An Evaluation of Parylene Thin Films to Prevent Encrustation for a Urinary Bladder Pressure MEMS Sensor System

Recent developments in urological implants have focused on preventive strategies to mitigate encrustation and biofilm formation. Parylene, a conformal, pinhole-free polymer coating, has gained attention due to its high biocompatibility and chemical resistance, excellent barrier properties, and low friction coefficient. This study aims to evaluate the effectiveness of parylene C in comparison to a parylene VT4 grade coating in preventing encrustation on a urinary bladder pressure MEMS sensor system. Additionally, silicon oxide (SiOx) applied as a finish coating was investigated for further improvements. An in vitro encrustation system mimicking natural urine flow was used to quantify the formation of urinary stones. These stones were subsequently analyzed using Fourier transform infrared spectrometry (FTIR). Encrustation results were then discussed in relation to coating surface chemical properties. Parylene C and VT4 grades demonstrated a very low encrustation mass, making them attractive options for encrustation prevention. The best performance was achieved after the addition of a hydrophilic SiOx finish coating on parylene VT4 grade. Parylene-based encapsulation proved to be an outstanding solution to prevent encrustation for urological implants.


Introduction
In the 1930s, Dr. Frederick Foley introduced the indwelling urinary catheter to urologic practice, and these catheters remain widely used in daily urological procedures today [1]. Despite their long history of use, urinary catheters still present various disadvantages. A significant concern is the formation of crystalline biofilms that encrust and block the catheter. Encrustation can occur rapidly, leading to urine flow obstruction and potential complications, such as incontinence or painful bladder distention. These challenges highlight the need for improved solutions to minimize encrustation and enhance patient comfort and care [2,3].
Recently, various preventive surface modification strategies against encrustation and biofilm formation have been investigated. Most urinary stents consist of polymer mixtures with optimized surface properties designed to reduce encrustation. New polymeric stents, exposure, protecting the implant material and preventing potential issues such as the corrosion and degradation of medical devices placed inside the human body [22]. Parylene demonstrates a high resistance to a wide range of chemicals and body fluids, including urine, and shows a low coefficient of friction, that reduces frictional forces and potentially minimizes irritation, discomfort, or damage to the surrounding tissues [23]. Silicon oxide layers have gained well-known recognition for their effective barrier capabilities [24][25][26][27]. However, the attributes of silicon oxide-based compounds extend beyond barrier functions, positioning them as promising coating materials for optical purposes. Silicon oxide-based compounds exhibit remarkable characteristics, such as hardness, transparency, and hydrophilicity [28][29][30][31]. Additionally, significant interest has been directed towards the surface functionalization of silicon oxides. Researchers have studied enhancing surface properties through the deposition of robust overlayers, particularly in the field of optoelectronic device miniaturization [32,33].
The aim of this study is to investigate the effectiveness of two parylene grade coatings, parylene C and VT4, as well as a silicon-based finish coating, ceramic-like SiO x , in preventing encrustation for a urinary bladder pressure MEMS sensor system. An in vitro encrustation system was developed and employed to simulate the natural urine flow in the body and quantify the percentage of mass encrustation. Additionally, Fourier transform infrared spectrometry (FTIR) was utilized to analyze the formation of urinary stones. Surface chemical properties, such as the contact angle and surface charge, were characterized to correlate and discuss the results.

Parylene Deposition
Parylene, commonly referred to as poly-para-xylylene and its derivates, films were deposited using the Gorham process through low-pressure chemical vapor deposition (LPCVD) at room temperature [34]. Parylene films were performed in a CX-30 PC hydride machine, able to deposit inorganic layers by plasma-enhanced chemical vapor deposited (PECVD), provided by Coat-X SA, La Chaux-de-Fonds, Switzerland. To enhance the adhesion of the parylene film to the substrates, an adhesion promoter, methacryloxypropyl trimethoxysilane (Silane A174), was evaporated in the chamber for 3 min prior to the parylene deposition. In order to maintain a constant pressure of 80 µbar in the deposition chamber, a precise control of the sublimation temperature ranging from 80 to 150 • C was employed. The pyrolysis temperature was set at 700 • C to effectively cleave the dimers into monomers. Afterwards, the monomers condensed and polymerized inside the chamber, leading to the creation of a polymeric film at normal room temperature.
Two different parylene grades, namely parylene C and VT4, were deposited and evaluated. Parylene-based encapsulation solution is considered a very promising alternative to protect biomedical devices. Parylene C, or poly(chloro-p-xylylene), is the most commonly used variant of parylene. It demonstrates very low permeability to gases and moisture [22,35]. In addition, parylene C offers improved chemical resistance compared to the basic parylene grade (parylene N), making it suitable for applications that involve exposure to harsh environments. Parylene VT4, poly(tetrafluoro-p-xylylene), also categorized as fluorinated parylene or parylene F, incorporates fluorine atoms within its aromatic sites. Fluorinated parylene grades are known to exhibit superior thermal stability and possess a low dielectric constant [22,36].

SiO x Finish Coatings
Silicon oxide (SiO x ) layers were obtained by dissociating a precursor called hexamethyldisiloxane (HMDSO) precursor and oxygen (O 2 ) gas molecules using a capacitivelycoupled high-frequency plasma at 13.56 MHz. By adjusting the ratio of O 2 to HMDSO, the wettability properties of the coating layer could be modified. The O 2 /HMDSO ratio allowed for the transformation of the layer's composition from purely inorganic to a Polymers 2023, 15, 3559 4 of 13 more polymer-like layer due to the incorporation of organic groups from the HMDSO precursor [37]. In this study, a ratio of 10:1 was used for the SiO x coating, similar to the layer developed by Hogg et al. [38].

In Vitro Encrustation Test
Chemically defined synthetic urine was prepared according to Griffith et al. [39]. Solutions A and B, described in Table 1, were prepared with distinct amounts of different salt components (Carl Roth GmbH, Karlsruhe, Germany). Solution A was supplemented with urease (Merck KGaA, Darmstadt, Germany) to induce the crystallization process. The following chemical equations explain the development of struvite (so-called infection stones). Urease triggers the hydrolysis of the urea, producing ammonia. The increase in urinary pH leads to increased precipitation of calcium and magnesium phosphate.
The temperature in the incubation system was set to 37 • C. The incubation system simulates the physiological conditions of a urinary bladder. A 500 mL bioreactor is used to simulate the physiological conditions in the urinary bladder. The typical filling volume of a human urinary bladder is estimated at 300 to 500 mL. The urine is well mixed by natural human movements and detrusor contractions. Natural micturition occurs in response to the filling pressure in the urinary bladder and by neuronal reflexes [40,41]. For our investigations, mixing was performed with the help of a magnetic stirrer with 80 revolutions per minute. Every 4 h 250 mL of synthetic urine was exchanged and every 24 h the medium was completely replaced. An experimental period of 7 days was allowed for each study. Catheterization every 4 h is recommended in the urological practice for patients with neurogenic bladder emptying disorders and residual urine in the urinary bladder should be expected. In preparation for a clinical study to analyze encrustations and biofilm on urinary bladder implants, in vitro studies were performed in the research department of Urology, Rostock University Medical Center and the parameters used in this study were determined by Buchholz et al. [42]. The encrustations were quantitatively analyzed by measuring the weight of the silicon wafer samples before and after the experiment. Samples were dried at 37 • C for 3 days to ensure that all residual liquid had evaporated.

Fourier Transform Infrared Spectroscopy
Encrustations deposited on silicon wafer samples were dried before the analysis and were ground in an agate mortar. The analysis of the implants was done by polarized light microscopy (BX43 Olympus, Hamburg, Germany) and the Urinary Stone Analyzer Fourier transform infrared spectrometry system FTIR ALPHA (Bruker, Billerica, MA, USA). Spectra were recorded between 2000 and 400 cm −1 (resolution 2 cm −1 ) for 120 scans and compared to the OPUS™ reference library, Version 7.5 (Bruker, Billerica, MA, USA). Semi-quantitative results were recorded in percentages. The qualitative analysis was based on the comparison of the spectrum of a sample with the spectrum of the reference material.

Contact Angle
Surface wettability was determined by the sessile drop method using the Drop Shape Analyzer-DSA25 (Krüss, Hamburg, Germany) [43]. One µL drop of distilled water and synthetic urine (pH 6.4; for formulation see Section 2.2) were deposited on the silicon wafer sample surface (n = 2 at 5 drops each). Distilled water and synthetic urine contact angle values were calculated with the supplied software (ADVANCE, V.1.7.2.1, Krüss, Hamburg, Germany) via Young's equation and the surface free energy according to Owens, Wendt, Rabel, and Kaelble (OWRK).

Surface Charge
Zeta potential measurements were conducted on wafer samples (2 × 1 cm) using the SurPASS system (Anton Paar, Ostfildern, Germany) to determine the surface charge. Silicon wafer samples were mounted with a gap height of 100 µm between the two samples. The measurements were performed in 0.001 mol/L KCl solution ranging from pH 5.0 to 8.0. The streaming current was determined depending on the pressure (max. 400 mbar). Finally, the zeta potential was calculated according to the method of Helmholtz-Smoluchowski. Measurements on each surface were performed in quadruplicate on three independent sample pairs.

In Vitro Encrustation Test
The formation of urinary stones in vivo depends on a variety of factors, such as pH, protein excretion, the presence of foreign material, bacterial infections, or dietary habits. Therefore, in vitro encrustation models have been developed to enable systematic studies that could contribute to a deeper understanding of the problem. We built our in vitro encrustation system based on this knowledge and used synthetic urine introduced by Griffith [39]. In this approach, two different unsaturated solutions were pumped into a bioreactor in which the polymer samples were placed. The initial pH of the synthetic urine was 5.5 and over time, the urease decomposed the urea into carbon dioxide and ammonia. This caused the pH to shift to the alkaline range, resulting in the precipitation of salt crystals. The rate of pH increase was caused by the urease reaction. The pH value reached the equilibrium state at a pH of 8.9. The encrustation mass was normalized, and each group comprised 4 samples. The mass of the samples with identical surface areas was measured before and after synthetic urine immersion. The normal distribution within each group was assessed using the Shapiro-Wilk test [44]. To compare the data groups, a two-tailed, unpaired Welch's t-test was performed, revealing statistically significant differences (p < 0.05). The data analysis was conducted using R software version 4.2.2 [45,46]. Figure 1 illustrates the results of the encrustation test, indicating the encrustation mass (mg) measured. The data is categorized based on different parylene grades and further classified according to the type of finish coating applied. For parylene C, the mean value of the encrustation mass is measured at 9.55 mg. In the case of parylene VT4, the encrustation decreases to 7.5 mg when the parylene comes into direct contact with synthetic urine ("No Finish" group). When parylene is covered with a SiO x finish coating, the encrustation levels decrease further to 5.23 mg and 4.15 mg for parylene C and VT4, respectively.

Fourier Transform Infrared Spectroscopy
Encrustations are mostly mixtures of substances. Depending on the excited vi tional and rotational states of the molecules, characteristic absorptions were measured ing Fourier transform infrared spectrometry. For an accurate qualitative and quantita analysis, suitable reference substances and mixtures must be available (OPUSTM libr Bruker Optik GmbH, Ettlingen, Germany). The qualitative analysis was based on the c parison of the spectrum of a sample with the spectrum of the reference material. The m ured absorption spectra of the mineral deposits are illustrated by the blue curve, while absorption spectra of the OPUS reference library are shown in red.

Fourier Transform Infrared Spectroscopy
Encrustations are mostly mixtures of substances. Depending on the excited vibrational and rotational states of the molecules, characteristic absorptions were measured using Fourier transform infrared spectrometry. For an accurate qualitative and quantitative analysis, suitable reference substances and mixtures must be available (OPUSTM library, Bruker Optik GmbH, Ettlingen, Germany). The qualitative analysis was based on the comparison of the spectrum of a sample with the spectrum of the reference material. The measured absorption spectra of the mineral deposits are illustrated by the blue curve, while the absorption spectra of the OPUS reference library are shown in red.
FTIR analysis of the encrustations confirms that calcium oxalate (whewellite and weddellite), phosphate crystals (struvite, brushite, and apatite), and protein are major constituents and correlate well with the studies on human implants [47][48][49]. The FTIR analysis of urine encrustation depicted by the blue curve in Figure 2 consists of ammonium magnesium phosphate hexahydrate (struvite), carbonate apatite (dahlite), and calcium oxalate dihydrate (weddellite), with a compound ratio of 70, 20, and 10%, respectively. The hit quality with respect to the reference curve, red curve, is 968.

Fourier Transform Infrared Spectroscopy
Encrustations are mostly mixtures of substances. Depending on the excited vibrational and rotational states of the molecules, characteristic absorptions were measured using Fourier transform infrared spectrometry. For an accurate qualitative and quantitative analysis, suitable reference substances and mixtures must be available (OPUSTM library, Bruker Optik GmbH, Ettlingen, Germany). The qualitative analysis was based on the comparison of the spectrum of a sample with the spectrum of the reference material. The measured absorption spectra of the mineral deposits are illustrated by the blue curve, while the absorption spectra of the OPUS reference library are shown in red.
FTIR analysis of the encrustations confirms that calcium oxalate (whewellite and weddellite), phosphate crystals (struvite, brushite, and apatite), and protein are major constituents and correlate well with the studies on human implants [47][48][49]. The FTIR analysis of urine encrustation depicted by the blue curve in Figure 2 consists of ammonium magnesium phosphate hexahydrate (struvite), carbonate apatite (dahlite), and calcium oxalate dihydrate (weddellite), with a compound ratio of 70, 20, and 10%, respectively. The hit quality with respect to the reference curve, red curve, is 968.

Contact Angle
The contact angle serves as a measure to characterize the hydrophilicity or hydrophobicity of a material. Typically, materials with a contact angle of <90 • are labeled as hydrophilic, while those with a contact angle >90 • are considered hydrophobic [50]. To closely emulate the in vivo conditions and to consider the potential impact of the solution on surface wettability, contact angle measurements using synthetic urine (hatched columns), as described earlier, and distilled water for reference measurements were conducted. Illustrated in Figure 3, the findings indicate that parylene C exhibits a lower water contact angle compared to parylene VT4, 91.9 • (±2.1) and 94.7 • (±1.6), respectively. This distinction is also observed when synthetic urine is used as the test liquid, 86.7 • (±1.8) for parylene C and 95.1 • (±2.7) for parylene VT4. Although the values obtained with synthetic urine differ slightly from those obtained with distilled water, both solutions confirm that parylene C possesses a more hydrophilic surface compared to parylene VT4. Furthermore, the application of a finish SiO x coating leads to significantly lower contact angle values of 56.7 • (±3.6) and 54.1 • (±2.7) for distilled water and synthetic urine, respectively. It has to be noted that the SiO x layer contact angle changed after several days of water immersion stabilizing at 71.5 • (±2.2). hexahydrate (struvite), carbonate apatite (dahlite), and calcium oxalate dihydrate (weddel a compound ratio of 70, 20, and 10%, respectively.

Contact Angle
The contact angle serves as a measure to characterize the hydrophilicity or phobicity of a material. Typically, materials with a contact angle of <90° are lab hydrophilic, while those with a contact angle >90° are considered hydrophobic closely emulate the in vivo conditions and to consider the potential impact of the on surface wettability, contact angle measurements using synthetic urine (hatch umns), as described earlier, and distilled water for reference measurements w ducted. Illustrated in Figure 3, the findings indicate that parylene C exhibits a low contact angle compared to parylene VT4, 91.9° (±2.1) and 94.7° (±1.6), respective distinction is also observed when synthetic urine is used as the test liquid, 86.7° ( parylene C and 95.1° (±2.7) for parylene VT4. Although the values obtained with s urine differ slightly from those obtained with distilled water, both solutions confi parylene C possesses a more hydrophilic surface compared to parylene VT4. Furth the application of a finish SiOx coating leads to significantly lower contact angle v 56.7° (±3.6) and 54.1° (±2.7) for distilled water and synthetic urine, respectively. be noted that the SiOx layer contact angle changed after several days of water im stabilizing at 71.5° (±2.2).

Surface Charge
The Zeta potential of the coated silicon wafer sample surfaces was measured range from 5.5 to 7.5 (see Appendix A, Figure A1). Specifically, the zeta potential pH 6.4, representing the average urine pH of healthy humans, was then extract the measurements. These results are presented and illustrated in Figure 4 for par VT4 films, and SiOx coating.

Surface Charge
The Zeta potential of the coated silicon wafer sample surfaces was measured in a pH range from 5.5 to 7.5 (see Appendix A, Figure A1). Specifically, the zeta potential value at pH 6.4, representing the average urine pH of healthy humans, was then extracted from the measurements. These results are presented and illustrated in Figure 4 for parylene C, VT4 films, and SiO x coating.
Zeta potential measurements detected negative charges for all examined materials. As depicted in Figure 4, within the characteristic pH value of 6.4, the parylene C coating demonstrates a more negative value of −65.0 mV (±3.3) when compared to parylene VT4, which displays −55.7 mV (±3.6). The SiO x coating exhibits a charge value of −51.9 mV (±3), making it the least negatively charged sample among all tested coatings. The complete data set of zeta potential measurements across the pH range of 5.5-7.5 are presented in Appendix A.  Zeta potential measurements detected negative charges for all examined materials. As depicted in Figure 4, within the characteristic pH value of 6.4, the parylene C coating demonstrates a more negative value of −65.0 mV (±3.3) when compared to parylene VT4, which displays −55.7 mV (±3.6). The SiOx coating exhibits a charge value of −51.9 mV (±3), making it the least negatively charged sample among all tested coatings. The complete data set of zeta potential measurements across the pH range of 5.5-7.5 are presented in Appendix A.

Discussion
As demonstrated in former studies, parylene-based encapsulation, and in particular parylene C grade, is considered a well-adapted solution for biomedical applications [20,21,23,51,52]. Implantation of biomaterials into the urinary tract is disadvantaged by stone formation, bacterial adherence and, ultimately, encrustation through biofilm formation resulting from a multifactorial disturbance of the delicate balance between numerous physico-chemical and biochemical processes [53,54]. Non-infectious stone formation and encrustation usually result from metabolic imbalances, often on the tubular level. In contrast, infectious stone formation and biofilm-induced encrustation are linked to the enzymatic activity of bacteria. The best known are urease-producing species, such as proteus mirabilis, which increase the pH of the urine. This alkalization, in turn, decreases the solubility of urinary calcium and magnesium salts and thus facilitates the encrustation [1,55]. From the implant functionality perspective, encrustation can lead to reduced sensitivity, measurement drift, implant dysfunction, or complete implant failure [56]. As the encrustation builds up, it can create a barrier between the implant and its surrounding environment, introducing various complications. In our case, the sensitivity of the MEMS sensors used for monitoring pressure can be impacted negatively due to the encrustation. When encrusted, the implant's sensing capabilities may be altered or distorted. This reduction in sensitivity can cause inaccurate readings or measurements. Encrustation can also lead to measurement drifts or fluctuations caused by the alteration of the encrusted implant surface. Consequently, the reliability and accuracy of the measurements may deteriorate, making it challenging to obtain consistent data for long-term analysis or monitoring purposes [14].
The first phase of our investigations involved conducting urinary encrustation tests to evaluate the efficacy of different parylene films. Our aim was to use a reproducible in vitro system that simulates the in vivo infection situation realistically. To ensure this, we used defined amounts of urease instead of adding urease-producing bacteria. Furthermore, the quality and quantity of encrustations depend on the protein amount, which is

Discussion
As demonstrated in former studies, parylene-based encapsulation, and in particular parylene C grade, is considered a well-adapted solution for biomedical applications [20,21,23,51,52]. Implantation of biomaterials into the urinary tract is disadvantaged by stone formation, bacterial adherence and, ultimately, encrustation through biofilm formation resulting from a multifactorial disturbance of the delicate balance between numerous physico-chemical and biochemical processes [53,54]. Non-infectious stone formation and encrustation usually result from metabolic imbalances, often on the tubular level. In contrast, infectious stone formation and biofilm-induced encrustation are linked to the enzymatic activity of bacteria. The best known are urease-producing species, such as proteus mirabilis, which increase the pH of the urine. This alkalization, in turn, decreases the solubility of urinary calcium and magnesium salts and thus facilitates the encrustation [1,55]. From the implant functionality perspective, encrustation can lead to reduced sensitivity, measurement drift, implant dysfunction, or complete implant failure [56]. As the encrustation builds up, it can create a barrier between the implant and its surrounding environment, introducing various complications. In our case, the sensitivity of the MEMS sensors used for monitoring pressure can be impacted negatively due to the encrustation. When encrusted, the implant's sensing capabilities may be altered or distorted. This reduction in sensitivity can cause inaccurate readings or measurements. Encrustation can also lead to measurement drifts or fluctuations caused by the alteration of the encrusted implant surface. Consequently, the reliability and accuracy of the measurements may deteriorate, making it challenging to obtain consistent data for long-term analysis or monitoring purposes [14].
The first phase of our investigations involved conducting urinary encrustation tests to evaluate the efficacy of different parylene films. Our aim was to use a reproducible in vitro system that simulates the in vivo infection situation realistically. To ensure this, we used defined amounts of urease instead of adding urease-producing bacteria. Furthermore, the quality and quantity of encrustations depend on the protein amount, which is why we decided to optimize our system and use albumin in a concentration of 333 mg/L, resembling a macroalbuminuria in our in vitro system [57]. Urinary encrustations consist of a mixture of crystals. In clinical practice, according to the guidelines for diagnosis, therapy, and metaphylaxis of urolithiasis, FTIR is recommended as a method for the urinary analysis of encrustations. The comparison of the analyzed crystal compounds with real combinations of urinary stones ensured the presence of urinary encrustation on tested samples. Among the parylene tested, grade C exhibited slightly less efficiency in preventing encrustation compared to grade VT4. However, when compared to other polymeric materials, parylene films present excellent results. Rebl et al. [58] investigated different polymers in a systematic screening approach to determine which surface parameter properties indicate low encrustation properties. The study showed that the most promising tested candidates for preventing encrustation on ureteral stents were a thermoplastic urethane, Elastollan 1185A 10 FC and a styrene-butadiene copolymer, Styroflex 2G 66, with 2.4% and 2.1% of mass encrustation, respectively. In comparison, parylene C and VT4 only exhibited an encrustation mass of 9.55 mg and 7.5 mg, which corresponds to a percentage of 2.2% and 1.7%, respectively, making them attractive options for encrustation prevention. Particularly, parylene-based encapsulation solutions prove to be an outstanding choice due to their properties, such as excellent barrier performance, thermal stability, pinhole-free coating, and biocompatibility. Furthermore, we observed that the addition of a SiO x layer to the coatings significantly improved their efficiency in preventing encrustation. This finding suggests that surface coatings might hold the key to enhancing encrustation prevention even further, reaching 5.23 mg and 4.15 mg of encrustation mass when parylene C and VT4, respectively, are covered with a finish coating of SiO x . Considering that the hydrophobicity of a surface can significantly influence interactions with surrounding fluids and substances, we next explored the contact angles of the coatings. Both parylene C and VT4 displayed comparable contact angles, indicating a slight hydrophobic nature. On the other hand, SiO x showed a notably strong hydrophilic character. Lastly, we analyzed the zeta potential of the coatings, which is a crucial factor affecting surface charge and interactions with surrounding substances. Parylene C exhibited the most negatively charged surface, possessing a zeta potential of −65 mV. In contrast, both parylene VT4 film and SiO x coating displayed similar zeta potential values, ranging from 55 to 52 mV. Interestingly, we discovered that the zeta potential alone does not entirely explain the encrustation results. While parylene C demonstrated a strong negative zeta potential, indicating heightened repulsion forces, it did not directly correlate with more effective prevention of encrustation. This finding partially aligns with the assumption discussed by Rebl et al. [58], suggesting that a negative surface charge of about −60 mV was the most suitable for use as stent materials, as the deposition of crystalline biofilms was minimized. It could be hypothesized that an excessively negative surface (inferior to −60 mV) may not be advantageous in preventing encrustation. Furthermore, our investigations into zeta potential and contact angle indicate that hydrophobicity might play a more essential role than zeta potential in explaining the differences in encrustation results among the coatings. This leads us to consider other chemical and physical surface properties that are potential contributing factors in the encrustation prevention mechanism. Additionally, the results revealed that the interaction of various surface properties, rather than individual factors, may hold the key to understanding and optimizing encrustation prevention. Further developments and characterizations have to be conducted to explore the exact mechanisms governing encrustation.
When considering encapsulation materials for in vivo implants or sensors, it was found that biocompatible parylene films alone demonstrate interesting barrier properties, even when in direct contact with fluids [59]. However, the barrier performance can be improved by several orders of magnitude once parylene is combined with inorganic thin films to build up multilayer structures [25,38,60,61]. A multilayer parylene-based barrier can prevent the penetration of moisture, gases, chemicals, and other contaminants that can degrade sensor performance for long-term implantation. Moreover, parylene-based encapsulation, deposited through a vapor-phase process, results in a uniform, conformal and pinhole-free coating. It can cover high-aspect ratio geometries, ensuring uniform encapsulation of 3D devices. This capability is particularly beneficial for MEMS sensors, which often have complex microstructures that need protection. Furthermore, the parylenebased solution can as well be considered an optimal solution for electronic sensors that may be exposed to a wide range of operating temperatures, due to its excellent thermal stability [22,62], combined with effective electrical insulator properties [36,63].

Conclusions
In conclusion, our investigations in encrustation prevention and the properties of parylene thin films highlighted the suitability of parylene as an encapsulation solution for biomedical and, more precisely, for urological applications. Parylene-based coatings, with their barrier properties, conformal deposition capability, thermal stability, biocompatibility, and electrical insulation, prove to be very promising candidates for sensor protection. The study demonstrated that parylene films can effectively protect urological MEMS sensors from adverse effects, and the SiO x finish coating additionally enhances the efficiency of the parylene-based encapsulation in preventing encrustation, suggesting the potential of composite coatings to optimize sensor protection even further. Understanding to a certain level the interaction of surface properties, such as surface charge and wettability, contributes to improving the development of surface treatments or finish coatings for encrustation prevention. Finally, a parylene-based solution stands out for its exceptional intrinsic properties, making it an outstanding choice for long-term urological implant encapsulation and effectively preventing encrustation.

Data Availability Statement:
The data presented in this study are available on request from the corresponding author.

Conflicts of Interest:
The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. Figure A1 presents the measured zeta potential values for a pH from 5.5 to 7.5 for parylene C, VT4 films, and SiO x coating. After conducting measurements on each coating, it is evident that all of them exhibited a negative charge. However, there are noticeable differences in the slopes of the charge curves between parylene C ( Figure A1a) and parylene VT4 ( Figure A1b). For instance, parylene C displayed a significantly steeper slope. Figure A1c illustrates the measurement results for the SiOx coating, which shows a lower slope compared to the other two coatings. After conducting measurements on each coating, it is evident that all of them exhibited a negative charge. However, there are noticeable differences in the slopes of the charge curves between parylene C ( Figure A1a) and parylene VT4 ( Figure A1b). For instance, parylene C displayed a significantly steeper slope. Figure A1c illustrates the measurement results for the SiO x coating, which shows a lower slope compared to the other two coatings.