Cyclic Olefin Copolymer Surface Research Articles

Bioactive modification of cyclic olefin copolymer (COC) film surfaces by hyaluronic acid and chitosan for enhanced cell adhesion

Cyclic olefin copolymer (COC) has recently emerged as an attractive material in biomedical fields for its high purity, excellent stability and chemical resistance, particularly in applications of microfluidic chips, prefilled syringes and bone regeneration. However, the high hydrophobicity of COC has inhibited the adhesion of cells and biological macromolecules, such as proteins, etc., significantly limiting its broader applications. In this study, we propose a new method to modify COC surfaces by sequential coating with polydopamine (PDA) followed by hyaluronic acid (HA) or O-carboxymethyl chitosan (CMC), while comparing the impacts of the positively charged HA and negatively charged CMC on protein adsorption and cell adhesion. FTIR and XPS measurements confirmed the successful modification on COC films, resulting in surfaces with highly increased hydrophilicity, anti-oxidative properties, and improved protein adsorption. Moreover, negatively charged HA, with signal transduction capabilities showed a greater effect in promoting cell adhesion. Thus, we present a straightforward strategy for enhancing the hydrophilicity of COC surfaces, offering new insights into COC modification and potential biomedical applications.

Improving assay feasibility and biocompatibility of 3D cyclic olefin copolymer microwells by superhydrophilic modification via ultrasonic spray deposition of polyvinyl alcohol

Sample partitioning is a crucial step towards digitization of biological assays on polymer microfluidic platforms. However, effective liquid filling into microwells and long-term hydrophilicity remain a challenge in polymeric microfluidic devices, impeding the applicability in diagnostic and cell culture studies. To overcome this, a method to produce permanent superhydrophilic 3-dimensional microwells using cyclic olefin copolymer (COC) microfluidic chips is presented. The COC substrate is oxidized using UV treatment followed by ultrasonic spray coating of polyvinyl alcohol solution, offering uniform and long-term coating of high-aspect ratio microfeatures. The coated COC surfaces are UV-cured before bonding with a hydrophobic pressure-sensitive adhesive to drive selective filling into the wells. The surface hydrophilicity achieved using this method remains unchanged (water contact angle of 9°) for up to 6 months and the modified surface is characterized for physical (contact angle & surface energy, morphology, integrity of microfeatures and roughness), chemical composition (FTIR, Raman spectroscopy) and coating stability (pH, temperature, time). To establish the feasibility of the modified surface in biological applications, PVA-coated COC microfluidic chips are tested for DNA sensing (digital LAMP detection of CMV), and biocompatibility through protein adsorption and cell culture studies (cell adhesion, viability, and metabolic activity). Kidney and breast cells remained viable for the duration of testing (7 days) on this modified surface, and the coating did not affect the protein content, morphology or quality of the cultured cells. The ultrasonic spray coated system, coating with 0.25 % PVA for 15 cycles with 0.12 A current after UV oxidation, increased the surface energy of the COC (naturally hydrophobic) from 22.04 to 112.89 mJ/m2 and improved the filling efficiency from 40 % (native untreated COC) to 94 % in the microwells without interfering with the biocompatibility of the surface, proving to be an efficient, high-throughput and scalable method of microfluidic surface treatment for diagnostic and cell growth applications.

Assessing Surface Adsorption in Cyclic Olefin Copolymer Microfluidic Devices Using Two-Dimensional Nano Liquid Chromatography-Micro Free Flow Electrophoresis Separations.

Surface interactions are a concern in microscale separations, where analyte adsorption can decrease the speed, sensitivity, and resolution otherwise achieved by miniaturization. Here, we functionally characterize the surface adsorption of hot-embossed cyclic olefin copolymer (COC) micro free-flow electrophoresis (μFFE) devices using two-dimensional nLC × μFFE separations, which introduce a 3- to 5 s plug of analyte into the device and measure temporal broadening that arises from surface interactions. COC is an attractive material for microfluidic devices, but little is known about its potential for surface adsorption in applications with continuous fluid flow and temporal measurements. Adsorption was minimal for three small molecule dyes: positively charged rhodamine 123, negatively charged fluorescein, and neutral rhodamine 110. Temporal peak widths for the three dyes ranged from 3 to 7 s and did not change significantly with increasing transit distance. Moderate adsorption was observed for Chromeo P503-labeled myoglobin and cytochrome c with temporal peak widths around 20 s. Overall, the COC surface adsorption was low compared to traditional glass devices, where peak widths are on the order of minutes. Improvements in durability, long-term performance, and ease of fabrication, combined with low overall adsorption, make the COC μFFE devices a practical choice for applications involving time-resolved continuous detection.

Design, fabrication, and characterization of picowell arrays on cyclic olefin copolymer surfaces generated with a 10.5 MeV N4+ ion microbeam

Handling of picoliter-to-nanoliter-scale volumes and objects has increasing importance in life sciences. This is the volume scale of cell extractions and individual living cells. Here, we introduce a method of generating a picoliter-scale device by direct writing of picowell arrays on a ZEONOR™ copolymer surface with high-energy medium-mass ion microbeam. Arrays of various microstructures were written in the sample using a microbeam of 10.5 MeV N4+ ions at various implanted ion fluences. The best array was obtained by implantation of annuli of 10 and 11 μm of inner and outer diameters with a fluence of 7.8 × 1012 ions/cm2.

High nitrogen and argon diffusion in cyclic olefin copolymer foil versus temperature

Measurements of nitrogen and argon diffusion coefficient in cyclic olefin copolymer (COC) have been performed at different temperatures ranging between 21 °C and 101 °C. Optical transparent COC foils have been prepared with 10 μm thickness and total surface of about 25 cm2. The foils have exhibited high purity in composition. The morphology of the COC surface has been investigated by Scanning Electron and Atomic Force Microscopies. The room temperature measured diffusion coefficients, of about 6.56 × 10−3 cm2/s and 6.30 × 10−3 cm2/s for N2 and Ar, respectively, have been obtained with a home-made experimental set-up by measuring the gas pressure gradient reduction applied to the two faces of COC thin foils versus the time. The foils show a significant increase of the N2 and Ar diffusion coefficients with the temperature. The native amorphous nature, the obtained nano-porous structure, the damage suffered by the thin foils of COC under high applied pressure are responsible of the evaluated high diffusion coefficients for nitrogen and argon gases. The experimental apparatus to measure the diffusion coefficients vs. temperature, the obtained results, the COC sheets microstructure, the measurements comparison with the literature data and possible COC applications in biomedicine are presented and discussed.

Laminated Cyclic Olefin Copolymer Foil by Pulsed Laser Deposition

A cyclic olefin copolymer (COC) is a thermoplastic polymer endowed with glass-like optical transparency, unique biocompatibility, low autofluorescence, good chemical stability, and excellent water vapor barriers. COC is a promising new material for optics, medical devices, nanotechnology, and microelectronics. The applicability of the COC depends on its modification through different techniques from plasma treatment to lithography. Presently, pulsed laser deposition (PLD) is employed to deposit an aluminum thin film on selected areas of the COC surface. The study of the wettability, morphology, composition, and optical characteristics of both pristine and modified COC has been evaluated by scanning electron and atomic force microscopies, the sessile drop method, and UV/ViS optical spectroscopy. The prospective recycling of the COC deposited by PLD is proposed.

Antifouling surface for biomedical devices: Modification of COC surface by quaternary ammonium moieties via diazonium chemistry

Prefilled biomedical devices (PFD) are growing in the pharmaceutical market due to the ease of delivering a precise dose of protein drugs. As an appealing alternative to the fragile glass, cyclic olefin copolymer (COC) was suggested. However, in the case of COC, the stability of the drug may be negatively impacted by protein aggregation. To potentially improve the surface properties of COC for PFDs, we performed functionalization of COC with quaternary ammonium moieties (QAS) using the advantages of diazonium surface chemistry. The successful functionalization of COC using QAS-diazonium salts (QAS-DS) with different alkyl chain lengths (C4, C8, C9, C10, C12) was confirmed by Raman spectroscopy and XPS measurements. Optical and fluorescence measurements revealed the optimal length of the alkyl chain-COC-C4 for improved antibiofouling performance towards bovine serum albumin (BSA). Moreover, in contrast to glass, polypropylene (PP), and pristine COC, COC-C4 allows storing the insulin for at least 2 weeks without the changes in protein structure according to dynamic light scattering and TEM images. Additionally, diazonium functionalization allows for conserving the high permeability resistance, transparency, and mechanical stiffness. The improved stability of insulin in a COC-C4 container is explained by the formation of an additional hydration layer serving as a barrier to undesired interaction with biomolecules.

Micropatterning of cells via adjusting surface wettability using plasma treatment and graphene oxide deposition.

The wettability of a polymer surface plays a critical role in cell-cell interaction and behavior. The degree to which a surface is hydrophobic or hydrophilic affects the adhesion and behavior of cells. Two distinct techniques for patterning the surface wettability of a Cyclic Olefin Copolymer (COC) substrate were developed and investigated in this article for the purpose of patterning cell growth. These include oxygen plasma treatment and graphene oxide (GO) coating to alter the wettability of the COC substrate and create hydrophilic patterned regions on a hydrophobic surface. When the two techniques are compared, patterning the surface of COC using GO film results in a more stable wettability over time and increases the roughness of the patterned area. Interestingly, both developed techniques were effective at patterning the COC surface’s wettability, which modulated cell adhesion and resulted in micropatterning of cell growth. The novel methods described herein can be used in the fields of cell and tissue culture as well as in the development of new biological assays.

Permanent Hydrophobic Surface Treatment Combined with Solvent Vapor-Assisted Thermal Bonding for Mass Production of Cyclic Olefin Copolymer Microfluidic Chips.

A hydrophobic surface modification followed by solvent vapor-assisted thermal bonding was developed for the fabrication of cyclic olefin copolymer (COC) microfluidic chips. The modifier species 1H,1H,2H,2H-perfluorooctyl trichlorosilane (FOTS) was used to achieve the entrapment functionalization on the COC surface, and a hydrophobic surface was developed through the formation of a Si–O–Si crosslink network. The COC surface coated with 40 vol % cyclohexane, 59 vol % acetone, and 1 vol % FOTS by ultrasonic spray 10 and 20 times maintained its hydrophobicity with the water contact angle increasing from ∼86 to ∼115° after storage for 3 weeks. The solvent vapor-assisted thermal bonding was optimized to achieve high bond strength and good channel integrity. The results revealed that the COC chips exposed to 60 vol % cyclohexane and 40 vol % acetone for 120 s have the highest bond strength, with a burst pressure of ∼17 bar, which is sufficient for microfluidics applications such as droplet generation. After bonding, the channel maintained its integrity without any channel collapse. The hydrophobicity was also maintained, proved by the water contact angle of ∼115° on the bonded film, as well as the curved shape of water flow in the chip channel by capillary test. The combined hydrophobic treatment and solvent bonding process show significant benefits for scale-up production compared to conventional hydrophilic treatment for bonding and hydrophobic treatment using surface grafting or chemical vapor deposition since it does not require nasty chemistry, long-term treatment, vacuum chamber, and can be integrated into production line easily. Such a process can also be extended to permanent hydrophilic treatment combined with the bonding process and will lay a foundation for low-cost mass production of plastic microfluidic cartridges.

Covalently Attaching Hollow Silica Nanoparticles on a COC Surface for the Fabrication of a Three-Dimensional Protein Microarray.

Compared to traditional two-dimensional (2D) biochips, three-dimensional (3D) biochips exhibit the advantages of higher probe density and detection sensitivity due to their designable surface microstructure as well as enlarged surface area. In the study, we proposed an approach to prepare a 3D protein chip by deposition of a monolayer of functionalized hollow silica nanoparticles (HSNs) on an activated cyclic olefin copolymer (COC) substrate. First, the COC substrate was chemically modified through the photografting technique to tether poly[3-(trimethoxysilyl) propyl methacrylate] (PTMSPMA) brushes on it. Then, a monolayer of HSNs was deposited on the modified COC and covalently attached via a condensation reaction between the hydrolyzed pendant siloxane groups of PTMSPMA and the Si-OH groups of HSNs. The roughness of the COC substrate significantly increased to 50.3 nm after depositing a monolayer of HSNs (ranging from 100 to 700 nm), while it only caused a negligible reduction in the light transmittance of COC. The HSN-modified COC was further functionalized with epoxide groups by a silane coupling agent for binding proteins. Immunoglobulin G could be effectively immobilized on this substrate with the highest immobilization efficiency of 75.2% and a maximum immobilization density of 1.236 μg/cm2, while the highest immobilization efficiency on a 2D epoxide group-modified glass slide was only 57.4%. Moreover, immunoassay results confirmed a competitive limit of detection (LOD) (1.06 ng/mL) and a linear detection range (1-100 ng/mL) of the 3D protein chip. This facile and effective approach for fabricating nanoparticle-based 3D protein microarrays has great potential in the field of biorelated detection.

Enhanced capillary zone electrophoresis in cyclic olefin copolymer microchannels using the combination of dynamic and static coatings for rapid analysis of carnosine and niacinamide in cosmetics

Cosmetics that have medicinal effects, including anti-inflammatory and antioxidant, have become a daily care routine consumption. The peptide additives, such as carnosine and nicotinamide, were frequently used to realize these medicinal effects. To accomplish rapid and effective quantitation of carnosine and niacinamide in cosmetics, capillary zone electrophoresis was executed in cyclic olefin copolymer microchips having both dynamic and static coatings. The static coating of cyclic olefin copolymer microchannel was constructed from bovine serum albumin adsorption, immobilization, and active site closure, while the dynamic coating was formed by adding surfactant into running buffer of capillary zone electrophoresis. The static coating can improve the hydrophilicity of cyclic olefin copolymer surface and avoid nonspecific peptide adsorption. The dynamic coating of sodium dodecyl sulfate in running buffer proved to be useful in flow velocity adjustment and the column efficiency enhancement in the capillary zone electrophoresis separation channel of the cyclic olefin copolymer microchip device. A separation resolution up to 4.24 on the mixture of carnosine and nicotinamide was obtained. Moreover, an analysis method was established and applied to simultaneous carnosine and nicotinamide determination in a liquid whitening essence and a solid antiglycation pill, and the results were verified by comparison with high-performance liquid chromatography methods, indicating its potential in complex sample analysis.

Tuning the Surface Wettability of Cyclic Olefin Copolymer by Plasma Treatment and Graphene Oxide Deposition and Reduction.

Selective altering of surface wettability in microfluidic channels provides a suitable platform for a large range of processes, such as the phase separation of multiphase systems, synthesis of reaction controlled, nanoliter sized droplet reactors, and catalyst impregnation. Herein we study the feasibility to tune the wettability of a flexible cyclic olefin copolymer (COC). Two methods were considered for enhancing the surface hydrophilicity. The first is argon/oxygen plasma treatment, where the effect of treatment duration on water contact angle and COC surface morphology and chemistry were investigated, and the second is coating COC with GO dispersions of different concentrations. For enhancing the hydrophobicity of GO-coated COC surfaces, three reduction methods were considered: chemical reduction by Hydroiodic acid (HI), thermal reduction, and photo reduction by exposure of GO-coated COC to UV light. The results show that as the GO concentration and plasma treatment duration increased, a significant decrease in contact angle was observed, which confirmed the ability to enhance the wettability of the COC surface. The increase in hydrophilicity during plasma treatment was associated with the increase in surface roughness on the treated surfaces, while the increase during GO coating was associated with introducing oxygen-containing groups on the GO-coated COC surfaces. The results also show that the different reduction methods considered can increase the contact angle and improve the hydrophobicity of a GO-coated COC surface. It was found that the significant improvement in hydrophobicity was related to the reduction of oxygen-containing groups on the GO-coated COC modified surface.

Development of Direct Grafting on Cyclic Olefin Copolymers to Improve Hydrophilicity by Using Bioactive Polymers

ObjectivesTo improve the hydrophilicity of cyclic olefin copolymer, a simple and rapid method using two-stage with ultraviolet irradiation was developed in order to graft a bioactive polymer on the surface of these polymers. Materials and MethodsA bioactive polymer, poly(sodium styrene sulfonate) was grafting in two steps on the cyclic olefin copolymer surface. The process consists to activate the surface with ozone and grafting to under UV irradiation in presence of sodium styrene sulfonate. The presence of polymer on the surfaces was characterized by water contact angle, Fourier transform infrared spectroscopy, scanning electron microscopy with energy dispersive spectroscopy and the quantity of polymer grafted was determined by a colorimetric method. ResultsFirst, the time of UV irradiation for the grafting was studied. The results showed that the maximum grafting rate is reached after 60 minutes of reaction. Second, the influence of the presence of additive on the grafting was investigated. The degree of grafting is significantly reduced compared to a sample without additive. ConclusionWe have developed a simple and fast method to graft a hydrophilic and bioactive polymer covalently to a COC surface.

Preparation and Reliability of Anti-Reflection Film on Cyclic Olefin Copolymer Surface

Preparation and Reliability of Anti-Reflection Film on Cyclic Olefin Copolymer Surface

Fabrication of superhydrophobic transparent cyclic olefin copolymer (COC)‐SiO2 nanocomposite surfaces

AbstractA superhydrophobic cyclic olefin copolymer (COC) nanocomposite coating was produced with a very simple and easy method. Self‐cleaning superhydrophobic COC surfaces were obtained by only adding surface hydrophobized SiO2 nanoparticles by dip coating method. The influence of concentration of SiO2 and the coating temperatures on the wettability of the surfaces were investigated. The surface wettability of the coatings was examined with the contact angle measurements and the surface roughness and morphology were analyzed by using atomic force microscope and scanning electron microscopy analysis. Surfaces with certain amounts of COC and SiO2 showed superhydrophobic character with high water contact angle of 1690. Also, the obtained superhydrophobic surfaces show superior water repellent, high transparency, and self‐cleaning characteristics.

Facile Surface Functionalization of Cyclic Olefin Copolymer Film with Anhydride Groups for Protein Microarray Fabrication.

Immobilization of protein at high efficiency is a challenge for fabricating polymer-based protein chips. Here, a simple but effective approach was developed to fabricate a cyclic olefin copolymer (COC)-based protein microarray with a high immobilization density. In this strategy, poly(maleic anhydride-co-vinyl acetate) (poly(MAH-co-VAc)) brushes were facilely attached on the COC surface via UV-induced graft copolymerization. The introduction of poly(MAH-co-VAc) brushes resulted in an obvious increase in the surface roughness of COC. The functionalized COC showed little reduction in transparency compared with pristine COC, indicating that the photografting treatment did not alter its optical property. The graft density of the anhydride groups on the modified COC could be tuned from 0.46 to 3.2 μmol/cm2. The immobilization efficiency of immunoglobulin G (IgG) on functionalized COC reached 88% due to the high reactivity between anhydride groups and amine groups of IgGs. An immunoassay experiment demonstrated that the microarray showed high sensitivity to the target analyte.

Droplet Coalescence by Selective Wettability Enhancement in Microfluidic Devices.

A new approach for droplet coalescence in microfluidic channels based on selective surface energy alteration is demonstrated. The proposed method involves patterning the surface of cyclic olefin copolymer (COC), a hydrophobic substrate attached to a polydimethylsiloxane hydrophobic microchannel, with graphene oxide (GO) using standard microfabrication techniques. Surface wettability and adhesion analyses confirmed the enhancement of the COC surface energy upon GO patterning and the stability of the GO film on COC. Three representative cases are illustrated to demonstrate the effectiveness of the method on the coalescence of droplets for different droplet flow regimes, as well as the effect of changing the size of the patterned surface area on the fusion process. The method achieves droplet coalescence without the need for precise synchronization.

Plasma Polymer Layers with Primary Amino Groups for Immobilization of Nano- and Microparticles

The assembly of nano- and micro-scale building blocks on surface has been the focus of intense interest in materials science for years. In this work, (3-aminopropyl)triethoxysilane (APTES) carrying one primary amino group was deposited on various substrate surfaces using the plasma polymerization method. The key plasma parameters i.e. pressure and power were varied to obtained the highest density of primary amino groups. The influence of such parameters on the characteristics of deposited layers (e.g. chemical structure, adhesion strength, growth rate, etc.) was systemically investigated using various characterization methods such as XPS, FTIR, ellipsometry and so on. Meanwhile, three types of particles (AuNPs, zeolites and gold@zeolites) with sizes from nano- to submicro-range were synthesized and further used as model building blocks. Subsequently, the prepared particles were deposited onto cyclic olefin copolymer (COC) substrate surfaces, which were pre-functionalized by deposition of the plasma polymer layer using the parameters of pressure = 1.0 mbar and power = 30 W. The results confirmed the formation of membrane structures consisting of highly packed particles on the COC surface, and such immobilized structures showed high stability against flowing water, evidencing the good immobilization ability of deposited APTES layers with amino groups.

Highly Transparent Cyclic Olefin Copolymer Film with a Nanotextured Surface Prepared by One-Step Photografting for High-Density DNA Immobilization.

Compared with conventional glass slides and two-dimensional (2D) planar microarrays, polymer-based support materials and three-dimensional (3D) surface structures have attracted increasing attention in the field of biochips because of their good processability in microfabrication and low cost in mass production, as well as their improved sensitivity and specificity for the detection of biomolecules. In the present study, UV-induced emulsion graft polymerization was carried out on a cyclic olefin copolymer (COC) surface to generate 3D nanotextures composed of loosely stacked nanoparticles with a diameter of approximately 50 nm. The introduction of a hierarchical nanostructure on a COC surface only resulted in a 5% decrease in its transparency at a wavelength of 550 nm but significantly increased the surface area, which markedly improved immobilization density and efficiency of an oligonucleotide probe compared with the functional group and polymer brush-modified substrates. The highest immobilization efficiency of the probes reached 93%, and a limit of detection of 75 pM could be obtained. The hybridization experiment demonstrated that the 3D gene chip exhibited excellent sensitivity for target DNA detection and single-nucleotide polymorphism discrimination. This one-step approach to the construction of nanotextured surfaces on the COC has promising applications in the fields of biochips and immunoassays.

Heterogeneous-phase Sonogashira cross-coupling reaction on COC surface for the grafting of biomolecules – Application to isatin

The grafting of 5-iodoisatin heterocycle on a cyclic olefin copolymer (COC) and a gold surface was performed using a heterogeneous phase Sonogashira reaction consisting of coupling 5-iodoisatin with an arylalkyne previously introduced onto the surfaces. This optimized strategy takes advantage of the well-established methodology to functionalize COC or gold surfaces using aryldiazonium surface chemistry. Herein, we reported the first example of an isatin decorated polymeric or metallic surface. The surfaces were analyzed with a combination of techniques such as IR (Infrared spectroscopy), XPS (X-Ray photoelectron spectroscopy) and SPR (surface plasmon resonance). Docking studies showed that isatin and two derivatives interact with AmiC, a dimeric protein produced by Pseudomonas aeruginosa. Bacterial adhesion on isatin−COC platform was also observed. This general strategy for robust surface functionalization represents an easy approach for patterning surfaces with compounds of biological interest, allowing access to a large panel of original biosensors.