PMMA microfluidic chip fabrication using laser ablation and low temperature bonding with OCA film and LOCA

A new PMMA microfluidic chip fabrication method by combining laser ablation technology with low-temperature bonding using optically clear adhesive (OCA) film and liquid optically clear adhesive (LOCA) was presented in this paper. The deformation and clogging issues of the microfluidic channel were well solved. The effective bonding area ratio of microfluidic chips could be greatly improved by adjusting bonding temperature and bonding time. The crevices around the microchannels were effectively eliminated by coating treatment of LOCA. The bonding strength and waterproof of PMMA microfluidic chips coating with/without LOCA were also evaluated in this paper.

     

Rapid prototyping of PMMA microfluidic chips utilizing a CO<Subscript>2</Subscript> laser

A commercially available CO₂ laser scriber is used to perform the direct-writing ablation of polymethyl-methacrylate (PMMA) substrates for microfluidic applications. The microfluidic designs are created using commercial layout software and are converted into the command signals required to drive the laser scriber in such a way as to reproduce the desired microchannel configuration on the surface of a PMMA substrate. The aspect ratio and surface quality of the ablated microchannels are examined using scanning electron microscopy and atomic force microscopy surface measurement techniques. The results show that a smooth channel wall can be obtained without the need for a post-machining annealing operation by performing the scribing process with the CO₂ laser beam in an unfocused condition. The practicality of the proposed approach is demonstrated by fabricating two microfluidic chips, namely a cytometer, and an integrating microfluidic chip for methanol detection, respectively. The results confirm that the proposed unfocused ablation technique represents a viable solution for the rapid and economic fabrication of a wide variety of PMMA-based microfluidic chips.     

Miniaturized DNA amplification platform with soft-lithographically fabricated continuous-flow PCR microfluidic device on a portable temperature controller

Fabrication of 3D microfluidic devices is normally quite expensive and tedious. A strategy was established to rapidly and effectively produce multilayer 3D microfluidic chips which are made of two layers of poly(methyl methacrylate) (PMMA) sheets and three layers of double-sided pressure sensitive adhesive (PSA) tapes. The channel structures were cut in each layer by cutting plotter before assembly. The structured channels were covered by a PMMA sheet on top and a PMMA carrier which contained threads to connect with tubing. A large variety of PMMA slides and PSA tapes can easily be designed and cut with the help of a cutting plotter. The microfluidic chip was manually assembled by a simple lamination process.The complete fabrication process from device design concept to working device can be completed in minutes without the need of expensive equipment such as laser, thermal lamination, and cleanroom. This rapid frabrication method was applied for design of a 3D hydrodynamic focusing device for synthesis of gold nanoparticles (AuNPs) as proof-of-concept. The fouling of AuNPs was prevented by means of a sheath flow. Different parameters such as flow rate and concentration of reagents were controlled to achieve AuNPs of various sizes. The sheet-based fabrication method offers a possibility to create complex microfluidic devices in a rapid, cheap and easy way.

     

Modeling of capacitively coupled contactless conductivity detection on microfluidic chips

A novel equivalent circuit model of capacitively coupled contactless conductivity detection (C4D) on microfluidic chips is presented. The impedance of the solution in microchannels facing the two electrodes for C4D was first introduced in the model of C4D on microfluidic chips. The electrodes and the solution facing electrodes were divided into individual segments in the model, and the effect of the length of divided segments on the model was studied. A back-calculating method was put forward to calculate the stray capacitance between the electrodes, and the variation between the calculated value and the simulated value was only 6 %. To evaluate the accuracy of the model, a hybrid poly (methyl methacrylate) (PMMA)/polydimethylsiloxane (PDMS) microchip was fabricated and a simple model was built. Compared with the outputs of the simple model, the data predicted by the novel model show a much closer fit to experimental results, and the variations were within 8 % over a wide concentration range of 1–500 μm for potassium chloride.     

Solvent vapor treatment controls surface wettability in PMMA femtosecond-laser-ablated microchannels

A solvent vapor treatment was applied to femtosecond-laser-ablated microchannels in PMMA to selectively restore the original hydrophilic wetting behavior of the pristine surface. The hydrophobic surface of the microchannels from the submicron porosity induced by ablation becomes smoother and more transparent after the treatment. This simple and low-cost method, together with suitable masking, can produce wettability patterns that may be exploited to develop passive microfluidic elements such as valves and mixers.     

A low temperature ultrasonic bonding method for PMMA microfluidic chips

Bonding is a bottleneck for mass-production of polymer microfluidic devices. A novel ultrasonic bonding method for rapid and deformation-free bonding of polymethyl methacrylate (PMMA) microfluidic chips is presented in this paper. Convex structures, usually named energy director in ultrasonic welding, were designed and fabricated around micro-channels and reservoirs on the substrates. Under low amplitude ultrasonic vibration, localized heating was generated only on the interface between energy director and cover plate, with peak temperature lower than T _g (glass transition temperature) of PMMA. With the increasing of temperature, solution of PMMA in isopropanol (IPA) increases and bonding was realized between the contacting surfaces of energy director and cover plate while no solution occurs on the surfaces of other part as their lower temperature. PMMA microfluidic chips with micro-channels of 80 μm × 80 μm were successfully bonded with high strength and low dimension loss using this method.     

Printing 3D microfluidic chips with a 3D sugar printer

This study demonstrated how to quickly and effectively print two-dimensional (2D) and three-dimensional (3D) microfluidic chips with a low-cost 3D sugar printer. The sugar printer was modified from a desktop 3D printer by redesigning the extruder, so the melting sugar could be extruded with pneumatic driving. Sacrificial sugar lines were first printed on a base layer followed by casting polydimethylsiloxane (PDMS) onto the layer and repeating. Microchannels were then printed in the PDMS solvent, microfluidic chips dropped into hot water to dissolve the sugar lines after the PDMS was solidified, and the microfluidic chips did not need further sealing. Different types of sugar utilized for printing material were studied with results indicating that maltitol exhibited a stable flow property compared with other sugars such as caramel or sucrose. Low cost is a significant advantage of this type of sugar printer as the machine may be purchased for only approximately $800. Additionally, as demonstrated in this study, the printed 3D microfluidic chip is a useful tool utilized for cell culture, thus proving the 3D printer is a powerful tool for medical/biological research.     

Rapid prototyping of glass-based microfluidic chips utilizing two-pass defocused CO2 laser beam method

A method is proposed for the scribing of glass substrates utilizing a commercial CO₂ laser system. In the proposed approach, the substrate is placed on a hotplate and the microchannel is then ablated using two passes of a defocused laser beam. The aspect ratio and surface quality of the microchannels formed after the first and second laser passes are examined using scanning electron microscopy and atomic force microscopy. The observation results show that the second laser pass yields an effective reduction in the surface roughness. The practicality of the proposed approach is demonstrated by fabricating a microfluidic chip for formaldehyde concentration detection. It is shown that the detection results obtained for five Chinese herbs with formaldehyde concentrations ranging from 5 to 55 ppm deviate by no more than 5.5 % from those obtained using a commercial macroscale device. In other words, the results confirm that the proposed defocused ablation technique represents a viable solution for the rapid and low-cost fabrication of a wide variety of glass-based microfluidic chips.     

Plasma assisted thermal bonding for PMMA microfluidic chips with integrated metal microelectrodes

Fracture of integrated metal microelectrodes likely happens during the thermal bonding process of PMMA [poly (methylmethacrylate)] microfluidic chips. In this paper, the fracture behaviors are studied. The fracture is mainly caused by the plastic deformation of the electrode plate (the PMMA plate with microelectrodes) and the thermal stress of microelectrodes, which is due to the high bonding temperature. To decrease the bonding temperature, a plasma assisted thermal bonding method is evaluated and first used to eliminate the fracture of microelectrodes. In this process, the surface of the cover plate (the PMMA plate with microchannels) is modified using oxygen plasma before the electrode plate is thermally bonded to the cover plate. The parameters of the oxygen plasma treatment are optimized, and the contact angle is decreased from 71.7° to 43.6°. The thermal bonding temperature is optimized, which decreases the temperature from 100 °C to 85 °C. Testing of bonding strength shows an average failure pressure of 1.75 MPa, which is comparable to the bonding strength of 1.46 MPa for chips bonded at 100 °C without plasma modification. In order to demonstrate this bonding method, a PMMA microfluidic chip with integrated copper interdigitated microelectrode arrays for AC electroosmotic pump is fabricated.     

Corona discharge assisted thermal bonding of polymer microfluidic devices

We present a study on the use of corona discharge surface treatment to achieve a fast thermal diffusion bonding process for the creation of microfluidic chips. Wafer scale bonding at 100 mm diameter was attempted. Polymethyl methacrylate (PMMA) wafers were hot embossed to create microchannels before bonding to another blank PMMA wafer. Corona discharge treatment of the PMMA resulted in a more hydrophilic surface. The average water contact angle on PMMA surface decreased from 74.5° before treatment to 35.5° after the treatment. The optimized bonding condition was found to be: 108°C for 4 min at a contact pressure of 3.1 MPa. The bonded chips could withstand an internal gauge pressure in the microchannels of at least seven bars. The rectangular shape of the cross section of the microchannels was conserved with some contraction in the dimensions of 3.7% on the mean widths and 2.1% on the mean depths. Bonding strength was found to increase with the bonding temperature and time while the effect of bonding pressure is evident at lower pressures. At higher pressures, the effect of bonding pressure seemed to have reduced. These effects could be explained by the diffusion mechanisms of the process.     

Fabrication of polyimide microfluidic devices by laser ablation based additive manufacturing

Polyimide microfluidic devices (MFDs) have been attached enormous significance because of its excellent organic-solvent inertness, biocompatibility, and thermal stability. In this paper, a novel fabrication method based on the thought of additive manufacturing, which is adding materials layer by layer from bottom to top, was used to construct a multilayer polyimide MFD. The MFD has sophisticated three-dimensional (3D) microchannels with adjustable cross-sectional geometries and high bonding strength, which leads to good reagent mixing performance, large surface-to-volume ratio, and great durability. Starting from a single polyimide film, ultraviolet (UV) laser was utilized to ablate microchannels on the film. Due to the studies over the influence of UV laser on the channel width, the microchannel edge shape is under control, varying from trapezoid to rectangle. From monolayer to multilayer MFDs, thermal bonding with fluorinated ethylene propylene (FEP) nanoparticle dispersion as the adhesive was adopted to stack polyimide films tightly with precise alignment. In this way, microchannels can be connected vertically between layers to form 3D structures. Besides, a homogeneous adhesive interlayer and polyimide-FEP mixing regime were formed, which can provide high bonding strength. Results of computational fluid dynamics simulation of 3D microchannel structures and organic synthesis experiment revealed that our device has great reagent mixing efficiency and promising application prospects in diverse research fields, especially organic chemical and biological studies.

     

A 3D printed centrifugal microfluidic platform for automated colorimetric urinalysis

Colorimetric urinalysis is a commonly performed test for rapid and low-cost diagnosis. Conventional colorimetric urinalysis is manually conducted using dipsticks and suffers from difficulties in control of sample distribution and color interpretation. This paper reports a microfluidic platform for conducting automated colorimetric urinalysis. Centrifugal microfluidic technology was used for regulating the distribution of urine sample in designed volume and time sequence. The prototype of the microfluidic chip was fabricated using 3D printing technology. To test the feasibility of the prototype system, commercial urinalysis strips were integrated with the microfluidic system for detecting glucose, specific gravity, PH, and protein from simulated urine sample. The color change of the strips was recorded using a smartphone and analyzed to quantify the interested parameters. The H (hue), S (saturation) and V (value) coordinates of the HSV color space were extracted and related to the change of the four parameters. The intensity change of V channel showed good representation of the change of glucose concentration and specific gravity. The intensity change of S channel decreased as the increase of PH and protein concentration. The proposed Lab-on-CD platform has potential for automating colorimetric urinalysis to reduce the user errors, thus to made the testing results conducted by non-professionals more reliable.

     

New disposable microfluidic chip without evaporation effect for semen analysis in clinics and homes

The number of infertile couples considering using assisted reproductive technologies (ARTs) is growing. Several key indices, such as sperm concentration and motility, are considered when determining an appropriate technique among the existing ARTs. While microscopy is the only way to observe sperms, this method tends to overlook the actual swimming ability of sperms because sperms can be observed only within a very narrow field of view (FOV). In this paper, we propose a microfluidic chip capable of measuring the motility of sperms by inducing the actual swimming ability of sperms in microchannels. To determine whether sperms swim by themselves and reach the target point, 5–10 min is required in an incubator at 37 °C, which inevitably causes the evaporation of the fluid at the microfluidic chip inlet or outlet. A unique structure has been added to the microfluidic chip to prevent unwanted fluid flow due to evaporation, and counting and sorting capabilities of the fabricated device have been experimentally demonstrated. The microfluidic chip is shown to have a good agreement with commercial chips in total sperm counting. Another feature of sorting motile and progressive sperm to 95% on one chip is also verified. This feature differentiates our solution from the existing commercial chips and can help increase the success rate of ARTs. The developed MFC can provide a way to determine the actual swimming motility of sperms using a microscope in small clinics or a portable kit which is publicly available without the expensive sperm analysis equipment.

     

Low-cost polymer microfluidic device for on-chip extraction of bacterial DNA

A polymer microfluidic device for on-chip extraction of bacterial DNA has been developed for molecular diagnostics. In order to manufacture a low-cost, disposable microchip, micropillar arrays of high surface-to-volume ratio (0.152 μm⁻¹) were constructed on polymethyl methacrylate (PMMA) by hot embossing with an electroformed Ni mold, and their surface was modified with SiO₂ and an organosilane compound in subsequent steps. To seal open microchannels, the organosilane layer on top plane of the micropillars was selectively removed through photocatalytic oxidation via TiO₂/UV treatment at room temperature. As a result, the underlying SiO₂ surface was exposed without deteriorating the organosilane layer coated on lateral surface of the micropillars that could serve as bacterial cell adhesion moiety. Afterwards, a plasma-treated PDMS substrate was bonded to the exposed SiO₂ surface, completing the device fabrication. To optimize manufacturing throughput and process integration, the whole fabrication process was performed at 6 inch wafer-level including polymer imprinting, organosilane coating, and bonding. Preparation of bacterial DNA was carried out with the fabricated PDMS/PMMA chip according to the following procedure: bacterial cell capture, washing, in situ lysis, and DNA elution. The polymer-based microchip presented here demonstrated similar performance to Glass/Si chip in terms of bacterial cell capture efficiency and polymerase chain reaction (PCR) compatibility.     

3D-printed peristaltic microfluidic systems fabricated from thermoplastic elastomer

Recent advancements in 3D printing technology have provided a potential low-cost and time-saving alternative to conventional PDMS (polydimethylsiloxane)-based microfabrication for microfluidic systems. In addition to reducing the complexity of the fabrication procedure by eliminating such intermediate steps as molding and bonding, 3D printing also offers more flexibility in terms of structural design than the PDMS micromolding process. At present, 3D-printed microfluidic systems typically utilize a relatively ‘stiff’ printing material such as ABS (acrylonitrile butadiene styrene copolymers), which limits the implementation of large mechanical actuation for active pumping and mixing as routinely carried out in a PDMS system. In this paper, we report the development of an active 3D-printed microfluidic system with moving parts fabricated from a flexible thermoplastic elastomer (TPE). The 3D-printed microfluidic system consists of two pneumatically actuated micropumps and one micromixer. The completed system was successfully applied to the detection of low-level insulin concentration using a chemiluminescence immunoassay, and the test result compares favorably with a similarly designed PDMS microfluidic system. Prior to system fabrication and testing, the material properties of TPE were extensively evaluated. The result indicated that TPE is compatible with biological materials and its 3D-printed surface is hydrophilic as opposed to hydrophobic for a molded PDMS surface. The Young’s modulus of TPE is measured to be 16 MPa, which is approximately eight times higher than that of PDMS, but over one hundred times lower than that of ABS.     

High throughput blood plasma separation using a passive PMMA microfluidic device

Since plasma is rich in many biomarkers used in clinical diagnostic experiments, microscale blood plasma separation is a primitive step in most of microfluidic analytical chips. In this paper, a passive microfluidic device for on-chip blood plasma separation based on Zweifach–Fung effect and plasma skimming was designed and fabricated by hot embossing of microchannels on a PMMA substrate and thermal bonding process. Human blood was diluted in various times and injected into the device. The main novelty of the proposed microfluidic device is the design of diffuser-shaped daughter channels. Our results demonstrated that this design exerted a considerable positive influence on the separation efficiency of the passive separator device, and the separation efficiency of 66.6 % was achieved. The optimum purity efficiency of 70 % was achieved for 1:100 dilution times.     

Fabrication of microfluidic channels based on melt-electrospinning direct writing

Microfluidics is a flourishing field, enabling a wide range of applications. However, the current fabrication methods for creating the microchannel structures of microfluidic devices, such as photolithography and 3D printing, mostly have the problems of time-consuming, high cost or low resolution. In this work, we developed a simple and flexible method to fabricate PDMS microfluidic channels, based on poly(ε-caprolactone) (PCL) master mold additive manufactured by a technique termed melt-electrospinning direct writing (MEDW). It relies on the following steps: (1) direct writing of micrometric PCL 2D or 3D pattern by MEDW. (2) Casting PDMS on the printed PCL pattern. (3) Peeling off of patterned PDMS from the embedded sacrificial PCL layer. (4) Bonding the PDMS with microchannel to another PDMS layer by hot pressing. The process parameters during MEDW such as collector speed, nozzle dimension and temperature were studied and optimized for the quality and dimension of the printed micropatterns. Multilayer fiber deposition was developed and applied to achieve microscale architectures with high aspect ratio. Thus, the microchannels fabricated by the proposed approach could possess tunable width and depth. Finally, T-shape and cross-channel devices were fabricated to create either laminar flow or microdroplets to illustrate the applicability and potential of this method for microfluidic device manufacture.     

Effects of contact-stress on hot-embossed PMMA microchannel wall profile

Hot-embossing (thermal-compression) based microchannel fabrication techniques have gained much attention recently due to their low-cost setup and ease of implementation. However, not much effects have been attempted in trying to understand or characterize the mechanics of the hot-embossing process in fabricating microchannels. Most research groups still rely on trial-and-error processes to hot-emboss microchannels for microfluidic control applications. The present paper describes the application of the contact-stress analysis to understand the mechanism of using molds with micro-features to hot-emboss PMMA substrates. Experimental results showing that the resulting microchannel wall profile can be predicted with good accuracy via a close-form solution of the analysis are also presented.     

The effect of injection molding PMMA microfluidic chips thickness uniformity on the thermal bonding ratio of chips

Injection molding PMMA microfluidic chips can significantly improve the efficiency of chips forming. However, due to the coexistence of macro and micro effects in the injection molding process, the thickness uniformity of molding substrates is poor, which will seriously affect the thermal bonding quality of chips. In this paper, the effect of injection molding PMMA microfluidic chips thickness uniformity on the thermal bonding ratio and the quality of micro-channels was studied by experiments and simulations. The results show that when the following three conditions were satisfied during injection molding process, chips bonding ratio reaches to 93.9?% and the distortions of micro-channels caused by thermal bonding were acceptable. Firstly, the cover plates flatness error is smaller than 50–60?μm and substrates flatness error is smaller than 80–90?μm. Secondly, the maximum thickness difference of stack chips (cover plate stack with substrate) is smaller than 70–80?μm. Thirdly, chips thickness of the middle is larger than that of the two ends along their length direction and chips thickness distribute evenly along their width direction. These conclusions can be used for the parameters selection and moulds design during injection molding process of PMMA microfluidic chips.     

Interfacing microfluidics to LDI-MS by automatic robotic spotting

We developed a method of interfacing microfluidics with mass spectrometry (MS) using a robotic spotting system to automate the contact spotting process. We demonstrate that direct and automated spotting of analyte from multichannel microfluidic chips to a custom microstructured MALDI target plate was a simple, robust, and high-throughput method for interfacing parallel microchannels using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Using thermoplastic cyclic olefin copolymer (COC) polymer microfluidic chips containing eight parallel 100 μm × 46 μm microchannels connected to a single input port, spotting volume repeatability and MALDI-MS signal uniformity are evaluated for a panel of sample peptides. The COC microfluidic chips were fabricated by hot embossing and solvent bonding techniques followed by chip dicing to create open ends for MS interfacing. Using the automatic robotic spotting approach, microfluidic chip-based reversed-phase liquid chromatography (RPLC) separations were interfaced with electrochemically etched nanofilament silicon (nSi) target substrate, demonstrating the potential of this approach toward chip-based microfluidic separation coupled with matrix-free laser desorption/ionization mass spectrometry.