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.

Wearable System Based on Ultra-Thin Parylene C Tattoo Electrodes for EEG Recording.

In an increasingly interconnected world, where electronic devices permeate every aspect of our lives, wearable systems aimed at monitoring physiological signals are rapidly taking over the sport and fitness domain, as well as biomedical fields such as rehabilitation and prosthetics. With the intent of providing a novel approach to the field, in this paper we discuss the development of a wearable system for the acquisition of EEG signals based on a portable, low-power custom PCB specifically designed to be used in combination with non-conventional ultra-conformable and imperceptible Parylene-C tattoo electrodes. The proposed system has been tested in a standard rest-state experiment, and its performance in terms of discrimination of two different states has been compared to that of a commercial wearable device for EEG signal acquisition (i.e., the Muse headset), showing comparable results. This first preliminary validation demonstrates the possibility of conveniently employing ultra-conformable tattoo-electrodes integrated portable systems for the unobtrusive acquisition of brain activity.

An Inkjet Printed Flexible Electrocorticography (ECoG) Microelectrode Array on a Thin Parylene-C Film.

Electrocorticography (ECoG) is a conventional, invasive technique for recording brain signals from the cortical surface using an array of electrodes. In this study, we developed a highly flexible 22-channel ECoG microelectrode array on a thin Parylene film using novel fabrication techniques. Narrow (<40 µm) and thin (<500 nm) microelectrode patterns were first printed on PDMS, then the patterns were transferred onto Parylene films via vapor deposition and peeling. A custom-designed, 3D-printed connector was built and assembled with the Parylene-based flexible ECoG microelectrode array without soldering. The impedance of the assembled ECoG electrode array was measured in vitro by electrochemical impedance spectroscopy, and the result was consistent. In addition, we conducted in vivo studies by implanting the flexible ECoG sensor in a rat and successfully recording brain signals.

Cell viability and cytotoxicity of inkjet-printed flexible organic electrodes on parylene C.

This study reports on the fabrication of biocompatible organic devices by means of inkjet printing with a novel combination of materials. The devices were fabricated on Parylene C (PaC), a biocompatible and flexible polymer substrate. The contact tracks were inkjet-printed using a silver nanoparticle ink, while the active sites were inkjet-printed using a poly (3,4ethylenedioxythiophene)/polystyrene sulfonate (PEDOT:PSS) solution. To insulate the final device, a polyimide ink was used to print a thick film, leaving small open windows upon the active sites. Electrical characterization of the final device revealed conductivities in the order of 103 and 102 S.cm-1 for Ag and PEDOT based inks, respectively. Cell adhesion assays performed with PC-12 cells after 96 h of culture, and B16F10 cells after 24 h of culture, demonstrated that the cells adhered on top of the inks and cell differentiation occurred, which indicates Polyimide and PEDOT:PSS inks are non-toxic to these cells. The results indicate that PaC, along with its surface-treated variants, is a potentially useful material for fabricating cell-based microdevices.

A portable multi-sensor module for monitoring external ventricular drains.

External ventricular drains (EVDs) are used clinically to relieve excess fluid pressure in the brain. However, EVD outflow rate is highly variable and typical clinical flow tracking methods are manual and low resolution. To address this problem, we present an integrated multi-sensor module (IMSM) containing flow, temperature, and electrode/substrate integrity sensors to monitor the flow dynamics of cerebrospinal fluid (CSF) drainage through an EVD. The impedimetric sensors were microfabricated out of biocompatible polymer thin films, enabling seamless integration with the fluid drainage path due to their low profile. A custom measurement circuit enabled automated and portable sensor operation and data collection in the clinic. System performance was verified using real human CSF in a benchtop EVD model. Impedimetric flow sensors tracked flow rate through ambient temperature variation and biomimetic pulsatile flow, reducing error compared with previous work by a factor of 6.6. Detection of sensor breakdown using novel substrate and electrode integrity sensors was verified through soak testing and immersion in bovine serum albumin (BSA). Finally, the IMSM and measurement circuit were tested for 53 days with an RMS error of 61.4 µL/min.

Fabrication of a Multilayer Implantable Cortical Microelectrode Probe to Improve Recording Potential.

Intracortical neural probes are a key enabling technology for acquiring high fidelity neural signals within the cortex. They are viewed as a crucial component of brain-computer interfaces (BCIs) in order to record electrical activities from neurons within the brain. Smaller, more flexible, polymer-based probes have been investigated for their potential to limit the acute and chronic neural tissue response. Conventional methods of patterning electrodes and connecting traces on a single supporting layer can limit the number of recording sites which can be defined, particularly when designing narrower probes. We present a novel strategy of increasing the number of recording sites without proportionally increasing the size of the probe by using a multilayer fabrication process to vertically layer recording traces on multiple Parylene support layers, allowing more recording traces to be defined on a smaller probe width. Using this approach, we are able to define 16 electrodes on 4 supporting layers (4 electrodes per layer), each with a 30 µm diameter recording window and 5 µm wide connecting trace defined by conventional LWUV lithography, on an 80 µm wide by 9 µm thick microprobe. Prior to in vitro and in vivo validation, the multilayer probes are electrically characterized via impedance spectroscopy and evaluating crosstalk between adjacent layers. Demonstration of acute in vitro recordings in a cerebral organoid model and in vivo recordings in a murine model indicate the probe's capability for single unit recordings. This work demonstrates the ability to fabricate smaller, more compliant neural probes without sacrificing electrode density.

Bonding methods for chip integration with Parylene devices.

Flexible electronics require more compact interconnects for next-generation devices. Polymer devices can be bonded to integrated circuit chips, but combining flexible and rigid substrates poses unique technical challenges. Existing technologies either cannot achieve the density required for modern chips or employ specialized equipment and complex processes to do so. Here, we adapt several approaches to achieve fine-pitch bonding between rigid and flexible substrates including epoxy, ultrasonic wire, and anisotropic conductive film bonding and also introduce a novel technique called polymer ultrasonic on bump (PUB) bonding. Using Parylene C devices and various rigid substrates as our model testbed systems, we investigate these four methods across a range of bond pad size and pitch by measuring yield and resistance and by subjecting devices to thermomechanical reliability tests. We demonstrate that all methods are capable of bonding fine pitch interconnects (100 µm) at low temperature (<100 °C). Additionally, we focus on PUB bonding and join a packaged chip and a bare die to Parylene devices.

Rapid lipid bilayer membrane formation on Parylene coated apertures to perform ion channel analyses.

We present a chip design allowing rapid and robust lipid bilayer (LBL) membrane formation using a Parylene coated thin silicon nitride aperture. After bilayer formation, single membrane channels can be reconstituted and characterized by electrophysiology. The ability for robust reconstitution will allow parallelization and enhanced screening of small molecule drugs acting on or permeating across the membrane channel. The aperture was realized on a microfabricated silicon nitride membrane by using standard clean-room fabrication processes. To ensure the lipid bilayer formation, the nitride membrane was coated with a hydrophobic and biocompatible Parylene layer. We tested both Parylene-C and Parylene-AF4. The contact angle measurements on both Parylene types showed very good hydrophobic properties and affinity to lipids. No precoating of the Parylene with an organic solvent is needed to make the aperture lipophilic, in contradiction to Teflon membranes. The chips can be easily placed in an array utilizing a 3D printed platform. Experiments show repetitive LBL formation and destruction (more than 6 times) within a very short time (few seconds). Through measurements we have established that the LBL layers are very thin. This allows the investigation of the fusion process of membrane proteins i.e. outer membrane protein (OmpF) in the LBL within a few minutes.

A Parylene Neural Probe Array for Multi-Region Deep Brain Recordings.

A Parylene C polymer neural probe array with 64 electrodes purposefully positioned across 8 individual shanks to anatomically match specific regions of the hippocampus was designed, fabricated, characterized, and implemented in vivo for enabling recording in deep brain regions in freely moving rats. Thin film polymer arrays were fabricated using surface micromachining techniques and mechanically braced to prevent buckling during surgical implantation. Importantly, the mechanical bracing technique developed in this work involves a novel biodegradable polymer brace that temporarily reduces shank length and consequently, increases its stiffness during implantation, therefore enabling access to deeper brain regions while preserving a low original cross-sectional area of the shanks. The resulting mechanical properties of braced shanks were evaluated at the benchtop. Arrays were then implemented in vivo in freely moving rats, achieving both acute and chronic recordings from the pyramidal cells in the cornu ammonis (CA) 1 and CA3 regions of the hippocampus which are responsible for memory encoding. This work demonstrated the potential for minimally invasive polymer-based neural probe arrays for multi-region recording in deep brain structures.

A study of Love wave acoustic biosensors monitoring the adhesion process of tendon stem cells (TSCs).

The Love wave biosensor is considered to be one of the most promising probing methods in biomedical research and diagnosis, and has been applied to detect the mechano-biological behaviour of cells attached to the surface of the device. More efforts should be devoted to basic theoretical research and relevant device performance analysis that may contribute to the further developments of Love wave sensors. In this study, a 36º YX-LiTaO3-based Love wave sensor with a parylene-C wave guiding layer was adopted as a cell-based biosensor to monitor the adhesion process of tendon stem/progenitor cells (TSCs), a newly discovered cell type in tendons. A theoretical model is proposed to describe the Love wave propagation, in which the adherent cells are considered as a uniform viscoelastic layer. The effects of viscoelastic cell layer and wave guiding layer on the propagation velocity υ and propagation loss (PL) are investigated. The numerical results indicate that adherent cell layers of different storage or loss shear modulus in certain ranges can induce pronounced and characteristic variations in υ and PL, revealing the potential of Love wave sensors to provide useful quantitative measures on cellular mechanical properties. The sensor response to the adhesion of TSCs exhibits high consistency with experimental observations, which demonstrates the Love wave biosensor as a very promising sensor platform for investigating cellular activities under multiple physiological conditions.

Electrochemical characteristics of microelectrode designed for electrical stimulation.

BACKGROUND: Microelectrode arrays play an important role in prosthetic implants for neural signal recording or applying electrical pulses stimulation to target nerve system. Safety and long-term reliability are essential requirements for microelectrode arrays applied in electrical stimulation. In design and fabrication of the microelectrode array, soft materials are generally chosen to be the substrate for the aim of achieving better compliance with the surrounding tissue while maintaining minimal damage. By flexing of the array to the surface, the array is capable of keeping a more stable electrical contact resulting in a significantly improved signal detected. METHODS: In this study, we design and fabricate a flexible microelectrode array with gold as the electrode material and parylene-C as the substrate. The fabrication process of the array is presented. The in vitro electrochemical characteristics of the microelectrode are investigated by electrochemical impedance spectroscopy and cyclic voltammetry in a three-electrode electrochemical cell containing phosphate-buffered saline. Charge injection capacity measurements are carried out by multichannel systems and the CSC of the microarray is calculated. RESULTS: Electrochemical results showed that impedance decreased with frequency. The average impedance of the Au electrodes at 1 kHz was 36.54 ± 0.88 kΩ. The average phase angle at 1 kHz was - 73.52 ± 1.3°, and the CIC of the microelectrode was 22.3 µC/cm2. The results demonstrated that the microelectrode array performed as expected for neuronal signal recording or stimulation. CONCLUSIONS: With parylene-C as the substrate, the microarray has good flexibility. The electrochemical characteristics' results show that the array has the ability to resist any corrosion on metal-electrolyte interface and has good biocompatibility. This low-cost, flexible parylene-based, gold microelectrode array shows potential for use in implant neurological signal acquisition or neurostimulation applications.

One-step sonochemical fabrication and embedding of gentamicin nanoparticles into parylene C implant coating: towards controlled drug delivery.

A facile one-step sonochemical method was employed for the first time for gentamicin nanoparticles (GNPs) fabrication and embedding into the surface of parylene C implant coating. The developed system was thoroughly characterized in terms of particle size (NTA, STEM/EDX), surface dispersion (IR-image) and drug release kinetics (UV-Vis). It was revealed that the optimization of the applied ultrasound conditions resulted in the formation of GNPs with an average size in the narrow range of 30-70 nm and their docking into the parylene C nanopores, while the molecular structure of the antibiotic was preserved as confirmed by the FTIR spectra. The obtained surface morphology resulted in controlled elution of the drug up to 7 days, and the kinetics followed the Korsmeyer-Peppas model. The apparent benefits of the proposed sonochemical approach (short preparation time, direct drug accessibility, lack of chemical wastes) are pointed out.

Polymer-based interconnection cables to integrate with flexible penetrating microelectrode arrays.

There have been various types of interconnection methods for neural interfacing electrodes, such as silicon ribbon cables, wire bonding and polymer-based cables. In this study, interconnection cables were developed for integration with a Flexible Penetrating Microelectrode Array (FPMA) that was previously developed for neural signal recording or stimulation. Polyimide and parylene C were selected as base materials for the interconnection cables as both materials can preserve the flexibility of the FPMA better than other interconnection methods such as silicon ribbon cable or wire bonding. We conducted durability tests to determine if the interconnection cables were suitable for in-vivo implantation, by long-term soaking of the cables in phosphate buffered saline solution. We measured the changes in impedance over time, and equivalent circuit models were used to analyze the electrochemical phenomena on the surface of the cables. Lastly, we implanted the cable-integrated electrodes device onto rabbit's sciatic nerve and recorded neural signals to prove the feasibility of the developed FPMA integration system.

Parylene MEMS patency sensor for assessment of hydrocephalus shunt obstruction.

Neurosurgical ventricular shunts inserted to treat hydrocephalus experience a cumulative failure rate of 80 % over 12 years; obstruction is responsible for most failures with a majority occurring at the proximal catheter. Current diagnosis of shunt malfunction is imprecise and involves neuroimaging studies and shunt tapping, an invasive measurement of intracranial pressure and shunt patency. These patients often present emergently and a delay in care has dire consequences. A microelectromechanical systems (MEMS) patency sensor was developed to enable direct and quantitative tracking of shunt patency in order to detect proximal shunt occlusion prior to the development of clinical symptoms thereby avoiding delays in treatment. The sensor was fabricated on a flexible polymer substrate to eventually allow integration into a shunt. In this study, the sensor was packaged for use with external ventricular drainage systems for clinical validation. Insights into the transduction mechanism of the sensor were obtained. The impact of electrode size, clinically relevant temperatures and flows, and hydrogen peroxide (H2O2) plasma sterilization on sensor function were evaluated. Sensor performance in the presence of static and dynamic obstruction was demonstrated using 3 different models of obstruction. Electrode size was found to have a minimal effect on sensor performance and increased temperature and flow resulted in a slight decrease in the baseline impedance due to an increase in ionic mobility. However, sensor response did not vary within clinically relevant temperature and flow ranges. H2O2 plasma sterilization also had no effect on sensor performance. This low power and simple format sensor was developed with the intention of future integration into shunts for wireless monitoring of shunt state and more importantly, a more accurate and timely diagnosis of shunt failure.

Polymeric check valve with an elevated pedestal for precise cracking pressure in a glaucoma drainage device.

This paper presents the design, fabrication, and characterization of a polymeric micro check valve for a glaucoma drainage device (GDD) featuring the precise regulation of intraocular pressure (IOP) and effective aqueous humor turnover (AHT). The pedestal, slightly elevated by selective coating of a parylene C film, induces pre-stress in the thin valve membrane, which enhances the predictability of the cracking pressure of the GDD. The proposed GDD comprises a cannula and a normally closed polymeric micro check valve, which are made of PDMS, a biocompatible polymer, with three layers: top (cover), intermediate (thin valve membrane), and bottom (base plate). A feedback channel, located between the top and intermediate layers, prevents reverse flow by feeding the pressure of the outlet channel back to the thin valve membrane. To achieve a precise cracking pressure and sufficient drainage of humor for humans, the thicknesses of the valve membrane and parylene C film are designed to be 58 µm and 1 µm, respectively, which are confirmed using a COMSOL simulation. The experimental results show that the cracking pressure of the fabricated GDD lies within the range of normal IOP (1.33-2.67 kPa). The forward flow rate (drainage rate), 4.3 ± 0.9 µL/min at 2.5 kPa, is adequate to accommodate the rate of AHT in a normal human eye (2.4 ± 0.6 µL/min). The reverse flow was not observed when a hydrostatic pressure of up to 4 kPa was applied to the outlet and the feedback channel.

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).

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.

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.

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.

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.