micromachines

Review Techniques and Considerations in the Microfabrication of Parylene C Microelectromechanical Systems

Jessica Ortigoza-Diaz 1, Kee Scholten 1 ID , Christopher Larson 1 ID , Angelica Cobo 1, Trevor Hudson 1, James Yoo 1 ID , Alex Baldwin 1 ID , Ahuva Weltman Hirschberg 1 and Ellis Meng 1,2,* 1 Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USA; [email protected] (J.O.-D.); [email protected] (K.S.); [email protected] (C.L.); [email protected] (A.C.); [email protected] (T.H.); [email protected] (J.Y.); [email protected] (A.B.); [email protected] (A.W.H.) 2 Ming Hsieh Department of Electrical Engineering, University of Southern California, Los Angeles, CA 90089, USA * Correspondence: [email protected]; Tel.: +1-213-740-6952



Received: 31 July 2018; Accepted: 18 August 2018; Published: 22 August 2018


Abstract: Parylene C is a promising material for constructing flexible, biocompatible and corrosion- resistant microelectromechanical systems (MEMS) devices. Historically, Parylene C has been employed as an encapsulation material for medical implants, such as stents and pacemakers, due to its strong barrier properties and biocompatibility. In the past few decades, the adaptation of planar microfabrication processes to thin film Parylene C has encouraged its use as an insulator, structural and substrate material for MEMS and other microelectronic devices. However, Parylene C presents unique challenges during microfabrication and during use with liquids, especially for flexible, thin film electronic devices. In particular, the flexibility and low thermal budget of Parylene C require modification of the fabrication techniques inherited from silicon MEMS, and poor adhesion at Parylene-Parylene and Parylene-metal interfaces causes device failure under prolonged use in wet environments. Here, we discuss in detail the promises and challenges inherent to Parylene C and present our experience in developing thin-film Parylene MEMS devices.

Keywords: Parylene; microfabrication; MEMS

1. Introduction

1.1. History and Types of Parylene Parylene is the trade name for poly-(para-xylylene), a class of semicrystalline, hydrophobic polymers which can be deposited as thin, conformal, pinhole-free films using chemical vapor deposition (CVD). Parylene was discovered by Michael Mojzesz Szwarc in the late 1940s but was not commercialized until 1965 following the development of the Gorham deposition process at Union Carbide [1,2]. Types of Parylene that are commonly available include Parylene N, Parylene C, Parylene D and Parylene HT (Figure1). A comparison of the properties of these films can be found in [ 3]. Parylene N is composed of an aromatic ring with attached methylene groups [4]; it has been used as a dielectric and has the slowest deposition rate of the Parylenes [5]. Parylene C features a single chlorine atom on its benzene ring and is recognized for its chemical inertness, electrical resistivity, low moisture permeability and proven biocompatibility. Parylene D has two chlorine atoms, resulting in similar properties to Parylene C with slightly higher temperature resistance. Parylene HT is a fluorinated

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Micromachines 2018, 9, x FOR PEER REVIEW 2 of 25 variant of the Parylene N polymer and is marked by high temperature stability [6]. The two most stabilitycommon [6]. Parylene The two types most in common commercial Parylene applications types in arecommercial Parylene applications N and C, whereas are Parylene Parylene N Cand is theC, whereasmost common Parylene material C is the encountered most common in MEMS material devices. encountered in MEMS devices.

FigureFigure 1. 1. ChemicalChemical structure structure of of Parylene Parylene types. types.

ParyleneParylene C, C, referred referred from from here here on on as as Parylene, Parylene, is is a a US US Pharmacopeia Pharmacopeia class class VI VI material material [7], [7], having having thethe highest highest biocompatibility biocompatibility certification certification for for a a plas plastictic material. material. For For several several decades, decades, thin thin Parylene Parylene coatingscoatings were were used used to to create create waterproof waterproof insula insulationtion for for electronics electronics inte intendednded for for use use in in harsh harsh environments,environments, a a category category that that increasingly increasingly includ includeses biomedical biomedical implants. implants. Parylene Parylene exhibits exhibits low low intrinsicintrinsic stress stress inin additionaddition to to optical optical transparency, transparency, mechanical mechanical flexibility flexibility and compatibilityand compatibility with several with severalstandard standard micromachining micromachining processes processes [8–11]. [8–11]. While While Parylene Parylene can be can used be used in combination in combination with with rigid rigidsubstrates substrates such such as silicon as silicon and glass, and glass, it has beenit has increasingly been increasingly utilized utilized as a flexible as a structuralflexible structural material materialin the growing in the field growing of polymer-based field of polymer-based biomedical microelectromechanical biomedical microelectromechanical systems (bioMEMS). systems As a (bioMEMS).dynamic polymer As a material,dynamic Parylenepolymer presents material, unique Parylene challenges presents during unique microfabrication challenges andduring use microfabricationwhich are further and explored use which here. are further explored here.

1.2.1.2. Thin-Film Thin-Film Parylene Parylene Device Device Microfabrication Microfabrication Parylene-basedParylene-based bioMEMS bioMEMS are preparedprepared throughthrough a a combination combination of of microfabrication microfabrication processes processes and andcommonly commonly consist consist of a simpleof a simple sandwich sandwich design, design, with a with base layera base of layer Parylene, of Parylene, a thin layer a thin of patternedlayer of patternedmetal defining metal tracesdefining and traces other and components, other componen and a topts, and layer a top of Parylene. layer of Parylene. Figure2 depicts Figure 2 a depicts flexible adevice flexible in device which Parylenein which servesParylene as bothserves the as structural both the materialstructural and material insulator. and However, insulator. devices However, may devicesalso be may supported also be on supported standard rigidon standard substrates rigid such substrates as glass andsuch silicon as glass when and flexibilitysilicon when is not flexibility required. isRegardless not required. of the Regardless final format, of the microfabrication final format, microfabrication requires that Parylene requires be supportedthat Parylene by rigidbe supported substrate by rigid substrate during fabrication, with optional release of a free film device towards the end of duringMicromachines fabrication, 2018, 9, x withFOR PEER optional REVIEW release of a free film device towards the end of the process. 3 of 25 the process. Devices are realized using a combination of three process categories: additive processes (deposition), subtractive processes (etching) and patterning (e.g., photolithography). Parylene is deposited exclusively through a highly conformal CVD process at room temperature, with typical deposition rates on the order of ~2 μm/h. Other deposition methods are critical for polymer MEMS processing; spin coating is used to deposit photo-patternable polymer layers (photoresist) for use as an etch mask or shadow mask, or as a sacrificial layer, while physical vapor deposition (PVD) methods including evaporation and sputtering are used for metal deposition. Etching processes are limited to dry methods due to Parylene’s high chemical inertness. Reactive ion etching (RIE) and deep reactive ion etching (DRIE) are oxygen plasma-based techniques commonly used to etch Parylene.Figure Parylene 2. Cross devices section areof a predominantlytypical device showing patterned insulated using and standard exposed UV metal lithography features, suchprocesses, as Figure 2. Cross section of a typical device showing insulated and exposed metal features, such as traces and, moretraces andrecently, electrodes, nanoscale respectively. features can be patterned using electron beam lithography with appropriateand electrodes, protective respectively. layers [12] to prevent beam damage. 1.3. State-of-the-Art Parylene-Based Devices Devices are realized using a combination of three process categories: additive processes (deposition),Parylene subtractiveis used extensively processes to coat (etching) printed and circuit patterning boards, (e.g.,wires, photolithography). MEMS devices, and Parylenebiomedical is depositedimplants, and exclusively less commonly through as a a highly structural conformal or substrate CVD processmaterial at for room electronic temperature, and MEMS with devices. typical depositionStill, over the rates last on several the order years, of many ~2 µm/h. devices Other for depositiona large variety methods of applications are critical have for polymer been described MEMS processing;in the literature spin coatingfeaturing is usedParylene to deposit as either photo-patternable the structural or polymer substrate layers material (photoresist) (Figure for3). useParylene as an has been used as a flexible coiled cable to connect medical implants to external circuitry [13–15]. Radio frequency powered coils were fabricated with Parylene for wireless transmission (Figure 3a) [16,17] and more recently a new method to wirelessly transduce electrochemical impedance was developed using Parylene coils [18]. Parylene microsensors (Figure 3b) were developed to measure intraocular and intracranial pressures [19–21] and Parylene thermal sensors were created to detect small flows [22–25]. Other devices include neurocages for in vitro neural network study [26–28], bellows for drug delivery [29–31], an electrochemical patency sensor [32], microfluidic devices [7] and electrothermal valves [33]. In the field of neural prostheses Parylene was used to create both penetrating (Figure 3c) [34–39] and non-penetrating microelectrode arrays [40–42]. Microfluidic channels were integrated into Parylene neural probes to inject drugs [43–45]. Parylene-based cuff electrodes, which record neural activity within peripheral nerves, were also developed [46–48]. Parylene spinal cord stimulators have also been realized with high-density electrode sites [49,50].

Figure 3. (a) Wireless coils (Reprinted from Reference [16] with permission from Elsevier); (b) flow, pressure and patency sensors to monitor hydrocephalus treatment (©2016 IEEE. Reprinted, with permission, from Reference [23]); (c) hippocampal neural probe array (©2017 IEEE. Reprinted, with permission, from Reference [37]); and (d) retinal prosthesis that matches the curvature of the eye (Reprinted from Reference [49] with permission from Elsevier). Parylene is transparent and the opaque features are metal.

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Micromachines 2018, 9, 422 3 of 25 etch mask or shadow mask, or as a sacrificial layer, while physical vapor deposition (PVD) methods including evaporation and sputtering are used for metal deposition. Etching processes are limited to dry methods due to Parylene’s high chemical inertness. Reactive ion etching (RIE) and deep reactive ion etching (DRIE) are oxygen plasma-based techniques commonly used to etch Parylene. Parylene devices are predominantly patterned using standard UV lithography processes, and, more recently, nanoscaleFigure features 2. Cross cansection be of patterned a typical usingdevice electronshowing beaminsulated lithography and exposed with metal appropriate features, such protective as layerstraces [12] and to prevent electrodes, beam respectively. damage.

1.3. State-of-the-Art Parylene-Based Devices Parylene is used extensively to coat printed circuit boards, wires, MEMS devices, and biomedical implants,implants, andand less less commonly commonly as as a structurala structural or or substrate substrate material material for electronicfor electronic and and MEMS MEMS devices. devices. Still, overStill, theover last the several last several years, years, many many devices devices for a largefor a varietylarge variety of applications of applications have been have described been described in the literaturein the literature featuring featuring Parylene Parylene as either as the either structural the structural or substrate or substrate material material (Figure3). (Figure Parylene 3). hasParylene been usedhas been as a used flexible as coileda flexible cable coiled to connect cable to medical connect implants medical to implants external to circuitry external [13 circuitry–15]. Radio [13–15]. frequency Radio poweredfrequency coils powered were fabricatedcoils were withfabricated Parylene with for Parylene wireless for transmission wireless transmission (Figure3a) (Figure [ 16,17] 3a) and [16,17] more recentlyand more a recently new method a new tomethod wirelessly to wirelessly transduce transduce electrochemical electrochemical impedance impedance was developed was developed using Paryleneusing Parylene coils [coils18]. [18]. Parylene Parylene microsensors microsensors (Figure (Figure3b) 3b) were were developed developed to to measure measure intraocular intraocular and intracranial intracranial pressures pressures [19–21] [19–21 ]and and Parylene Parylene thermal thermal sensors sensors were were created created to detect to detect small smallflows flows[22–25]. [22 Other–25]. Otherdevices devices include include neurocages neurocages for in vitro for in neural vitro networkneural network study [26–28], study [bellows26–28], for bellows drug fordelivery drug [29–31], delivery an [ 29electrochemical–31], an electrochemical patency sensor patency [32], microfluidic sensor [32], devices microfluidic [7] and devices electrothermal [7] and electrothermalvalves [33]. In valvesthe field [33 of]. neural In the field prostheses of neural Paryle prosthesesne was Parylene used to create was used both to penetrating create both penetrating (Figure 3c) (Figure[34–39]3 andc) [ 34non-penetrating–39] and non-penetrating microelectrode microelectrode arrays [40–42]. arrays Microfluidic [40–42]. Microfluidic channels were channels integrated were integratedinto Parylene into neural Parylene probes neural to inject probes drugs to inject[43–45]. drugs Parylene-based [43–45]. Parylene-based cuff electrodes, cuff which electrodes, record whichneural recordactivity neural within activity peripheral within peripheralnerves, were nerves, also were developed also developed [46–48]. [ 46Parylene–48]. Parylene spinal spinal cord cordstimulators stimulators have havealso been also beenrealized realized with withhigh-density high-density electrode electrode sites sites[49,50]. [49 ,50].

Figure 3. 3. (a)( aWireless) Wireless coils coils (Reprinted (Reprinted from fromReference Reference [16] with [16 ]permission with permission from Elsevier); from Elsevier);(b) flow, (pressureb) flow, pressureand patency and patencysensors sensorsto monitor to monitor hydroc hydrocephalusephalus treatment treatment (©2016 (© IE2016EE. IEEE.Reprinted, Reprinted, with withpermission, permission, from fromReference Reference [23]); [(23c)]); hippocampal (c) hippocampal neural neural probe probe array array(©2017 (© 2017IEEE. IEEE. Reprinted, Reprinted, with withpermission, permission, from from Reference Reference [37]); [37 and]); and (d) (dretinal) retinal prosthesis prosthesis that that matc matcheshes the the curvature curvature of of the eye (Reprinted(Reprinted fromfrom Reference Reference [49 [49]] with with permission permission from from Elsevier). Elsevier). Parylene Parylene is transparent is transparent and the and opaque the featuresopaque features are metal. are metal.

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Parylene is also a common material for sensory neural prosthetics, such such as as retinal implants. High-density electrode arrays were fabricated on Parylene that was subsequentlysubsequently thermoformed to match the curvature of the eye (Figure3 3d)d) [[8,49,51].8,49,51]. An origami-like device was fabricated to match the curvature of the eye without the use of heat [[5522].]. Cochlear electrode arrays, which must conform to the complex anatomy of the inner ear, were develop developeded by exploiting Parylene’s properties as a thin and flexibleflexible substratesubstrate [[53].53]. Despite growing interest, many researchers report difficulties difficulties when processing Parylene MEMS, MEMS, as well as various various modes modes of of material material and and device device fail failure.ure. These These problems problems largely largely stem stem from from a lack a lack of ofwell-defined well-defined protocols protocols for for the the machining, machining, use use and and handling handling of of Parylene-based devices. Common processing techniques developed for semiconductor materials and glass are often incompatible with organic polymers, owing to Parylene’s limited thermal budget, gas permeability, low mechanicalmechanical strength and unique chemical properties. While manymany of these obstacles are surmountable, solutions are rarelyrarely discussed discussed in thein literature.the literature. Here weHere present we present a compilation a compilation of common of challenges common encountered challenges duringencountered the construction during the construction of Parylene of MEMS Parylene and MEMS a description and a description of current of current best practices best practices to avoid to theseavoid issues.these issues.

2. Challenges

2.1. Thermal Budget One of the most persistentpersistent challenges of Parylene is its limitedlimited thermalthermal budget, a consequenceconsequence of its thermoplastic nature; in atmosphere Parylene is subject to oxidation at temperatures greater ◦ ◦ ◦ than 100 °C,C, glass transition temperature around 90 °CC and a melting temperature at at 290 290 °CC[ [10].10]. These temperatures are commonly encountered andand even surpassed during standard silicon micromachining andand electricalelectrical packaging. packaging. For For example, example, during during photolithography, photolithography, photoresist photoresist must must be ◦ soft-bakedbe soft-baked at elevated at elevated temperatures temperatures (100–120 (100–120C) to °C remove) to remove residual residual solvent andsolvent exothermic and exothermic reactions ◦ duringreactions the during UV activation the UV of activation the resist canof the generate resist temperatures can generate of temperatures up to 200 C[ 54of ].up Soldering, to 200 °C plasma [54]. etching,Soldering, PVD plasma and other etching, methods PVD common and toother micromachining methods common require temperaturesto micromachining which can require cause Parylenetemperatures to burn, which bubble, can cause or crack Parylene (Figure to4 ).burn, bubble, or crack (Figure 4).

Figure 4. Images of ParyleneParylene damage due toto high heatheat oror radiationradiation exposure.exposure. (a) CrackedCracked ParyleneParylene after development and soft baking at 115 °C◦C for for 3 min; and ( b)) air bubbles appeared under under the the film, film, during hard bake at 90 ◦°CC for 15 min, in regions previously exposed toto UVUV lightlight duringduring lithography.lithography.

Thermal annealing is a common treatment for improving adhesion between Parylene-Parylene Thermal annealing is a common treatment for improving adhesion between Parylene-Parylene interfaces [55,56]. This process requires high temperature (>200 °C) compared to Parylene’s glass interfaces [55,56]. This process requires high temperature (>200 ◦C) compared to Parylene’s glass transition temperature and must be performed under vacuum to avoid the effects of oxidation transition temperature and must be performed under vacuum to avoid the effects of oxidation (browning, wrinkling and becoming brittle) as shown in Figure 5. (browning, wrinkling and becoming brittle) as shown in Figure5.

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(a) (b) (c)

Figure 5. Comparison of thermal annealed devices in the presence of oxygen ( a,b) and under intact vacuum (c). Devices were heated at 200 ◦°CC for 48 h.

2.2. Water Diffusion through Parylene Films Parylene is employed as encapsulation for medical implants, such as stents, pacemakers and neural probes [[57,58]57,58] duedue toto itsits strongstrong waterwater barrier barrier properties. properties. However, However, like like all all polymers, polymers, Parylene Parylene is isin in fact fact permeable permeable to to moisture moisture and and gases gases [59 [59].]. Both Both water water and andions ions inin solutionsolution (i.e.,(i.e., salt)salt) can diffuse through thin layers of ParyleneParylene in lessless timetime thanthan thethe intendedintended useuse duration.duration. For a Parylene-basedParylene-based bioMEMS oror microdevicemicrodevice with with insulation insulation layers layers only only a few a micronsfew microns thick, thick, limiting limiting permeation permeation is critical is criticalto prevent to prevent electrical electrical shorts, corrosion shorts, corrosion of encapsulated of encapsulated components components and catastrophic and catastrophic failure. The failure. most Theeffective most methodeffective atmethod preventing at preventing water permeation water permea is thetion useis the of use thermal of thermal annealing annealing to increase to increase the thecrystallinity, crystallinity, though though this only this serves only toserves slow permeation,to slow permeation, not prevent not it outright prevent [56 it,60 outright]. Unfortunately, [56,60]. Unfortunately,there is scarce datathere quantifying is scarce data the quantifying scale of the the problem, scale of particularlythe problem, for particularly the very thinfor the (~µ verym) films thin (~usedμm) in films Parylene-based used in Parylene-based microdevices. Belowmicrodevices. we describe Below some we observations describe some and measurementsobservations and we measurementshave collected onwe the have topic. collected on the topic.

2.2.1. Water Permeability Published values for water vapor transmission rate (WVTR) in Parylene can vary quite substantially betweenbetween sources. sources. Specialty Specialty Coating Coating Systems Systems (SCS) (SCS) [61] and [61] Para and Tech Para [62 ],Tech two prominent[62], two vendorsprominent for vendors Parylene for coatings, Parylene publish coatings, WVTR publ valuesish WVTR of 0.0830 values and of 0.0550 0.0830 g ·andmm/m 0.05502·day, g·mm/m respectively,2·day, respectively,at 37 ◦C. Menon at 37 et °C. al. Menon [63] measured et al. [63] water measured vapor water permeation vapor permeation in thin, small-area in thin, small-area Parylene structures Parylene structuresfor both annealed for both andannealed un-annealed and un-annealed films; WVTR films; values WVTR calculated values fromcalculated reported from permeation reported permeationmeasurements measurements are listed in Table are 1listed. WVTR in valuesTable may1. WVTR differ basedvalues on may deposition differ based parameters on deposition and may parametersbe non-linear and with may film be thickness non-linear for with very film thin thickness films, as transmission for very thin through films, as defects transmission or large through pores in defectsthin-films or large may dominatepores in thin-films over diffusion-driven may dominate transmission. over diffusion-driven transmission. In Table1 1,, we we provide provide our our own own WVTR WVTR measurements measurements forfor annealedannealed andand unannealedunannealed filmsfilms ofof varying thicknesses. Films were deposited on planar silicon wafers wafers using using a a PDS PDS Labcoter Labcoter 2010 2010 (SCS, (SCS, Indianapolis, IN); annealed films films were heated for 48 hh atat 200200 ◦°CC underunder vacuum.vacuum. The measurements were based on the beaker method for determinationdetermination of water vapor permeabilitypermeability [[64].64]. Glass beakers with ~40 mL of deionized water were sealed with Parylene (1.7 cm diameter circular aperture) using marine epoxy. The The beakers, beakers, kept kept at at room room temperature temperature and and approximately approximately 33% 33% relative relative humidity, humidity, were weighed weekly for 2 months (mean valuesvalues recordedrecorded inin TableTable1 ).1). Notably, our values values differ differ from from Menon Menon et et al. al. despite despite similar similar temperatures temperatures and and humidity. humidity. In agreementIn agreement with with Menon Menon et al. et we al. wesee seea significant a significant decrease decrease in WVTR in WVTR values values after after annealing annealing films; films; for 10for and 10 and 15 μ 15mµ thickm thick films films we we see see a 25% a 25% decrease decrease in in WVTR, WVTR, in in general general agreement agreement with with reports reports and anecdotes from researchers noting a decrease in wate waterr permeation and an increase in effective lifetime for annealed Parylene/Parylene-coated devices. devices. Th Thereere was was no no significant significant decrease decrease in in WVTR for the annealed 5 μµm film,film, which indicate that filmsfilms at this thickness have permeation driven by defects rather than diffusion through the bulk.bulk.

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MicromachinesTable 1. Water 2018, 9 vapor, x FOR transmission PEER REVIEW rate (WVTR) measurements for different un-annealed and annealed 6 of 25 Parylene film thickness. Table 1. Water vapor transmission rate (WVTR) measurements for different un-annealed and annealed Parylene film thickness.Thickness Mean WVTR Standard Temperature and Relative Reference (µm) (g·mm/m2·day) Error Humidity (Mean ± SE) Thickness Mean WVTR Standard Temperature and Relative Humidity Reference ◦ (µm)5 (g·mm/m 0.01942·day) Error 0.0012 20.6 ±(Mean0.14 ±C, SE) 34 ± 3% ◦ Un-annealed 510 0.0194 0.0176 0.0012 0.0010 20.7 20.6± ± 0.140.13 °C,C, 34 32 ± ±3%3% 15 0.0185 0.0025 20.8 ± 0.12 ◦C, 33 ± 3% This work Un-annealed 10 0.0176 0.0010 20.7 ± 0.13 °C, 32 ± 3% 155 0.0185 0.0185 0.0025 0.0014 20.6 20.8± ± 0.120.14 °C,◦C, 33 33 ± ±3%3% This work Annealed 510 0.0185 0.0128 0.0014 0.0010 20.7 20.6± ± 0.14 °C,◦C, 33 34 ± ±3%3% ◦ Annealed 1015 0.0128 0.0139 0.0010 0.0024 20.7 20.7± ± 0.140.13 °C,C, 34 35 ± ±3%3% Specialty Coating Systems15 - 0.0139 0.0830 0.0024 - 37 20.7◦C, ± 90%0.13 °C, ASTM 35 ± F12493% Specialty ParaCoating Tech Systems - - 0.0830 0.0550 - - 37 ◦°C,C, 90% 90% ASTM ASTM F1249 F1249 Para Tech - 0.0550 - 37 °C, 90% ASTM F1249 Menon et al., Un-annealed 9 0.0547 - Menon et al., Un-annealed 9 0.0547 - 20 ◦C, 30% ASTM D1653 2009 Annealed 9 0.0276 - 20 °C, 30% ASTM D1653 2009 Annealed 9 0.0276 -

2.2.2.2.2.2. Ion Ion Permeability Permeability ParyleneParylene is is known known for for having having excellentexcellent ionicionic barrier properties, properties, particularly particularly when when compared compared to to otherother polymers. polymers. UnderUnder salt-fog tests tests (ASTM (ASTM B117-(03)), B117-(03)), SCS SCS reported reported no evidence no evidence of corrosion of corrosion or salt or saltdeposits deposits on on Parylene-coated Parylene-coated PCB PCB boar boardsds after after 144 144h of hexposure of exposure [61] [and61] andMordelt Mordelt et al. etreported al. reported 25 25μµmm thick thick layers layers of of Parylene Parylene withstood withstood 0.9% 0.9% saline saline solution solution for for up up to to30 30days days before before breakdown breakdown [65]. [65 ]. VeryVery thin thin layers layers of Paryleneof Parylene (<10 (<10µm), μm), however, however, are are still still susceptible susceptible to ionto ion intrusion intrusion over over relatively relatively short timeshort periods. time periods. In many In Parylene-basedmany Parylene-based microdevices, microdevices, ionic ionic intrusion intrusion into into a Parylene a Parylene insulation insulation layer canlayer change can itschange dielectric its dielectric properties, properties, thereby increasingthereby increasing parasitic parasitic coupling coupling between between lines or decreasinglines or shuntdecreasing impedance shunt [66 impedance,67]. In this [66,67]. manner In this ion manner permeability ion permeability may affect may device affect performance device performance even if ions nevereven breach if ions the never Parylene breach barrier. the Parylene We observed barrier. that We theobserved use of that thermal the use annealing of thermal can lowerannealing the ratecan of ionlower diffusion the rate across of ion a thindiffusion Parylene across member a thin Paryle but havene member not yet but quantified have not the yet effect. quantified the effect.

2.3.2.3. Delamination/Adhesion Delamination/Adhesion ParyleneParylene suffers suffers from from poorpoor adhesionadhesion to to itself itself and and noble noble metals, metals, such such as gold as gold and andplatinum, platinum, a a considerableconsiderable drawbackdrawback in the implementation implementation of of Parylene Parylene for for bioMEMS. bioMEMS. The The adhesion adhesion of ofParylene Parylene devices, which consist of thin films of Parylene-metal-Parylene sandwiches, is compromised when devices, which consist of thin films of Parylene-metal-Parylene sandwiches, is compromised when devices devices are soaked in wet environments [58,60,66,68,69]. Weak adhesion can accelerate catastrophic are soaked in wet environments [58,60,66,68,69]. Weak adhesion can accelerate catastrophic failure of failure of Parylene devices; as Parylene films lift off a substrate, voids form in which water vapor can Parylene devices; as Parylene films lift off a substrate, voids form in which water vapor can condense, condense, creating continuous paths of solution that create electrical shorts and drive further creating continuous paths of solution that create electrical shorts and drive further delamination (Figure6). delamination (Figure 6). Several strategies were investigated to improve adhesion of Parylene to Severalsubstrates strategies such wereas silicon investigated and glass, to improve including adhesion melting, of anchoring, Parylene tosurface substrates roughening, such as siliconthermal and glass,annealing, including surface melting, plasma anchoring, treatment surface and roughening,the inclusion thermal of chemical annealing, layers, surface such as plasma silane treatment A-174 and and theplasma inclusion polymerized of chemical adhesion layers, such layers as silane [70–72] A-174 but andmany plasma of these polymerized techniques adhesion are not layers applicable [70–72 or] but manycalibrated of these for techniques adhesion are of notParylene applicable to Parylene, or calibrated or thin-film for adhesion metals of Paryleneused in topolymer Parylene, MEMS or thin-film and metalsflexible used electronics. in polymer MEMS and flexible electronics.

Figure 6. Parylene devices where delamination was noticeable on the macro scale. (a) Parylene layers Figure 6. Parylene devices where delamination was noticeable on the macro scale. (a) Parylene layers visibly split from each other; (b) detachment of the top Parylene layer from the metal and bottom visibly split from each other; (b) detachment of the top Parylene layer from the metal and bottom Parylene layers; and (c) electrodes and metal traces began to move or slide around between the Parylene layers; and (c) electrodes and metal traces began to move or slide around between the Parylene layers. Parylene layers.

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MicromachinesAdhesion 2018 between, 9, x FOR two PEER surfaces REVIEW is achieved through chemical and physical interventions. 7 of In 25 the case of Parylene-Parylene interfaces, adhesion is dominated by physical adsorption, whereas for Adhesion between two surfaces is achieved through chemical and physical interventions. In the Parylene-metal interfaces, adhesion is typically a combination of hydrogen bonding and Van der Waals case of Parylene-Parylene interfaces, adhesion is dominated by physical adsorption, whereas for forces [56]. Poor adhesion between Parylene and other materials may result from differences in surface Parylene-metal interfaces, adhesion is typically a combination of hydrogen bonding and Van der energy at the interface [73] between hydrophobic Parylene and hydrophilic metals, a phenomenon Waals forces [56]. Poor adhesion between Parylene and other materials may result from differences exacerbated by surface contamination. The presence of internal stress between layers [60] appears to in surface energy at the interface [73] between hydrophobic Parylene and hydrophilic metals, a further aggravate adhesion failure and hasten delamination. Delamination under wet conditions may phenomenon exacerbated by surface contamination. The presence of internal stress between layers be[60] induced appears by to water further vapor aggravate condensing adhesion within failure voids and createdhasten delamination. by surface particulates Delamination present under during wet CVDconditions [74], suggesting may be induced that surface by water cleanliness vapor iscondensing critical in within maximizing voids adhesion.created by Annealing surface particulates of Parylene ◦ (48present h at 200 duringC under CVD vacuum)[74], suggesting improves that adhesion. surface cleanliness Reports suggestis critical that in annealingmaximizing increases adhesion. the entanglementAnnealing of of Parylene the polymer (48 h chains at 200 while °C under reducing vacuum) stress improves by recrystallization adhesion. Reports of Parylene-Parylene suggest that interfacesannealing [57 increases,75]. Interposer the entanglement layers have of alsothe polymer been investigated chains while to reducing either modify stress theby recrystallization surface energy of a coatedof Parylene-Parylene material, thereby interfaces improving [57,75]. chemical Interposer adhesion, layers have or also to create been investigated a barrier against to either water modify vapor, minimizingthe surface water energy intrusion of a coated and material, subsequent thereby failure improving [76–78]. Plasma-enhancedchemical adhesion, Parylene or to create is a a method barrier to improveagainst adhesion water vapor, of Parylene minimizing to other water surfaces intrusion by cleaningand subsequent and modifying failure [76–78]. the film Plasma-enhanced within the process chamberParylene [79 is]. a For method a detailed to improve study ofadhesion methods of to Parylene improve to adhesion other surfaces of Parylene by cleaning layers and and modifying to platinum, thethe reader film iswithin referred the toprocess [56]. chamber [79]. For a detailed study of methods to improve adhesion of ParyleneDelamination layers and at to either platinum, the Parylene-Parylenethe reader is referred or to Parylene-metal[56]. interface can affect device performanceDelamination well before at either catastrophic the Parylene-Parylene failure occurs. Manyor Parylene-metal Parylene devices interface rely can on insulatedaffect device traces whichperformance terminate well in exposedbefore catastrophic electrodes; failure delamination occurs. Many can alterParylene this conductivedevices rely pathwayon insulated and traces lead to signalwhich drift. terminate These changesin exposed can electrodes; be observed delamination by monitoring can alter the this electrical/electrochemical conductive pathway and impedance lead to signal drift. These changes can be observed by monitoring the electrical/electrochemical impedance of an electrode and trace insulated in Parylene and immersed in water and understood using a of an electrode and trace insulated in Parylene and immersed in water and understood using a modified Randles circuit model [80] (Figure7). For a perfectly insulated electrode, the circuit modified Randles circuit model [80] (Figure 7). For a perfectly insulated electrode, the circuit consists consists of a solution resistance RS, charge transfer resistance Rct and a constant phase element of a solution resistance RS, charge transfer resistance Rct and a constant phase element Ydl to represent Y to represent the double layer capacitance. Delamination presents an alternate conduction path from dlthe double layer capacitance. Delamination presents an alternate conduction path from the electrode the electrode to the solution, with R representing resistance through the insulation and constant to the solution, with Rdelam representingdelam resistance through the insulation and constant phase element phase element Y representing the capacitance through the insulation between electrode trace and Ydelam representingdelam the capacitance through the insulation between electrode trace and electrolyte. A electrolyte.capacitance A C capacitancewire is also includedCwire is alsoto model included parasitic to model capacitances parasitic within capacitances connecting within cables, connecting which cables,causes which a phase causes roll-off a phase at high roll-off frequencies. at high frequencies.

Figure 7. Circuit model of a Parylene-metal-Parylene device with an exposed electrode under chronic Figure 7. Circuit model of a Parylene-metal-Parylene device with an exposed electrode under chronic soaking conditions. Rct represents the charge transfer resistance at the exposed electrode surface, soaking conditions. Rct represents the charge transfer resistance at the exposed electrode surface, while Ydl models the double-layer capacitance at the electrode-electrolyte interface as a constant phase while Ydl models the double-layer capacitance at the electrode-electrolyte interface as a constant element. Rdelam and Ydelam represent the resistive and capacitive charge transfer through the Parylene phase element. Rdelam and Ydelam represent the resistive and capacitive charge transfer through the insulation; the magnitude of Rdelam decreases as Parylene-Parylene delamination progresses. Rs Parylene insulation; the magnitude of Rdelam decreases as Parylene-Parylene delamination progresses. represents solution resistance; Cwire represents parasitic capacitance; WE represents working R represents solution resistance; C represents parasitic capacitance; WE represents working s electrode/exposed electrode; RE representswire reference electrode. electrode/exposed electrode; RE represents reference electrode. This model was confirmed using electrochemical impedance spectroscopy (EIS) data collected fromThis platinum model was electrodes, confirmed coated using and electrochemical insulated with impedance Parylene C spectroscopyfilms and soaked (EIS) in data 37 °C collected saline for from platinum14 days electrodes, (n = 8 electrodes) coated and(Figure insulated 8). All withelectrodes Parylene measured C films 300 and × soaked1500 μm in2 and 37 ◦ Cwere saline constructed for 14 days (n =from 8 electrodes) 2000 Å thick(Figure platinum8). All electrodesinsulated between measured 10 300 μm× thick1500 Paryleneµm2 and layers were constructedon the same from die. 2000EIS Å thickmeasurements platinum insulated were recorded between between 10 µm thickeach Paryleneelectrode layersand a large on the platinum same die. counter EIS measurements electrode using were a Gamry Reference 600 potentiostat (Gamry Instruments, Warminster, PA, USA), with an Ag/AgCl

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recordedMicromachines between 2018, 9, x each FOR PEER electrode REVIEW and alarge platinum counter electrode using a Gamry Reference 8 of 25 600 potentiostat (Gamry Instruments, Warminster, PA, USA), with an Ag/AgCl electrode used as aelectrode reference. used Modeling as a reference. results Modeling show that results both solutionshow that resistance both solution and delamination resistance and resistance delamination drop dramaticallyresistance drop after dramatically only one dayafter ofonly soaking, one day while of soaking, the interface while the capacitances interface capacitances gradually increase gradually in magnitudeincrease in over magnitude the testing over period. the Thetesting dramatic, period two. The order-of-magnitude dramatic, two droporder-of-magnitude in delamination resistance drop in maydelamination be due to resistance either water may penetration be due to through either thewate Parylener penetration or the earlythrough stages the of Parylene delamination or the and early the smallstages drop of delamination in solution resistance and the maysmall be drop due in to soluti delaminationon resistance around may the be exposed due to electrode, delamination which around would increasethe exposed the electrode’s electrode, effectivewhich would surface increase area. the electrode’s effective surface area.

Figure 8. The results of modelingmodeling electrochemicalelectrochemical impedanceimpedance spectroscopy (EIS) spectra between a thin-filmthin-film platinum electrode insulated between 10 µμm Parylene layers and a large platinum counter electrode during a 14-day soak in 1× phosphate buffered saline (PBS) at 37 °C.◦ Both (a) RS and (b) electrode during a 14-day soak in 1× phosphate buffered saline (PBS) at 37 C. Both (a) RS and Rdelam drop after the first day, while the magnitudes of both (c) the cross-insulation capacitance (Ycross) (b) Rdelam drop after the first day, while the magnitudes of both (c) the cross-insulation capacitance and (d) the double layer capacitance (Ydl) steadily increase over the course of the test. (Ycross) and (d) the double layer capacitance (Ydl) steadily increase over the course of the test.

2.4. Packaging and Electrical Connections Electrical packaging packaging of of thin thin film film electrodes electrodes (typically (typically 100–200 100–200 nm thick) nm on thick) free film on Parylene- free film Parylene-basedbased devices is exceptionally devices is exceptionally challenging. challenging.Numerous problems Numerous arise problemsfrom the thin arise profile, from flexibility the thin profile,and limited flexibility thermal and budget limited of thermalParylene budget films. Nota of Parylenebly, Parylene films. Notably,is fundamentally Parylene incompatible is fundamentally with incompatiblesoldering, due with to soldering,the high temperatures due to the high required temperatures (typically required 250 (typically°C) and 250the ◦lowC) and glass the transition low glass transitiontemperature temperature of Parylene of Parylene (~90 °C) (~90 [81].◦C) Similarly, [81]. Similarly, Parylene Parylene devices devices are are poorly poorly compatible compatible with conventional wirebonding,wirebonding, which which makes makes it difficult it difficult to package to package Parylene Parylene devices withdevices silicon with integrated silicon circuits.integrated Ball circuits. bonding typicallyBall bonding requires typically temperatures requires above temperatures 300 ◦C to achieve above thermocompression 300 °C to achieve [82], riskingthermocompression thermal damage [82], to risking Parylene, thermal and even damage when attemptedto Parylene, the and resulting even bond when between attempted thewire the andresulting the thin bond film between on the Parylene the wire detaches and thewhen thin film the toolon the retracts, Parylene since detaches the metal-metal when the bond tool is strongerretracts, thansince thethe metal-Parylenemetal-metal bond bond is stronger (Figure9 ).than the metal-Parylene bond (Figure 9). Batch and reversible electrical connections to Parylene devices can be achieved using zero-insertion force (ZIF) connectors (Hirose Electric Co., Ltd., Tokyo, Japan), which are hinged friction-force connectors with spring-like copper pins that contact targeted pads when closed. Designed originally for connecting flat flexible cables (FFC) to PCB, ZIF connectors can be made compatible with

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Parylene electronics by mounting Parylene devices on thicker sections of more rigid polymers such as polyetheretherketone (PEEK). While simple, reversible electrical connections are possible, the contact pads have large, fixed footprints compared to flip-chip or wire-bonding. Though ZIFs are designed for repeated connections, it should be noted that after approximately 15 cycles, connections can fail due to wearMicromachines and tear 2018 through, 9, x FOR the PEER Parylene REVIEW [ 83] substrate by the mechanical pins. 9 of 25

Figure 9. Holes left by gold removal during ultrasonic wire (ball) bonding on a gold thin film on Parylene substrate.

Batch and reversible electrical connections to Parylene devices can be achieved using zero- insertion force (ZIF) connectors (Hirose Electric Co., Ltd., Tokyo, Japan), which are hinged friction- force connectors with spring-like copper pins that contact targeted pads when closed. Designed originally for connecting flat flexible cables (FFC) to PCB, ZIF connectors can be made compatible with Parylene electronics by mounting Parylene devices on thicker sections of more rigid polymers such as polyetheretherketone (PEEK). While simple, reversible electrical connections are possible, the contactFigure pads 9. Holeshave leftlarge, by goldfixed removal footprints during compared ultrasonic to wireflip-chip (ball) orbonding wire-bonding. on a gold Thoughthin film ZIFson are Figure 9. Holes left by gold removal during ultrasonic wire (ball) bonding on a gold thin film on designedParylene for substrate. repeated connections, it should be noted that after approximately 15 cycles, connections can Parylenefail due substrate.to wear and tear through the Parylene [83] substrate by the mechanical pins. BatchOther and methods reversible include electrical the use connections of conductive to Parylene epoxies devices [84] or can adhesive be achieved films. usingAnisotropic zero- insertionconductiveOther force methods film (ZIF) (ACF), connectors include a common the (Hirose use material of Electric conductive for Co.,semiconductor Ltd., epoxies Tokyo, [84 packaging, ]Japan), or adhesive which comprises films.are hinged a Anisotropicthin friction- resin of conductiveforcesuspended connectors filmpolymer (ACF),with spheresspring-like a common which copper material form pins a forunidirectional th semiconductorat contact targetedconductive packaging, pads path when comprises under closed. mild a thinDesigned heat resin and oforiginallypressure. suspended forACF connecting polymer curing temperatures spheres flat flexible which are cables form relatively a(FFC) unidirectional highto PCB, (150–200 ZIF conductive connectors °C) but oxidation path can underbe madeof Parylene mild compatible heat can and be ◦ pressure.withavoided Parylene ACFby applying electronics curing temperatures the by film mounting under are an relativelyParylene inert atmosphere, devices high (150–200 on orthicker loweringC) butsections oxidation the ofcuring more of temperature Parylenerigid polymers can and be avoidedsuchadjusting as polyetheretherketone by the applying time required the film (PEEK). underto cure. anWhile For inert simple,high atmosphere, bo reversiblend yield, or loweringelectricalalignment theconnections betw curingeen temperature theare possible,substrates and the is adjustingcontactimportant pads the and timehave in required large,the case fixed to of cure. footprintsbuilding For high a compared custom bond yield, ji gto or alignmentflip-chip adapting or between anwire-bonding. existing the substrates flip Though chip is bonder, important ZIFs are the anddesignedlevelness in the for and case repeated thermo-mechanical of building connections, a custom itproperties should jig or adapting be of no theted bond anthat existing after head approximately are flip critical. chip bonder, In 15 this cycles, the way, levelness connections ACF can and be thermo-mechanicalcansuccessfully fail due to used wear for propertiesand electrical tear through ofpackaging the the bond Pary to head Parylenelene are [83] critical. devices substrate Inincluding by this the way, mechanical ASIC ACF integration can pins. be successfully (Figure 10) used[85–88].Other for In electrical methodsunpublished packaging include results, the to we Paryleneuse achieved of conductive devices large-area including ep packagingoxies ASIC[84] ofor integration Parylene adhesive electronics (Figurefilms. Anisotropic10 with)[85 –pitch88]. Inconductiveand unpublished width offilm contacts results, (ACF), down wea common achieved to (100 material large-areaμm pitch) for using packaging semiconductor ACF of(Dexerials Parylene packaging, CP13341-18AA, electronics comprises with Dexerials, pitch a thin and resin Tokyo, width of µ ofsuspendedJapan). contacts downpolymer to (100 spheresm pitch) which using form ACF a unidirectional (Dexerials CP13341-18AA, conductive path Dexerials, under Tokyo, mild Japan).heat and pressure. ACF curing temperatures are relatively high (150–200 °C) but oxidation of Parylene can be avoided by applying the film under an inert atmosphere, or lowering the curing temperature and adjusting the time required to cure. For high bond yield, alignment between the substrates is important and in the case of building a custom jig or adapting an existing flip chip bonder, the levelness and thermo-mechanical properties of the bond head are critical. In this way, ACF can be successfully used for electrical packaging to Parylene devices including ASIC integration (Figure 10) [85–88]. In unpublished results, we achieved large-area packaging of Parylene electronics with pitch and width of contacts down to (100 μm pitch) using ACF (Dexerials CP13341-18AA, Dexerials, Tokyo, Japan).

FigureFigure 10. 10.Schematic Schematic representationrepresentation ofof aa Parylene-basedParylene-based neuralneuralprobe probeconsisting consistingof of three three PEDOT PEDOT (poly(3,4-ethylenedioxythiophene))-nanostructured(poly(3,4-ethylenedioxythiophene))-nanostructured electrodes and and one one gold gold electrode electrode as control. as control. The Thedevice device is anisotropic is anisotropic conductive conductive film film (ACF) (ACF) bonded bonded onto onto a flexible a flexible polyimide polyimide cable, cable, which which is then is thensoldered soldered onto onto a pin a connector pin connector adapted adapted to the to wireless the wireless acquisition acquisition system. system. The cross-section The cross-section shows showsbond bondpads from pads the from device the device bonded bonded via ACF via ACFto the to bond the bond pads padsof the of polyimide the polyimide cable. cable. Reprinted Reprinted from from[88] [with88] with permission permission from from Elsevier. Elsevier.

Figure 10. Schematic representation of a Parylene-based neural probe consisting of three PEDOT (poly(3,4-ethylenedioxythiophene))-nanostructured electrodes and one gold electrode as control. The device is anisotropic conductive film (ACF) bonded onto a flexible polyimide cable, which is then soldered onto a pin connector adapted to the wireless acquisition system. The cross-section shows bond pads from the device bonded via ACF to the bond pads of the polyimide cable. Reprinted from [88] with permission from Elsevier.

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Alternatively, another strategy is to directly incorporate integrated circuits with Parylene devices during the fabrication process to achieve the densest connections. Rodger et al. developed a method to form interconnects between Parylene devices and bare silicon integrated circuit dies during wafer-level processing, by etching through-holes in a carrier wafer, affixing the dies with temporary adhesives, and then evaporating metal. But because thin-film metal is deposited directly on top of the inserted chip, this method is extremely sensitive to the planarity of the dies [89]. Chang et al. developed a method to spread conductive epoxy over a Parylene layer to create interconnects to a silicon die, which was held in place by a PDMS mold, however, this method was prone to shorts between bond pads resulting from bridging by the low viscosity epoxy [90]; this required selective repair using laser ablation.

2.5. Sterilization Parylene coatings for biomedical devices and Parylene-based bioMEMS require sterilization before use in vivo. However, many standard sterilization protocols require application of high heat or oxidative stress, which can damage or otherwise change Parylene bulk properties. For example, an autoclave creates a high temperature and high humidity environment for sterilization, which can cause Parylene bilayers to delaminate and Parylene coatings to lose adhesion [57,91]. Alternative methods, such as the use of ethylene oxide, have been used successfully without damage to thin-film Parylene devices [36]. Several methods for sterilizing Parylene devices are described in literature and a brief summary of various methods and the major conclusions drawn regarding the effect on Parylene, is compiled in Table2. Notably, steam autoclaving, one of the most common methods, is also one of the most destructive. Other potentially damaging methods include electron beam sterilization, which can cause ionization and a decrease in crystallinity of bulk Parylene and gamma sterilization, which appears to decrease the adhesion between Parylene and metal. We previously examined the use of hydrogen peroxide plasma as a means to sterilize Parylene-based electrochemical sensors. Devices were visibly unchanged following treatment and electrode characterization, using EIS and cyclic voltammetry, indicated no changes in electrode properties following treatment [32].

2.6. Handling Finally, we note that owing to the thin and flexible nature of Parylene devices, they can be potentially damaged by rough handling. Electrical traces incorporated into Parylene devices or ribbon cables are actually surprisingly robust, able to survive down to a bend radius of 100 µm and under fatigue testing of up to 100,000 bends [76]. However, we observed that wrinkling or crumpling of Parylene devices, which can happen inadvertently, can cause destructive creases in thin metal connections. Parylene devices are also very light and can easily be blown away by the nitrogen streams commonly used for cleaning microdevices, or by the venting of a vacuum chamber, or even by exhalation. They are also subject to strong static forces, owing to Parylene’s properties as an electrical insulator. We recommend handling Parylene devices gingerly, with tweezers, held by the edge of the device or even by a purpose built Parylene tab designed into the structure. Weakly adhesive double-sided tape can be used to secure Parylene devices temporarily, during post-processing, packaging or imaging. Micromachines 2018, 9, 422 11 of 25

Table 2. Sterilization methods used and their effect on Parylene. “No adverse effects recorded” indicates the sterilization method was used in literature but no adverse effects on adhesion or bulk properties was recorded, while “n/a” indicates no use of the sterilization method was found in literature.

Effect on Parylene-Parylene Effect on Parylene to Effect on Parylene Adhesion to Sterilization Method Effect on Bulk Parylene Reference Adhesion Metal Adhesion Other Materials Chemical structure changed: partial Electron beam No adverse breakage of C-Cl bonds, ionization of No adverse effects recorded n/a [92,93] ISO 11137 effects recorded polymer, crystallinity decrease Recombination, cross-linking (increases Decreased adhesion, To silicon wafer: Gamma radiation strength and decreases elongation), loss n/a causing loss of electrical Crystallinity increased, no change in [91,94] ISO 11137 in bond strength insulation capabilities Young’s modulus Decreased electrical Formation of inorganic chlorides, For sterilization after thermal Ethylene oxide insulation capabilities To glass: reduction of chlorine amount. EtO is annealing, no adverse effects [93,95,96] ISO 11135 (but not as damaging as No adverse effects recorded toxic, carcinogenic, flammable, explosive recorded gamma sterilization To silicon: Parylene became brittle and hard, Autoclave (steam) Significant decrease in adhesion, decreased adhesion, changed chemical Decreased adhesion Decreased adhesion [57,91,97–99] ISO 17665 Parylene crystallinity increased, stability, did not contaminate electrical stability decreased To Silastic: No change in adhesion. Recommended Parylene withstood implantation and H O Plasma “best suitability for Parylene” (based on was unaffected. However, coating 2 2 n/a n/a [93,100,101] ISO/NP 22441 * XRD testing), successfully killed bacteria was easily peeled off after without degradation of Parylene coating implantation, suggesting poor Parylene-Silastic adhesion 0.5–0.75 mg/mL concentration of Antibiotic coating tetracycline nanoparticles completely n/a n/a n/a [102] No standard eradicated E. coli but not aureus bacteria * NP: the standard is a new proposal and is still under consideration by the ISO. Micromachines 2018, 9, x FOR PEER REVIEW 12 of 25

Micromachines 2018, 9, 422 12 of 25 3. Micromachining of Parylene Films Even though processes for silicon were successfully adapted to micromachine Parylene, there is 3. Micromachining of Parylene Films a lack of well-defined protocols and standards when working with this polymer. Parylene-based MEMSEven and though microdevices processes forare silicontypically were construc successfullyted using adapted a tocombination micromachine of Parylene,bulk and there surface is a lackmicromachining of well-defined and protocols photolithography. and standards In a when typical working process with flow, this a polymer. foundational Parylene-based Parylene layer MEMS is anddeposited microdevices on a support are typically substrate, constructed almost always using a a combination silicon wafer of with bulk andits native surface oxide micromachining layer intact, andusing photolithography. CVD. Subsequent In layers a typical of metal process or flow,polymer a foundational are then deposited Parylene layerand patterned is deposited using on aphotolithography. support substrate, Metal almost layers always commonly a silicon serve wafer as conductive with its native traces oxideor electrodes layer intact, and are using deposited CVD. Subsequentusing evaporation layers ofor metal sputtering or polymer and patterned are then deposited by lift-off. and Additional patterned polymer using photolithography. layers include Metaladditional layers Parylene commonly films, serve which as conductivemay be patterned traces or on-top electrodes of sacrificial and are photoresist deposited using patterns evaporation to create orthree-dimensional sputtering andpatterned structures. by lift-off.Structures Additional may be polymer createdlayers using include O2 plasma additional etching Parylene through films, a whichphotoresist may bemask, patterned to create on-top MEMS of sacrificial components photoresist using patterns bulk-micromachining, to create three-dimensional or to expose structures. metal Structureselectrodes covered may be by created polymer using insu Olation.2 plasma Finally, etching the throughcomplete a device photoresist is removed mask, from to create the support MEMS componentssubstrate and using packaged. bulk-micromachining, Below we describe or to challeng exposees metal and electrodessolutions coveredencountered by polymer during insulation.each step Finally,of fabrication the complete for Parylene-based device is removed microdevices. from the support substrate and packaged. Below we describe challenges and solutions encountered during each step of fabrication for Parylene-based microdevices. 3.1. Deposition 3.1. Deposition Parylene is deposited by CVD, producing a highly uniform and conformal coating [103]. TypicallyParylene the film is deposited is transparent by CVD, and producing homogenous; a highly however, uniform in some and conformal instances coatingParylene [103 coatings]. Typically may thebe marred film is transparentby odd “spherule” and homogenous; inclusions. however, The macros in somecopic instancesappearance Parylene is hazy coatings and white, may sometimes be marred bydescribed odd “spherule” as “cloudy” inclusions. Parylene. The The macroscopic microscopic appearance appearance is is hazypresented and white, in Figure sometimes 11. The describedspherules asmay “cloudy” be unreacted Parylene. Parylene The microscopicmonomers that appearance bond to each is presented other in inthe Figure gas phase 11. The prior spherules to deposition, may be a unreactedresult of insufficient Parylene monomersmolecular collisions that bond before to each deposition other in the caused gas phase by a high prior volume-to-surface-area to deposition, a result of insufficientthe deposition molecular chamber collisions [104]. Incr beforeeasing deposition the surface caused area of by the a high chamber, volume-to-surface-area by including structures of the depositionwith large chambersurface-area [104 ].such Increasing as a mesh, the surfacemay prevent area of the chamber,formation by of including these spherules. structures SCS, with a largemanufacturer surface-area of Parylene such as a coating mesh, may tools, prevent describes the formationthe cause ofas these high spherules.deposition SCS, rates a manufacturerand chamber ofpressure. Parylene coating tools, describes the cause as high deposition rates and chamber pressure. This phenomenon was repeatedly observed when coating Parylene-based devices that were previously subjected to some form of mechanical action, such as ultrasonic treatment or scrubbing during a metal-liftoff process. These devices, when insulated with CVD Parylene, frequently present with this cloudy appearance, with the densest appearancesappearances of spherules along the edges of thin-filmthin-film metal structures or at locations where the mechanicalmechanical action was most severe. It is unclear whether these phenomena interfere with adhesion between the Parylene and other layers and whether they impact the integrity of the Parylene coating.coating.

Figure 11.11.( a()a Deposited) Deposited Parylene Parylene layer layer incorporating incorporating spherules spherules which resultswhich inresults a cloudy in ina appearancecloudy in whenappearance observed when by observed eye; and by ( beye;) magnified and (b) magnified photograph photograph revealing revealing the presence the presence of small of clusters small ofclusters spherules. of spherules.

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3.2. Lithographic Processes Microfabrication commonlycommonly entails entails photolithographic photolithographic patterning patterning of photoresistof photoresist to serve to serve as an as etch an etchmask, mask, lift-off lift-off mask, mask, or patterned or patterned sacrificial sacrificial layer. Photolithography layer. Photolithography involves involves a series ofa sub-processes,series of sub- processes,such as coating, such as pre/post coating, baking, pre/post UV baking, light exposure UV light and exposure development. and development. These processes These involve processes the involveuse of heat the anduse UVof heat radiation and UV and radiation all can compromiseand all can compromise the integrity the of Paryleneintegrity films.of Parylene films. For example, the combination of Parylene gas permeability and the off-gassing of photoresist during UV exposure [54] [54] can lead to the formation of bubbles in Parylene film.film. Figure 12 shows a representative imageimage of of this this phenomenon, phenomenon, following following UV UV exposure exposure of aof 20 aµ 20m thickμm thick positive positive resist resist layer layeron top on of top a 10 ofµ ma 10 thick μm Parylene thick Parylene film. The film. phenomenon The phenomenon tends totends be more to be pronounced more pronounced with thicker with thickerresists and resists higher and exposurehigher exposure dosage ofdosage UV radiation. of UV radiation.

Figure 12. Observed gas bubbles in a Parylene coated wafer following UV exposure of a photoresist Figure 12. Observed gas bubbles in a Parylene coated wafer following UV exposure of a coating. photoresist coating.

Photodegradation of Parylene has been reported in literature through a two-step process Photodegradation of Parylene has been reported in literature through a two-step process involving involving direct photolytic processes resulting in the formation of UV and IR absorbing structures, direct photolytic processes resulting in the formation of UV and IR absorbing structures, followed by followed by photo-induced oxidation of the methylene groups and benzene ring [105]. It is also well photo-induced oxidation of the methylene groups and benzene ring [105]. It is also well known that UV known that UV radiation can deteriorate the thermal and electrical properties of Parylene films if the radiation can deteriorate the thermal and electrical properties of Parylene films if the doses are large doses are large (>12 J/cm2) [106]. Although the small doses of UV exposure during lithography are (>12 J/cm2)[106]. Although the small doses of UV exposure during lithography are unlikely to reach unlikely to reach the threshold for full photodegradation, it is hypothesized that some combination the threshold for full photodegradation, it is hypothesized that some combination of minor oxidation of minor oxidation and mechanical/thermal stress may be responsible for the observed phenomenon and mechanical/thermal stress may be responsible for the observed phenomenon when thick resist when thick resist films are used. For example, bubbles between the Parylene and substrate may films are used. For example, bubbles between the Parylene and substrate may appear following the appear following the UV exposure step for photolithography (Figure 12). Piercing the Parylene UV exposure step for photolithography (Figure 12). Piercing the Parylene bubbles in select non-critical bubbles in select non-critical areas and the use of a vacuum (after piercing) was found to aid in areas and the use of a vacuum (after piercing) was found to aid in removal of the bubbles. removal of the bubbles. Photolithography has long been implemented and thoroughly characterized on silicon and Photolithography has long been implemented and thoroughly characterized on silicon and glass glass wafer substrates. In adapting traditional microfabrication techniques to Parylene substrates, wafer substrates. In adapting traditional microfabrication techniques to Parylene substrates, photoresist coating protocols for silicon have largely been ported over and calibrated on a case-by-case photoresist coating protocols for silicon have largely been ported over and calibrated on a case-by- basis. In order to provide a practical guide for achieving desired photoresist thickness on Parylene case basis. In order to provide a practical guide for achieving desired photoresist thickness on and to better characterize the process, spin curves were created for two different photoresists on Parylene and to better characterize the process, spin curves were created for two different Parylene-coated silicon substrates and compared to those for silicon and glass substrates. Spin curves photoresists on Parylene-coated silicon substrates and compared to those for silicon and glass were produced for both AZ P4620 (Integrated Micro Materials, Argyle, TX, USA), a common etch mask substrates. Spin curves were produced for both AZ P4620 (Integrated Micro Materials, Argyle, TX, and sacrificial layer resist and AZ 5214E-IR (Integrated Micro Materials, Argyle, TX, USA), a common USA), a common etch mask and sacrificial layer resist and AZ 5214E-IR (Integrated Micro Materials, lift-off resist. The spin-coating parameters used are listed in Table3. Five 100 mm silicon wafers Argyle, TX, USA), a common lift-off resist. The spin-coating parameters used are listed in Table 3. coated in 8 µm of Parylene were coated with photoresist at spin rates from 1000 rpm to 5000 rpm Five 100 mm silicon wafers coated in 8 μm of Parylene were coated with photoresist at spin rates in 1000 rpm intervals. Five 100 mm prime silicon wafers and glass wafers were also coated at each from 1000 rpm to 5000 rpm in 1000 rpm intervals. Five 100 mm prime silicon wafers and glass wafers spin rate for comparison. 5 mm-wide strips of photoresist near the wafer center and wafer edge were were also coated at each spin rate for comparison. 5 mm-wide strips of photoresist near the wafer swabbed away from the surface using acetone and thickness was measured at these points using a center and wafer edge were swabbed away from the surface using acetone and thickness was surface profilometer. measured at these points using a surface profilometer.

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Table 3. Parameters for photoresistAZ P4620 spin curves on different AZ 5214E-IR surfaces. Surfaces Silicon,AZ Parylene-coated P4620 silicon, glass AZ 5214E-IR (100 mm wafers) Pre-spinSurfaces Silicon, 500 Parylene-coated rpm for 5 s silicon, glass 500(100 rpm mm forwafers) 8 s Spin accelerationPre-spin 500 rpm for 5 s ~1000 rpm/sec 500 rpm for 8 s SpinMain acceleration spin 1000, 2000, ~10003000, 4000,rpm/sec 5000 rpm for 45 s ◦ ◦ BakeMain spin 5 1000, min at2000, 90 3000,C 4000, 5000 rpm 70 for s at45 90s C Bake 5 min at 90 °C 70 s at 90 °C

−1/2 To compare the spin curves of different surfaces, thicknesses were plotted against ωrpm and To compare the spin curves of different surfaces, thicknesses were plotted against ωrpm–½ and least-squares linear regression was performed on each set, followed by testing for coincidence of the least-squares linear regression was performed on each set, followed by testing for coincidence of the regressionregression lines lines (Figure (Figure 13 13).). No No significant significant differencedifference was was found found among among the the spin spin curves curves on on Parylene, Parylene, siliconsilicon and and glass glass with with AZ AZ P4620, P4620, nor nor with with AZAZ 5214E-IR5214E-IR ( p < 0.05). 0.05). These These spin spin curves curves may may serve serve as asa a startingstarting point point in in the the practical practical design design of of a a ParyleneParylene microfabricationmicrofabrication process. process.

Figure 13. Spin curves for (a) AZ P4620 and (b) AZ 5214E-IR resists on silicon, glass and Parylene. Figure 13. Spin curves for (a) AZ P4620 and (b) AZ 5214E-IR resists on silicon, glass and Parylene. Error bars represent standard deviation (n = 5). Error bars represent standard deviation (n = 5). 3.3. Metal Deposition 3.3. Metal Deposition Metal deposition is a key process in the fabrication of polymer MEMS devices to create conductiveMetal deposition elements is such a key as processtraces and in theelectrodes fabrication. The of deposition polymer MEMSof metal devices on Parylene, to create however, conductive is elementsrife with such complications. as traces and Both electrodes. sputtering and The evapor depositionation can of metal induce on significant Parylene, intrinsic however, and isextrinsic rife with complications.stress which Bothcan induce sputtering curvature and evaporation in the resulting can induce free-film significant Parylene intrinsic devices. andIn addition, extrinsic stressthe whichdeposition can induce of high curvature melting point in the metals, resulting such free-film as platinum, Parylene through devices. high temperature In addition, processes, the deposition such of highas evaporation, melting point can metals, lead to such cracking as platinum, of the metal through film or high the temperatureunderlying Parylene processes, due such to thermal as evaporation, stress, cana leadresult to of crackingmismatch of in the the metalthermal film coe orfficients the underlying of expansion Parylene and film due stress. to thermal stress, a result of mismatchFigure in the 14 shows thermal an coefficients image of platinum of expansion (2000 Å) and deposited film stress. on a Parylene coated silicon wafer (10 μmFigure thick Parylene14 shows film), an image with stress of platinum induced (2000cracks. Å) The deposited platinum on was a Paryleneevaporated coated with silicona Temescal wafer (10BJD-1800µm thick e-beam Parylene evaporator film), with using stress an induced uncooled cracks. stage; The during platinum evaporation was evaporated wafer withtemperature a Temescal BJD-1800surpassed e-beam 110 °C evaporator as measured using with an temperature uncooled stage; moni duringtor stickers evaporation (Omega waferEngineering, temperature Norwalk, surpassed CT, 110USA)◦C as placed measured on the with back temperature of the wafer. monitor Changes stickers in the deposition (Omega Engineering, rate and tool Norwalk, power were CT, insufficient USA) placed onto the prevent back of cracking. the wafer. Improving Changes the in thermal the deposition contact ratebetween and toolthe wafer power and were the insufficient stage is difficult, to prevent in part because the Parylene which coats the back of the silicon wafer serves as an insulator. Breaking cracking. Improving the thermal contact between the wafer and the stage is difficult, in part because the deposition into a series of four steps with 15 min pauses between each deposition can prevent the Parylene which coats the back of the silicon wafer serves as an insulator. Breaking the deposition cracking with metals such as titanium, evaporated at a lower temperature but is insufficient for into a series of four steps with 15 min pauses between each deposition can prevent cracking with platinum. Ultimately, the most reliable method to avoid cracking was to use a tool (CHA Industries metals such as titanium, evaporated at a lower temperature but is insufficient for platinum. Ultimately, MARK 40, Fremont, CA, USA) with a larger throw distance between the metal target and the wafer thestage most (22 reliable″ compared method with to 8″ avoid for the cracking Temescal) was and to depositing use a tool the (CHA platinum Industries in four MARK 500 Å steps. 40, Fremont, Heat CA,was USA) measured with a with larger temperature throw distance monitor between stickers the as previously metal target described and the and wafer was stage maintained (22” compared below with77 8”°C.for the Temescal) and depositing the platinum in four 500 Å steps. Heat was measured with temperature monitor stickers as previously described and was maintained below 77 ◦C.

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Figure 14. (a) Stress-induced cracking of deposited platinum likely due to excess heat generated Figure 14. (a) Stress-induced cracking of deposited platinum likely due to excess heat generated during Figureduring 14.the (process;a) Stress-induced and (b) cracked cracking metal of tracesdeposited after lift-off.platinum likely due to excess heat generated theduring process;Figure the14. and process;(a) ( bStress-induced) cracked and (b) metal cracked cracking traces metal of after tracesdeposited lift-off. after lift-off.platinum likely due to excess heat generated Depositingduring the process; metal andthrough (b) cracked sputtering metal traces can avoidafter lift-off. thermal stress and cracking but can impart severeDepositingDepositing film stress, metal metal warping through through the sputtering Parylenesputtering canfilm can avoidand avoid forcing thermal thermal released stress stress devices and and cracking tocracking curve. but Figurebut can can impart 15a impart is an severe filmsevereimage stress,Depositing filmof warping a stress,Parylene metal thewarping substrate Parylene through the Parylenepatterned filmsputtering and film forcingwith can and aavoid releasednegativeforcing thermal released devicesprofile stress photoresistdevices to and curve. crackingto Figurecurve.for metal but Figure15a lift-offcan is an15a impartimage is(AZ an of a Paryleneimage5214E-IR)severe offilm substrate a and Parylenestress, sputter patternedwarping substrate coated the withwith patternedParylene 2000 a negative Å film ofwith platinum. and profile a negativeforcing photoresist The released rippledprofile fordevicesphotoresistappearance metal to lift-offcurve. foris typical metal Figure (AZ of 5214E-IR)lift-off Parylene15a is (AZ an and 5214E-IR)image of aand Parylene sputter substratecoated with patterned 2000 Å ofwith platinum. a negative The profilerippled photoresist appearance for is typicalmetal lift-offof Parylene (AZ sputterfilms coated coated with by sputtering 2000 Å of and platinum. highlights The the rippled severity appearance of film stress is (Figure typical 15b). of Parylene films coated by films5214E-IR) coated and by sputter sputtering coated and with highlights 2000 Å theof platinum. severity of The film rippled stress appearance(Figure 15b). is typical of Parylene sputteringFigure and 16 highlights shows a micromachine the severity ofd filmParylene-based stress (Figure neural 15 b).probe array prepared with sputtered platinum.filmsFigure coated The 16 by highshows sputtering level a micromachine of and intrinsic highlights stressd Parylene-based the(estim severityated as of 510 neuralfilm MPa stress probe provided (Figure array by 15b).prepared LGA Thin with Films, sputtered Santa Figure 16 shows a micromachined Parylene-based neural probe array prepared with sputtered platinum.Clara,Figure CA, The USA) 16 highshows forces level a micromachinethe of intrinsicfinal device stressd toParylene-based (estimcurve atedseverely, as 510neural rendering MPa probe provided it array unusable. byprepared LGA By Thin comparison, with Films, sputtered Santa the platinum. The high level of intrinsic stress (estimated as 510 MPa provided by LGA Thin Films, Santa Clara, Clara,sameplatinum. CA,devices TheUSA) highare forces shownlevel the of finalintrinsicprepared device stress with to (estimcurve e-beam atedseverely, evaporated as 510 rendering MPa providedplatinum, it unusable. by demonstrating LGA By Thin comparison, Films, reduced Santa the CA,samecurvature.Clara, USA) devices forcesCA, USA) the are finalforces shown device the preparedfinal to curve device with severely, to curve e-beam rendering severely, evaporated rendering it unusable. platinum, it unusable. By comparison, demonstrating By comparison, the same reduced devicesthe are showncurvature.same devices prepared are with shown e-beam prepared evaporated with platinum,e-beam evaporated demonstrating platinum, reduced demonstrating curvature. reduced curvature.

Figure 15. (a) Severe wrinkling/rippling seen in sputtered deposited platinum film results from

Figurecompressive 15. (a stresses) Severe of wrinkling/rippling a higher magnitude; seen and in(b )sputte wrinkledred areasdeposited around platinum the device film metal results features. from Figure 15. (a) Severe wrinkling/rippling seen in sputtered deposited platinum film results from compressiveFigure 15. ( astresses) Severe of wrinkling/rippling a higher magnitude; seen and in (b )sputte wrinkledred depositedareas around platinum the device film metal results features. from compressivecompressive stresses stresses of of a highera higher magnitude; magnitude; andand (b) wrinkled wrinkled areas areas around around the the device device metal metal features. features.

Figure 16. (a) Top view; and (b) side view of neural probe arrays after release from silicon carrier

Figurewafer. 16.Arrays (a) Top fabricated view; and with (b )sputtered side view platin of neuralum possessedprobe arrays more after severe release curvature from silicon than carrier with platinumFigure 16. deposited (a) Top view; by e-beam. and (b ) side view of neural probe arrays after release from silicon carrier Figurewafer. 16. Arrays(a) Top fabricated view; and with (b) sidesputtered view platin of neuralum possessed probe arrays more after severe release curvature from siliconthan with carrier wafer. Arrays fabricated with sputtered platinum possessed more severe curvature than with wafer.platinum Arrays deposited fabricated by with e-beam. sputtered platinum possessed more severe curvature than with platinum platinum deposited by e-beam. deposited by e-beam.

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3.4. Etching 3.4. Etching Due to the inertness of Parylene it is not practical to etch it chemically. Although there are reports of wetDue etching to the inertnessParylene ofusing Parylene chloronapthelene it is not practical or benzoyl to etch it benzonate chemically. at Although 150 °C there[107], arethis reports is an ◦ extremeof wet etching temperature Parylene for using Parylene chloronapthelene and can affect or benzoyl the bulk benzonate properties at 150 of unetchedC[107], this sections. is an extreme Thus, mechanismstemperature forto selectively Parylene andetch can Parylene affect theare limited bulk properties to dry techniques. of unetched Parylene sections. can Thus, be removed mechanisms with oxygento selectively plasma etch etching Parylene [108–111], are limited reactive to ion dry beam techniques. etching Parylene[112], oxygen can bereactive removed ion etching with oxygen (RIE) plasmaand a deep etching reactive [108 ion–111 etching], reactive (DRIE) ion like beam method etching involving [112], oxygen alternating reactive cycles ion of etching oxygen (RIE) plasma and etching a deep andreactive fluorocarbon ion etching passivation (DRIE) likelayer method deposition involving [108,112–116]. alternating The latter cycles method of oxygen is referred plasma to etching as O2 DRIE. and fluorocarbonPhotoresist passivation etch masks layer are deposition most commonly [108,112 used–116 ].to The lithographically latter method pattern is referred Parylene, to as O 2despiteDRIE. the lowPhotoresist selectivity etch (approximately masks are most commonly1:1). Other usedmaterials to lithographically including some pattern metals Parylene, can be despite used theas maskinglow selectivity materials (approximately if a high etch 1:1). rate Other and materialsgood selectivity including are some required metals [115] can but be usedthe coating as masking and etchingmaterials of if metal a high masks etch ratemay and induce good many selectivity of th aree thermal required mismatch [115] but problems the coating described and etching above. of Additionally,metal masks mayre-deposition induce many of metal of the during thermal the mismatch etch process problems is common described and above.as such Additionally,photoresists remainre-deposition the most of metalcommon during choice the [116,117]. etch process Across is common a broad andrange as of such processes, photoresists AZ P4620, remain a positive- the most tonecommon photoresist, choice [was116, 117used]. Acrossas a Parylene a broad etch range mask of for processes, both O2 RIE AZ and P4620, an O a2 positive-tone DRIE process photoresist, (presented wasin [113]) used to as etch a Parylene a variety etch of maskstructures for both into O Parylene2 RIE and film, an O ranging2 DRIEprocess from 1 (presentedto 15 μm deep. in [113 Selectivity]) to etch ratesa variety typically of structures vary between into Parylene 0.9 and film, 1, for ranging etch rates from varying 1 to 15 betweenµm deep. 0.55 Selectivity and 0.80 rates μm/min. typically vary betweenThe 0.9most and common 1, for etch problem rates varying we observe between during 0.55 plasma and 0.80 etchingµm/min. of Parylene is the formation of gas bubbles,The most either common within problem photores weist observe layers or during between plasma the support etching substrate of Parylene and is Parylene the formation coating. of Thegas bubbles,apparent either cause withinis the off-gassing photoresist of layers volatile or co betweenmponents the of support photoresist substrate or remnants and Parylene of the coating.solvent Theused apparent to distribute cause the is thephotoresist. off-gassing Minor of volatile off-gassing components from photoresists of photoresist may or remnantsbe inconsequential, of the solvent or evenused tounnoticeable, distribute the when photoresist. processing Minor on off-gassing rigid substrates, from photoresists however Parylene may be inconsequential, is gas-permeable or evenand evenunnoticeable, minor volatile when processing products oncan rigid produce substrates, bubbling however when Parylene under isvacuum. gas-permeable Bubbles and may even deform minor volatilephotoresist products masks, can creating produce holes bubbling which when lead underto etch vacuum. damage, Bubbles or deform may the deform Parylene photoresist itself making masks, futurecreating processing holes which difficult. lead toFigure etch 17 damage, shows ora re deformpresentative the Parylene example itself photoresist making bubbling future processing observed followingdifficult. Figure a O2 DRIE17 shows using a representative 80 W RF and example900 W ICP photoresist power. This bubbling phenomenon observed occurs following more a O readily2 DRIE whenusing 80using W RF high and power, 900 W high ICP power.density, This inductively phenomenon coupled occurs plasmas. more readily Very thick when photoresist using high power,layers (>10high μ density,m) and, inductively in particular, coupled very plasmas.thick edge Very beads thick are photoresist more susceptible, layers (>10 likelyµm) due and, to inthe particular, residual verysolvent thick not edge driven beads off during are more soft-baking susceptible, steps. likely We also due observed to the residual the appearance solvent not of gas driven bubbles off during when processingsoft-baking multi-layer steps. We alsoParylene observed devices the featuring appearance three-dimensional of gas bubbles whenParylene processing structures multi-layer defined usingParylene sacrificial devices layers. featuring This is three-dimensional a relatively commo Parylenen technique structures where photoresist defined using is patterned sacrificial and layers. then Thiscoated is ain relatively Parylene commonto create techniqueParylene-based where microfluidic photoresist isor patterned mechanical and structures. then coated These in Parylene sacrificial to layerscreate Parylene-basedare particularly microfluidicsusceptible to or forming mechanical bubbl structures.es during Thesesubsequent sacrificial etch layerssteps, areas gas particularly expands rapidlysusceptible under to formingthe low pressure bubbles required during subsequent for plasma etch etching, steps, faster as gas than expands the rate rapidly of diffusion under through the low pressurethe Parylene required film. for plasma etching, faster than the rate of diffusion through the Parylene film.

Figure 17. Out-gassing of photoresist solvent results in bubbling observed in sacrificialsacrificial photoresist structures sandwiched in Parylene following O2 deep reactive ion etching (DRIE). structures sandwiched in Parylene following O2 deep reactive ion etching (DRIE).

The formation of these gas bubbles appears particularly sensitive to the hard-baking step The formation of these gas bubbles appears particularly sensitive to the hard-baking step following following photoresist development. In a simple experiment, Parylene coated 4″ silicon wafers were photoresist development. In a simple experiment, Parylene coated 4” silicon wafers were masked with masked with 10 μm thick AZ P4620 and, following development, hard-baked on a hot plate at 90 °C

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Micromachines 2018, 9, x FOR PEER REVIEW 17 of 25 10 µm thick AZ P4620 and, following development, hard-baked on a hot plate at 90 ◦C for either 0, 2,for or either 12 h. 0, Following 2, or 12 h. a briefFollowing O2 DRIE a brief process O2 DRIE (approximately process (approximately 2 µm etch), we2 μ observedm etch), we catastrophic observed bubblingcatastrophic for bubbling the sample for baked the sample for 2 h, baked with minimalfor 2 h, with or no minimal bubbling or forno bubbling unbaked samplesfor unbaked and samples bakedand samples for 12 h.baked We hypothesizefor 12 h. We thathypothesize after 2 h that of hard after baking, 2 h of hard volatiles baking, diffuse volatiles through diffuse the Parylenethrough layerthe Parylene and become layer trappedand become between trapped the between Parylene the and Parylene silicon wafer and si substratelicon wafer once substrate the wafer once cools. the Wewafer suspect cools. theseWe suspect volatiles these are volatiles responsible are responsible for later bubbling for later in bubbling the DRIE. in Bythe contrast,DRIE. By 12 contrast, h of hard 12 bakingh of hard may baking completely may completely drive off photoresist drive off photoresist volatiles from volatiles the wafer, from the while wafer, omitting while the omitting hard bake the entirelyhard bake prevents entirely any prevents diffusion any of diffusion volatiles of under volatiles the Parylene.under the We Parylene. strongly We recommend strongly recommend avoiding a hard-bakeavoiding a stephard-bake when etchingstep when Parylene etching through Parylene photoresist through masks. photoresist If a hard-bake masks. If is a required, hard-bake or is if resistrequired, is intended or if resist for is use intended as a sacrificial for use structure, as a sacrificial we recommend structure, we a lengthy recommend hard-bake a lengthy at low hard-bake (<100 ◦C) temperatureat low (<100 °C) under temperature an inert atmosphere under an inert to minimize atmosphere thermal to minimize stress and thermal oxidation. stress and oxidation.

3.5. Photoresist Stripping Generally, photoresists (whether a mask or sacrificialsacrificial layer) are removed with acetone or other organic solvents. Inorganic solvents, such as sulfuric acid, are used when photoresist cannot be easily removed withwith organic organic solvents solvents alone. alone. Oxygen Oxygen plasma, plasma, a dry method,a dry method, is also used is also to remove used photoresistto remove masksphotoresist but is masks often impracticalbut is often asimpractical it removes as Parylene it removes at theParylene same rate.at the Figure same 18rate. shows Figure residual 18 shows AZ P4620residual photoresist AZ P4620 from photoresist the etch from mask the on etch a platinum mask on electrode a platinum after electrode acetone after soaking. acetone soaking.

Figure 18. Oxygen plasma treated AZ P4620 phot photoresistoresist residue on metal feature.

3.5.1. Sacrificial Layer 3.5.1. Sacrificial Layer Stripping of sacrificial photoresist used to define features such as channels in Parylene devices Stripping of sacrificial photoresist used to define features such as channels in Parylene devices can can be particularly challenging after O2 DRIE process. For example, in our experience, long soak be particularly challenging after O2 DRIE process. For example, in our experience, long soak duration duration in acetone (30 h at room temperature) was required to remove sacrificial photoresist used in acetone (30 h at room temperature) was required to remove sacrificial photoresist used to define a to define a microfluidic channel. Such lengthy soaks may lead to delamination of weakly adhered microfluidic channel. Such lengthy soaks may lead to delamination of weakly adhered Parylene layers. Parylene layers. To address both the length soak time and preservation of device integrity, several To address both the length soak time and preservation of device integrity, several parameters were parameters were evaluated to accelerate dissolution of AZ P4620 used as a sacrificial layer for evaluated to accelerate dissolution of AZ P4620 used as a sacrificial layer for microfluidic channels microfluidic channels (26.3 mm in length [48]). The combination of increased acetone volume, heating (26.3 mm in length [48]). The combination of increased acetone volume, heating (40 ◦C) and agitation (40 °C) and agitation (magnetic stir-bar) significantly reduced soak time, mitigating risk of Parylene (magnetic stir-bar) significantly reduced soak time, mitigating risk of Parylene delamination and delamination and reducing clearance time. reducing clearance time.

3.5.2. Oxygen Plasma Exposed Photoresist Photoresist subjected to prolonged oxygen plasma can become crosslinked and difficult difficult to strip using acetone alone (Figure 1919a,b).a,b). This necessitatesnecessitates the use of moremore aggressiveaggressive strippers.strippers. Several solutions were evaluated to remove this photoresistphotoresist from platinum electrodes and contact pads but only piranha solution and homemade stripper successfullysuccessfully removedremoved anyany residualresidual photoresist.photoresist. Upon mixing the Piranha solution (4 parts sulfuric acid (H2SO4) and 1 part 30% hydrogen peroxide (H2O2)), an exothermic reaction occurs that raises the solution temperature above 100 °C. Soaking the Parylene device in a piranha solution at temperatures above 60 °C resulted in metal delamination. Consequently, devices were soaked only after the solution cooled down to 40 °C for 3 min. Although piranha was successful, evidence that Parylene was partially oxidized after thermal

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Upon mixing the Piranha solution (4 parts sulfuric acid (H2SO4) and 1 part 30% hydrogen ◦ peroxide (H2O2)), an exothermic reaction occurs that raises the solution temperature above 100 C. Soaking the Parylene device in a piranha solution at temperatures above 60 ◦C resulted in metal delamination. Consequently, devices were soaked only after the solution cooled down to 40 ◦C for Micromachines 2018, 9, x FOR PEER REVIEW 18 of 25 3 min. Although piranha was successful, evidence that Parylene was partially oxidized after thermal treatmenttreatment suggests suggests that that this this method method is is tootoo aggressiveaggressive for Parylene-based Parylene-based devices. devices. On On the the other other hand, hand, thethe homemade homemade stripper, stripper, consisting consisting of of 1 1 part part RemoverRemover PG ( (NN-methyl-2-pyrrolidone-methyl-2-pyrrolidone based) based) and and 1 part 1 part of AZof AZ 726 (<3%726 (<3% tetramethylammonium tetramethylammonium hydroxide hydroxide based developer),based developer), successfully successfully removed removed photoresist ◦ residuephotoresist after aresidue 15-min after soak a at15-min 50 C soak as shown at 50 °C in as Figure shown 19 inc,d. Figure 19c,d.

Figure 19. DRIE oxygen plasma exposed AZ P4620 photoresist residue on (a) a platinum electrode; Figure 19. DRIE oxygen plasma exposed AZ P4620 photoresist residue on (a) a platinum electrode; and (b) contact pads. Cleaned (c) platinum electrode; and (d) contact pads with homemade stripper. and (b) contact pads. Cleaned (c) platinum electrode; and (d) contact pads with homemade stripper. 3.6. Release 3.6. Release Releasing the device from the support or carrier wafer is the final step in Parylene MEMS processing.Releasing Most the devicecommonly, from the the support support is a or silicon carrier wafer wafer with is a the thin final native step oxide in Parylene layer and MEMS the processing.Parylene adhesion Most commonly, to this material the support is quite weak. is a silicon In such wafer cases, withParylene a thin devices native can oxide be simply layer peeled and the Paryleneoff using adhesion tweezers, to thisor the material wafer can is quite be submerged weak. In such in water cases, and Parylene the devices devices allowed can be to simply float to peeled the offsurface. using tweezers, In some cases, or the however, wafer can the beadhesion submerged between in waterParylene and and the the devices support allowed can be tovery float strong to the surface.and releasing In some Parylene cases, however, without thedestroying adhesion the between thin-film Parylene devices can and be the nearly support impossible. can be very In many strong andcases releasing this adhesion Parylene is deliberate; without destroying sacrificial adhesion the thin-film layers devices such as canaluminum be nearly [45,118] impossible. or chrome In [85] many caseshave this been adhesion used for is complex deliberate; Parylene sacrificial processing adhesion and layers devices such are asthen aluminum released using [45,118 KOH] or chromeor anodic [85 ] haveNaCl been [45,118] used foretching complex for Al, Parylene or chrome processing etchant and for devicesCr [85]. areWe thenalso releaseddemonstrated using the KOH release or anodic of NaClParylene [45,118 devices] etching from for a Al, support or chrome substrate etchant of polyethylene for Cr [85]. Weterephthalate also demonstrated (PET) by theboiling release the of Paryleneensemble devices in water from for a support several substrateminutes. ofIn polyethyleneother scenarios, terephthalate the adhesion (PET) may by be boiling unintentional the ensemble or inundesirable. water for several We observed minutes. that In Parylene other scenarios, devices annealed the adhesion on wafer may at be 200 unintentional °C for 48 h under or undesirable. vacuum Weand observed became that virtually Parylene impossible devices to annealedremove. Inon such wafer situations,at 200 ◦C the for only 48 hremaining under vacuum option andmay becamebe to virtuallyetch away impossible the underlying to remove. silicon In suchor other situations, carrier substrate. the only remaining option may be to etch away the underlying silicon or other carrier substrate. 4. Discussion 4. DiscussionApplying complex, high-resolution micromachining processes to Parylene C substrates is possibleApplying but complex,will require high-resolution modification of micromachining nearly every protocol processes developed to Parylene for Csilicon substrates or other ispossible rigid substrates. No single definitive set of guidelines exists but we can describe a useful compilation of but will require modification of nearly every protocol developed for silicon or other rigid substrates. best practices. No single definitive set of guidelines exists but we can describe a useful compilation of best practices. Efforts should be taken to minimize exposure to heat during every step of the fabrication process. Avoiding the glass transition temperature (90 °C) of Parylene is typically unrealistic but avoiding or minimizing the use of high temperature (>100 °C) processes can prevent oxidization, thermal stress, the formation of gas bubbles, or irreversible changes to Parylene morphology. High temperature anneals (200 °C for 48 h in vacuum) are useful to improve moisture barrier properties or

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Efforts should be taken to minimize exposure to heat during every step of the fabrication process. Avoiding the glass transition temperature (90 ◦C) of Parylene is typically unrealistic but avoiding or minimizing the use of high temperature (>100 ◦C) processes can prevent oxidization, thermal stress, the formation of gas bubbles, or irreversible changes to Parylene morphology. High temperature anneals (200 ◦C for 48 h in vacuum) are useful to improve moisture barrier properties or to shape Parylene by exploiting thermoplasticity, but must be done under vacuum or inert atmosphere and Parylene must be allowed to cool slowly to room temperatures over several hours. Rapid heating above 120 ◦C on a hotplate or during PVD can introduce destructive stress and must be avoided. Parylene C is broadly amenable to most photolithography techniques, including electron-beam lithography but users should be aware of the risk of oxidation due to radiation exposure and complications from gas transport in Parylene films arising from off-gassing of thick photoresist films. Avoiding the use of a hard-bake following development, removing thick edge beads and avoiding high intensity or long duration UV exposure, are all recommended practices. Patterned photoresist masks have been used with success to transfer high-aspect ratio structures to Parylene substrates using O2 RIE and DRIE but this method requires very thick photoresist films due to low selectivity during O2 etching. Metal deposition onto Parylene films can prove incredibly challenging. Evaporative PVD can introduce thermal stress and cracking of either the Parylene or metal structures, while sputtering can introduce film-stress which can warp or wrinkle the Parylene film. These challenges are exacerbated by high-melting point metals and thicker metal films. The use of cooled stages or heat-sinking may help during evaporative PVD but the insulative nature of Parylene coatings makes such thermal control difficult. We have observed the best results by using an e-beam deposition system with a throw distance (distance between target and metal crucible) greater than 20” and splitting depositions of thick films into multiple steps punctuated with 15 min pauses. Finally, for those Parylene-based bioMEMS intended for chronic use under wet-saline environment, we note that the risk of water permeation or delamination remains one of the largest obstacles. We observed WVTR decreasing significantly, for films thicker than 5 µm, following a 48 h thermal anneal and this is consistent with various literature and anecdotal reports about the advantages of annealing Parylene devices and the difficulties using very thin Parylene as a moisture barrier. The large variation in WVTR measurements between different sources prompts a call for more research into how deposition parameters change barrier properties. New methods to improve Parylene adhesion to thin-film metal would similarly help increase Parylene-device lifetime in vivo.

5. Conclusions In conclusion, while applying micromachining to Parylene substrates can be challenging, with attention to the limited thermal budget and polymeric properties of Parylene, most processes can be successfully transferred to this thin, flexible material. We believe that the observations and recommendations we list here can serve as the basis for a series of best-practices regarding Parylene microfabrication. Continuing research is needed, particularly on the adhesion and barrier properties in the construction of multi-layer devices. By solving these and other challenges Parylene stands to become a key material in a new generation of flexible electronic microdevices and polymer MEMS.

Author Contributions: J.O.-D. wrote the paper, designed and performed WVTR experiments and analyzed the data; K.S. analyzed the WVTR data and assisted with the organization and editing; C.L. wrote the spin curve section, designed and performed spinning experiments; A.C. contributed to the metal deposition, etching and photoresist stripping sections; T.H. designed and performed bubbling experiments; J.Y. wrote the packaging section; A.B. wrote the sterilization section and contributed to the delamination section; A.W.H. contributed to the metal deposition section; and E.M. guided the organization and scope and assisted with editing. Funding: This research was sponsored in part by the NSF under award numbers CBET-1343193 and EFRI-1332394, NIH under award number U01 NS099703 and Defense Advanced Research Projects Agency (DARPA) BTO under the auspices of Doug Weber/Eric Van Gieson through the DARPA Contracts Management Office Cooperative Agreement HR0011-15-2-0006. In addition, the following fellowship support is acknowledged: USC-CONACyT Micromachines 2018, 9, 422 20 of 25

Fellowship (J.O.-D.), Viterbi School of Engineering Ph. D. Merit Fellowship (A.C.), USC Provost Fellowships (C.L., J.Y.), and Alfred E. Mann Institute Fellowship (A.B.). Acknowledgments: The authors would like to thank Donghai Zhu and members of the USC Biomedical Microsystems Laboratory for their assistance. Conflicts of Interest: The authors declare no conflict of interest.

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