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Low-pressure, high-temperature thermal bonding of polymeric microfluidic devices and their applications for electrophoretic separation
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A new method for thermally bonding poly(methyl methacrylate) (PMMA) substrates has been demonstrated. PMMA substrates are first engraved by CO 2 -laser micromachining to form microchannels. Both channel width and depth can be adjusted by varying the laser power and scanning speed. Channel depths from 50 µm to 1500 µm and widths from 150 µm to 400 µm are attained. CO 2 laser is also used for drilling and dicing of the PMMA parts. Considering the thermal properties of PMMA, a novel thermal bonding process with high temperature and low bonding pressure has been developed for assembling PMMA sheets. A high bonding strength of 2.15 MPa is achieved. Subsequent inspection of the cross sections of several microdevices reveals that the dimensions of the channels are well preserved during the bonding process. Electroosmotic mobility of the ablated channel is measured to be 2.47 × 10 −4 cm 2 V −1 s −1 . The functionality of these thermally bonded microfluidic substrates is demonstrated by performing rapid and high-resolution electrophoretic separations of mixture of fluorescein and carboxyfluorescein as well as double-stranded DNA ladders (X174-Hae III dsDNA digest). The performance of the CO 2 laser ablated and thermally bonded PMMA devices compares favorably with those fabricated by other professional means.
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... If the microfluidic element is not fabricated in the volume of material, it needs to be sealed, so the injected fluid would not escape the system. There are some ways to complete this stage; for example, one may use the direct thermal bonding technique [19]. In simple words, a material is heated to a melting point and applied to the sample surface, and as a result, a hermetic seal is created. ...
... In addition, they excel in good chemical properties and optical clarity. Thermoplastics have already been used in microfluidic device sealing, and results show great adhesion and hermetic seal [19,41]. As a result, it is comparatively very cheap and usable with cm scale microfluidic chips. ...
Expansion of the microfluidics field dictates the necessity to constantly improve technologies used to produce such systems. One of the approaches which are used more and more is femtosecond (fs) direct laser writing (DLW). The subtractive model of DLW allows for directly producing microfluidic channels via ablation in an extremely simple and cost-effective manner. However, channel surface roughens are always a concern when direct fs ablation is used, as it normally yields an RMS value in the range of a few µm. One solution to improve it is the usage of fs bursts. Thus, in this work, we show how fs burst mode ablation can be optimized to achieve sub-µm surface roughness in glass channel fabrication. It is done without compromising on manufacturing throughput. Furthermore, we show that a simple and cost-effective channel sealing methodology of thermal bonding can be employed. Together, it allows for production functional Tesla valves, which are tested. Demonstrated capabilities are discussed.
... Subsequently, a second, non-modified capping slide is bonded to the first one in order to enclose the channels and seal the entire device. A proper bonding is essential to avoid the leakage of fluids or the formation of air bubbles that can affect the quality of the devices, and often requires the use of high temperature, [17] high pressure, and/or organic solvents. [18] These techniques are therefore not compatible with most biomolecule-functionalized layers. ...
... The short OEG spacer between the PLL backbone and the reactive moiety is employed to ensure good antifouling properties of the PLL coating. [17] At the same time, the OEG chain enables a good display of the reactive DBCO and azide moieties at the surface, thus allowing a more efficient reaction. ...
The production of a new class of microfluidic devices built from thermoplastic materials has recently aroused interest in a high‐volume and cost‐effective fabrication of sensing devices. During device formation, the bonding of two slides, one containing the microchannels and another used as a non‐modified capping layer, is generally performed at high temperature, high pressure, and/or employing organic solvents. Such bonding procedures, however, are not compatible with the use of slides pre‐functionalized with biomolecules. Here a low‐temperature, UV‐light‐free, and solvent‐free bonding method for polymeric devices, based on poly‐l‐lysine (PLL) polymers modified with click‐chemistry moieties is presented. The advantages obtained from the use of PLL and the appended complementary click‐chemistry groups enable a fast adsorption of polymers onto the substrates at room temperature, followed by a fast and stable bonding between two complementarily functionalized slides under mild conditions. Bonded fluidic devices show a resistance to high fluid pressures well above those needed for practical application. The optimal density (2–5%) of reactive groups appended to PLL is assessed using lap shear tests. The here developed method achieves bonding at low temperature, which promises fabrication of microfluidic devices functionalized with biomolecules prior to the sealing process, applicable to a wide range of polymeric materials. Microfluidic devices pre‐functionalized with sensitive (bio)molecules need careful device bonding. Easy functionalization of polymeric substrates with click moiety‐functionalized poly‐l‐lysine polymers permits rapid and low‐temperature bonding, which provides sufficient strength for microfluidic applications.
... This results can be explained based on the increased power, which can be associated with a greater amount of energy transferred to the PMMA surface, leading to the removal of larger material volumes and the generation of microchannels that are wider and deeper. 37,38,39,40 However, in this study, due to the increasing speed parameter, the laser speed did not form the sharp tip of the microwell structure. ...
Three-dimensional (3D) cell culture systems are becoming increasingly popular due to their ability to mimic the complex process of angiogenesis in cancer, providing more accurate and physiologically relevant data than traditional two-dimensional (2D) cell culture systems. Microwell systems are particularly useful in this context as they provide a microenvironment that more closely resembles the in vivo environment than traditional microwells. Poly(ethylene glycol) (PEG) microwells are particularly advantageous due to their bio-inertness and the ability to tailor their material characteristics depending on the PEG molecular weight. Although there are several methods available for microwell fabrication, most of them are time-consuming and expensive. The current study utilizes a low-cost laser etching technique on poly(methyl methacrylate) materials followed by molding with PDMS to produce microwells. The optimal conditions for making concave microwells are an engraving parameter speed of 600 mm/s, power of 20%, and a design diameter of the microwell of 0.4 mm. The artificial tumor achieved its full size after 7 days of cell growth in a microwell system, and the cells developed drugs through a live/dead assay test. The results of the drug testing revealed that the IC50 value of zerumbone-loaded liposomes in HepG2 was 4.53 pM, which is greater than the IC50 value of zerumbone. The HepG2 cancer sphere’s 3D platform for medication testing revealed that zerumbone-loaded liposomes were very effective at high doses. These findings generally imply that zerumbone-loaded liposomes have the capacity to target the liver and maintain medication delivery.
... In order to reduce the prospect of channel collapse during thermal bonding, several practices have also been developed. For thermoplastic substrates it has been found that elevating the temperature above while applying a lower pressure [226] or applying high pressure at temperature well below [219] allows reducing the channel deformation and attaining a stable bond. ...
The thesis is discussing about ultrafast laser-matter interaction and micromachining of polymeric lab on a chip devices using femtosecond laser.
Relying on this I have fabricated and validated two different prototypes of polymeric lab on a chip, (1) a device for capturing circulating tumour cell and (2) a device for neuronal cell culturing. As part of the fabrication of the lab on a chip, a new simple and low-cost solvent assisted thermal bonding technology has also been established. Furthermore, in order to avoid a time consuming trial and error process, an accurate statistical Design of Experiment procedure to estimate the influence of the laser repetition rate, pulse energy, scanning speed, and hatch distance on the femtosecond laser micro-milled depth of the microstructures has also been defined.
... Bonding is an essential step in creating multilayer PDMS bio-microfluidic devices. PDMS can be bonded to different substrates, including the PDMS material itself, using different bonding techniques such as thermal bonding [18][19][20][21][22][23], solvent-assisted bonding [10,[24][25][26][27][28][29][30][31][32], adhesive-based bonding [24,31,[33][34][35], and surface modification bonding [13,[36][37][38][39][40][41][42][43][44][45]. ...
Polydimethylsiloxane (PDMS) is a widely used material for soft lithography and microfabrication. PDMS exhibits some promising properties suitable for building microfluidic devices; however, bonding PDMS to PDMS and PDMS to other materials for multilayer structures in microfluidic devices is still challenging due to the hydrophobic nature of the surface of PDMS. This paper presents a simple yet effective method to increase the bonding strength for PDMS-to-PDMS using isopropyl alcohol (IPA). The experiment was carried out to evaluate the bonding strength for both the natural-cured and the heat-cured PDMS layer. The results show the effectiveness of our approach in terms of the improved irreversible bonding strength, up to 3.060 MPa, for the natural-cured PDMS and 1.373 MPa for the heat-cured PDMS, while the best bonding strength with the existing method in literature is 1.9 MPa. The work is preliminary because the underlying mechanism is only speculative and open for future research.
... More recently, laser ablation and writing on compact materials such as polymethylmethacrylate (PMMA) and polyethyleneterephthalate (PET) have made constructing microfluidic chips even cheaper and more feasible. Applications of these devices include, but are not limited to, electrotaxis [9], phototaxis [10], electrophoretic separation [11], wound-healing assay [10] and analysis of biomolecules [12,13]. ...
Microfluidic gradient generators (MGGs) provide a platform for investigating how cells respond to a concentration gradient or different concentrations of a specific chemical. Among these MGGs, those based on Christmas-tree-like structures possess advantages of precise control over the concentration gradient profile. However, in designing these devices, the lengths of channels are often not well considered so that flow rates across downstream outlets may not be uniform. If these outlets are used to culture cells, such non-uniformity will lead to different fluidic shear stresses in these culture chambers. As a result, cells subject to various fluidic stresses may respond differently in aspects of morphology, attachment, alignment and so on. This study reports the rationale for designing Christmas-tree-like MGGs to attain uniform flow rates across all outlets. The simulation results suggest that, to achieve uniform flow rates, the lengths of vertical channels should be as long as possible compared to those of horizontal channels, and modifying the partition of horizontal channels is more effective than elongating the lengths of vertical channels. In addition, PMMA-based microfluidic chips are fabricated to experimentally verify these results. In terms of chemical concentrations, perfect linear gradients are observed in devices with modified horizontal channels. This design rationale will definitely help in constructing optimal MGGs for cell-based applications including chemotherapy, drug resistance and drug screening.
... For these reasons, thermoplastics such as PMMA have been considered reliable and robust materials since the early years of microfluidics 10 . Different protocols have been described to fabricate closed channels in thermoplastics, such as solvent bonding 15 , heat bonding 16 , and ultraviolet (UV)/ozone surface treatment bonding 17 . ...
... However, microchannels are prone to collapse once applied with high temperature and pressure, making it challenging to maintain channel integrity. 9 Meanwhile, to reduce the surface energy of bonding surfaces, UV/ozone or oxygen plasma treatment is typically applied to make surfaces more hydrophilic, 10 resulting in a processing time often longer than 1 h. 7 During solvent bonding, thermoplastic substrates are dissolved in organic solvents with similar solubility. ...
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.
In this paper, we investigate the use of a commercial CO2 laser system for fabrication of microfluidic systems in polymers. We discuss the cutting process with the laser system and present a straightforward model for the channel depth of microchannels dependent on the fabrication parameters. In particular, we examine the influence of the cutting sequence, the number of cut passes, the laser beam velocity and the laser radiant flux. The model allows the prediction of microchannel depths within a maximum deviation of 8 µm for channels that are up to 210 µm in depths. It was shown that, at constant channel depth, the channel width could be varied by 27% by using different cutting parameters. The optimum cutting sequence for the production of a channel -junction is also presented in the paper. The laser system is shown to be a flexible and rapid tool for the production of polymer microfluidic prototypes.
An integrated microfluidic design, modeling, and rapid prototyping process is presented. It is based on laser cutting and lamination of individual thin layers of plastic. The process allows the rapid and low-cost manufacturing of both simple and complex 3-dimensional microfluidic flow structures that are routinely designed, fabricated, and tested within the space of 24 hours. It has yielded microfluidic elements and systems, such as mixers, separators, and detectors, as well as complete microfluidic integrated circuits that have been used with complex biological samples such as whole blood. Both active, machine-controlled microfluidic disposables as well as passive, self-contained cards that do not require any external instrument are presented. Such devices include a disposable hematology analyzer chip, as well as blood separation and analysis tools.
A new method for thermally bonding poly(methyl methacrylate) (PMMA) substrates to form microfluidic systems has been demonstrated. A PMMA substrate is first imprinted with a Si template using applied pressure and elevated temperature to form microchannel structures. Ibis embossing method has been used to successfully pattern over 65 PMMA pieces using a single Si template. Thermal bonding for channel enclosure is accomplished by clamping together an imprinted and a blank substrate and placing the assembly in boiling water for 1 h. The functionality of these water-bonded microfluidic substrates was demonstrated by performing high-resolution electrophoretic separations of fluorescently labeled amino acids. Testing of bond strength in four microdevices showed an average failure pressure of 130 kPa, which was comparable to the bond strength for devices sealed in air. Subsequent profilometry of separated substrates revealed that the dimensions of the channels were well preserved during the bonding process. This new methodology for generation of microfluidic constructs should facilitate the permanent incorporation of hydrated, molecular size-selective membranes in microdevices, thus circumventing problems associated with membrane swelling in microfluidic systems upon exposure to water.
This paper describes a novel technique for bonding polymeric-microfluidic devices using microwave energy and a conductive polymer (polyaniline). The bonding is achieved by patterning the polyaniline features at the polymer joint interface by filling of milled microchannels. The absorbed electromagnetic energy is then converted into heat, facilitating the localized microwave bonding of two polymethylmethacrylate (PMMA) substrates. A coaxial open-ended probe was used to study the dielectric properties at 2.45 GHz of the PMMA and polyaniline at a range of temperatures up to 120 °C. The measurements confirm a difference in the dielectric loss factor of the PMMA substrate and the polyaniline, which means that differential heating using microwaves is possible. Microfluidic channels of 200 µm and 400 µm widths were sealed using a microwave power of 300 W for 15 s. The results of the interface evaluations and leak test show that strong bonding is formed at the polymer interface, and there is no fluid leak up to a pressure of 1.18 MPa. Temperature field of microwave heating was found by using direct measurement techniques. A numerical simulation was also conducted by using the finite-element method, which confirmed and validated the experimental results. These results also indicate that no global deformation of the PMMA substrate occurred during the bonding process.
Thermally unstable polymers such as poly(methyl methacrylate) are degraded considerably during industrial processing. This degradation and its reduction to a minimum have been investigated in both lab and continuous pilot-scale experiments. A three-step degradation mechanism, starting at 180 °C, was proved by Thermogravimetrical Analysis (TGA) and a kinetic approach to describe it was derived. The knowledge of this degradation behavior was then applied to a pilot-scale process with a production rate of 10 kg/h and the process yield loss during the devolatilization step was investigated. Using heat stabilizers, the overall process yield could be improved by 10 %, whereas the residual organic volatiles concentration (VOC) was drastically reduced to values below 1000 ppm. In order to preserve the molecular weight of the final product these stabilizers were added into the process, separately, at the end of the polymerization reaction but before the devolatilization step.
This report describes a UV laser photoablation method for the production of miniaturized liquid-handling systems on polymer substrate chips. The fabrication of fluid channel and reservoir networks is accomplished by firing 200 mJ pulses from an UV excimer laser at substrates moving in predefined computer-controlled patterns. This method was used for producing channels in polystyrene, polycarbonate, cellulose acetate, and poly(ethylene terephthalate). Efficient sealing of the resulting photoablated polymer channels was accomplished using a low-cost film lamination technique. After fabrication, the ablated structures were observed to be well defined, i.e., possessing high aspect ratios, as seen by light, scanning electron, and atomic force microscopy. Relative to the original polymer samples, photoablated surfaces showed an increase in their hydrophilicity and rugosity as a group, yet differences were noted between the polymers studied. These surface characteristics demonstrate the capability of generating electroosmotic flow in the cathodic direction, which is characterized here as a function of applied electric field, pH, and ionic strength of common electrophoretic buffer systems. These results show a correlation between the ablative changes in surface conditions and the resulting electroosmotic flow. The effect of protein coatings on ablated surfaces is also demonstrated to significantly dampen the electroosmotic flow for all polymers. All of these results are discussed in terms of developing liquid-handling capability, which is an essential part of many μ-TAS and chemical diagnostic systems.
Microfabricated electrophoretic separation devices have been produced by an injection-molding process. The strategy for producing the devices involved solution-phase etching of a master template on a silicon wafer, followed by electroforming more durable injection-molding masters in nickel from the silicon master. One of the nickel electroforms was then used to prepare an injection mold insert, from which microchannel chips in an acrylic substrate were mass-produced. The microchannel devices were used to demonstrate high-resolution separations of double-stranded DNA fragments with total run times of less than 3 min. Run-to-run and chip-to-chip reproducibility was good, with relative standard deviation values below 1% for the run-to-run data and in the range of 2-3% for the chip-to-chip comparisons. Such devices could lead to the production of low-cost, single-use electrophoretic chips suitable for a variety of separation applications, including DNA sizing, DNA sequencing, random primary library screening, and rapid immunoassay testing.
Microfluidic devices have been fabricated on poly(methyl methacrylate) substrates by two independent imprinting techniques. First-generation devices were fabricated using a small-diameter wire to create an impression in plastics softened by low-temperature heating. The resulting devices are limited to only simple linear channel designs but are readily produced at low cost. Second-generation devices with more complex microchannel arrangements were fabricated by imprinting the plastic substrates using an inverse three-dimensional image of the device micromachined on a silicon wafer. This micromachined template may be used repeatedly to generate devices reproducibly. Fluorescent analtyes were used to demonstrate reproducible electrophoretic injections. An immunoassay was also performed in an imprinted device as a demonstration of future applications.
Micromachining was performed in polymethylmethacrylate (PMMA) using X-ray lithography for the fabrication of miniaturized devices (microchips) for potential applications in chemical and genetic analyses. The devices were fabricated using two different techniques: transfer mask technology and a Kapton mask. For both processes, the channel topography was transferred (1:1) to the appropriate substrate via the use of an optical mask. In the case of the transfer mask technique, the PMMA substrate was coated with a positive photoresist and a thin Au/Cr plating base. Following UV exposure, the resist was developed and a thick overlayer (approximately 3 microns) of Au electroplated onto the PMMA substrate only where the resist was removed, which acted as an absorber of the X-rays. In the other technique, a Kapton film was used as the X-ray mask. In this case, the Kapton film was UV exposed using the optical mask to define the channel topography and following development of the resist, a thick Au overlayer (8 microns) was electrodeposited onto the Kapton sheet. The PMMA wafer during X-ray exposure was situated directly underneath the Kapton mask. In both cases, the PMMA wafer was exposed to soft X-rays and developed to remove the exposed PMMA. The resulting channels were found to be 20 microns in width (determined by optical mask) with channel depths of approximately 50 microns (determined by x-ray exposure time). In order to demonstrate the utility of this micromachining process, several components were fabricated in PMMA including capillary/chip connectors, injectors for fixed-volume sample introduction, separation channels for electrophoresis and integrated fiber optic fluorescence detectors. These components could be integrated into a single device to assemble a system appropriate for the rapid analysis of various targets.
Poly(dimethylsiloxane) (PDMS) capillary electrophoresis (CE) microchips were modified by a dynamic coating method that provided stable electroosmotic flow (EOF) with respect to pH. The separation channel was coated with a polymer bilayer consisting of a cationic layer of Polybrene (PB) and an anionic layer of dextran sulfate (DS). According to the difference in charge, PB- and PB/ DS-coated channels supported EOF in different directions; however, both methods of channel coating exhibited a pH-independent EOF in the pH range of 5-10 due to chemical control of the effective zeta-potential. The endurance of the PB-coated layer was determined to be 50 runs at pH 3.0, while PB/DS-coated chips had a stable EOF for more than 100 runs. The effect of substrate composition and chip-sealing methodology was also evaluated. All tested chips showed the same EOF on the PB/DS-coated channels, as compared to uncoated chips, which varied significantly. No significant variation for separation and electrochemical detection of dopamine and hydroquinone between coated and uncoated channels was observed.