Synthesis of Pigmented Parylene Coatings and Control of the

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Chromatism Based on Chemical Vapor Deposition Copolymerization

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Ting-Ying Wu1, Yu-Chih Chiang2, Jia-Rong Jhang3, Zhen-Yu Guan1, Chih-Hao Chiu4,

Sheng-Tung Huang3,*, Chen-Chi Wu5,*, Hsien-Yeh Chen1,6,*

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1Department of Chemical Engineering, National Taiwan University, Taipei 10617,
Taiwan

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2School of Dentistry, Graduate Institute of Clinical Dentistry, National Taiwan
University, Taipei 10048, Taiwan
3Institute of Biotechnology, National Taipei University of Technology, Taipei 10617,
Taiwan
4
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Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Taoyuan 33378,
Taiwan
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5Department of Otolaryngology, National Taiwan University Hospital, Taipei 10018,
Taiwan
6 Molecular Imaging Center, National Taiwan University, Taipei 10617, Taiwan
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Keywords: color identification; chromatism; chemical vapor deposition (CVD);

Parylene; medical coating
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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4408085
 Abstract

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Coloring and identification procedures for medical devices are important to reduce the

risks of defective medical devices or incorrect operations and implantations. The study

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herein reports a novel platform of color pigment-modified Parylene coatings to fulfill

the needs of medical coatings, providing a surface modification route to alter the

important property of color for an underneath material and/or device from its original

color. Modification with a naphthalimide derivative is employed for the Parylene

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precursor. The synthesis of the final color Parylene coating is performed based on a

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vapor-phase deposition polymerization process, and the coating is conformally coated

on a variety of materials regardless of the shape or dimension. Furthermore, control of

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the color to create a series of color-changing Parylene coatings is enabled by vapor

deposition copolymerization with a second Parylene derivative source, and predictable

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color tuning from a primary to a secondary and/or tertiary color is achievable in the

experiments and shows accordance with color theory. The reported coating platform

represents a colored coating tool and is biocompatible for biotechnological applications.

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 Introduction

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With the development of biomedical technology/biomaterials, prospective

biomaterials are being designed with functions that mimic natural biological activities.1-
4 In nature, color plays a vital role in conveying information,5 e.g., bright colors often

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represent warnings and toxicity, and red colors often represent danger.6-9 Color

identification is a fundamental element and is deeply influencing in daily life, ranging,

from inside out, from mood swings to decision-making and emergency alerts.5, 7 For

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instance, specific identification colors can speed up instinctive recognition and control

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activities, enhancing the communication/connection between users and devices and

reducing the burden of medical operations when applied to medical devices.10, 11 In

many cases, a purposeful coloring procedure during the manufacturing of medical

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devices is performed and is clinically used for early detection and identification by the
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naked eye12 and to reduce the risks of defective/damaged medical devices or incorrect

operations and implantations.11 However, color is mostly presented by pigments and

dyes, which are limited for various reasons, such as dispersibility13, 14, durability13,
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stability15, desired color performance13, and inorganic pigments containing heavy

metals that are toxic to humans.16, 17 For structural color, the mechanism of color
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presentation is based on a diffraction strategy resulting from particle stacking; therefore,

the surface morphology/architecture needs to be carefully constructed, thereby reducing

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the defects.18 Currently, common biomedical coating materials, such as polyamide19,

poly(methyl methacrylate)20, polyurethane21, and silicone22, are fabricated and

constructed on the surface based on an irritative solvent system, which causes negative
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effects on the environment. Additionally, due to the fabrication approaches, the

formation of pinholes in the coating that yield hermetic seals on the surface of the
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medical device cannot be avoided.20, 23 In the present study, we report a series of

pigment-modified poly-p-xylylene coatings (commercially named ParyleneTM, US

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 military regulations MIL-I-46058C, IPC-CC-830 certification and nontoxic test

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certificates, SGS nontoxic test certification, UL94V-0 combustion test certification, and

the United States Pharmacopoeia (USP) XXII, VI level of biocompatibility), and the

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accordant chromatism control of various colored Parylene coating products is

achievable based on vapor deposition copolymerization. The native properties of

Parylene are acknowledged to be advantageous: (i) no solvents, catalysts, initiators, or

other additives are required, and a high polymerization yield with no byproducts is

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achieved during the vapor-phase deposition polymerization process;24 (ii) the Parylene

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coatings are deposited at approximately 20 °C or a lower temperature,24, 25 which avoids

the possibility of heat damage for delicate and precision medical devices; (iii) the vapor-
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phase polymerization process renders a homogeneous and conformal coating film

regardless of the substrate material or geometry;26, 27 and (iv) a variety of modified

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functionalities can be installed on the backbone of poly-p-xylylene.28-31 We therefore

hypothesize the synthesis of a color pigment-modified Parylene coating through

modification with a naphthalimide derivative32, 33 containing a chromophore/functional

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group based on a donor-acceptor system, and the resultant modified Parylene can

represent a color-functionalized coating platform for any mentioned materials and

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applications, providing new color identification specifications and function.

Additionally, control and modification of chromatic properties are achieved based on

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vapor-phase copolymerization with a second Parylene derivative source during the

synthesis process to produce a state-of-the-art series of color-changing Parylene

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coatings. The copolymerization ratio exhibits a predictable relation with the resultant

color-display property and performance, which shows accordance with color theory in

forming primary, secondary, and/or tertiary colors. Furthermore, the biocompatibility

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and stability of the color-modified Parylene platform were examined, showing

suppressed cytotoxicity and excellent biocompatibility, which is consistent with

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 existing Parylene derivatives. The present study establishes a unique interface coating

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platform that provides an important color identification capability that fulfills the

shortage in meeting the current needs in biotechnological applications.

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 Results and discussion

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In this study, colored pigment-modified Parylene coatings based on vapor-phase

deposition polymerization were first reported; moreover, the chromatic property could

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be precisely regulated to form a series of color-changing Parylene coatings based on

highly controllable vapor deposition copolymerization. To give a color-display

property, naphthalimide derivatives were used to modify [2,2]-para-cyclophane. The

detailed synthesis approach is shown in Figure S1. In brief, pigment-modified Parylene

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was synthesized from the pigmented Parylene coating precursor 4-morpholine-1,8-

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naphthalimido-[2,2]-para-cyclophane (4), which resulted from modification of the

commercial product [2,2]-para-cyclophane by grafting a wavelength-absorbing

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chromophore, i.e., a derivative of 4-morpholine-1,8-naphthalimido (MPNA), based on

donor-acceptor theory.32, 33 Through further chemical structure/property analysis,

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including 1H nuclear magnetic resonance (1H NMR), 13C NMR, electrospray ionization

mass spectrometry (ESI-MS), ultraviolet‒visible (UV‒Vis) spectroscopy and infrared

reflection absorption spectroscopy (IRRAS), as shown in Figure S2(a-e), both the

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chemical structure and desired color identification property were verified; therefore,
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this colored derivative was used for further research. For the most important step of

coating formation and color display, vapor-phase deposition polymerization was used

to form the resultant modified Parylene coatings, which resulted from the cyclophane
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derivative acting as a pigmented Parylene precursor. For the preparation of pigment-

modified Parylene coatings, as shown in Figure 1(a), the pigmented Parylene precursor
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was sublimated at 393 K (120 °C), pyrolyzed into the intermediate radicals MPNA-p-

quinodimethane and p-quinodimethane at 873 K (600 °C), carried by argon with a flow
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rate of 30 sccm and polymerized/deposited on the substrate at 298 K (25 °C) to form

color pigment-modified Parylene coatings (5). The whole process was operated under

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 a pressure of 0.67 mbar and monitored by real-time mass analysis, as shown in Figure

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1(b), which revealed the characteristic signals of 100 and 210 amu representative of the

fragments of MPNA-p-quinodimethane and the signal of 104 amu representative of p-

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quinodimethane. Therefore, the vapor fragments from the desired pigmented Parylene

coatings based on real-time detection indicated that the conditions for formation of the

resultant modified Parylene coatings were present in the environment. In the presence

of the radicals MPNA-p-quinodimethane and p-quinodimethane, polymerization

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simultaneously occurred in the gas phase and on the substrate to form color pigment-

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modified Parylene coatings. To verify the desired color performance, the optical/color-

display property of the resultant modified Parylene coatings was studied by UV‒Vis
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spectroscopy, as shown in Figure 1(c); the maximum signal of UV‒vis absorbance was

revealed at 430 nm, showing a redshift compared to the pigmented Parylene precursor
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in Figure S2(d) due to the polarity enhancement from thin film formation34, 35. The

peak band ended at a wavelength of approximately 500 nm, which indicated that the

color of the pigmented Parylene coatings belongs to the yellow/orange region,

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achieving the goal of developing Parylene coatings with a warm color display ability.
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To confirm the chemical structure, the element composition of the color pigment-

modified Parylene coatings was detected by X-ray photoelectron spectroscopy (XPS),

as shown in Figure 1(d), and the results revealed the existence of N, C and O in the
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survey spectrum (left-hand side plot); furthermore, the detailed composition revealed

by the high-resolution C1s spectrum, right-hand side plot of Figure 1(d), could be
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deconvoluted into five distinct peaks comprising C-C/H (285.0 eV), N-C=O (288.2 eV),

C-C-N (286.3 eV), C-C-O (286.7 eV) and π–π* (291.0 eV). The composition ratios of
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each distinct peak from the experiment, comprising 74.13, 7.12, 11.95, 6.8 and 3.68%,

respectively, corresponded with the calculated values in the inset of the right-hand side

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 plot of Figure 1(d), thereby confirming the chemical composition of the currently

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developed color pigment-modified Parylene coatings fabricated via vapor-phase

deposition polymerization. The additional data of the resultant modified coatings

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obtained by IRRAS analysis are shown in Figure S3. In addition, the stability of the

coating is a vital issue for further application; therefore, the solvent resistance of the

color pigment-modified Parylene coatings was demonstrated, as revealed in Figure S4,

based on various solvents, and the results showed significant resistance to ethanol, ethyl

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acetate (EA) and toluene. For extension of the potential application/function of the

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coatings, color-changing Parylene coatings could also be constructed by adjusting the

vapor deposition copolymerization. The detailed chemical mechanism of the color-

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changing Parylene coatings produced by vapor deposition copolymerization is

illustrated in Figure 2(a). In brief, both the pigmented Parylene coating precursor and
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the colorless Parylene coating precursor dichloro-[2,2]-para-cyclophane (6) would

sublimate, pyrolyze into the radicals MPNA-p-quinodimethane, p-quinodimethane and

chloro-p-quinodimethane in the intermediate state of copolymerization at a pyrolysis

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temperature of 873 K (600 °C) and deposit on 298 K (20 °C) substrates to form

copolymer (7), i.e., the color-changing Parylene coatings. A series of color-changing

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Parylene coatings with various chromatism could be produced by manipulating the inlet

composition ratio (colorless Parylene coating precursor/pigmented Parylene coating

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precursor) resulting from the operating conditions of a changing sublimation

temperature for the colorless Parylene precursor and a fixed sublimation temperature
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(120 °C) for the pigmented Parylene precursor. The operating conditions for the

colorless Parylene precursor in the copolymerization system are revealed in Figure 2(b),

showing a linear relation of the natural logarithm of pressure (P), i.e., the pressure
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obtained based on the relation of the mass loss and system temperature derived by

Langmuir and others36, 37, and the inverse sublimation temperature (1/T), which could

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 be described by the Clausius-Clapeyron equation38, as shown in the following equation:

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∆𝐻𝑠𝑢𝑏 1
ln 𝑃 = ―
𝑅 𝑇 ()+ 𝑐𝑜𝑛𝑠𝑡𝑎𝑛𝑡

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where P, R, ∆H𝑠𝑢𝑏 and T are the vapor pressure, universal gas constant, latent heat of

sublimation and system temperature, respectively. Therefore, the inlet composition

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could be well manipulated by this temperature-control system, thereby providing

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predictable and controllable initial conditions for this colored coating tool. To

demonstrate chromatism control of the colored coating system, under the heating

conditions of 317, 322 and 331 K for the colorless Parylene precursor, the resultant
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products of various colored Parylene coatings covered on SiO2 transparent substrates

were analyzed by XPS, as shown in Figure 2(c). The element ratios of A, indicative of
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chlorine (Cl) from the colorless Parylene precursor, and B, indicative of nitrogen (N)

from the pigmented Parylene precursor, were 3/1, 8/1 and 16/1 for the sublimation

conditions of 317, 322 and 331 K for the colorless Parylene precursor, respectively.
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Furthermore, a linear relation existed between the sublimation temperature and the
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composition of the coatings, which implied a predictable and controllable colored

coating system. In addition to the chemical element analysis, resultant optical images

of color-changing Parylene coatings deposited on SiO2 transparent substrates are shown

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in Figure 2(d). From left to right, the proportions of elements, A/B, contained in each

sample were as follows: 1/0, 16/1, 8/1, 3/1 and 0/1, corresponding to each sample in
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the optical images below. Through naked-eye observation, the color

performance/chromatism was enhanced due to the increment of the N content from the
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pigmented Parylene precursor in the color-changing coating, resulting from the

operating conditions with a lower sublimation temperature for colorless Parylene

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 coatings. Additionally, the color-changing coatings based on vapor deposition

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copolymerization, as shown in Figure 2(d), allowed direct access to the background

information, logo and text of National Taiwan University, which indicated that the

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color-changing Parylene coatings had excellent transparency, which is vital for medical

devices.25 For advanced optical analysis based on UV‒vis spectroscopy, the optical

performance was characterized via the UV‒vis absorbance spectrum shown in Figure

2(d). The absorbance spectra from top to bottom correspond to the order of the top

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images from left to right, and the products at the corresponding position had the same

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fabrication parameters in vapor deposition polymerization/copolymerization. For the

coating with a 1/0 A/B ratio, the spectrum revealed a significant signal at 320 nm, which
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was the characteristic peak of the colorless Parylene coating, poly(2-chloro-para-

xylylene). As the proportion of B increased, the peak intensity at 320 nm gradually

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decreased and disappeared; in contrast, the characteristic peak at 430 nm belonging to

the pigmented Parylene coatings gradually increased. The results showed that the

intensity of the UV‒vis absorption peak at 430 nm had a positive correlation with the
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trend of the color chromatism and the proportional ratio of B from XPS. Overall, these

resultant products indicated that vapor deposition copolymerization could produce

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resultant color-changing coatings with distinct color performance/chromatism based on

simple regulation of the sublimation temperature, thereby demonstrating the highly

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controllable and predictable properties of this colored coating tool. Aside from

presenting the color of the coatings, primary and secondary colors with various
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identifiable chromatism could be created by mixing with initial substrates through

vapor-phase deposition polymerization, thereby broadening the application of the

coatings; for instance, color regulation is commonly applied in dental applications for
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mimicking natural teeth.39, 40 In addition, various colorful substrates are usually used in

medical devices, such as white tooth implants, red hip bone implants, green ureteral

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 stents and blue condylar buttress plates. Therefore, white, blue, red and green substrates

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were used to demonstrate color manipulation with pigmented Parylene coatings. Based

on subtractive color theory, a secondary color results from the mixture of primary colors;

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for instance, the mixture of blue and yellow would be green, and the mixture of red and

yellow would be orange. A tertiary color could be obtained by mixing primary and

secondary colors, such as yellow‒green resulting from the combination of yellow

belonging to the primary colors and green belonging to the secondary colors.41

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Therefore, to verify the feasibility of chromatism/color blending based on this colored

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coating tool, pigmented Parylene coatings were deposited on various colored substrates.

The optical images of the resultant products after vapor deposition/polymerization with
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an inlet composition of 100% pigmented Parylene precursor are displayed in the bottom

row of Figure 3(a); from left to right, the resultant substrates presented colors of yellow,
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green, orange, and yellow‒green, which correspond to the substrates with original

colors of white, blue, red and green, respectively. The results indicated that subtractive

color theory could be applied via the colored coating tool supported by a layer-by-layer
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approach due to the superior intrinsic transparent property of color pigment-modified

Parylene coatings. In addition to the original optical performance of primary, secondary

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and tertiary colors, another aspect of color, chromatism control, could also be achieved

on colored substrates to broaden the application of the coatings and complete coating
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platform. Herein, vapor deposition copolymerization was utilized for application to

various colored substrates. As shown in Figure 3(a), resultant color-changing coatings

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with higher to lower chromatic degrees were obtained on each color substrate via

different operating conditions (sublimation temperature) of vapor deposition

copolymerization, leading to various composition ratios of the pigmented Parylene

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precursor/colorless Parylene precursor. The resulting images in rows 2 to 4 (counting

from top to bottom), produced by vapor deposition copolymerization under operating

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 conditions with final surface element ratios of 16/1, 8/1 and 3/1, as mentioned in Figure

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2, showed that the chromatism/color display of the color-changing Parylene coatings

decreased with increasing A content from the colorless Parylene precursor (decreasing

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B content from the pigmented Parylene precursor). In addition to observations by the

naked eye, the CIELAB color space model, defined by the Commission International

d'Eclairage (CIE), has been widely utilized to measure object color/chromatism, which

is independent of equipment. As shown in Figure 3(b), the CIELAB color space is

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composed of three components/parameters, L, a and b, which individually represent

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different colors, including red (+a), yellow (+b), green (-a) and blue (-b), and lightness,

including black (L=0) and white (L=100).42, 43 Furthermore, the color difference, ΔE*,
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used to measure the perceptibility between two images/objects, can be defined by the

following equation:
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ΔE * = ΔL 2 + Δa 2 + Δb 2
2
∗ ∗ ∗
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which is composed of Δ L*(L*sample-L*standard), Δ a*(a*sample-a*standard) and Δ b*

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(b*sample-b*standard)44. The larger the value of ΔE* is, the larger the difference in the

object colors, and the higher the visual perceptibility with the human naked eye45;
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according to previous studies, ΔE* equal to/exceeding the value of 1 means that the

color difference is visually perceptible.44, 46 To express the color more objectively, each
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sample of color-changing Parylene coatings on various colored substrates was analyzed

and plotted in the three-dimensional (3D) CIELAB color space, as shown in Figure

3(c). There were four streamlines/groups representing the four different colored
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substrates/color systems, including white, blue, red and green. Each color system

comprised five spots, corresponding to the samples in Figure 3(a), and showed a

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 similar shift direction in the coordinate system with increasing B content from the

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pigmented Parylene precursor. Additional quantitative data based on the

chromaticity/color difference, Δ E*, were measured based on the above equation in

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comparison to the original substrate, as revealed in Figure 5S. In brief, the larger the

ΔE* value is, the greater the chromaticity/color difference from the original substrate.

The resultant analysis in Figure 5S shows that the ΔE* value became larger as the

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content of B from the pigmented Parylene precursor increased, corresponding to the

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results from naked-eye observation and the 3D CIELAB color space; moreover, the

chromatic degrees on each different substrate had mostly similar differences under the

same operating conditions, thereby expressing the superior capability for chromatism
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control of this color-functionalized coating platform. To focus on the impact of
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chromatism/color based on this colored coating tool by excluding the influence of light-

dark contrast (L-axis), the resultant samples of color-changing Parylene coatings coated

on the white substrate were quantified and plotted on the two-dimensional (2D)
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chromatic coordinate space composed of the a- and b-axes based on the CIELAB color

chart (L=50), as shown in Figure 3(d). The original white colored substrate was
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initially close to the center; however, the sample spot gradually shifted to a higher b

value, approaching the yellow region (higher chromatism), when the inlet content of
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the pigmented Parylene precursor gradually increased, which corresponded to the

expectation (the copolymerization condition) and naked-eye observation. Furthermore,

based on these coordinates, it was easier to observe that in addition to the b value, the
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a value would also be positively enlarged and drive the sample spot toward the red

region with increasing pigmented Parylene precursor content (B content) due to the
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polarity-enhancement consequence.34, 35 From the above discussion, these resulting

products implied that the colored coating platform could not only fabricate a series of

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 color-changing Parylene coatings but also further demonstrate the capability of color

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blending by integrating the excellent optically transparent property of the coatings;

moreover, a chromatism control model based on this color-functionalized coating

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platform was also provided and established. In addition to the chromatic property of the

developed coatings, as future potential coatings for medical devices, the

biocompatibility needs to be assessed. To verify the biocompatibility of the currently

developed pigmented Parylene coatings, a cell viability test was executed via acute

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toxicity studies based on a direct contact approach and an extract approach, and 3T3

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cells were utilized to perform the proceeding analysis. As shown in Figure 3(e), there

was no significant difference in fluorescence images between day 1 and day 3 among
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the groups of color pigment-modified Parylene coatings and TCPS in distinct tests

based on both approaches. Additionally, for the statistical analysis of each group and
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test method, as shown in Figure 3(e), there was also no significant difference in the cell

viability after 3 days of the biotests with the two distinct approaches compared to the

tissue-culture polystyrene (TCPS) group, thereby confirming the biocompatibility of

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the color pigment-modified Parylene coatings fabricated by vapor-phase deposition

polymerization.
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 Conclusion

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For the Parylene coating family, historical records of environmentally friendly

processing conditions, solvent- and moisture-free fabrication procedures for sensitive

materials and devices, and, most importantly, agreed-upon biocompatibility have been

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shown, and these coatings have been market-approved in many biotechnological

products. The present study introduces and synthesizes a series of colored Parylene

coatings that were introduced into the family, providing a solution to the urgent need

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for biocompatible coatings for biomaterials and biomedical devices. Predictable control

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of the color among primary, secondary, and/or tertiary colors for the coated materials

and devices from their original colors is also shown for the colored Parylene coatings.

With the existing chemically functionalized Parylene materials already on the shelf and
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the feasibility of vapor deposition copolymerization with various combinations of
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Parylene precursors to produce controlled ratios of multifunctional Parylene

copolymers that have been demonstrated, we foresee the possibility of a new

chromatism modification capability for Parylene coatings and unlimited applications

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for prospective biomaterials and biomedical devices.

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Figure 1. (a) Polymerization mechanism of color pigment-modified Parylene coatings
based on vapor-phase deposition polymerization. (b) Real-time mass analysis of color
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pigment-modified Parylene coating formation during vapor-phase deposition
polymerization. (c) UV‒vis spectrum of the final product, i.e., color pigment-modified
Parylene coatings. (d) Plot on the left-hand side: survey spectrum from XPS analysis
of the color pigment-modified Parylene coatings based on vapor-phase deposition
polymerization; plot on the right-hand side: C1s spectrum of the color pigment-
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modified Parylene coatings comprising various peaks from different bonds with
different binding energies. The percentage of the peaks except for π-π* applied to all
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the other kinds of experimental data. The π-π* value was additionally calculated based
on the overall experimental value.
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Figure 2. Color-changing Parylene coatings (7) obtained through vapor-phase

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deposition copolymerization: (a) Mechanism of color-changing Parylene coatings

based on vapor deposition copolymerization. (b) Plot of the copolymerization
conditions: sublimation temperature of the colorless Parylene precursor vs. ln Pc. (c)
Plot of the element composition from copolymerization based on XPS analysis:
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sublimation temperature of the colorless Parylene precursor vs. element ratio of the
surface composition (A/B, A is representative of chlorine from the colorless Parylene
precursor; B is representative of nitrogen from the pigmented Parylene precursor). (d)
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Optical images of color-changing Parylene coatings fabricated under various

copolymerization conditions on SiO2 transparent substrates (top), and UV‒vis analysis
of the coatings fabricated under various copolymerization conditions (bottom).
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 Figure 3. (a) Optical images of the various color-changing Parylene coatings with

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various chromatic degrees deposited on four different colored substrates. A/B is the
element ratio of the surface composition. A is representative of chlorine from the
colorless Parylene precursor; B is representative of nitrogen from the pigmented

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Parylene precursor. (b) Schematic diagram of the CIELAB color space. (c) Various
samples from (a), i.e., various color-changing Parylene coatings on four different
colored substrates, plotted on the 3D CIELAB color space chart. (d) Samples composed
of various color-changing Parylene coatings on a white substrate plotted in the 2D
chromatic coordinates based on the CIELAB color space at L=50. Figures (c) and (d)

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were created based on MATLAB packages.47, 48 (e) Cytotoxicity testing and statistical
analysis of the pigment-modified Parylene coatings based on the direct contact method

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and extract method at day 1 and day 3.

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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4408085
 Methods
Synthesis of product (4), a pigmented Parylene derivative precursor

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First, for the synthesis of product (2), a mixed solution comprising sulfuric acid (4.4
mL, 76.8 mmol) and nitric acid (2.7 mL, 38.4 mmol) was slowly added dropwise to
[2,2]-para-cyclophane (1) (4.0 g dissolved in 370 mL of dichloromethane, 19.2 mmol)

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over an hour in an ice bath. After 4 hr, most of the organic solvent was first removed
by a rotary concentrator and then extracted with 150 mL of ethyl acetate 3 times. After
the extraction, anhydrous magnesium sulfate was added to remove the residual water
in the extracted solution. Then, the mixture with the resultant product (2) could be
collected after rotary evaporation. Subsequently, the desired product (2) (2.94 g) was

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obtained by column chromatography (eluent: n-hexane/ethyl acetate = 19/1) with a
yield of 60%. Rf = 0.5 (with silica gel 60; n-hexane/ethyl acetate=19/1); 1H-NMR (300

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MHz, CDCl3): δ7.19 (d, J=1.5 Hz, 2H), 6.77 (dd, J=8.1, 1.8 Hz, 1H), 6.61-6.55 (m, 4
H), 6.66 (d, J=8.1 Hz, 1H), 4.05-3.97 (m, 1H), 3.21-2.82 (m, 6H), 2.90-2.15 (m, 1H).
For the second step of the synthesis of product (3), product (2) (3.0 g, 11.84 mmol) was
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dissolved in 160 mL of ethyl acetate and hydrogenated with 60 psig of hydrogen in the
presence of 180 mg of a palladium-on-carbon catalyst (10% wt) at room temperature
for 12 hr. After filtering, a small amount of methanol was added to the mixture
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containing product (3) for further recrystallization. Subsequently, 1.86 g of product (3)
was obtained by recrystallization, and a temperature of -75 °C was achieved by using a
mixed ice bath of dry ice and isopropanol, with a yield of 70%. Rf = 0.7 (with silica gel
60; n-hexane/ethyl acetate=3/1); 1H-NMR (300 MHz, CDCl3): δ7.15 (dd, J=7.8,1.8 Hz,
1H), 6.56 (dd, J=7.8, 1.8 Hz, 1H), 6.37 (dd, J=7.8, 1.8 Hz, 2H), 6.24 (d, J=7.5, 1H),
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6.11 (dd, J=7.8, 1.8 Hz, 2H), 5.36 (d, J=1.8 Hz, 1H), 3.44 (s, 2H), 3.14-2.89 (m, 6H),
2.84-2.75 (m, 1H), 2.70-2.60 (m, 1H). Finally, for the synthesis of product (4), the
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above product (3) (50 mg, 0.224 mmol), 4-chloro-1,8-naphthalic anhydride (65 mg,
0.279 mmol) and morpholine (0.03 mL, 0.336 mmol) were added to 0.25 mL of
dimethyl sulfoxide and then synthesized by a microwave method in the instrument with
a power of 150 W and a temperature of 150 °C. After reaction for 2 hr, the mixture
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containing product (4) was filtered with water; simultaneously, the filter cake was
soaked in a water solution during the removal process. After the process, the filter cake
was dissolved in dichloromethane; then, magnesium sulfate anhydrous was
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subsequently added to remove the residual water. The mixture with the resultant desired
product (4) could be obtained after the rotary evaporation process. Finally, the mixture
with the resultant desired product (4) was purified by column chromatography (eluent:
n-hexane/ethyl acetate=3/1) to obtain a yellow powder, i.e., pigmented Parylene
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precursor (4) (36 mg), with a yield of 33% and a melting point of 247-248 °C. Rf = 0.4
(with silica gel 60; n-hexane/ethyl acetate=3/1); 1H-NMR (300 MHz, CDCl3): δ8.73

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 (dd, J=17.1, 7.2 Hz, 1H), 8.54-8.42 (m, 2H), 7.74 (dt, J=27.3, 8.1, 1H), 7.32-7.21 (m,
1H), 6.84-6.80 (m, 2H), 6.69 (s, 2H), 6.57-6.48 (m, 2H), 6.39 (d, J=7.5 Hz, 1H), 4.11-

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4.03 (m, 4H), 3.32-3.22 (m, 6H), 3.11-2.95 (m, 4H), 2.90-2.75 (m, 2H) (Figure S2a);
13C-NMR (300 MHz, CDCl3): 164.1, 163.6, 155.5, 138.8, 138.7, 138.5, 137.7, 134.7,

134.4, 134.1, 132.9, 132.7, 132.3, 131.8, 131.5, 131.3, 130.0, 128.4, 125.8, 123.9, 123.2,

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117.5, 117.0, 114.9, 66.8, 53.2, 35.2, 35.1, 34.8, 31.0 (Figure S2b); EIS-MS (ESI+):
m/z(%)=489.22(85) (Figure S2c).

Vapor deposition polymerization and copolymerization

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Color pigment-modified Parylene coatings (5) were fabricated by polymerization of
pigmented Parylene precursor (4), a colored dimeric derivative. In the vapor-phase

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deposition polymerization, the precursor of pigmented Parylene coatings was
sublimated at a temperature of approximately 393 K (120 °C), and the sublimating
material was carried by argon into the pyrolysis region for transformation into radicals,
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quinodimethanes, at 873 K (600 °C). After the formation of radicals based on pyrolysis,
polymerization occurred in the deposition chamber and formed color pigment-modified
Parylene coatings on the template maintained at 298 K (25 °C). For the color-changing
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Parylene coatings (7) based on vapor deposition copolymerization, the sublimation
ratio of colorless Parylene precursor (6) and the pigmented Parylene precursor was
controlled by the different sublimation temperatures. Under the fixed temperature of
393 K (120 °C) for the pigmented Parylene precursor, the temperature of the colorless
Parylene precursor was controlled at 317, 322 and 331 K (44, 49 and 58 °C),
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corresponding to 3/1, 8/1 and 16/1 for each group of modulated visually identifiable
colored coatings, respectively. After sublimation, various radicals formed at 600 °C and
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copolymerized on the template, whose temperature was held at 298 K (25 °C), to
produce various color-changing Parylene coatings from various inlet ratios of the
colorless Parylene precursor/pigmented Parylene precursor.
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Characterizations
For the vapor composition during vapor-phase deposition polymerization, masses from
45 to 400 amu were detected by a real-time mass spectrometer (RGA, Hiden Analytical,
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UK) operated under 10−7 mbar with an electron ionization energy of 70 eV and an
emission current of 20 μA. The mass spectra were established by Hiden Analytical
software (MASsoft7 professional). The X-ray photoelectron spectroscopy (XPS)
spectrum was obtained by a theta probe X-ray photoelectron spectrometer (Thermal
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Scientific, UK) with an X-ray source of monochromatized Al Kα. The survey, C1s, N1s
and Cl2p spectra were collected with an X-ray power of 150 eV and a pass energy of

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 200 eV (for survey spectra) or 20.0 eV (for individual elemental spectra). Each
elemental spectrum was fitted by Xpspeak41 software. A U-3010 UV/VIS spectrometer

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(Hitachi, Japan) with a mercury lamp was used to collect the absorbance spectrum of
the coating between 200 and 800 nm. Infrared reflection absorption spectroscopy
(IRRAS) spectra were used to analyze the compositions of the materials. The spectrum

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over a scanning range of 600 to 4000 cm-1 was collected by a Spectrum 100 FTIR
Spectrometer (PerkinElmer, USA) equipped with a liquid nitrogen-cooled mercury
cadmium telluride (MCT) detector and Spectrum software (Version 6.3.5.0176). The
parameters L, a and b of each colored coating sample were quantified by Adobe
Photoshop CC 2017. The 2D and 3D CIELAB charts were graphed based on MATLAB

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packages via MATLAB R2022b 47, 48.

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Biocompatibility test
Two methods, the direct contact method and extract method, were used to confirm the
cell survival situation on the newly developed coating. The tested substrates covered
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with color pigment-modified Parylene coatings were first cleaned with alcohol and
distilled water. For the direct contact method, 3T3 fibroblasts directly contacted the
tested substrates for culture for the cytotoxicity test. In contrast, for the extract method,
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3T3 fibroblasts were cultured in a medium that had been exposed to color pigment-
modified Parylene coatings for three days. For the control group, 3T3 fibroblasts were
cultured in tissue-culture polystyrene (TCPS) for further comparison49. Each group was
incubated with 3T3 fibroblasts at a cell density of 105 cells/cm2. On day 1 and day 3,
the live or dead cells in each group were characterized by a fluorescence-based
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LIVE/DEAD kit (Thermo Fisher Scientific, USA) and observed by a fluorescence

microscope (Leica Microsystems, Germany). Moreover, the cell viability of each group
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was confirmed by a commercial MTT assay kit (Sigma‒Aldrich, USA). MTT signals
were obtained by an ELX800 microplate reader (BioTek Instruments, USA) based on
the absorbance wavelength of 570 nm, and the MTT signal percentage was determined
using TCPS as a control group.
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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4408085
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 Data Availability. All data generated or analyzed during this study are included in this

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published article and its supporting information files.

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Author Contributions

*Corresponding Author: [email protected] (S.-T. H.); [email protected]

(C.-C. Wu); [email protected] (H.-Y. C.)

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Tel.: +886-2-33669476 (H.-Y.C.)

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Conflicts of interest
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The authors declare no competing conflicts of interest.
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Acknowledgment
The authors gratefully acknowledge funding support from the National Science and
Technology Council of Taiwan (111-2221-E-002-030-MY3; 108-2221-E-002-169-
MY3; 109-2314-B-002-041-MY3).
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 Table of Contents

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A series of vapor phase-synthesized color pigment-modified Parylene coatings are
fabricated with tuning of the chromatism, providing a surface modification route to alter
the color property for an underneath material or device from its original color.

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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4408085