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 shrinkable BOPS-based microfluidic devices

Biaxially oriented polystyrene (BOPS) is a commercialized packaging material, which has the advantages of biocompatibility, non-toxic, transparency, light-weight and cost-effective. Due to the stress accumulated from both directions in plane during the fabrication process, when BOPS was reheated above the glass transition temperature, an isotropic shrinkage will occur. This study proposed a low-cost and rapid prototyping method for the fabrication of BOPS-based microfluidics device. Both laser ablation and micro-milling were used for the fabrication of microchannels on the surface of the BOPS sheet, after thermal induced shrinkage, microchannels with finer microstructure could be achieved. For the sealing of fabricated microchannels on BOPS, two approaches were made using a layer of BOPS or a layer of polyester adhesive film. The thermal induced shrinkage and bonding strength were carefully studied in this study. Several microfluidic devices, including a droplet generator and a diffusion mixer were also fabricated for demonstration. The proposed fabrication method for BOPS-based microfluidics is simple, rapid, cost-effective and without the requirement of cleanroom facility, with help of thermal induced shrinkage, finer structure with high resolution could be achieved with conventional lab tools.     

Design optimization of capillary-driven micromixer with square-wave microchannel for blood plasma mixing

A numerical and experimental investigation is performed into the flow characteristics and mixing performance of three microfluidic polydimethylsiloxane blood plasma mixing devices incorporating square-wave, curved and zigzag microchannels, respectively. For each device, the plasma is introduced into the microfluidic channel under the effects of capillary action alone. Of the three devices, that with the square-wave microchannel is found to yield the best mixing performance, and is therefore selected for design optimization. Four microfluidic micromixers incorporating square-wave microchannels with different widths in the x- and y-directions are fabricated using conventional photolithography techniques. The mixing performance of the four microchannels is investigated both numerically and experimentally. The results show that given an appropriate specification of the microchannel geometry, a mixing efficiency of approximately 76 % can be obtained within 4 s. The practical feasibility of the micromixer is demonstrated by performing prothrombin time (PT) tests using a total liquid volume of 4.0 μL (2.0 μL of plasma and 2.0 μL of PT reagent). It is shown that the mean time required to complete the entire PT test (including loading, mixing and coagulation) is less than 30 s.

     

Convective–diffusive transport in parallel lamination micromixers

Effective mixing and a controllable concentration gradient are important in microfluidic applications. From the scaling law, decreasing the mixing length can shorten the mixing time and enhance the mixing quality. The small sizes lead to small Reynolds numbers and a laminar flow in microfluidic devices. Under these conditions, molecular diffusion is the main transport effect during the mixing process. In this paper, we present complete 2D analytical models of convective–diffusive transport in parallel lamination micromixers for a binary system. An arbitrary mixing ratio between solute and solvent is considered. The analytical solution indicates the two important parameters for convective–diffusive transport in microchannels: the Peclet number and the dimensionless mixing length. Furthermore, the model can also be extended to the mixing of multiple streams—a common and effective concept of parallel mixing in microchannels. Using laser machining and adhesive bonding, polymeric micromixers were fabricated and tested to verify the analytical results. The experimental results agree well with the analytical models.This revised version was published online in March 2005 with corrections to Eq. 12.     

A centrifugal force-based serpentine micromixer (CSM) on a plastic lab-on-a-disk for biochemical assays

In this paper, a centrifugal force-based serpentine micromixer (CSM) on a plastic lab-on-a-disk (LOD) for biochemical assay was designed, fabricated, and fully characterized with numerical and experimental methods. The CSM comprised two inlets, an outlet, and a serpentine microchannel composed of five circumferential channels with connecting radial channels in one layer. The centrifugal force induced in the rotating disk thoroughly mixed the sample and reagent together throughout the serpentine microchannel of the CSM. Despite its simple geometry, effective mixing performance was achieved inside the CSM because of transverse secondary flows and the three-dimensional stirring effect in the microchannel. Numerical simulation showed that the interfaces of the two streams inside the circumferential microchannel were efficiently stirred by the induced transversal velocity field. The plastic LOD was fabricated by CNC-micromilling on one layer of the thermoplastic substrate, followed by thermal bonding with a cover plastic substrate. Mixing performance of the CSM was also investigated experimentally by means of colorimetric analysis using phenolphthalein. High levels of distributive mixings were obtained within a short required mixing length. As a proof-of-concept example, a biochemical assay of albumin level was successfully determined with the help of the LOD containing the CSM. Owing to the mass-producible simple geometry, excellent mixing performance, and convenience, the CSM can be applied to biochemical assays based on the centrifugal microfluidics.     

Six-layer lamination of a new dry film negative-tone photoresist for fabricating complex 3D microfluidic devices

We present a new epoxy-based negative-tone dry film photoresist (DFR) for fabricating multilayer microfluidic devices using a lamination process combined with a standard photolithography technology. As proof-of-concept, a complex 3D-hydrodynamic focusing device was produced via a six-layer lamination process of 33 µm-thick DFR layers. The bonding strength of the new DFR was tested on silicon, glass, and titanium substrates, respectively. A maximum bonding strength of 37 MPa was obtained for the dry film photoresist laminated on glass. No leakage was found, and burst tests proved excellent robustness and sealing reliability of the microchannels.     

Femtosecond laser-induced modification of surface wettability of PMMA for fluid separation in microchannels

The modification of polymer surface wettability is receiving increasing interest in recent years. As surface wettability affects the flowing resistance, and thus the separation ratio and/or mixing ratio of samples in different microchannels, the controlled modification of surface wettability is highly desirable. In this study, microfluidic channels with controlled surface wettability were achieved and fabricated using femtosecond (fs) laser direct ablation of polymethyl methacrylate at various fluences. Varied flow velocities and separation ratio of water in microfluidic channels have been successfully obtained through fs laser-induced modification in wetting characteristics of the microchannel surfaces. A concave flow front was observed in a microchannel with hydrophilic surface. Correspondingly, a convex flow front was observed with hydrophobic surface. For an untreated channel, a straight flow front was observed. These results would be attractive for various microfluidic chip applications, such as control of the reagent reaction through controlling liquid medium separation or control of mixing ratio in different channels.     

The effect of asymmetry on micromixing in curvilinear microchannels

The necessity of microscale mixing processes has been tremendously increasing in most of the microsize chemical and biochemical devices during recent years, particularly in the design of lab-on-a-chip and micrototal analysis systems. Different approaches were implemented in the available micromixers in the literature for improving the mixing performance. Due to the absence of any external source, mixing by utilizing passive mixing techniques is more economical. In curvilinear microchannels, which offer effective passive mixing, chaotic advection results in continuous radial perforation of inter-diffusion layer between the fluid streams due to the transverse secondary flows. In this study, the effects of Dean vortices and secondary flows were investigated in asymmetrical polydimethylsiloxane curvilinear rectangular microchannels, which were fabricated by one-step lithography process and had repeated S-shape patterns with a curvature of 280° along the channel. Moreover, the effect of asymmetry was assessed by comparing the mixing results with symmetrical microchannels. Mixing performance was analyzed by using NaOH and phenolphthalein solutions as mixing fluids, which entered from the channel inlets. According to the results, the significant effects of stretching and contracting motion of Dean vortices revealed themselves above a certain Dean number value, thereby making the asymmetrical microchannel outperform the symmetrical channel in the mixing performance. Below this threshold, the symmetrical microchannel was observed to be superior to the asymmetrical microchannel.     

Film transfer and bonding techniques for covering single-chip ejector array with microchannels and reservoirs

This paper describes a novel covering technique for an MEMS ejector array that is integrated with liquid reservoirs and microchannels on a single chip. The covering technique is based on wicking of a low viscous epoxy through the gap between the ejector wafer and a plate containing a parylene film, and allows the integrated ejector array to be fully covered by the parylene film with excellent uniformity, repeatability and yield. The technique is batch-processible and is suitable to cover many microfluidic systems with a thin film. The parylene film is tightly attached to the ejector array chip (with excellent bonding strength owing to the epoxy), so that liquid is automatically brought into the ejectors from the reservoirs through the microchannels (due to capillary force), as the ejectors shoot out liquid droplets. This automatic liquid supply makes the liquid level (in the ejector) be maintained constant throughout the entire ejection process until more than 90% of the liquid stored in the reservoir is delivered to the ejector through the microchannel. This paper describes also a number of other covering methods that we have experimentally tried, and compares those with the new covering technique. [1459].     

Thermal bonding of PMMA: effect of polymer molecular weight

Microfluidics devices have attracted increasing interest over the last decade. Glass was initially the materials of choice for these devices but polymers such as polymethylmethacrylate (PMMA) have a great potential to be used for these devices because of their low cost, ease of fabrication and chemical properties. A key step in fabrication of these microfluidic devices is the enclosing of microchannels by cover plate, i.e., layer to layer bonding. This investigation focused on the thermal bonding of PMMA layers of different molecular weights. The bond strength and the effect of temperature and pressure on bond strength between various PMMA pairs of different molecular weights were studied. Thermal bonding was realized using a hot embossing system. PMMA strips made from predefined parameters were prepared and a customized CNC machine mold was used to determine the optimized parameters of the thermal bonding. The PMMA pairs investigated are of molecular weights 96.7, 120, 350 and 996 kDa using Instron machine; the shear strength of the thermally bonded specimens was determined. For the PMMA pairs investigated, the greatest shear strength of 1.589 ± 0.286 MPa was observed between molecular weights of 350 and 996 kDa.     

Adhesive bonding by SU-8 transfer for assembling microfluidic devices

SU-8 is largely used to make microfluidic molds or components, but mainly for producing high-precision and thermally stable structures. We present a versatile method that employs SU-8 as glue to perform an adhesive bonding between micro-patterned structures. More in general, this technique enables an easy assembly of microfluidic devices, which can also be made by different materials, where selective bonding is required. The adhesive bonding is achieved by transferring a thin layer of SU-8 5 (thickness ≤15?μm) on a substrate by means of a polyimide foil. The method is described in detail and an example of its application is given. Finally, a shear test is carried out to prove sufficient adhesion strength for microfluidic applications.     

Investigation of strain transmission of surface-bonded FBGs used as strain sensors

Bonding an FBG on a substrate as a sensor using an adhesive, the strain transferred from the substrate through the bonding layer to FBG is smaller than that on the substrate. The strain transmission loss becomes large when the substrate is thin and/or made by a low-modulus material, e.g. the polyimide film used in lithium battery and chip on film manufacturing industry. Moreover, the FBG and the bonding layer affect the original strain distribution on the thin and low-modulus substrate. As a result, the substrate strain sensed by the FBG is underestimated and thus required to be corrected. Based on elasticity, an analytical model is proposed to characterize the strain transmission of an FBG used as a strain sensor when it is surface-bonded on a structure using an adhesive. The proposed strain transmission formula takes the influences caused by the stiffness of substrate and FBG as well as the bonding layer characteristics, i.e. the length, thickness and shear lag parameter into consideration. Validated respectively by numerical simulations using finite element method and experiments, this formula provides a simple but accurate correction for the bonded FBG to reflect the true structural strain.     

Integrated structure of PMMA microchannels for DNA separation by microchip capillary electrophoresis

We proposed and fabricated an integrated structure of microchannels consists of three different functional PMMA layers for post-genome analysis, gene diagnosis, and screenings of useful materials for pharmaceutical. This integrated structure with 96 microchip capillary electrophoresis units in one chip is characterized as the simple structure with low cost and new aspects of the serial unit bio-chemical operation from DNA amplification to their analysis using microchip capillary electrophoresis. The design of the structure was performed using computational fluid dynamics, heat transmission, and electrophoresis simulation. To improve DNA separation resolution, microchannel with narrow width at the corner was adapted. The deep X-ray lithography process using synchrotron radiation “New SUBARU”, nano-imprint, and fusion bonding without bonding adhesive was applied for the fabrication of the integrated structure of microchannels. It was demonstrated that the proposed integrated structure of microchannels results in a good performance of the on-chip DNA amplification and separation in a small MCE unit area of 9 mm × 9 mm.     

Design optimization of micromixer with square-wave microchannel on compact disk microfluidic platform

This paper presents a passive micromixer on a compact disk (CD) microfluidic platform that performs plasma mixing function. The driving force of CD microfluidic platform including, the centrifugal force due to the system rotation, the Coriolis force as a function of the rotation angular frequency and velocity of liquid. Numerical simulations are performed to investigate the flow characteristics and mixing performance of three CD microfluidic mixers with square-wave, curved and zig-zag microchannels, respectively. Of the three microchannels, the square-wave microchannel is found to yield the best mixing performance, and is therefore selected for design optimization. Four CD microfluidic micromixers incorporating square-wave PDMS microchannels with different widths in the x- and y-directions are fabricated using conventional photolithography techniques. The mixing performance of the four microchannels is investigated both numerically and experimentally. The results show that given an appropriate specification of the microchannel geometry and a CD rotation speed of 2,000 rpm, a mixing efficiency of more than 93 % can be obtained within 5 s.     

Microinjection molded disposable microfluidic lab-on-a-chip for efficient detection of agglutination

Previous diagnosing methods based on agglutination have a limitation in view of emergency and point-of-care diagnoses due to the requirement of large scale equipments and much agglutination time. In this paper, we propose a low cost microfluidic lab-on-a-chip for more efficient detection of agglutination. In the present lab-on-a-chip, two inlet microwells, flow guiding microchannels, chaotic micromixer and reaction microwell are fully integrated. Mold inserts for the lab-on-a-chip were manufactured by UV photolithography and nickel electroplating process. The complete lab-on-a-chip was realized by the microinjection molding of cyclic olefin copolymer and the subsequent thermal bonding. The improved serpentine laminating micromixer, developed by our group, integrated in the lab-on-a-chip showed the high-level of chaotic mixing, thereby enabling us to get a reliable mixing of sample and reagent. The performance of the fabricated lab-on-a-chip was demonstrated by agglutination experiments with simulated bloods of 10 μl and simulated sera of 10 μl. The results of agglutination inside the reaction microwell were clearly read by means of the level of light transmission. The present microfluidic lab-on-a-chip could be widely applied to various clinical diagnostics based on agglutination tests.     

Polymerase chain reaction compatibility of adhesive transfer tape based microfluidic platforms

Laser patterned adhesive transfer tapes are a rapid, versatile, and low cost option to fabricate microfluidic platforms. In this work, we examined the compatibility with polymerase chain reaction (PCR) of different types of adhesive tape materials patterned with a CO₂ laser cutter. Acrylic, polyimide, and silicone-based tapes were considered. We performed a systematic study on off-the-shelf adhesive tapes with respect to fluid handling, PCR inhibition, reagent loss, and on-chip PCR reaction. A novel microfluidic PCR approach was implemented that combines the advantages of previously reported systems. It uses a thermal gradient from a single heating element and the thermocycling was carried out by passing the reaction mixture back and forth in a microfluidic channel strategically placed along the thermal gradient. Only the silicone-based tapes were compatible with on-chip PCR. The overall fabrication process takes less than 30 min, uses only off-the-shelf finished or semi-finished materials, and is amenable to large-scale reel-to-reel processing.     

Fabrication of SU-8 photoresist micro–nanofluidic chips by thermal imprinting and thermal bonding

Micro–nanofluidic chips have been widely applied in biological and medical fields. In this paper, a simple and low-cost fabrication method for micro–nano fluidic chips is proposed. The nano-channels are fabricated by thermal nano-imprinting on an SU-8 photoresist layer followed by thermal bonding with a second SU-8 photoresist layer. The micro-channels are produced on the second layer by UV exposure and then thermal bonded by a third layer of SU-8 photoresist. The final micro–nano fluidic chip consists of micro-channels (width of 200.0 ± 0.1 μm and, depth of 8.0 ± 0.1 μm) connected by nano-channels (width of 533 ± 6 nm and, depth of 372 ± 6 nm), which has great potential in molecular filtering and detection.

     

Evaluation of Si liquid cooling structure with microchannel and TSV for 3D application

The development of 3D integration has caused a major technology paradigm shift to all integrated circuit (IC) devices, interconnects, and packages. Despite the benefits of 3D integration, this process faces the key challenge of thermal management, especially for high power and high density IC devices. Due to the limitations of conventional thermal solutions, liquid cooling technology has become a field of great interest for IC thermal management. In this study, an on-chip liquid cooling module with three different through Si vias (TSVs) and a fixed microchannel structure has been fabricated on an Si wafer using deep reactive ion etching and anodic bonding, followed by a grinding and dicing process. Pressure drop, coolant flow, and temperature difference before and after liquid flow were experimentally measured. TSV depth and diameter have been shown to have little effect on the change of pressure drop; however, shallower TSV depth and larger TSV diameter led to improved liquid cooling performance. The trapezoidal TSV showed slightly more effective cooling than did the scalloped TSV or the straight TSV.

     

Rubber-assisted embossing of polymer thin films using molds with through-thickness microchannels

A flexible microfluidic chip is difficult to fabricate using the standard hot embossing technology. In this study, rubber-assisted embossing of polymer thin films using molds with through-thickness microchannels was investigated. The polymer film was thermoformed into the microchannels by rubber as a soft counter-tool. Different processing conditions, as well as material selections, affecting the thickness uniformity and replicated depth were examined. Results indicated that smoother surfaces on the embossed articles were created, and the thickness uniformity and the depth of the embossed channel were significantly affected by the embossing temperature, the embossing pressure, and the rubber hardness. The embossed film was sealed on one side with a layer of transparent adhesive film to form closed microchannels, and desired 3-D flow characteristics were obtained with this flexible microfluidic chip.     

Rapid polymer microchannel fabrication by hot roller embossing process

Using thermoplastic polymers as substrate material is an attractive approach to develop low-cost, disposable microfluidic devices. This study investigates a simple and rapid polymer replication method of fabricating microchannels by a hot roller embossing process. The hot roller embosser used in this study was modified from a commercially available film laminator, and the roller micromold was fabricated by spin coating an SU-8 layer on a flexible copper sheet. A straight microchannel measuring 5?cm long, 200?μm wide, and 41.4?μm deep was used to evaluate the imprinting performance on cyclic olefin copolymer and polyvinylchloride film. This study also investigates the effects of hot roller embossing temperature, rolling speed, and embossing pressure on the microchannel depth and geometry transfer efficiency.