSC value of the IrOx-coated bullet-shaped titanium microelectrode was 30.12 mC/cm2 electrode performance of the IrOx thin film using chemical bath deposition. We would like to further correlated to the electrode performance of the IrOx thin film using chemical bath deposition. We explain the reason we only deposited IrOx on the bullet-shaped titanium microelectrode. The IrOx would like to further explain the reason we only deposited IrOx on the bullet-shaped titanium and Pt in the composite films were prepared using chemical bath deposition and DC sputtering, microelectrode. The IrOx and Pt in the composite films were prepared using chemical bath deposition respectively.and DC sputtering, We only respectively. demonstrated We only the demonstrated feasibility of the the chemicalfeasibility bath of the deposition chemical bath of IrO depositionx on the bullet-shaped titanium microelectrode to prevent cracks on the sputtered Pt film formed on the curved of IrOx on the bullet-shaped titanium microelectrode to prevent cracks on the sputtered Pt film titanium substrate. However, IrOx/Pt composite film can be deposited on the bullet-shaped titanium formed on the curved titanium substrate. However, IrOx/Pt composite film can be deposited on the microelectrode as long as both IrOx and Pt films can be prepared using chemical bath deposition [26]. bullet-shaped titanium microelectrode as long as both IrOx and Pt films can be prepared using chemical bath deposition [26].

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FigureFigure 5. 5.( a(a)) Optical Optical microscope microscope image image of IrO of x IrO-coatedx-coated bullet-shaped bullet-shaped titanium titanium microelectrode; microelectrode; (b) cyclic (b) voltammogramcyclic voltammogram of IrOx of-coated IrOx-coated bullet-shaped bullet-shaped titanium titanium microelectrode. microelectrode.

InIn orderorder toto evaluateevaluate thethe biocompatibilitybiocompatibility ofof thethe IrO IrOx/Ptx/Pt composite films,films, anan MDA-MB-231MDA-MB-231 cellcell lineline waswas culturedcultured onon toptop ofof thethe IrOIrOxx/Pt/Pt composite composite films films and and on on a a culture dish as the control group. TheThe cell viability was was assessed assessed by by measuring measuring the the optical optical density density (OD) (OD) of the of the resulting resulting solution solution at 595 at 595nm. nm The. The cell cell viability viability percentages percentages were were calculated calculated as: as: OD ODsamplesample/OD/ODcontrolcontrol. Figure. Figure 6 shows6 shows the the cell cellviability viability results. results. Each Each sample sample of IrO ofx IrO/Pt xcomposite/Pt composite film filmhad hada viability a viability of ~90 of%, ~90%, which which indicates indicates that thatthe theIrOx IrO/Pt x composite/Pt composite film film provides provides a biocompatiblea biocompatible environment environment for for cell cell survival. The The IrO IrOx/Ptx/Pt compositecomposite filmsfilms fabricatedfabricated inin thisthis studystudy havehave goodgood crystallinitycrystallinity andand hydrophilicity;hydrophilicity; thesethese propertiesproperties cancan provideprovide aa desirabledesirable matrixmatrix forfor cellcell attachmentattachment accordingaccording toto studiesstudies onon thethe relationshiprelationship betweenbetween crystallinitycrystallinity andand biocompatibilitybiocompatibility [[10,27]10,27]..

Figure 6. Cell viability percentage of IrOx/Pt composite films. Figure 6. Cell viability percentage of IrOx/Pt composite films. 4. Conclusions 4. Conclusions In this study, we successfully developed a hybrid deposition process to prepare IrOx/Pt composite filmsIn on thistitanium study substrates, we successfully by combining developed chemical a bath hybrid deposition deposition and sputtering. process to A prepare relationship IrOx/Pt is composite films on titanium substrates by combining chemical bath deposition and sputtering. A foundcomposite as well; films when on thetitanium deposited substrates thickness by ofcombining IrOx increases, chemical the surface bath deposition roughness and also sputtering increases, but. A relationship is found as well; when the deposited thickness of IrOx increases, the surface roughness therelation contactship angle is found decreases. as well; These when IrO thex/Pt deposited composite thickness films with of differentIrOx increases, compositions the sur canface beroughness used for manyalso increases, applications. but Furthermore, the contact the angle chemical decrease baths.deposition These IrO isx/Pt a simple composite and inexpensive films with alternative different compositions can be used for many applications. Furthermore, the chemical bath deposition is a forcomposition fabrication.s can In be addition, used for the many IrOx /Pt applications. composite Furthermore, films were characterized the chemical by bath their deposition morphology, is a composition,simple and inexpensive crystallinity, alternative surface roughness for fabrication. by SEM, In XRD, addition, and the contact IrOx/Pt angle, composite respectively. films wereAs a characterized by their morphology, composition, crystallinity, surface roughness by SEM, XRD, and result,characterized the IrO byx/Pt their composite morphology, films composition, present higher crystallinity, charge storage surface capacities roughness than by PtSEM film, XRD, does, and so theycontact can angle, be utilized respectively. in implantable As a result, neurostimulation the IrOx/Pt composite devices films and largelypresent enhance higher charge the efficiency. storage capacities than Pt film does, so they can be utilized in implantable neurostimulation devices and Additionally,capacities than we Pt successfully film does,demonstrated so they can be the utilized chemical inbath implantable deposition neurostimulation of IrOx film on the devices surface and of largely enhance the efficiency. Additionally, we successfully demonstrated the chemical bath thelargely bullet-shaped enhance the titanium efficiency. microelectrode Additionally, and the we redox successfully behavior demonstrated of the IrOx-coated the chemical bullet-shaped bath deposition of IrOx film on the surface of the bullet-shaped titanium microelectrode and the redox titaniumdeposition microelectrode of IrOx film on was the identical surface to of that the of bullet the IrO-shapex-coatedd titanium titanium microelect sheet. rode and the redox behavior of the IrOx-coated bullet-shaped titanium microelectrode was identical to that of the IrOx- coated titanium sheet.

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Author Contributions: Conceptualization, P.-C.C. and J.O.; Methodology, P.-C.C.; Software, T.-W.C. and C.-N.H.; Validation, P.-C.C., T.N., T.T., and J.O.; Formal Analysis, P.-C.C., T.N., and T.-W.C.; Investigation, P.-C.C., T.N., T.T., and J.O.; Resources, P.-C.C. and J.O.; Data Curation, P.-C.C., T.N., T.T., and J.O.; Writing-Original Draft Preparation, P.-C.C.; Writing-Review & Editing, P.-C.C. and J.O.; Supervision, P.-C.C. and J.O.; Project Administration, P.-C.C. and J.O.; Funding Acquisition, P.-C.C. and J.O. Funding: This research was funded by financial supports from the Ministry of Science and Technology of Taiwan (MOST 106-2221-E-027-048, 107-2221-E-027-009-MY2, and 107-2633-B-009-003) and the Japan Science and Technology Agency (JST) under funding program of The Japanese–Taiwanese Cooperative Program on “Bioelectronics” and “Biophotonics”. Acknowledgments: The authors acknowledge Precision Research and Analysis Center at NTUT and partly by the Center for Neuromodulation Medical Electronics Systems from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education in Taiwan. Conflicts of Interest: The authors declare no conflict of interest.

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