Fabrication Of Microfluidic Chips Research Articles

One-step bonding and hydrophobic surface modification method for rapid fabrication of polycarbonate-based droplet microfluidic chips

Chip bonding and hydrophobic surface modification are two critical processes for the fabrication of a droplet microfluidic chip from the thermoplastic polycarbonate (PC) material. In this paper, we describe a novel one-step method, which simultaneously bonded and modified two PC substrates. The mechanism of this one-step method is that n-pentane acts as a sacrificial solvent and acetone is the solvent that bonds the PC substrates. Additionally, entrapment functionalization and the Si-O-Si cross-linked network play a central role in the hydrophobic surface modification process. The method was optimized to achieve a high bonding strength, low surface roughness, and high optical transmittance. The naturally hydrophilic PC substrate surface was modified to become a hydrophobic surface, with surface tension decreased from 33.6 mN/m to 14.8 mN/m. Monodisperse droplets generated using a droplet generation chip fabricated by this method had an average diameter of 101.3 μm and coefficient of variation of 0.55%. A droplet digital polymerase chain reaction experiment was successfully carried out using droplets generated from this chip, which demonstrated the effectiveness of this method. This novel one-step method holds great potential for manufacturing droplet-based microfluidic chips using PC in large-scale, and it may have broad applications in microfluidic research fields.

Fabrication of sandwich-like microfluidic chip with circular cross-section micro-channels

In microfluidic chips, most micro-channel cross-section shapes are rectangular or triangular in existing chip fabricating technologies, including hot embossing, lithography, etching, injection molding, etc. However, compared with the above micro-channel shapes, a circular shape has advantages in aspects of fluid flow, droplet generation, heat transfer and blood vessel replication. This paper presents a sandwich-like microfluidic chip with circular cross-section micro-channels. The sandwich-like structure includes three layers. The top and bottom layers are PDMS material while the middle layer is composed of micron glass capillaries (used as micro-channels) with circular cross-sections. The glass capillaries are made of borosilicate tube by a glass heating process. Sphere shaped paraffin wax is used as a sacrificial material to form micro-channel junctions. To test the functions of the fabricated micro sandwich-like microfluidic chip, a droplet generating experiment was conducted in the T-junction chip. The droplet size can be controlled in the range of 20–400 [Formula: see text]m by varying the water and oil flow rates. This proposed microfluidic chip structure has the advantages of short processing cycle, low cost and small flow resistance.

Microfabrication of Nonplanar Polymeric Microfluidics.

For four decades, microfluidics technology has been used in exciting, state-of-the-art applications. This paper reports on a novel fabrication approach in which micromachining is used to create nonplanar, three-dimensional microfluidic chips for experiments. Several parameters of micromachining were examined to enhance the smoothness and definition of surface contours in the nonplanar poly(methyl methacrylate) (PMMA) mold inserts. A nonplanar PMMA/PMMA chip and a nonplanar polydimethylsiloxane (PDMS)/PMMA chip were fabricated to demonstrate the efficacy of the proposed approach. In the first case, a S-shape microchannel was fabricated on the nonplanar PMMA substrate and sealed with another nonplanar PMMA via solvent bonding. In the second case, a PDMS membrane was casted from two nonplanar PMMA substrates and bonded on hemispherical PMMA substrate via solvent bonding for use as a microlens array (MLAs). These examples demonstrate the effectiveness of micromachining in the fabrication of nonplanar microfluidic chips directly on a polymeric substrate, as well as in the manufacture of nonplanar mold inserts for use in creating PDMS/PMMA microfluidic chips. This technique facilitates the creation of nonplanar microfluidic chips for applications requiring a three-dimensional space for in vitro characterization.

Novel solvent bonding method for creation of a three-dimensional, non-planar, hybrid PLA/PMMA microfluidic chip

Fused deposition modeling (FDM) is an approach of 3D printing and has been used in the fabrication of microfluidic systems. Unfortunately, the poor optical transparency of the resulting microfluidic devices makes the characterization and quantification of experiment results difficult. In this study, we developed a method of solvent bonding PMMA and poly(lactic acid) (PLA) thermoplastic materials for the creation of hybrid microfluidic chips. The benefits of the proposed method are as follows: (1) simplified fabrication of complex 3D microfluidic chips; (2) optical characterization and quantification of fabrication results; and (3) the ability to print and embed tubing connectors within the microfluidic chip to facilitate assembly. Three experiments were conducted to evaluate the efficacy of the proposed scheme. We fabricated one microfluidic chip with an S-microchannel to examine the fundamental fabrication results. We also fabricated two application-oriented microfluidic chips respectively featuring a 3D non-planar micromixer and a double emulsion generator. Our experiment results demonstrate the efficacy of this bonding method in the rapid formation of strong bonds (exceeding 13 bars) between PLA and PMMA substrates. The two application examples further demonstrate that the proposed scheme is applicable to the fabrication of complex microfluidic chips quickly and easily without sacrificing their intended functionalities.

Multiplex quantification of metals in airborne particulate matter via smartphone and paper-based microfluidics

On-site spatial variation study of airborne trace metals has been known to be the key to providing a comprehensive evaluation of air pollution information at any targeted location. However, the existing portable approaches either do not allow sample analysis in the longitudinal direction or is not yet practically applicable due to due to the lack of a portable detection method. In this paper, by integrating paper based colorimetric detection via cellphone and unmanned aerial vehicle (UAV) in-air sampling, we present an approach for on-site multiaxial quantification of airborne trace metals in an arrayed format. Using a self-built sampler mounting on a UAV, our approach enables automatic, multiaxial air PM sampling. In addition, by relying only on a cellphone and a custom-made field reaction kit, samples collected in-air can be readily processed, detected in an arrayed format and interpreted on-site within 30 min. Finally, an ultrafast batch-to-batch paper microfluidic chip fabrication protocol enables 48 chips to be fabricated under 30 s at a cost of 1.92 $, making the approach well-suited for disposable on-site use. Our system was first calibrated for 6 metals commonly found in airborne PM (i.e. Co, Cu, Fe, Mn, Cr and Ni), and the corresponding metals detection limits were found to be 8.16, 45.84, 1.86 × 102, 10.08, 1.52 × 102 and 80.40 ng. The validity of our approach was then demonstrated by characterizing 6 metals commonly found in air PM using a certified ash sample, and the experimentally determined metal weight percentage showed a good agreement with the manufacture certified value. Finally, the approach was used for on-site airborne trace metals spatial variation study at 4 difference locations in Fuzhou City (China), thus demonstrating the significance of our approach in supplementing air pollution information gathering and progressing rapid, on-site air toxicity assessment research.

Low-cost rapid prototyping of glass microfluidic devices using a micromilling technique

A method is proposed for rapid prototyping of glass microfluidic devices utilizing a commercial micromilling machine. In the proposed approach, micromilling is performed with the glass substrates immersed in cool water, which could efficiently remove debris and increase the life of milling tools. We also investigate the effects of spindle speed, feed rate, cutting depth, cooling mode, and tool type on finished channel geometries, bottom surface roughness, and burring along the channel sides. It was found that low cutting depths, high spindle speeds and low feed rate produce smoother channels. Several functional microfluidic devices were demonstrated with this rapid prototyping method. The results confirm that the proposed micromilling technique represents a viable solution for the rapid and economic fabrication of glass-based microfluidic chips. We believe that this method will greatly improve the accessibility of glass microfluidic devices to researchers.

Experimental study of fabricating a four-layers Cantor fractal microfluidic chip by CO2 laser system

In this paper, we design a four-layers Cantor fractal microfluidic chip and study suitable materials and parameters to fabricate the microfluidic chip. The effect of changing the parameters of CO2 laser processing on different materials is studied by using CO2 laser processing method. Three kinds of materials are selected to process the microchannel. Then, three kinds of laser powers and three kinds of laser moving speeds are selected to form an orthogonal experiment. The better microchannels in the test range are compared by orthogonal experiment. Finally, the method of hot-pressing bonding is used to seal the four-layers Cantor fractal microfluidic chip. The experimental results show that CO2 laser processing plays an important role in the fabrication of microfluidic chips and it is a high efficiency and low-cost method. The combination method of CO2 laser processing and hot-pressing bonding provides a flexible and fast method for the complete fabrication of microfluidic chips.

Fast Microfluidic Chip Fabrication Technique by Laser Erosion and Sticky Tape Assist Bonding Technique.

Disposable microfluidic chips are becoming increasingly important for biological and chemical researches. Future advances in their commercial applications depends on the mass fabrication of low cost microfluidic chip. In this study we are presenting a simple, low cost and fast way of fabricating PMMA microfluidic chips based on laser erosion. The influence of the width and depth of PMMA microchannels on erosion current and erosion times was analyzed. To bond the open PMMA microchannels at low pressure and temperature, sticky tape assist bonding method was proposed. By this method, the microfluidic chip can be fully sealed without using any equipment. The leakage test indicated that the bonded microfluidic chip can endure an pressure up to 0.82 MPa.

Fabrication of Microfluidic Chip for Investigation of Wound Healing Processes

This work describes a microfludic cell culture device embedded with microstructured posts fabricated by a photolithography technique and a replica-molding technique. BALB/3T3 fibroblast cells were cultured inside the PDMS microfludic chip to form a confluent state, and an external pressure was applied to the top part of the microfluidic chip to remove the cells from the contact areas of the posts. The applied pressure was removed after the formation of wound areas in the cell layer, and the wound healing processes were investigated by monitoring the migration and proliferation of BALB/3T3 fibroblast cells. The function of the microfluidic chip actuated by an applied pressure was investigated by a fluorescent material, and the formation of the wound areas by an applied pressure was investigated by optical microscopy. After the formation of the wound in the cell layer, optical microscopic images of the cells at the same positions were captured by an optical microscope at intervals of 12 h in order to monitor the wound healing processes by migration and proliferation of the cells. Finally, the wound healing was quantitatively assessed by plotting a growth curve. In conclusion, because the microfluidic device developed in this work is very simple and easy to use, the device might be applicable to assessing the wound healing processes and monitoring the migration and proliferation of other cells.

Fabrication of Polyethylene Terephthalate Microfluidic Chip Using CO2 Laser System

Abstract CO2 laser machining technology is a wide and low-cost method for fabrication of microfluidic chips on polyethylene terephthalate (PET). In this paper, the influence of CO2 laser parameters including laser power and laser moving velocity on the depth and width of PET microchannel are studied. Laser power is set from 4 W to 20 W and laser moving velocity is set from 5 mm/s to 25 mm/s in the experiment. Compared with experimental results, some rules for the depth and width on laser parameters are obtained. The depth and width of the microchannel increase with the increase of laser power at the same laser moving velocity. However, the depth and width of the microchannel first increase and then decrease with the increase of laser moving velocity at the same laser power. The PET microfluidic chip is fabricated by a hot bonding machine.

Blood-brain barrier on a chip.

The blood-brain barrier (BBB) plays a vital role in the maintenance of brain homeostasis. It strictly restricts the passage of molecules from the brain vasculature into the brain via its high transendothelial electrical resistance and low paracellular and transcellular permeability. Specialized brain endothelial cells, astrocytes, pericytes, neurons, and microglia contribute synergistically to the functional properties of the BBB. Because of its complexity and relative inaccessibility, BBB research is fraught with difficulties. Most studies rely on animal or cell culture models, which are not able to fully recapitulate the properties of the human BBB. The recent development of three-dimensional (3D) microfluidic models of the BBB could address this issue. This chapter aims to provide an overview of the recent advances in modeling the BBB on microdevices, and illustrate important considerations for the design of such models. In addition, protocols for the fabrication of a 3D BBB microfluidic chip and BBB assessment experiments, including immunocytochemistry for analyzing cell morphology and protein marker expression, permeability assay, and calcium imaging for studying neuronal function as a measure of BBB integrity, are presented here. It is envisioned that continued advancements in microtechnology can lead to the creation of realistic in vivo-like BBB-on-chip models.

Flowing label-free bacteria trapped by small magnetic fields

Trapping of biological entities suspended in flowing liquids is of high interest for lab-on-a-chip devices. Micro-magnetofluidic techniques offer a wireless, remote control, label-free, programmable, isothermal method for such trapping. We investigated trapping of nonmagnetic entities suspended in flowing fluids by uniform magnetic fields. Alignment and chain formation of bacteria and polybeads suspended in flowing ferrofluids was observed under low magnetic fields. Individual bacteria as well as bacteria clusters were trapped in flowing ferrofluids by external magnetic fields, demonstrating trapping over a broad size range. In contrast to the conventional studies of bacteria in a stationary fluid, this work demonstrates continuous label-free trapping and alignment of biological entities in flowing fluids in a simple microchannel with low cost microfluidic chip fabrication, facile sample preparation and remote isothermal control of trapping by small uniform magnetic fields. This is a new approach to noninvasive manipulation for bioassays using perfusion-based systems as well as to bioprinting, drug efficacy, cell phenotype, molecular interactions and tissue engineering studies.

Surface Microfabrication of Conventional Glass Using Femtosecond Laser for Microfluidic Applications

Recently, a lot of attention has been paid to a single-cell analysis using microfluidic chips, since each cell is known to have several different characteristics. The microfluidic chip manipulates cells and performs high-speed and high-resolution analysis. In the meanwhile, femtosecond (fs) laser has become a versatile tool for the fabrication of microfluidic chips because the laser can modify internal volume solely at the focal area, resulting in three-dimensional (3D) microfabrication of glass materials. However, little research on surface microfabrication of materials using an fs laser has been conducted. Therefore, in this study, we demonstrate the surface microfabrication of a conventional glass slide using fs laser direct-writing for microfluidic applications. The fs laser modification, with successive wet etching using a diluted hydrofluoric (HF) acid solution, followed by annealing, results in rapid prototyping of microfluidics on a conventional glass slide for fluorescent microscopic cell analysis. Fundamental characteristics of the laser-irradiated regions in each experimental procedure were investigated. In addition, we developed a novel technique combining the fs laser direct-writing and the HF etching for high-speed and high-resolution microfabrication of the glass. After establishing the fs laser surface microfabrication technique, a 3D microfluidic chip was made by bonding the fabricated glass microfluidic chip with a polydimethylsiloxane (PDMS) polymer substrate for clear fluorescent microscopic observation in the microfluidics.

Large-Area and High-Throughput PDMS Microfluidic Chip Fabrication Assisted by Vacuum Airbag Laminator.

One of the key fabrication steps of large-area microfluidic devices is the flexible-to-hard sheet alignment and pre-bonding. In this work, the vacuum airbag laminator (VAL) which is commonly used for liquid crystal display (LCD) production has been applied for large-area microfluidic device fabrication. A straightforward, efficient, and low-cost method has been achieved for 400 × 500 mm2 microfluidic device fabrication. VAL provides the advantages of precise alignment and lamination without bubbles. Thermal treatment has been applied to achieve strong PDMS–glass and PDMS–PDMS bonding with maximum breakup pressure of 739 kPa, which is comparable to interference-assisted thermal bonding method. The fabricated 152 × 152 mm2 microfluidic chip has been successfully applied for droplet generation and splitting.

Enclosed casting of epoxy resin for rapid fabrication of rigid microfluidic chips

A commercially available epoxy resin from Hexion was demonstrated as a complementary material to PDMS (polydimethylsiloxane) for rapidly fabricating rigid microfluidic devices. The fabrication process was streamlined to include the master mold fabrication, one or two times of the PDMS casting, and an enclosed casting of epoxy resin. The use of PDMS as intermediate molds not only guaranteed the easy demolding, but also enabled the novel enclosed casting. This process can produce epoxy resin microdevices in suitable shapes with even surfaces and preformed via holes, eliminating the inconvenient device preparations, such as cutting and drilling. A series of facile bonding methods were developed for epoxy resin with most of common materials used in microfluidics, yielding improved bonding strengths of 261kPa for epoxy-PDMS, 1185kPa for epoxy-glass, and 1516kPa for epoxy-epoxy. To further demonstrate the material versatility, we performed three critical microfluidic applications on epoxy resin-based microdevices, including multilayer pneumatic microvalves, on-chip PCR with improved efficiencies, and ultra-high-speed flow cytometry imaging of microbeads at a flow rate of 8.3m/s. This study validated the feasibility of utilizing epoxy resin as a routine material for rapidly testing out new designs, for which PDMS may not work, in a laboratory setting.

Emerging Droplet Microfluidics.

Droplet microfluidics generates and manipulates discrete droplets through immiscible multiphase flows inside microchannels. Due to its remarkable advantages, droplet microfluidics bears significant value in an extremely wide range of area. In this review, we provide a comprehensive and in-depth insight into droplet microfluidics, covering fundamental research from microfluidic chip fabrication and droplet generation to the applications of droplets in bio(chemical) analysis and materials generation. The purpose of this review is to convey the fundamentals of droplet microfluidics, a critical analysis on its current status and challenges, and opinions on its future development. We believe this review will promote communications among biology, chemistry, physics, and materials science.

Open microfluidic gel electrophoresis: Rapid and low cost separation and analysis of DNA at the nanoliter scale.

Gel electrophoresis is one of the most applied and standardized tools for separation and analysis of macromolecules and their fragments in academic research and in industry. In this work we present a novel approach for conducting on-demand electrophoretic separations of DNA molecules in open microfluidic (OM) systems on planar polymer substrates. The approach combines advantages of slab gel, capillary- and chip-based methods offering low consumable costs (<0.1$) circumventing cost-intensive microfluidic chip fabrication, short process times (5min per analysis) and high sensitivity (4ng/μL dsDNA) combined with reasonable resolution (17 bases). The open microfluidic separation system comprises two opposing reservoirs of 2-4μL in volume, a semi-contact written gel line acting as separation channel interconnecting the reservoirs and sample injected into the line via non-contact droplet dispensing and thus enabling the precise control of the injection plug and sample concentration. Evaporation is prevented by covering aqueous structures with PCR-grade mineral oil while maintaining surface temperature at 15°C. The liquid gel line exhibits a semi-circular cross section of adaptable width (∼200-600μm) and height (∼30-80μm) as well as a typical length of 15-55mm. Layout of such liquid structures is adaptable on-demand not requiring time consuming and repetitive fabrication steps. The approach was successfully demonstrated by the separation of a standard label-free DNA ladder (100-1000bp) at 100V/cm via in-line staining and laser induced fluorescent end-point detection using an automated prototype.

Fabrication of a SERS-encoded microfluidic paper-based analytical chip for the point-of-assay of wastewater

New environmental problems have arisen due to the production of numerous toxic materials with the development of industrial technologies. Although various technologies have been developed to solve these critical problems, the results were not satisfactory. Therefore, this study introduces a label-free, paper-based biosensing strip sensor to directly analyze the components of wastewater on site. Raman spectroscopy was used for fingerprinting the chemically-vibrational responses of the wastewater. In order to enhance the low signal intensity of the Raman results, the surface-enhanced Raman scattering (SERS) effect was implemented by using gold nanoparticles (AuNPs). Dense and uniform AuNPs were synthesized and distributed onto paper by a power-free successive ionic layer absorption and reaction (SILAR) method. The biosensing ability of the SERS paper strip showed a sensitivity of 10–10 M and an enhancement factor of 2.8 × 107 for rhodamine 6G. Two organic toxic drugs were selected to mimic wastewater. It was demonstrated that the SERS paper strip was sensitive to concentrations of 10–9 M and 10-5 M with correlation coefficients of 0.85 and 0.99 for 4-aminobenzoic acid and pyrocatechol, respectively. Therefore, the proposed SERS-encoded gold paper analytical strip has the potential to be used for the point-of-assay of wastewater.

Capillary-Driven Microfluidic Chips for Miniaturized Immunoassays: Efficient Fabrication and Sealing of Chips Using a "Chip-Olate" Process.

The fabrication of silicon-based microfluidic chips is invaluable in supporting the development of many microfluidic concepts for research in the life sciences and in vitro diagnostic applications such as the realization of miniaturized immunoassays using capillary-driven chips. While being extremely abundant, the literature covering microfluidic chip fabrication and assay development might not have addressed properly the challenge of fabricating microfluidic chips on a wafer level or the need for dicing wafers to release chips that need then to be further processed, cleaned, rinsed, and dried one by one. Here, we describe the "chip-olate" process wherein microfluidic structures are formed on a silicon wafer, followed by partial dicing, cleaning, and drying steps. Then, integration of reagents (if any) can be done, followed by lamination of a sealing cover. Breaking by hand the partially diced wafer yields individual chips ready for use.

Plasma free reversible and irreversible microfluidic bonding.

We demonstrate a facile, plasma free process to fabricate both reversibly and irreversibly sealed microfluidic chips using a PDMS-based adhesive polymer mixture. This is a versatile method that is compatible with current PDMS microfluidics processes. It allows for easier fabrication of multilayer microfluidic devices and is compatible with micropatterning of proteins for cell culturing. When combined with our Shrinky-Dink microfluidic prototyping, complete microfluidic device fabrication can be performed without the need for any capital equipment, making microfluidics accessible to the classroom.