Hot Embossing to Fabricate Parylene-Based Microstructures and Its Impact on the Material Properties.

This study aims to establish and optimize a process for the fabrication of 3D microstructures of the biocompatible polymer Parylene C using hot embossing techniques. The different process parameters such as embossing temperature, embossing force, demolding temperature and speed, and the usage of a release agent were optimized, utilizing adhesive micropillars as a use case. To enhance compatibility with conventional semiconductor fabrication techniques, hot embossing of Parylene C was adapted from conventional stainless steel substrates to silicon chip platforms. Furthermore, this adaptation included an investigation of the effects of the hot embossing process on metal layers embedded in the Parylene C, ensuring compatibility with the ultra-thin Parylene printed circuit board (PCB) demonstrated previously. To evaluate the produced microstructures, a combination of characterization methods was employed, including light microscopy (LM) and scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and Fourier-transform infrared spectroscopy (FTIR). These methods provided comprehensive insights into the morphological, chemical, and structural properties of the embossed Parylene C. Considering the improved results compared to existing patterning techniques for Parylene C like plasma etching or laser ablation, the developed hot embossing approach yields a superior structural integrity, characterized by increased feature resolution and enhanced sidewall smoothness. These advancements render the method particularly suitable for diverse applications, including but not limited to, sensor optical components, adhesive interfaces for medical wearables, and microfluidic systems.

Evaluation of the Impact of Parylene C Deposition Method on the Functional Properties of Fabrics.

The article presents the results of research on the impact of the use of an original, innovative method of deposition of Parylene C on the functional properties of fabrics with various potential applications (e.g., thermal and chemical protective clothing, packaging, covers and others). Verification of the effects of the method used was based on interdisciplinary research taking into account the impact of coating fabrics on changes in their structure (micro-CT), surface properties (contact angle), barrier properties (water and chemical liquid wetting), electrostatic properties (charge decay), biophysical properties describing heat and mass transfer (by the Alambeta system and thermal imaging) and flammable properties. Four fabrics made of synthetic organic fibres (meta-aramid, para-aramid) and natural inorganic fibres (basalt) were selected for testing. Given the complex structure of textile substrates, the results confirmed that the two assumed thicknesses of the Parylene C coating were consistent with the actual measurements. The findings indicated that the coatings significantly reduced water and acid absorption in the fabrics compared to unmodified ones. Thermal insulation property tests revealed that coated fabrics exhibited higher thermal conductivity than unmodified fabrics. Additionally, the presence of Parylene C on aramid fabrics resulted in a modest increase in their ignition resistance.

Parylene C Coating Efficacy Studies: Enhancing Biocompatibility of 3D Printed Polyurethane Parts for Biopharmaceutical and CGT Applications.

Additive manufacturing, particularly Vat photopolymerization, presents a promising technique for producing complex, tailor-made structures, making it an attractive option for generating single-use components used in biopharmaceutical manufacturing equipment or cell culture devices. However, the potential leaching of cytotoxic compounds from Vat photopolymer resins poses a significant concern, especially regarding cell growth and viability in cell culture applications. This study explores the potential of parylene C coating to enhance the inertness of a polyurethane-based photopolymer resin, aiming to prevent cytotoxicity and improve biocompatibility. The study includes an analysis of extractables from the resin and photoinitiator to evaluate the resin's composition and to define selected marker compounds for investigating the coating efficiency. The time-dependent accumulation of relevant extractable compounds over a 70-day period are assessed to address the long-term use of the coated components. The impact of irradiation on the material and the coating was evaluated, along with an accelerated aging study to address the long-term performance of the coating. Biocompatibility in terms of in vitro cell growth studies is evaluated using Chinese hamster ovary cells, a standard cell line in biopharmaceutical manufacturing. Results demonstrate that parylene C coating significantly reduces the release of cytotoxic compounds, such as the photoinitiator diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (TPO). Although accelerated aging indicates a reduction in the barrier properties of the coating over time, the parylene C coating still effectively slows the release of extractables and significantly improves cell compatibility of the 3D printed parts. The findings suggest that parylene C-coated components can be safely integrated into biopharmaceutical manufacturing processes, with recommendations to minimize storage times between coating application and use to ensure optimal performance.

Parylene Double-Layer Coated Screen-Printed Carbon Electrode for Label-Free and Reagentless Capacitive Aptasensing of Gliadin.

Celiac patients are required to strictly adhere to a gluten-free diet because even trace amounts of gluten can damage their small intestine and leading to serious complications. Despite increased awareness, gluten can still be present in products due to cross-contamination or hidden ingredients, making regular monitoring essential. With the goal of guaranteeing food safety for consuming labeled gluten-free products, a capacitive aptasensor was constructed to target gliadin, the main allergic gluten protein for celiac disease. The success of capacitive aptasensing was primarily realized by coating a Parylene double-layer (1000 nm Parylene C at the bottom with 400 nm Parylene AM on top) on the electrode surface to ensure both high insulation quality and abundant reactive amino functionalities. Under the optimal concentration of aptamer (5 µM) used for immobilization, a strong linear relationship exists between the amount of gliadin (0.01-1.0 mg/mL) and the corresponding ΔC response (total capacitance decrease during a 20 min monitoring period after sample introduction), with an R2 of 0.9843. The detection limit is 0.007 mg/mL (S/N > 5), equivalent to 0.014 mg/mL (14 ppm) of gluten content. Spike recovery tests identified this system is free from interferences in corn and cassava flour matrices. The analytical results of 24 commercial wheat flour samples correlated well with a gliadin ELISA assay (R2 = 0.9754). The proposed label-free and reagentless capacitive aptasensor offers advantages of simplicity, cost-effectiveness, ease of production, and speediness, making it a promising tool for verifying products labeled as gluten-free (gluten content <20 ppm).

A parylene/graphene UV photodetector with ultrahigh responsivity and long term stability.

Long term stability, high responsivity, and fast response speed are essential for the commercialization of graphene photodetectors (GPDs). In this work, a parylene/graphene UV photodetector with long term stability, ultrahigh responsivity and fast response speed, is demonstrated. Parylene as a stable physical and chemical insulating layer reduces the environmental sensitivity of graphene, and enhances the performances of GPDs. In addition, utilizing bilayer electrodes reduces the buckling and damage of graphene after transferring. The parylene/graphene UV photodetector exhibits an ultrahigh responsivity of 5.82 × 105AW-1under 325 nm light irradiation at 1 V bias. Additionally, it shows a fast response speed with a rise time of 80µs and a fall time of 17µs, and a long term stability at 405 nm wavelength which is absent in the device without parylene. The parylene/graphene UV photodetector possesses superior performances. This paves the way for the commercial application of the high-performance graphene hybrid photodetectors, and provides a practical method for maintaining the long term stability of two dimensional (2D) materials.

Surface Acoustic Wave Resonator Chip Setup for the Elimination of Interfering Conductivity Responses.

A surface acoustic wave (SAW) resonator chip setup is presented that eliminates interfering signal responses caused by changes in the electrical environment of the surrounding media. When using a two-port resonator, applying electrically shielding layers between the interdigital transducers (IDTs) can be challenging due to the limited dimensions. Therefore, a layered setup consisting of an insulating polymer layer and a conductive gold layer was preferred. The SAW resonators were provided with polycarbonate housings, resulting in SAW resonator chips. This setup enables easy application of a wide range of coatings to the active part of the resonator surface, while ensuring subsequent electrical and fluidic integration of the resonator chips into a microfluidic array for measurements. The signal responses of uncoated SAW resonators and those with polymer coatings with and without a gold layer were tested with aqueous potassium chloride (KCl) solutions up to 3 mol/L, corresponding to conductivities up to 308 mS/cm. The use of a polymer coating at the thickness of the first Love mode resonance and a conductive gold layer completely reduced the electrical impact on the SAW resonator signal response, making small signals resulting from changes in viscosity and density of the KCl solutions visible.

On reactive Ion Etching of Parylene-C with Simple Photoresist Mask for Fabrication of High Porosity Membranes to Capture Circulating and Exfoliated Tumor Cells.

A high porosity micropore arrayed parylene membrane is a promising device that is used to capture circulating and exfoliated tumor cells (CTCs and ETCs) for liquid biopsy applications. However, its fabrication still requires either expensive equipment or an expensive process. Here, we report on the fabrication of high porosity (>40%) micropore arrayed parylene membranes through a simple reactive ion etching (RIE) that uses photoresist as the etching mask. Vertical sidewalls were observed in etched parylene pores despite the sloped photoresist mask sidewalls, which was found to be due to the simultaneous high DC-bias RIE induced photoresist melting and substrate pedestal formation. A theoretical model has been derived to illustrate the dependence of the maximum membrane thickness on the final pore-to-pore spacing, and it is consistent with the experimental data. A simple, yet accurate, low number (<50) cell counting method was demonstrated through counting cells directly inside a pipette tip under phase-contrast microscope. Membranes as thin as 3 µm showed utility for low number tumor cell capture, with an efficiency of 87-92%.

Complete Prevention of Bubbles in a PDMS-Based Digital PCR Chip with a Multifunction Cavity.

In a chamber-based digital PCR (dPCR) chip fabricated with polydimethylsiloxane (PDMS), bubble generation in the chambers at high temperatures is a critical issue. Here, we found that the main reason for bubble formation in PDMS chips is the too-high saturated vapor pressure of water at an elevated temperature. The bubbles should be completely prevented by reducing the initial pressure of the system to under 13.6 kPa to eliminate the effects of increased-pressure water vapor. Then, a cavity was designed and fabricated above the PCR reaction layer, and Parylene C was used as a shell covering the chip. The cavity was used for the negative generator in sample loading, PDMS degassing, PCR solution degassing in the digitization process and water storage in the thermal reaction process. The analysis was confirmed and finally achieved a desirable bubble-free, fast-digitization, valve-free and no-tubing connection dPCR.

Ultrathin Parylene C-based sensitivity-gain nanoplasmonic sensor integrated on VCSEL for Aß42 detection.

As Alzheimer's disease prevalence continues to rise, there is an increasing demand for efficient on-chip biosensors capable of early biomarker detection. This study presents a novel biosensor chip leveraging vertical cavity surface emitting laser (VCSEL) technology, with Parylene C serving as the antibody coupling layer and utilizing a streamlined one-step antibody modification method. Integration of Parylene C enhances chip sensitivity from 34.28 µW/RIU to 40.32 µW/RIU. Moreover, post-testing removal of Parylene C enables chip reusability without significant alteration of results. The sensor demonstrates effective detection of Aß42, an Alzheimer's biomarker, exhibiting a linear range of 1-200 ng/mL and a detection limit of 0.26 ng/mL. These findings underscore the reusability and reliability of the ultrathin Parylene C-based VCSEL biosensor chip, highlighting its potential for point-of-care Alzheimer's disease diagnosis.

Fabrication of Zigzag Parylene Nanofibers in Liquid Crystals with Electric Field-Induced Defect Structures.

Liquid crystals (LCs) have been adopted to induce tunable physical properties that dynamically originated from their unique intrinsic properties responding to external stimuli, such as surface anchoring condition and applied electric field, which enables them to be the template for aligning functional guest materials. We fabricate the fiber array from the electrically modulated (in-plain) nematic LC template using the chemical vapor polymerization (CVP) method. Under an electric field, an induced defect structure with a winding number of -1/2 contains a periodic zigzag disclination line. It is known that LC defect structures can trap the guest materials, such as particles and chemicals. However, the resulting fibers grow along the LC directors, not trapped in the defects. To show the versatility of our platform, nanofibers are fabricated on patterned electrodes representing the alphabets 'CVP.' In addition, the semifluorinated moieties are added to fibers to provide a hydrophobic surface. The resultant orientation-controlled fibers will be used in controllable smart surfaces that can be used in sensors, electronics, photonics, and biomimetic surfaces.

Nationwide multicenter study on adverse events associated with a patency capsule: Additional survey of appropriate use of patency capsule study.

BACKGROUND AND AIM: The PillCam patency capsule (PC) without a radio frequency identification tag was released to preclude retention of the small bowel capsule endoscope (CE) in Japan in 2012. We conducted a multicenter study to determine tag-less PC-related adverse events (AEs). METHODS: We first conducted a retrospective survey using a standardized data collection sheet for the clinical characteristics of PC-related AEs among 1096 patients collected in a prospective survey conducted between January 2013 and May 2014 (Cohort 1). Next, we retrospectively investigated additional AEs that occurred before and after Cohort 1 within the period June 2012 and December 2014 among 1482 patients (Cohort 2). RESULTS: Of the 2578 patients who underwent PC examinations from both cohorts, 74 AEs occurred among 61 patients (2.37%). The main AEs were residual parylene coating in 25 events (0.97%), PC-induced small bowel obstruction, suspicious of impaction, in 23 events (0.89%), and CE retention even after patency confirmation in 10 events (0.39%). Residual parylene coating was significantly associated with Crohn's disease (P < 0.01). Small bowel obstruction was significantly associated with physicians with less than 1 year of experience handling the PC and previous history of postprandial abdominal pain (P < 0.01 and P < 0.03, respectively). CE retention was ascribed to erroneous judgment of PC localization in all cases. CONCLUSIONS: This large-scale multicenter study provides evidence supporting the safety and efficiency of a PC to preclude CE retention. Accurate PC localization in patients without excretion and confirmation of previous history of postprandial abdominal pain before PC examinations is warranted (UMIN000010513).

Feasibility of Parylene C for encapsulating piezoelectric actuators in active medical implants.

Parylene C is well-known as an encapsulation material for medical implants. Within the approach of miniaturization and automatization of a bone distractor, piezoelectric actuators were encapsulated with Parylene C. The stretchability of the polymer was investigated with respect to the encapsulation functionality of piezoelectric chips. We determined a linear yield strain of 1% of approximately 12-µm-thick Parylene C foil. Parylene C encapsulation withstands the mechanical stress of a minimum of 5×105 duty cycles by continuous actuation. The experiments demonstrate that elongation of the encapsulation on piezoelectric actuators and thus the elongation of Parylene C up to 0.8 mm are feasible.

Reliable Memristive Synapses Based on Parylene-MoOx Nanocomposites for Neuromorphic Applications.

Memristive devices, known for their nonvolatile resistive switching, are promising components for next-generation neuromorphic computing systems, which mimic the brain's neural architecture. Specifically, these devices are well-suited for functioning as artificial synapses due to their analogue tunability and low energy consumption. However, the improvement of their performance and reliability remains a pressing challenge. In this study, we report the development and comprehensive characterization of memristive devices based on a parylene-MoOx (PPX-Mo) nanocomposite layer, which exhibit improved characteristics over their parylene-based counterparts: lower switching voltage and energy, smaller dispersion, and better resistive plasticity. A robust statistical analysis identified the optimal synthesis parameters for these devices, providing valuable insights for future device optimization. The most probable resistive switching mechanism of the devices is proposed. By successfully integrating these memristors into a neuromorphic computing model and showcasing their scalability in crossbar geometry, we demonstrate their potential as functional artificial synapses. The results obtained from this study can be useful for the development of hardware-brain-inspired computational systems.

Defect-Passivated Photosensor Based on Cesium Lead Bromide (CsPbBr3) Perovskite Quantum Dots for Microbial Detection.

A defect-passivated photosensor based on cesium lead bromide (CsPbBr3) perovskite quantum dots (QD) was fabricated using parylene films, and the photosensor was applied for the microbial detection. The CsPbBr3 perovskite QDs were synthesized to be homogeneous in size under thermodynamic control, and the perovskite QD-based photosensor was fabricated using MoS2 flakes as the electron transfer layer. In this work, a parylene film with functional groups was deposited on a photosensor for physical protection (waterproof) and defect (halide vacancy) passivation of the perovskite QD. As the first effect of the parylene film, the physical protection of the perovskite QD from water was estimated by comparing the photosensor performance after incubation in water. As the second effect of the parylene, the interaction between the functional groups of the parylene film and the halide vacancies of the perovskite QDs was investigated through the bandgap, crystal structure, and trap-state density analysis. Additionally, density functional theory analysis on Mulliken charges, lattice parameters, and Gibbs free energy demonstrated the effect of the defect passivation by parylene films. Finally, the parylene-passivated QD-based photosensor was applied to the detection of two kinds of food-poisoning and gastroduodenal disease bacteria (Listeria monocytogenes and Helicobacter pylori).

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.

Immunohistological responses in mice implanted with Parylene HT - ITO ECoG devices.

Transparent epidural devices that facilitate the concurrent use of electrophysiology and neuroimaging are arising tools for neuroscience. Testing the biocompatibility and evoked immune response of novel implantable devices is essential to lay down the fundamentals of their extensive application. Here we present an immunohistochemical evaluation of a Parylene HT/indium-tin oxide (ITO) based electrocorticography (ECoG) device, and provide long-term biocompatibility data at three chronic implantation lengths. We implanted Parylene HT/ITO ECoG devices epidurally in 5 mice and evaluated the evoked astroglial response, neuronal density and cortical thickness. We found increased astroglial response in the superficial cortical layers of all mice compared to contralateral unimplanted controls. This difference was largest at the first time point and decreased over time. Neuronal density was lower on the implanted side only at the last time point, while cortical thickness was smaller in the first and second time points, but not at the last. In this study, we present data that confirms the feasibility and chronic use of Parylene HT/ITO ECoG devices.

Functionalized Parylene Films for Enhancement of Antibody Production by Hybridoma Cells.

In this study, the influence of microenvironments on antibody production of hybridoma cells was analyzed using six types of functionalized parylene films, parylene-N and parylene-C (before and after UV radiation), parylene-AM, and parylene-H, and using polystyrene as a negative control. Hybridoma cells were cultured on modified parylene films that produced a monoclonal antibody against the well-known fungal toxin ochratoxin-A. Surface properties were analyzed for each parylene film, such as roughness, chemical functional groups, and hydrophilicity. The proliferation rate of the hybridoma cells was observed for each parylene film by counting the number of adherent cells, and the total amount of produced antibodies from different parylene films was estimated using indirect ELISA. In comparison with the polystyrene, the antibody-production by parylene-H and parylene-AM was estimated to be observed to be as high as 210-244% after the culture of 24 h. These results indicate that the chemical functional groups of the culture plate could influence antibody production. To analyze the influence of the microenvironments of the modified parylene films, we performed cell cycle analysis to estimate the ratio of the G0/G1, S, and G2/M phases of the hybridoma cells on each parylene film. From the normalized proportion of phases of the cell cycle, the difference in antibody production from different surfaces was considered to result from the difference in the proliferation rate of hybridoma cells, which occurred from the different physical and chemical properties of the parylene films. Finally, protein expression was analyzed using an mRNA array to determine the effect of parylene films on protein expression in hybridoma cells. The expression of three antibody production-related genes (CD40, Sox4, and RelB) was analyzed in hybridoma cells cultured on modified parylene films.

A bio-instructive parylene-based conformal coating suppresses thrombosis and intimal hyperplasia of implantable vascular devices.

Implantable vascular devices are widely used in clinical treatments for various vascular diseases. However, current approved clinical implantable vascular devices generally have high failure rates primarily due to their surface lacking inherent functional endothelium. Here, inspired by the pathological mechanisms of vascular device failure and physiological functions of native endothelium, we developed a new generation of bioactive parylene (poly(p-xylylene))-based conformal coating to address these challenges of the vascular devices. This coating used a polyethylene glycol (PEG) linker to introduce an endothelial progenitor cell (EPC) specific binding ligand LXW7 (cGRGDdvc) onto the vascular devices for preventing platelet adhesion and selectively capturing endogenous EPCs. Also, we confirmed the long-term stability and function of this coating in human serum. Using two vascular disease-related large animal models, a porcine carotid artery interposition model and a porcine carotid artery-jugular vein arteriovenous graft model, we demonstrated that this coating enabled rapid generation of self-renewable "living" endothelium on the blood contacting surface of the expanded polytetrafluoroethylene (ePTFE) grafts after implantation. We expect this easy-to-apply conformal coating will present a promising avenue to engineer surface properties of "off-the-shelf" implantable vascular devices for long-lasting performance in the clinical settings.

Characterization of thin film Parylene C device curvature and the formation of helices via thermoforming.

In microfabricated biomedical devices, flexible, polymer substrates are becoming increasingly preferred over rigid, silicon substrates because of their ability to conform to biological tissue. Such devices, however, are fabricated in a planar configuration, which results in planar devices that do not closely match the shape of most tissues. Thermoforming, a process which can reshape thermoplastic polymers, can be used to transform flat, thin film, polymer devices with patterned metal features into complex three-dimensional (3D) geometries. This process extends the use of planar microfabrication to achieve 3D shapes which can more closely interface with the body. Common shapes include spheres, which can conform to the shape of the retina; cones, which can be used as a sheath to interface with an insertion stylet; and helices, which can be wrapped around nerves, blood vessels, muscle fibers, or be used as strain relief feature. This work characterizes the curvature of thin film Parylene C devices with patterned metal features built with varying Parylene thicknesses and processing conditions. Device curvature is caused by film stress in each Parylene and metal layer, which is characterized experimentally and by a mathematical model which estimates the effects of device geometry and processing on curvature. Using this characterization, an optimized process to thermoform thin film Parylene C devices with patterned metal features into 0.25 mm diameter helices while preventing cracking in the polymer and metal was developed.

Fabrication of High Aspect Ratio Nano-Channels by Thermal Nano-Imprinting and Parylene Deposition.

A low-cost method of fabrication of high aspect ratio nano-channels by thermal nano-imprinting and Parylene deposition is proposed. SU-8 photoresist nano-channels were first manufactured by thermal nano-imprinting, and Parylene deposition was carried out to reduce the width of the nano-channels and increase the aspect ratio. During the process, the side walls of the SU-8 nano-channels were covered with the Parylene film, reducing the width of the nano-channels, and the depth of the channels increased due to the thickness of the Parylene film deposited on the surface of the SU-8 nano-channels, more so than that at the bottom. The influence of Parylene mass on the size of nano-channels was studied by theoretical analysis and experiments, and the deposition pressure of Parylene was optimized. The final high aspect ratio nano-channels are 46 nm in width and 746 nm in depth, of which the aspect ratio is 16. This simple and efficient method paves the way for the production of high aspect ratio nano-channels.