Fabrication Of Microfluidic Devices Research Articles

A Flexible Method for Nanofiber-based 3D Microfluidic Device Fabrication for Water Quality Monitoring.

Water pollution seriously affects human health. Accurate and rapid detection and timely treatment of toxic substances in water are urgently needed. A stacked multilayer electrostatic printing technique was developed for making nanofiber-based microfluidic chips for water-quality testing. Nanofiber membrane matrix structures for microfluidic devices were fabricated by electrospinning. A hydrophobic barrier was then printed through electrostatic wax printing. This process was repeatedly performed to create three-dimensional nanofiber-based microfluidic analysis devices (3D-µNMADs). Flexible printing enabled one-step fabrication without the need for additional alignment or adhesive bonding. Practical applications of 3D-µNMADs include a colorimetric platform to quantitatively detect iron ion concentrations in water. There is also great potential for personalized point-of-care testing. Overall, the devices offer simple fabrication processes, flexible prototyping, potential for mass production, and multi-material integration.

Adhesive bonding strategies to fabricate high-strength and transparent 3D printed microfluidic device.

Recently, the use of 3D printing technologies has become prevalent in microfluidic applications. Although these technologies enable low-cost, rapid, and easy fabrication of microfluidic devices, fabricated devices suffer from optical opaqueness that inhibits their use for microscopic imaging. This study investigates bonding strategies using polydimethylsiloxane (PDMS) and printer resin as interlayer materials to fabricate high-strength optically transparent 3D-printed microfluidic devices. First, we fabricated microfluidic structures using a stereolithography 3D printer. We placed 3D-printed structures on interlayer materials coated surfaces. Then, we either let these 3D-printed structures rest on the coated slides or transferred them to new glass slides. We achieved bonding between 3D-printed structures and glass substrates with UV exposure for resin and with elevated temperature for PDMS interlayer materials. Bonding strength was investigated for different interlayer material thicknesses. We also analyzed the bright-field and fluorescence imaging capability of microfluidic devices fabricated using different bonding strategies. We achieve up to twofold (9.1 bar) improved bonding strength and comparable fluorescence sensitivity with respect to microfluidic devices fabricated using the traditional plasma activated PDMS-glass bonding method. Although stereolithography 3D printer allows fabrication of enclosed channels having dimensions down to ∼600 μm, monolithic transparent microfluidic channels with 280 × 110 μm2 cross section can be realized using adhesive interlayers. Furthermore, 3D-printed microfluidic chips can be integrated successfully with Protein-G modified substrates using resin interlayers for detection of fluorescent-labeled immunoglobulin down to ∼30 ng/ml. Hence, this strategy can be applied to fabricate high-strength and transparent microfluidic chips for various optical imaging applications including biosensing.

Fast fabrication of a 3D prototyping microfluidic device for liquid cross-flow and droplet high-throughput generation

Microfluidic applications require the optimization of chip structure and dimensions. The quick and easy fabrication of chips plays an important role in the progress of research. However, the standard soft lithography technique requires several hours to produce a replication mold. Shortening the mold fabrication time still faces some challenges. We present a fast and easy method to fabricate a positive mold for multi-layer or 3D microdevice construction. Single-layer positive molds with triangular, rectangular, and circular patterns were produced in less than 50 min. A depth-to-width ratio is achieved in the range of 0.6–2.4 and the minimum pattern size reached 50 µm. One additional layer only increases the total time by 5 min. Based on the fabricated positive molds, we created microchips with different depth channels and 3D structures, realizing the cross-flow of multiple liquids and the large-scale production of mono-disperse droplets with controllable size. By using the formed droplets as templates, hydrogel particles with controllable structures were synthesized uniformly. The established method is fast, simple, and compatible with standard soft lithography equipment, displaying the potential to accelerating research progress.

Enhancing droplet transition capabilities using sloped microfluidic channel geometry for stable droplet operation.

Droplet-based microfluidics technology allows for the generation and control of droplets that function as independent chemical and biological reactors, enabling broad ranges of high-throughput assays. As more complex multi-step assays are being realized in droplet format, maintaining droplet stability throughout the assay becomes a critical requirement. Unfortunately, as droplets go through multiple manipulation steps, droplet breakage is commonly seen, especially where droplets have to go through sharp transitions in direction and shape. Standard microfabrication techniques typically result in inherent sharp geometry in Z-direction due to their two-dimensional fabrication nature. Recent advancement in micro- and nano- fabrication technology using two-photon polymerization (2PP) is enabling complex 3D microstructures with sub-micrometer resolution to be readily fabricated. Here, utilizing this microfabrication technique, we present a simple solution to the droplet stability challenge by utilizing sloped-geometry microfluidic channels to enable microdroplets to smoothly transition between microfluidic channels having two different heights without breakage. The technique and innovation demonstrated here have the potential to replace conventional droplet microfluidic device fabrication approaches and enable droplet microfluidic platforms to achieve significantly higher level of efficiency, accuracy, and stability never realized before.

マイクロ流体紙基板分析デバイス(µPAD) 作製と応用

マイクロ流体紙基板分析デバイス(µPAD) 作製と応用

Fabrication of high-quality glass microfluidic devices for bioanalytical and space flight applications

Microfabricated glass microfluidic and Capillary Electrophoresis (CE) devices have been utilized in a wide variety of applications over the past thirty years. At the Berkeley Space Sciences Laboratory, we are working to further expand this technology by developing analytical instruments to chemically explore our solar system. This effort requires improving the quality and reliability of glass microfabrication through quality control procedures at every stage of design and manufacture. This manuscript provides detailed information on microfabrication technology for the production of high-quality glass microfluidic chips in compliance with industrial standards and space flight instrumentation quality control.•The methodological protocol provided in this paper includes the scope of each step of the manufacturing process, materials and technologies recommended and the specific challenges that often confront the process developer.•Types and sources of fabrication error at every stage have been identified and their solutions have been proposed and verified.•We present robust and rigorous manufacturing and quality control procedures that will assist other researchers in achieving the highest possible quality glass microdevices using the latest apparatus in a routine and reliable fashion.

Fabrication of surface-treated microfluidic devices for in-Situ observation of yeast cells

Fabrication of surface-treated microfluidic devices for in-Situ observation of yeast cells

A self-driven microfluidic surface-enhanced Raman scattering device for Hg2+ detection fabricated by femtosecond laser.

In this paper, we proposed a novel approach for rapid and flexible fabrication of self-driven microfluidic surface enhanced Raman scattering (SERS) chips for quantitative analysis of Hg2+ by femtosecond laser direct writing. In contrast to traditional microfluidic chips, the microchannels of the device can drive a liquid sample flow without external driving force. The sample flow speed is tunable since the wettability and capillarity properties of the channels, which depend on the roughness and the inner diameter of the microchannels, can be controlled by optimizing the laser processing parameters. The SERS active detection sites, which exhibit high enhancement effects and fine reproducibility, were integrated through the femtosecond laser-induced periodic surface structures (LIPSS), followed by 30 nm Ag deposition. The SERS performance of the as-prepared microfluidic SERS detection chip was studied with R6G as probe molecules. The quantitative analysis of Hg2+ was realized by simply injecting the Hg2+ sample and the probe molecules R6G from the two inlets, separately, and collecting the SERS signal at the detection site. The lowest detection limit for Hg2+ is 10-9 M. It should be mentioned that this study is not only limited to Hg2+ quantitative analysis, but is also mainly aimed to develop a new technique for the design and fabrication of novel self-driven microfluidic devices depending on practical application requirements.

Fabrication of unconventional inertial microfluidic channels using wax 3D printing.

Inertial microfluidics has emerged over the past decade as a powerful tool to accurately control cells and microparticles for diverse biological and medical applications. Many approaches have been proposed to date in order to increase the efficiency and accuracy of inertial microfluidic systems. However, the effects of channel cross-section and solution properties (Newtonian or non-Newtonian) have not been fully explored, primarily due to limitations in current microfabrication methods. In this study, we overcome many of these limitations using wax 3D printing technology and soft lithography through a novel workflow, which eliminates the need for the use of silicon lithography and polydimethylsiloxane (PDMS) bonding. We have shown that by adding dummy structures to reinforce the main channels, optimizing the gap between the dummy and main structures, and dissolving the support wax on a PDMS slab to minimize the additional handling steps, one can make various non-conventional microchannels. These substantially improve upon previous wax printed microfluidic devices where the working area falls into the realm of macrofluidics rather than microfluidics. Results revealed a surface roughness of 1.75 μm for the printed channels, which does not affect the performance of inertial microfluidic devices used in this study. Channels with complex cross-sections were fabricated and then analyzed to investigate the effects of viscoelasticity and superposition on the lateral migration of the particles. Finally, as a proof of concept, microcarriers were separated from human mesenchymal stem cells using an optimized channel with maximum cell-holding capacity, demonstrating the suitability of these microchannels in the bioprocessing industry.

Experimental characterization to fabricate CO2 laser ablated PMMA microchannel with homogeneous surface

Polymethyl methacrylate (PMMA) is widely used for fabrication of microfluidic devices. PMMA, in the recent times, has emerged as an alternative to glass base microfluidic devices owing its convenience in handling, low cost, less weight and excellent optical properties. Due to the high transparency of PMMA and absorption properties in near infrared and UV regions, laser machining can be employed. This work reports characterization of a CO2 laser system, with a wavelength of 10.6 µm, for microfluidic channel fabrication on PMMA. Variety of channels were fabricated by varying CO2 laser system parameters – power, scan speed, pulse frequency and resolution. Power was varied up to its limiting value of 30 W. Surface profile for each of the fabricated channel was recorded and obtained data was analysed. Optimization was done to identify and establish parameters to obtain channels corresponding to specified width and depth. The profile of the channels was observed to have Guassian profile which can be attributed to the Guassian nature of incident laser beam. Effects of post processing using acetone and dichloromethane (DCM) vapour exposure were also studied.

Microfluidic device fabrication mediated by surface chemical bonding.

This review discusses various bonding strategies for fabricating microfluidic devices, with a special emphasis on the modification of the surface assisted by the use of chemicals to assemble microfluidic devices under mild conditions such as room temperature and atmospheric pressure. The paper includes an overview of the wide ranges of bonding methods used in the fabrication of microfluidic systems, such as anodic bonding, fusion bonding, thermal bonding, solvent bonding, and surface chemical bonding. Among these, surface chemical bonding plays a crucial role between the polydimethylsiloxane (PDMS) and thermoplastics in order to assemble a microfluidic device in a simple and facile manner. The first section reviews relevant research on the sealing for microfluidic devices; in the second section, the materials used for device fabrication are reviewed. The third section discusses the different sealing processes used in the fabrication of microfluidic devices on silicon, glass, thermoplastic, and elastomer. Overall, this review concludes with a discussion on the importance of the surface chemical modification for bonding an elastomer - PDMS - with rigid materials at room temperature under atmospheric pressure and detailed discussions on their bond strengths.

Simple and fast fabrication of microfluidic paper-based analytical device by contact stamping for multiple-point standard addition assay: Application to direct analysis of urinary creatinine

In this work, a microfluidic paper-based analytical device (μPAD) for simultaneous multiple-point standard addition assay was fabricated by rubber stamping the hydrophobic barrier pattern onto a laboratory filter paper. The μPAD has a central zone from which an applied sample flows into eight surrounding narrow channels to which had been added the standard solutions. Each channel is connected to a circular area loaded with the reagent. The opposite end of this reagent zone is connected by second narrow channel to the final circular detection zone. The μPAD was applied to the measurement of creatinine in human urine. After addition of a urine sample, the orange-colored product arising from the Jaffé reaction is formed at the eight detection zones. A digital image of the μPAD is then recorded and the ratio of the red/green (R/G) intensity obtained using the ImageJ™ program is used in the quantitation of creatinine. The normal standard addition calibration line is constructed using the intensity ratio against the added creatinine concentrations (50–1000 mg L−1). Good linearity was achieved (r2 ˃ 0.99). There were no significant differences between the creatinine content using an HPLC method (paired t-test at 95% confidence, tstat = 1.78, tcritical = 2.26, n = 10). The use of simultaneous multiple-point standard addition calibration allows rapid determination of creatinine in urine with elimination of matrix interference.

Roll-to-roll wax transfer for rapid and batch fabrication of paper-based microfluidics

This study proposed a novel method for the rapid fabrication of paper-based microfluidic devices using a roll-to-roll wax transfer method. In this approach, a custom-made device was designed and fabricated for the direct roll-to-roll wax transfer from commercially available wax ribbon to the surface of paper substrate. After wax transfer, a thermal reflow process was conducted to enable the melt wax penetration through the whole thickness of the hydrophilic paper substrate to form hydrophobic wax barriers. Compared with the conventional approaches for paper-based microfluidics (wax printing, photolithography, and inkjet printing), the proposed fabrication technique for paper-based microfluidic devices is suitable for the batch fabrication of paper-based microfluidic chips at high production speed. Additional advantages including simple fabrication process, low material and fabrication cost, low-energy consumption, and without the requirement of cleanroom environment or facilities. The paper-based microfluidics fabricated with the proposed roll-to-roll wax transfer method is widely adaptable for microfluidic applications in biological and chemical fields.

Tailoring Electrospun Poly(l-lactic acid) Nanofibers as Substrates for Microfluidic Applications.

Novel microfluidic substrates based on electrospun poly(l-lactic acid) (PLLA) membranes were developed to increase the limited range of commercially available paper substrates, commonly used for the fabrication of microfluidic paper-based analytical devices. PLLA's advantageous properties include biodegradability, biocompatibility, ease of being processed in various tailored morphologies, and cost effectiveness, among others. Oriented and nonoriented electrospun PLLA membranes were fabricated using electrospinning and the influence of fiber orientation, addition of hydrophilic additives, and plasma treatments on the morphology, physicochemical properties, and capillary flow rates were evaluated and compared with the commercial Whatman paper. In addition, a proof-of-concept application based on the colorimetric detection of glucose in printed PLLA and paper-based microfluidic systems was also performed. The results show the potential of PLLA substrates for the fabrication of portable, disposable, eco-friendly, and cost-effective microfluidic systems with controllable properties that can be tailored according to specific biotechnological application requirements, being a suitable alternative to conventional paper-based substrates.

Non-woven fabric-based microfluidic devices with hydrophobic wax barrier

This study proposed a novel method for the fabrication of non-woven based microfluidic devices with a wax hydrophobic barrier. Current microfluidic devices were fabricated with glass or polymer material, and paper is also widely used for the fabrication of low-cost microfluidic devices. The application of non-woven fabric based microfluidic devices provides a new option of bulk materials for microfluidics. Compared with the glass or polymer material used in microfluidics, non-woven fabric is low-cost, easy to process and disposable. Fluid can penetrate through the non-woven fabric material with capillary force without the requirement of external pumps. As fiber-based material, comparing with paper, non-woven fabric material is more durable with higher mechanical strength, and various types of non-woven fabric material also provide a board choice of surface chemical/physical properties for microfluidic applications. In this study, the hydrophilic non-woven fabric is chosen as the bulk material for microfluidic devices, a wax pattern transfer protocol is also proposed in this study for the deposition of hydrophobic barriers. For a demonstration of the proposed fabrication technique, a microfluidic mixer was also fabricated in this study.

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.

Rapid Fabrication of Custom Microfluidic Devices for Research and Educational Applications

Rapid Fabrication of Custom Microfluidic Devices for Research and Educational Applications

Rapid Fabrication of Custom Microfluidic Devices for Research and Educational Applications.

Microfluidic devices allow for the manipulation of fluids, particles, cells, micro-sized organs or organisms in channels ranging from the nano to submillimeter scales. A rapid increase in the use of this technology in the biological sciences has prompted a need for methods that are accessible to a wide range of research groups. Current fabrication standards, such as PDMS bonding, require expensive and time consuming lithographic and bonding techniques. A viable alternative is the use of equipment and materials that are easily affordable, require minimal expertise and allow for the rapid iteration of designs. In this work we describe a protocol for designing and producing PET-laminates (PETLs), microfluidic devices that are inexpensive, easy to fabricate, and consume significantly less time to generate than other approaches to microfluidics technology. They consist of thermally bonded film sheets, in which channels and other features are defined using a craft cutter. PETLs solve field-specific technical challenges while dramatically reducing obstacles to adoption. This approach facilitates the accessibility of microfluidics devices in both research and educational settings, providing a reliable platform for new methods of inquiry.

Unveiling the Potential of Droplet Generation, Sorting, Expansion, and Restoration in Microfluidic Biochips.

Microfluidic biochip techniques are prominently replacing conventional biochemical analyzers by the integration of all functions necessary for biochemical analysis using microfluidics. The microfluidics of droplets offer exquisite control over the size of microliter samples to satisfy the requirements of embryo culture, which might involve a size ranging from picoliter to nanoliter. Polydimethylsiloxane (PDMS) is the mainstream material for the fabrication of microfluidic devices due to its excellent biocompatibility and simplicity of fabrication. Herein, we developed a microfluidic biomedical chip on a PDMS substrate that integrated four key functions—generation of a droplet of an emulsion, sorting, expansion and restoration, which were employed in a mouse embryo system to assess reproductive medicine. The main channel of the designed chip had width of 1200 μm and height of 500 μm. The designed microfluidic chips possessed six sections—cleaved into three inlets and three outlets—to study the key functions with five-day embryo culture. The control part of the experiment was conducted with polystyrene (PS) beads (100 μm), the same size as the murine embryos, for the purpose of testing. The outcomes of our work illustrate that the rate of success of the static droplet culture group (87.5%) is only slightly less than that of a conventional group (95%). It clearly demonstrates that a droplet-based microfluidic system can produce a droplet in a volume range from picoliter to nanoliter.

Three-Dimensional Printed Devices in Droplet Microfluidics.

Droplet microfluidics has become the most promising subcategory of microfluidics since it contributes numerous applications to diverse fields. However, fabrication of microfluidic devices for droplet formation, manipulation and applications is usually complicated and expensive. Three-dimensional printing (3DP) provides an exciting alternative to conventional techniques by simplifying the process and reducing the cost of fabrication. Complex and novel structures can be achieved via 3DP in a simple and rapid manner, enabling droplet microfluidics accessible to more extensive users. In this article, we review and discuss current development, opportunities and challenges of applications of 3DP to droplet microfluidics.