Cyclic Olefin Copolymer Microchannels Research Articles

Microfluidic fabrication using cyclic olefin copolymer and hydrocarbon solvents

Cyclic olefin copolymer (COC) is a promising material in microfluidic applications due to their unique physical, chemical, and optical properties. This study implements a new and versatile fabrication process to fabricate COC microchannels, combining the fabrication and bonding processes in a single step, taking advantage of COCs’ swelling behavior in linear non-polar hydrocarbon solvents and their chemical compatibility with photolithography. Dodecane was selected as the hydrocarbon solvent based on the degree of swelling and Flory-Huggins interaction parameter, which resulted in the highest degree of swelling and affinity to COC. The effect of dodecane immersion time on the COC microchannel height was investigated, achieving a maximum average height of 50 ± 3 µm after 180 min. Bonding quality was quantified by a leakage test (maximum flow rate of 1730 ± 205 µL/min (Re = 237)), and a tensile test (800 ± 90 kPa). Furthermore, the effectiveness of the implemented process was demonstrated through the successful execution of three highly diverse microfluidic applications. These applications included a serpentine microchannel featuring semicircular obstacles that facilitated passive mixing, pinched flow fractionation which enabled the separation of a system of three different sizes of microparticles, and droplet microfluidics that allowed for the efficient generation of water in oil droplets.

A mass manufacturable thermoplastic based microfluidic droplet generator on cyclic olefin copolymer

The rapid progress of droplet microfluidics and its wide range of applications have created a high demand for the mass fabrication of low-cost, high throughput droplet generator chips aiding both biomedical research and commercial usage. Existing polymer or glass based droplet generators have failed to successfully meet this demand which generates the need for the development of an alternate prototyping technique. This work reports the design, fabrication and characterization of a mass manufacturable thermoplastic based microfluidic droplet generator on cyclic olefin copolymer (COC). COC chips with feature size as low as 20 µm have been efficiently fabricated using injection molding technology leading to a high production of inexpensive droplet generators. The novelty of this work lies in reoptimising surface treatment and solvent bonding methods to produce closed COC microchannels with sufficiently hydrophobic (contact angle of 120°) surfaces. These COC based droplet generators were shown to generate stable monodisperse droplets at a rate of 1300 droplets/second in the dripping regime. These new mass manufacturable, disposable and cheap COC droplet generators can be custom designed to cater to the rapidly increasing biomedical and clinical applications of droplet microfluidics.

Patterning multilayer microfluidic electrochemical devices by maskless laminar flow lithography

Laminar flow lithography (LFL) is a fabrication technique that leverages the tendency of multiple fluids flowing in a microfluidic channel to remain confined to distinct parallel streams, enabling the substrate to be selectively etched to form patterned lines. The purpose of this investigation was to evaluate LFL as a fabrication technique for patterning multiple layers of parallel metal electrodes to produce microfluidic electrochemical cells. To understand how channel geometry impacts the location and width of the etched structures, finite element modelling (FEM) was used to simulate the profiles of the diffusive gradients that govern the extent and location of etching. LFL was then employed to fabricate two different electrochemical devices requiring parallel electrodes of different materials. First, a three layer Ag–Au–Ni thin film stack was patterned by LFL, yielding a three electrode device with electrically isolated and independently sized Ag, Au, and Ni electrodes within a cyclic-olefin copolymer (COC) microchannel. Second, a functional alkaline direct methanol fuel cell was fabricated by performing two sequential LFL processes to pattern a bi-metallic Ag–Ni film also deposited in a COC microchannel. The electrical characteristics of these Ag–Ni devices were then evaluated. Ag–Ni fuel cells produced a peak open circuit voltage of 185 mV and a peak power density of 12.0 ± 0.4 μW cm−2 (equivalent to 696 ± 20 μW cm−3, in terms of chamber volume) while flowing 10 μL min−1 of dilute methanol anolyte and dilute hydrogen peroxide catholyte solutions. Fabrication methods presented in this investigation are applicable to many aspects of microfluidics and can be adapted for other types of microfluidic devices where in situ etching is required.

PEGylation of magnetic poly(glycidyl methacrylate) microparticles for microfluidic bioassays

In this study, magnetic poly(glycidyl methacrylate) microparticles containing carboxyl groups (PGMA-COOH) were coated using highly hydrophilic polymer poly(ethylene glycol) (PEG). PEG was used to reduce nonspecific interactions with proteins and cells while decreasing adhesion of particles to the walls of a microfluidic devices from poly(dimethylsiloxane) (PDMS) and cyclic olefin copolymer (COC). Zeta potential measurement, infrared spectroscopy, scanning electron microscopy, anti-PEG ELISA assay, and bioaffinity interactions between biotin and streptavidin-HRP successfully proved the presence of PEG on the surface of microspheres. Both neat and PEGylated microspheres were then incubated with the inert protein bovine serum albumin or cells to evaluate the rate of nonspecific adsorption (NSA). PEG with Mr of 30,000Da was responsible for 45% reduction in NSA of proteins and 74% for cells compared to neat particles. The microspheres' behavior in PDMS and COC microchannels was then evaluated. Aggregation and adhesion of PEGylated microspheres significantly decreased compared to neat particles. Finally, the model enzyme horseradish peroxidase was immobilized on the microspheres through the heterobifunctional PEG chain. The possibility for subsequent covalent coupling of the ligand of interest was confirmed. Such PEGylated microparticles can be efficiently used in PDMS microchips as a carrier for bioaffinity separation or of enzyme for catalysis.

Superhydrophilic Multilayer Silica Nanoparticle Networks on a Polymer Microchannel Using a Spray Layer-by-Layer Nanoassembly Method

Nanoporous and superhydrophilic multilayer silica nanoparticle networks have been developed on a hydrophobic cyclic olefin copolymer (COC) microchannel using a spray layer-by-layer (LbL) electrostatic nanoassembly method. This powerful and promising LbL method provides a simple, cost-effective, and high-throughput nanoporous silica multilayer selectively onto the hydrophobic polymer surfaces. These newly developed multilayer networks have also been successfully characterized by contact angle measurement, environmental scanning electron microscopy (ESEM), energy-dispersive X-ray spectroscopy (EDS), and atomic force microscopy (AFM). The superhydrophilic effect, which was confirmed by the contact angle measurements, of the silica networks ensured the hydrophilic nature of the selectively constructed nanoporous silica nanoparticles onto the patterned hydrophobic COC microchannel. The capillary effect of the developed surface was characterized by measuring the length of a test liquid driven by the induced capillary forces in an on-chip capillary pumping platform with horizontal microchannels. The pumping capability achieved from the sprayed nanoporous surface for the on-chip micropump was mainly due to the strong capillary imbibition driven by the multicoated bilayers of hydrophilic silica nanoparticles. The developed networks with spray-assembled nanoparticles were also applied for an on-chip blood plasma separation platform with closed microchannels. The spray LbL method developed in this work can be a highly practical approach for the modification of various polymer microchannels because of several advantages such as an extremely simple process for the multilayer formation and flexibly controlled surface functionality at room temperature.

High Performance of Cyclic Olefin Copolymer-Based Capillary Electrophoretic Chips

This paper demonstrates a simple, one step, and low cost surface modification technique for producing cyclic olefin copolymer (COC) polymer-based microcapillary electrophoresis chips consisting highly hemocompatible microchannels by UV-photografting with N-vinylpyrrolidone (NVP) monomer. An optimal condition has been identified to achieve the best surface grafting process. It has been found that this surface treatment enables extremely high surface wettability, hemocompatibility, and bond strength to the microchannels. The surface grafting was confirmed by attenuated total reflection Fourier transform-infrared spectroscopic (ATR-FTIR) study. In vitro protein adsorption using fluorescent labeled bovine serum albumin (FITC-BSA) into the COC microchannel results indicates that the modified chips have excellent protein resistance ability because of the increase of surface hydrophilicity. Hence, the modified chips showed fast, reproducible and high efficient separations of proteins (up to 51,000 theoretical plates per meter). Moreover, this surface modification process show no loss in the optical transparency to the modified microchannel surfaces: an important requirement for real capillary electrophoresis since the fluorescent intensity is directly related to the amount of adsorbed protein on the surface. Therefore, we believe that this simple and promising route of surface modification could be very useful for developing high performance COC microfluidic devices for the separation of proteins, amino acids, and other biomolecules.

Charge Tunable Zwitterionic Polyampholyte Layers Formed in Cyclic Olefin Copolymer Microchannels through Photochemical Graft Polymerization

Zwitterionic layers immobilized on various surfaces exhibit ideal biocompatibility and antifouling capability, but direct immobilization of zwitterionic molecules provides limited choice of surface charges. In this paper, the formation of charge tunable zwitterionic polyampholyte layers onto the surface of microfluidic channels of cyclic olefin copolymer by photochemical graft polymerization of mixed acrylic monomers, [2-(acryloyloxy) ethyl] trimethyl ammonium chloride and 2-acrylamido-2-methyl-1-propanesulfonic, under UV illumination was reported. With this method, surface charge of the resulting modification layers could be tailored through the initial monomer ratio and reaction conditions. The incorporation of both monomers into the grafted layers was confirmed by X-ray photoelectron spectroscopy (XPS) and attenuated total reflection Fourier transform infrared (ATR-FTIR). The results indicate that the modified layers are hydrophilic with contact angles of 33.0-44.3°, and the isoelectric points of the modified layers can be tuned from <3 to >9 simply by adjusting the monomer ratios. Elimination of the nonspecific adsorption of proteins on the zwitterionic layers thus formed was proved by fluorescent microscopy and streaming potential measurement. The uniformity of the modified layers was verified through a comparison of electrophoresis inside the modified and native microchannels. A whole blood coagulation time measurement was performed to show its applicability.

Fabrication of various cross-sectional shaped polymer microchannels by a simple PDMS mold based stamping method

We describe a facile and simple stamping method to fabricate various cross-sectional shaped microfluidic channels in transparent polymer materials such as polydimethylsiloxane (PDMS), poly(methylmethacrylate) (PMMA), polystyrene (PS), and cyclic olefin copolymer (COC). First, microchannels of circular, rectangular, and triangular shape and different size were fabricated on a silicon wafer through an isotropic or anisotropic wet etching process, and the resultant microchannels on silicon wafers were transferred to PDMS through a replication technique. The produced PDMS with replicated convex microchannels served as a master mold. A variety of polymer solutions were pressed down against the PDMS master mold, and cured until the solvent was evaporated, generating circular, rectangular, and triangular shaped PDMS, PMMA, PS, and COC microchannels. The microchannels could be repeatedly prepared with a narrow standard deviation, thus demonstrating high reproducibility of the proposed method. The microchannel dimensions, shape, and surface roughness could be controlled by tuning the channel width of the mask, the wet etching direction, the etchant solution, and the concentration of KOH, respectively, when the microchannels were fabricated on a silicon wafer. This simple but efficient PDMS mold based stamping method can be widely used for fabricating different shaped microchannels on diverse polymer materials with high reproducibility, low cost, and high speed.

New “one-step” method for the simultaneous synthesis and anchoring of organic monolith inside COC microchip channels

A new method for monolith synthesis and anchoring inside cyclic olefin copolymer (COC) microchannels in a single step is proposed. It is shown that type I photoinitiators, typically used in a polymerization mixture to generate free radicals during monolith synthesis, can simultaneously act as type II photoinitiators and react with the plastic surface through hydrogen abstraction. This mechanism is used to "photograft" poly(ethylene glycol) methacrylate (PEGMA) on COC surfaces. Contact angle measurements were used to observe the changes in surface hydrophilicity when increasing initiator concentration and irradiation duration. The ability of type I photoinitiators to synthesize and anchor a monolith inside COC microchannels in a single step was proved through SEM observations. Different concentrations of photoinitiators were tried. Finally, electrochromatographic separations of polycyclic aromatic hydrocarbons were realized to illustrate the beneficial effect of anchoring on chromatographic performances. The versatility of the method was demonstrated with two widely used photoinitiators: benzoin methyl ether (BME) and azobisisobutyronitrile (AIBN).

Thermal bonding of microfluidic devices: Factors that affect interfacial strength of similar and dissimilar cyclic olefin copolymers

Thermal bonding of the same polymer is an important method for obtaining good thermal sealing between two polymeric substrates in microfluidic devices. It is worthwhile to use different grades of the same polymer which have different glass transition temperatures ( T g) because no change in microchannel profile and dimensions would occur in the higher T g substrate during thermal bonding. However, apart from using different grades of a polymer with different T g, there is no fundamental basis for the selection of suitable substrate pairs. Thus an in-depth study of the thermal bond strength of different grades of TOPAS cyclic olefin copolymer (COC) was conducted. The strength development and chain inter-diffusion across the bonded interface between different TOPAS grades was studied, and the influence of molecular weight ( M w ) and bonding temperature was considered. Bonding in both symmetric (between two substrates of the same COC grade) and non-symmetric interfaces (between two substrates of different COC grades) was compared. Bonding was conducted at both below and above the T g. The thermal bond strengths were assessed from lap shear specimens prepared using a range of bonding temperature, time and pressure. Thermal bonding between 5013 and 6015 polymer substrates at 125 °C for 6 min time under 2 MPa pressure was found to be the most favorable conditions at which no deformation in the geometry of the COC microchannel has been observed. The failure surfaces of the specimens were characterized by scanning electron microscopy (SEM). Through the above, a basis for selecting different grades of TOPAS to obtain thermally bonded COC microfluidic devices with high strength was developed. The principles established are believed to be applicable to other polymeric microfluidic chips.

Hydrophobic–hydrophilic conversion in microfluidic polymer channels with TiO2 thin films

In this study, recoverable and maintainable hydrophilic micropatterns on polymer-based microfluidic devices were developed through liquid phase deposition of a photocatalytic TiO2. The TiO2-coated region in the microchannel could be hydrophilized through brief UV irradiation upon request. A titanium oxide film was deposited either on bare polymer substrates or on a titanium-sputtered surface using an aqueous TiCl3 solution at 80 °C. A cyclic olefin copolymer (COC) coated with the TiO2 film displayed effective photocatalytic activity, which reduced the water contact angle from 50° to less than 5°. The Ti seed layer was facilitated to pave the substrate with TiO2 grains during the liquid phase deposition. Thus, the photocatalytic effect could be achieved with less number of LPD cycles. Even after contamination from an organic solvent or photoresist, the surface became hydrophilic upon 5 min of UV irradiation. The photocatalytic effect was so stable that super-hydrophilicity of the surface could be promptly recovered after a month of storage under atmospheric conditions. A COC microchannel was fabricated with TiO2 patterns to allow for controlled delivery of the aqueous liquid without the need for external pumps or valves. A hydrogel pattern self-organized along the TiO2 pattern demonstrated a practical application of the recoverable hydrophilicity in microchannels. Functional hydrogels can easily and stably be integrated into a polymer microchannel using this approach.

Low-temperature (below Tg) thermal bonding of COC microfluidic devices using UV photografted HEMA-modified substrates: high strength, stable hydrophilic, biocompatible surfaces

Cyclic olefin copolymer (COC) based microfluidic devices offer unique opportunities in developing high quality chips for a variety of applications but critical issues such as the bonding strength, biocompatibility and flow need to be addressed before this can be realized. In this study, we introduce a simple microfluidic device fabricated on COC (Topas) substrates that were modified by ultraviolet (UV) photo-grafting of a hydrophilic monomer 2-hydroxyethyl methacrylate (HEMA). This water soluble acrylic monomer was used to increase the bond strength, surface wettability and hemocompatibility. Thermal bonding of the microfluidic chips was accomplished at temperatures well below the glass transition temperature (Tg) of the COC polymer. Moreover, this process produced COC microchannels with modified surfaces that had stable permanent hydrophilic properties. Therefore, it can be used for Bio-MEMS applications in electrophoretic analysis where stable electro-osmotic flow (EOF) is important. The bond strength and burst pressure of the HEMA modified chips increased significantly to 1.70 MPa and 4.20 MPa for bonding at 10 °C below Tg. The COC surfaces were characterized using contact angle, EOF measurements, and Fourier transform infrared spectroscopy. The hydrophilicities of the substrates improved significantly with increase in degree of poly-HEMA immobilization and a maximum grafting yield of about 0.13% was obtained for a short irradiation time of 12 min with 25% of HEMA monomer. In vitrofibrinogen and fluorescent labeled bovine serum albumin adsorption results indicated that the COC surface can easily be tuned against protein adsorption by controlling the grafting yield. The in vitroplatelet adhesion tests confirmed that the hydroxyl functionality greatly improved the surface hemocompatibility of COC by reducing the number and the degree of activation of the adherent platelets.

Label-Free Detection of Heparin, Streptavidin, and Other Probes by Pulsed Streaming Potentials in Plastic Microfluidic Channels

In this paper, pulsed streaming potentials generated in plastic microfluidic channels are used for the label-free detection of some model analytes. The microchannels are fabricated with the commodity plastic cyclic olefin copolymer (COC), and the detection signal arises from a change in the surface charge upon analyte adsorption on the modified microchannel surface. The role of the surface modification is to confer the microchannel with a predetermined charge and a particular specificity toward the adsorption of the target analyte. In this work, several target probes displaying different levels of specificity were investigated. Heparin and streptavidin were detected by adsorption on microchannel surfaces modified with protamine and biotin, respectively, whereas bovine serum albumin (BSA) and methylene blue (MB) showed nonspecific adsorption on almost any modified or unmodified COC microchannel surface. The magnitude of the streaming potential was found to be proportional to the liquid pressure and the surface charge of the microchannel in accord with the Smoluchowski equation. Because the relative polarity of the streaming potential is determined by the surface charge, the most straightforward detection with this method occurs when the charge is reversed upon analyte adsorption. This strategy was used for the species described in this work, and the lowest concentrations detected were approximately 0.01 units/mL for heparin (below clinical relevance), approximately 10 (-9) M for BSA, and approximately 10 (-6) M for MB. Unlike the conventional method of steady flow, in this work, the streaming potentials were measured under pulsed conditions of flow and using nonreference electrodes. This approach removes the need of special electrolytes as it is usually required when using reference electrodes, and at the same time, it mitigates the interference of electrochemical drift from the electrodes. Relative standard deviations of approximately 1-2% and measuring times of approximately 10 s are readily attained with this experimental setup. The on-channel modification of the surface was carried out by UV-photografting methods given the significant UV transparency of COC.

Hydrophilic surface modification of cyclic olefin copolymer microfluidic chips using sequential photografting

The plastic material known as cyclic olefin copolymer (COC) is a useful substrate material for fabricating microfluidic devices due to its low cost, ease of fabrication, excellent optical properties, and resistance to many solvents. However, the hydrophobicity of native COC limits its use in bioanalytical applications. To increase surface hydrophilicity and reduce protein adsorption, COC surfaces were photografted with poly(ethylene glycol) methacrylate (PEGMA) using a two-step sequential approach: covalently-bound surface initiators were formed in the first step and graft polymerization of PEGMA was then carried out from these sites in the second step. Contact angle measurements were used to monitor and quantify the changes in surface hydrophilicity as a function of grafting conditions. As water droplet contact angles decreased from 88 degrees for native COC to 45 degrees for PEGMA-grafted surfaces, protein adsorption was also reduced by 78% for the PEGMA-modified COC microchannels as determined by a fluorescence assay. This photografting technique should enable the use of COC microdevices in a variety of bioanalytical applications that require minimal nonspecific adsorption of biomolecules.

Isoelectric focusing in cyclic olefin copolymer microfluidic channels coated by polyacrylamide using a UV photografting method

As an alternative material to glass or silicon, microfluidic devices made from a cyclic olefin copolymer (COC) were fabricated. This material is of interest because of the relative ease of fabrication, low costs, and solvent resistance. However, as a result of the strong hydrophobic interactions normally present, COC surfaces are not suitable for protein separations. To reduce the protein adsorption and make COC suitable for protein separations, UV-initiated grafting of polyacrylamide was used to coat the surface of COC devices. The change in surface properties caused by different graft times was studied. The surface hydrophilicity and electroosmotic mobility were characterized by contact angle and electroosmosis measurements. Isoelectric focusing was performed to test protein separations in polyacrylamide-coated COC microchannels. A single protein, carbonic anhydrase, was used to analyze the focusing effects and peak capacities in uncoated and polyacrylamide-coated COC devices. Peak capacities ranging from 75 to 190 were achieved with a polyacrylamide-coated surface. A mixture of two proteins, conalbumin labeled with Alexa Fluor 488 and beta-lactoglobulin A labeled with Alexa Fluor 546, was used to test protein separations. Linear and rapid separation of proteins was achieved in the polyacrylamide-coated COC microfluidic device.