Parylene Membrane Research Articles

Atomic force microscope based biomolecular force-clamp measurements using a micromachined electrostatic actuator

The authors describe a method for biomolecular force clamp measurements using atomic force microscope (AFM) cantilevers and micromachined membrane-based electrostatic actuators. The actuators comprise of Parylene membranes with embedded side actuation electrodes and are fabricated on a silicon substrate. The devices have a displacement range of 1.8 μm with 200 V actuation voltage, and displacement uncertainty is 0.8 nm, including the noise and drift. The settling time, limited by the particular amplifier is 5 ms, with an inherent range down to 20 μs. A force clamp measurement setup using these actuators in a feedback loop has been used to measure bond life-times between human IgG and anti-human IgG molecules to demonstrate the feasibility of this method for biological experiments. The experimental findings are compared with a molecular pulling experiment and the results are found to be in good agreement.

A combination herbal supplement for biochemically recurrent prostate cancer.

24 Background: After curative local therapy, thousands of men will have rising PSA as an early indicator of recurrent prostate cancer. For them, no standard of care exists, and concern over serious side effects of androgen deprivation (ADT) makes delaying ADT common. We tested Prostate Health Cocktail (PHC), which contains vitamins D & E, saw palmetto, lycopene, green tea and soy extracts, in this population, to see whether it could induce PSA declines. Methods: Eligible men had rising PSA with doubling time (DT) 3-36 months, with no evidence of metastases on CT and bone scans. After IRB approval, 28 men were treated with PHC 3 capsules PO daily for 4 week cycles. PSA was repeated after the first cycle, then every 2 cycles with imaging only as clinically indicated; the primary endpoint was PSA decline. PSA progression was defined as 25% increase and absolute increase of 5 ng/mL or return to baseline. Circulating tumor cells (CTCs) were measured at baseline and after 3 cycles using parylene membrane filters. Results: The median age was 67 (range 54-84) and baseline PSA was 2.9 ng/mL (1.1-53.2); the median number of cycles was 6 (1-13). Stable PSA was the best response for 23/28 men (83%) and 8/27 men (29.6%) had a PSA decline (1.1%-29.4% maximum decrease). 47% stopped therapy for progression with median time to progression=9.2 months. There was no association between Gleason score or baseline PSA, vitamin D or selenium level and PSA decline. CTCs were detected in 5 of the first 23 subjects. The median PSA for these men was 2.77 ng/mL (range 1.63-16.8). There was no significant change in testosterone or DHT during treatment. Median PSA DT at baseline was 7.8 months (range 3-36). One patient had grade 3 transaminitis in the setting of alcohol consumption, otherwise toxicities were limited to grade 1 or 2 hypercalcemia(1), hyperkalemia(2), hyperglycemia(4), flatulence(4), other GI(5), and rash(1). Conclusions: PHC demonstrated activity in men with biochemically recurrent prostate cancer, resulting in PSA declines in nearly a third of cases, and was not associated with changes in serum androgens or significant toxicities. For the first time, we are reporting that circulating tumor cells can be detected in men with biochemical recurrence using filter technology.

Non-lithographically microfabricated capacitive pressure sensor for biomedical applications

A novel micromachined capacitive pressure sensor fabricated on a metal substrate without using a photolithographic process is reported. The device is constructed by thermal bonding of a Parylene membrane onto a 1.5 × 1.5 × 0.2×mm 3 stainless-steel chip with a shallow cavity created using micro-electro-discharge machining. The fabrication approach enables rapid, low-cost manufacturing of the device with biocompatibility. The sensor is designed to provide a gauge pressure range of 200 mmHg or greater to be potentially suitable for invivo blood-pressure sensing applications. A highly linear response of 2 fF/mmHg is demonstrated with the fabricated devices. The temperature coefficient of the sensor is observed to be 250 ppm/ °C.

Piezoresistive pressure sensor using vertically aligned carbon-nanotube forests

A pressure sensor functionalised with vertically aligned carbon nanotubes is presented. The sensor is fabricated to have a multi-walled carbon-nanotube forest supported by a deflectable 8 m-thick Parylene-C membrane that is suspended by the silicon frame. The responses of the fabricated sensors are experimentally characterised. The sensitivities to positive and negative gauge pressures are found to be comparable in magnitude with the average values of -986 and +816 ppm/kPa, respectively. The measurement also reveals that the temperature coefficient of resistance for the forest suspended with the Parylene membrane is -515 ppm/°C and ~3× smaller than that for the forest fixed onto the silicon substrate.

Microprism using capillary alignment

When a microstructure is placed on a droplet, the structure is positioned and remains at a particular position due to capillary forces. By using this phenomenon, two-dimensional arrangements on droplets have been widely developed. In this study, we fabricate a three-dimensional structure (prism shape) by placing two circular plates on a droplet. The paper explains the dynamics of the positioning both experimentally and numerically. Through experiment and simulation, we found that the rotational positioning is determined by surface tension and the two plates are supported by internal pressure and surface tension. The apex angle of the prism can be easily tuned by changing its volume. As described at the end of the paper, a prism composed of a droplet of silicone oil and two transparent circular SU-8 plates is encapsulated by depositing an organic Parylene membrane. The shape of the liquid is fixed, and a non-evaporative and non-deformable prism is formed with a volume of less than 1 mm3.

패럴린 박막을 이용한 기계화학적 폭발물 센서

This paper reports a chemomechanical explosive sensor based on a thin polymer membrane. The sensor consists of thin parylene membrane and electrodes. Parylene membrane is functionalized with 4-mercaptophenol which interacts strongly with nitrotoluene based explosives. The membrane deflection caused by molecular interaction between the surface and explosives is monitored by capacitance between the membrane and the substrate. To measure the capacitance, electrodes are formed on the membrane and the substrate. While the previous cantilever system requires a bulky optical measuring system, this purely electric monitoring method offers a compact and effective system. Thus, this explosive sensor can be readily miniaturized and used in the field. The developed sensor can reliably detect dinitrotoluene and its limit of detection is evaluated as approximately 110 ppb.

Fabrication and characteristics of an ultra-thin carbon nanotube/parylene membrane at large strain

Multi-walled carbon nanotubes were embedded in a parylene membrane by filtering dispersed carbon nanotube solution through a template of anodic aluminum oxide, following by physical vapor deposition of parylene. The fabricated membrane was 2μm thick and showed special piezoresistive characteristics even at large strain. Its variations of the electrical resistance and exerted force due to tensile strain were fully characterized for the strain up to 20%. Linear relation between the force and strain was obtained when the strain was smaller than 2%. Positive correlation between the resistance and force was observed for a long range of larger strains. This investigation can be applied for designing flexible electronics and sensors based on carbon nanotube/polymer composites.

3D microfilter device for viable circulating tumor cell (CTC) enrichment from blood

Detection of circulating tumor cells has emerged as a promising minimally invasive diagnostic and prognostic tool for patients with metastatic cancers. We report a novel three dimensional microfilter device that can enrich viable circulating tumor cells from blood. This device consists of two layers of parylene membrane with pores and gap precisely defined with photolithography. The positions of the pores are shifted between the top and bottom membranes. The bottom membrane supports captured cells and minimize the stress concentration on cell membrane and sustain cell viability during filtration. Viable cell capture on device was investigated with scanning electron microscopy, confocal microscopy, and immunofluorescent staining using model systems of cultured tumor cells spiked in blood or saline. The paper presents and validates this new 3D microfiltration concept for circulation tumor cell enrichment application. The device provides a highly valuable tool for assessing and characterizing viable enriched circulating tumor cells in both research and clinical settings.

Portable Filter-Based Microdevice for Detection and Characterization of Circulating Tumor Cells

Sensitive detection and characterization of circulating tumor cells (CTC) could revolutionize the approach to patients with early-stage and metastatic cancer. The current methodologies have significant limitations, including limited capture efficiency and ability to characterize captured cells. Here, we report the development of a novel parylene membrane filter-based portable microdevice for size-based isolation with high recovery rate and direct on-chip characterization of captured CTC from human peripheral blood. We evaluated the sensitivity and efficiency of CTC capture in a model system using blood samples from healthy donors spiked with tumor cell lines. Fifty-nine model system samples were tested to determine the recovery rate of the microdevice. Moreover, 10 model system samples and 57 blood samples from cancer patients were subjected to both membrane microfilter device and CellSearch platform enumeration for direct comparison. Using the model system, the microdevice achieved >90% recovery with probability of 95% recovering at least one cell when five are seeded in 7.5 mL of blood. CTCs were identified in 51 of 57 patients using the microdevice, compared with only 26 patients with the CellSearch method. When CTCs were detected by both methods, greater numbers were recovered by the microfilter device in all but five patients. This filter-based microdevice is both a capture and analysis platform, capable of multiplexed imaging and genetic analysis. The microdevice presented here has the potential to enable routine CTC analysis in the clinical setting for the effective management of cancer patients.

Tunable gold-coated polymer gratings for surface plasmon resonance coupling and scanning

We propose an surface plasmon resonance (SPR) coupling device that can tune the coupling condition by changing the pitch of an Au grating. A grating with a micrometer-sized pitch was produced on a flexible thin parylene membrane, making an 8 mm × 8 mm diaphragm. An SPR can be coupled to the Au grating surface by direct laser irradiation, and the dependence of the SPR angles (within 6° to 56°) on the grating pitch (ranging from 1000 to 1500 nm) shows good agreement with the SPR theory. We demonstrate that the SPR matching condition can be tuned by changes in pitch due to strain caused by membrane expansion. The SPR angle shift reached about 0.2°, corresponding to about 0.6% strain, by 15 kPa pressure application. The SPR angle shift sensitivity to the pressure was 0.015° kPa−1. This value is almost equal to that calculated from strain measurements (0.014° kPa−1), and we conclude that the SPR angle shift was caused by the grating pitch change due to the pressure application. Theoretical consideration indicates that a refractive index change of about 0.01 RIU is possible with this device near the refractive index of water.

Characterization of Aligned Wafer-Level Transfer of Thin and Flexible Parylene Membranes

This paper reports a wafer-level transfer technique for forming thin, flexible, and freestanding parylene membranes. Parylene thin films (~1.3 mum) have been successfully transferred from one wafer to another to form a freestanding membrane encapsulating over wide and shallow cavities (< 5 mum deep and 2000 times 2000 mum2 square) with fine alignment (< 3.0 mum) and 87% yield. Transferred membranes may be a composite of parylene/metal/parylene, contain through-hole patterns of diverse size (5 times 5 ~ 2000 times 2000 mum2), have mild tension (1.14 MPa), and remain freestanding and flat through various standard post-transfer microfabrication processes such as photolithography, evaporation, and wet etching. They also provide excellent sealing against pressure of up to 20 kPa and long-term stability over repeated deflection. This paper focuses on two areas: (1) the study of issues involving optimum transfer conditions, minimum achievable gap between transferred membranes and device wafers, patterned-film and composite-layer transfer, and aligned transfer; and (2) the characterization of the post-transfer membrane properties, including stress/tension, sealing capability, effects of post-transfer processing, and long-term stability after a repeated deflection.

Reusable, reversibly sealable parylene membranes for cell and protein patterning

The patterned deposition of cells and biomolecules on surfaces is a potentially useful tool for in vitro diagnostics, high-throughput screening, and tissue engineering. Here, we describe an inexpensive and potentially widely applicable micropatterning technique that uses reversible sealing of microfabricated parylene-C stencils on surfaces to enable surface patterning. Using these stencils it is possible to generate micropatterns and copatterns of proteins and cells, including NIH-3T3 fibroblasts, hepatocytes and embryonic stem cells. After patterning, the stencils can be removed from the surface, plasma treated to remove adsorbed proteins, and reused. A variety of hydrophobic surfaces including PDMS, polystyrene and acrylated glass were patterned using this approach. Furthermore, we demonstrated the reusability and mechanical integrity of the parylene membrane for at least 10 consecutive patterning processes. These parylene-C stencils are potentially scalable commercially and easily accessible for many biological and biomedical applications.

Membrane microfilter device for selective capture, electrolysis and genomic analysis of human circulating tumor cells

This paper presents development of a parylene membrane microfilter device for single stage capture and electrolysis of circulating tumor cells (CTCs) in human blood, and the potential of this device to allow genomic analysis. The presence and number of CTCs in blood has recently been demonstrated to provide significant prognostic information for patients with metastatic breast cancer. While finding as few as five CTCs in about 7.5 mL of blood (i.e., 10 10 blood cells in) is clinically significant, detection of CTCs is currently difficult and time consuming. CTC enrichment is performed by either gradient centrifugation of CTC based on their buoyant density or magnetic separation of epithelial CTC, both of which are laborious procedures with variable efficiency, and CTC identification is typically done by trained pathologists through visual observation of stained cytokeratin-positive epithelial CTC. These processes may take hours, if not days. Work presented here provides a micro-electro-mechanical system (MEMS)-based option to make this process simpler, faster, better and cheaper. We exploited the size difference between CTCs and human blood cells to achieve the CTC capture on filter with ∼90% recovery within 10 min, which is superior to current approaches. Following capture, we facilitated polymerase chain reaction (PCR)-based genomic analysis by performing on-membrane electrolysis with embedded electrodes reaching each of the individual 16,000 filtering pores. The biggest advantage for this on-membrane in situ cell lysis is the high efficiency since cells are immobilized, allowing their direct contact with electrodes. As a proof-of-principle, we show beta actin gene PCR, the same technology can be easily extended to real time PCR for CTC-specific transcript to allow molecular identification of CTC and their further characterization.

2.4 and 5.2 GHz Dual-Band Antenna Fabricated on Flexible Parylene Membrane

A 2.4 and 5.2 GHz dual-band monopole antenna fabricated on a flexible parylene membrane for Bluetooth and wireless local area network (WLAN) modules was designed and fabricated. The measured results show a good antenna performance and agree very well with the design simulations in both return loss and radiation characteristics. Parylene is a flexible polymer film; it can be deposited on various substrates and peeled off after completing device processes as stand-alone thin-and-flexible-substrate-containing devices. Owing to its excellent physical and chemical properties such as its low dielectric constant, light weight, low conductivity, and inertness to chemicals, parylene is also suitable for fabrication of many other RF devices.

Yield strength of thin-film parylene-C

For the first time, the yield strength of thin-film parylene-C is measured from membrane load-deflection experiments and surface profile analysis. To do so, the onset pressure which causes plastic deformation of the membrane is first experimentally measured. Then a new 2-step displacement model, together with the energy minimization technique [1], is developed to convert the onset pressure to the yield strength on the pre-stressed parylene membrane under a uniform pressure loading. The results depict a Yield Strength of 59 MPa (or 0.012 of strain) for thin-film parylene-C in comparison to 55 MPa reported by parylene vendor (measured from large samples) [2]. To double check with the result, the balloon model [3] is further used to compare with the stress value from our model at the center of parylene membranes and good agreements are obtained.

Surface micromachined electrostatically actuated micro peristaltic pump.

An electrostatically actuated micro peristaltic pump is reported. The micro pump is entirely surface micromachined using a multilayer parylene technology. Taking advantage of the multilayer technology, the micro pump design enables the pumped fluid to be isolated from the electric field. Electrostatic actuation of the parylene membrane using both DC and AC voltages was demonstrated and applied to fluid pumping based on a 3-phase peristaltic sequence. A maximum flow rate of 1.7 nL min(-1) and an estimated pumping pressure of 1.6 kPa were achieved at 20 Hz phase frequency. A dynamic analysis was also performed with a lumped-parameter model for the peristaltic pump. The analysis results allow a quantitative understanding of the peristaltic pumping operation, and correctly predict the trends exhibited by the experimental data. The small footprint of the micro pump is well suited for large-scale integration of microfluidics. Moreover, because the same platform technology has also been used to fabricate other devices (e.g. valves, electrospray ionization nozzles, filters and flow sensors), the integration of these different devices can potentially lead to versatile and functional micro total analysis systems (microTAS).

Thin-walled Tube Supported by Coil Spring for Small Diameter Active Catheters

New fabrication method of small diameter tubular structures which are suitable for active catheters and active guide wires was developed. These tubular structures consist of metal spring coil and evaporated parylene membrane. An anticoagulant polyurethane is used as outer membrane structure. Fabrication process is simple and the fabricated tubes are kink-free and buckling-free in spite of its flexibility and thin wall.

Determination of the Water Vapor Permeability and Continuity of Ultrathin Parylene Membranes

A method has been developed to determine the water vapor permeability of very thin dielectric films over a large range of thicknesses. It is shown that the permeability of poly(chloro‐p‐xylylene) unsupported thin films is the same throughout the range of thicknesses tested: 292–73,388Aå. The results agree with values reported on thick samples under similar test conditions and with thick samples obtained by standard flow methods. The results also compare favorably with the water vapor permeability of other polymeric materials. Since the permeability obtained indicates that thick () films are structurally continuous, then ultrathin (<300Aå) films of poly(chloro‐p‐xylylene) must also be free of voids. In addition, the method is sensitive enough to detect discontinuities as small as 1µ in diameter.