Fabrication Of Microfluidic Devices Research Articles

Surface Passivation of Norland Optical Adhesive Improves the Guiding Efficiency of Gliding Microtubules in Microfluidic Devices.

The microtubule-kinesin biomolecular motor system, which is vital for cellular function, holds significant promise for nanotechnological applications. In vitro gliding assays have demonstrated the ability to transport microcargo by propelling microtubules across kinesin-coated surfaces. However, the uncontrolled directional motion of microtubules has posed significant challenges, limiting the system's application for precise cargo delivery. Microfluidic devices provide a means to direct microtubule movement through their geometric features. Norland Optical Adhesive (NOA) is valued for its mold-free application in microfluidic device fabrication; however, microtubules often climb up channel walls, limiting controlled movement. In this study, a surface passivation method for NOA is introduced, using polyethylene glycol via a thiol-ene click reaction. This technique significantly improved the directional control and concentration of microtubules within NOA microchannels. This approach presents new possibilities for the precise application of biomolecular motors in nanotechnology, enabling advancements in the design of microfluidic systems for complex biomolecular manipulations.

Fabrication of microchannels on silica glass by femtosecond laser multi-scan: From surface generation mechanism to morphology control

Femtosecond laser processing has become a critical technique for the microfabrication of hard and brittle materials, particularly in microfluidic device applications. This study focuses on the fabrication of microchannels with controllable cross-sectional profiles in silica glass, a material known for its excellent physical and chemical properties. Through a combination of experimental research and theoretical analysis, the surface generation mechanisms governing microchannel morphology are investigated, alongside the influence of various processing parameters on the surface roughness at the microchannel bottom. A comprehensive optimization method is developed to control sidewall taper and surface roughness by adjusting laser scanning paths and modes. Utilizing a composite scanning approach, the study achieves near-rectangular microchannels with average sidewall taper angles below 5° and surface roughness (Sa) of 2.53 μm. These results provide a new strategy for precise control of microchannel morphology in silica glass, offering significant potential to enhance the efficiency and precision of microfluidic device fabrication, with broad applications in both industrial and research settings.

Fabrication of Two-Layer Microfluidic Devices with Porous Electrodes Using Printed Sacrificial Layers.

Two-layer microfluidic devices with porous membranes have been widely used in bioapplications such as microphysiological systems (MPS). Porous electrodes, instead of membranes, have recently been incorporated into devices for electrochemical cell analysis. Generally, microfluidic channels are prepared using soft lithography and assembled into two-layer microfluidic devices. In addition to soft lithography, three-dimensional (3D) printing has been widely used for the direct fabrication of microfluidic devices because of its high flexibility. However, this technique has not yet been applied to the fabrication of two-layer microfluidic devices with porous electrodes. This paper proposes a novel fabrication process for this type of device. In brief, Pluronic F-127 ink was three-dimensionally printed in the form of sacrificial layers. A porous Au electrode, fabricated by sputtering Au on track-etched polyethylene terephthalate membranes, was placed between the top and bottom sacrificial layers. After covering with polydimethylsiloxane, the sacrificial layers were removed by flushing with a cold solution. To the best of our knowledge, this is the first report on the sacrificial approach-based fabrication of two-layer microfluidic devices with a porous electrode. Furthermore, the device was used for electrochemical assays of serotonin and could successfully measure concentrations up to 5 µM. In the future, this device can be used for MPS applications.

Advancing paper microfluidics: A strategic approach for rapid fabrication of microfluidic paper-based analytical devices (µPADs) enabling in-vitro sensing of creatinine

Paper-based microfluidic sensors for point-of-care applications represent an exceptional strategy for facilitating rapid sensing within clinical settings. Despite their considerable promise, the ongoing research objective lies in efficiently printing hydrophobic microfluidic channels (µPADs) onto hydrophilic paper while minimizing expenditure. This research paper introduces an advanced, economic, and efficient method for the rapid fabrication of µPADs on paper substrates, enabling immediate colorimetric detection of creatinine in artificial urine using Jaffe’s reagent. The process involves a modified DIY RepRap 3D printer with an integrated technical drawing pen filled with the solution of Polydimethylsiloxane (PDMS) and hexane. This solution creates hydrophobic domain barriers on a flexible nylon-based paper substrate, effectively confining the aqueous medium within the microfluidic channels. We report visual detection of a broad spectrum of creatinine concentrations ranging from 5 mg/dL to 450 mg/dL through the vibrant Janovsky complex appearance on the microfluidic domains. The study identifies the limiting concentration on µPADs as 500 mg/dL. The innovative procedure demonstrates exceptional selectivity, exhibiting a maximum interference of only 0.97 % from potentially interfering substances. This rapid, naked-eye detection of creatinine on nylon 6,6 membranes offers a user-friendly and economical approach, enhancing the capabilities of colorimetric visualization in point-of-care applications.

Review of Polymer MFD Manufacturing Using Laser Technology

This paper provides a comprehensive overview of microfluidic device (MFD) manufacturing processes. The review starts with an introduction elucidating the significance and advantageous of MFDs. Subsequently, a brief description about the materials that employed in MFD fabrication is presented. The manufacturing process used to create MFDs is then thoroughly examined, with a focus on the application of laser technology.

Advancing Tissue Culture with Light-Driven 3D-Printed Microfluidic Devices.

Three-dimensional (3D) printing presents a compelling alternative for fabricating microfluidic devices, circumventing certain limitations associated with traditional soft lithography methods. Microfluidics play a crucial role in the biomedical sciences, particularly in the creation of tissue spheroids and pharmaceutical research. Among the various 3D printing techniques, light-driven methods such as stereolithography (SLA), digital light processing (DLP), and photopolymer inkjet printing have gained prominence in microfluidics due to their rapid prototyping capabilities, high-resolution printing, and low processing temperatures. This review offers a comprehensive overview of light-driven 3D printing techniques used in the fabrication of advanced microfluidic devices. It explores biomedical applications for 3D-printed microfluidics and provides insights into their potential impact and functionality within the biomedical field. We further summarize three light-driven 3D printing strategies for producing biomedical microfluidic systems: direct construction of microfluidic devices for cell culture, PDMS-based microfluidic devices for tissue engineering, and a modular SLA-printed microfluidic chip to co-culture and monitor cells.

Two-Photon Polymerization 3D-Printing of Micro-scale Neuronal Cell Culture Devices.

Neuronal cultures have been a reference experimental model for several decades. However, 3D cell arrangement, spatial constraints on neurite outgrowth, and realistic synaptic connectivity are missing. The latter limits the study of structure and function in the context of compartmentalization and diminishes the significance of cultures in neuroscience. Approximating ex vivo the structured anatomical arrangement of synaptic connectivity is not trivial, despite being key for the emergence of rhythms, synaptic plasticity, and ultimately, brain pathophysiology. Here, two-photon polymerization (2PP) is employed as a 3D printing technique, enabling the rapid fabrication of polymeric cell culture devices using polydimethyl-siloxane (PDMS) at the micrometer scale. Compared to conventional replica molding techniques based on microphotolitography, 2PP micro-scale printing enables rapid and affordable turnaround of prototypes. This protocol illustrates the design and fabrication of PDMS-based microfluidic devices aimed at culturing modular neuronal networks. As a proof-of-principle, a two-chamber device is presented to physically constrain connectivity. Specifically, an asymmetric axonal outgrowth during ex vivo development is favored and allowed to be directed from one chamber to the other. In order to probe the functional consequences of unidirectional synaptic interactions, commercial microelectrode arrays are chosen to monitor the bioelectrical activity of interconnected neuronal modules. Here, methods to 1) fabricate molds with micrometer precision and 2) perform in vitro multisite extracellular recordings in rat cortical neuronal cultures are illustrated. By decreasing costs and future widespread accessibility of 2PP 3D-printing, this method will become more and more relevant across research labs worldwide. Especially in neurotechnology and high-throughput neural data recording, the ease and rapidity of prototyping simplified in vitro models will improve experimental control and theoretical understanding of in vivo large-scale neural systems.

Single-step batch fabrication of microfluidic paper-based analytical devices with a 3D printer and their applications in nanoenzyme-enhanced visual detection of dopamine.

Wax printing is the most widely used method for fabricating microfluidic paper-based analytical devices (μPADs), but it still suffers from disadvantages like discontinuation of wax printers and need for additional equipment for heating treatment. To address these issues, this work initially describes a new class of wax printing approach for high-precision, batch fabrication of μPADs using a household 3D printer. It only involves a one patterning step of printing polyethylene wax into rice paper body. Under optimized parameters, a fabrication resolution, namely the minimum hydrophilic channel width, down to ~189 ± 30 μm could be achieved. In addition, the analytical applicability of such polyethylene wax-patterned μPADs was demonstrated well with enhanced colorimetric detection of dopamine as a model analyte by combining metal-organic framework (MOF) based nanoenzymes (ZIF-67) with a smartphone (for portable quantitative readout). The developed nanosensor could linearly detect dopamine over a concentration range from 10 to 1000 μM, with a detection limit of ca. 2.75 μM (3σ). The recovery results for analyzing several real samples (i.e., pig feed, chicken feed, pork and human serum) were between 91.82 and 102.79%, further validating its good detection accuracy for potential practical applications in food safety and medical diagnosis.

Validation of Fluid Flow Speed Behavior in Capillary Microchannels Using Additive Manufacturing (SLA Technology)

This research explores fluid flow speed behavior in capillary channels using additive manufacturing, focusing on stereolithography (SLA). It aims to validate microchannels fabricated through SLA for desired fluid flow characteristics, particularly capillary-driven flow. The methodology involves designing, fabricating, and characterizing microchannels via SLA, with improvements such as an air-cleaning step facilitating the production of microchannels ranging from 300 to 1000 µm. Experimental validation assesses fluid flow speed behavior across channels of varying dimensions, evaluating the impact of channel geometry, surface roughness, and manufacturing parameters. The findings affirm the feasibility and efficacy of SLA in producing microchannels with consistent and predictable fluid flow behavior between 300 to 800 µm. This study contributes insights into microfluidic device fabrication techniques and enhances the understanding of fluid dynamics in capillary-driven systems. Overall, it underscores the potential of additive manufacturing, specifically SLA, in offering cost-effective and scalable solutions for microfluidic applications. The validated fluid flow speed behavior in capillary channels suggests new avenues for developing innovative microfluidic devices with improved performance and functionality, marking a significant advancement in the field.

Saturation Equation: An Analytical Expression for Partial Saturation during Wicking Flow in Paper Microfluidic Channels.

The design and fabrication of paper-based microfluidic devices is critically dependent on modeling fluid flow through porous paper membranes. A commonly observed phenomenon is partial saturation, i.e., regions of the paper membrane not being filled completely due to pores of different sizes. The most comprehensive model to date of partial saturation during wicking flow in paper is the Richards equation. However, the solution to the Richards equation requires numerical solvers like COMSOL, which makes it largely inaccessible to the paper microfluidics and lateral flow assay community. There is therefore a need for a simple and appropriate model of partial saturation in paper membranes, easily usable by the wider research community. In the current work, we present an approach to model paper membranes as a bundle of parallel capillaries whose radii follow a two-parameter log-normal distribution. Application of the Washburn equation to the bundle provides a distribution of fluid fronts, which can be used to calculate saturation. Using this approach, we developed the "saturation equation"─an explicit analytical expression to calculate saturation as a function of space and time in 1D wicking flow. Experimentally obtained data for spatiotemporal saturation for four different paper materials were fit to this analytical model to obtain parameters for each material. Results obtained from this analytical model match well with both experimental data and numerical results obtained from the Richards equation. The availability of an explicit analytical expression for partial saturation will enable incorporation of the critical phenomenon of partial saturation in the design of paper microfluidic devices.

Double-Sided Tape in Microfluidics: A Cost-Effective Method in Device Fabrication.

The demand for easy-to-use, affordable, accessible, and reliable technology is increasing in biological, chemical, and medical research. Microfluidic devices have the potential to meet these standards by offering cost-effective, highly sensitive, and highly specific diagnostic tests with rapid performance and minimal sample volumes. Traditional microfluidic device fabrication methods, such as photolithography and soft lithography, are time-consuming and require specialized equipment and expertise, making them costly and less accessible to researchers and clinicians and limiting the applicability and potential of microfluidic devices. To address this, researchers have turned to using new low-cost materials, such as double-sided tape for microfluidic device fabrication, which offers simple and low-cost processes. The innovation of low-cost and easy-to-make microfluidic devices improves the potential for more devices to be transitioned from laboratories to commercialized products found in stores, offices, and homes. This review serves as a comprehensive summary of the growing interest in and use of double-sided tape-based microfluidic devices in the last 20 years. It discusses the advantages of using double-sided tape, the fabrication techniques used to create and bond microfluidic devices, and the limitations of this approach in certain applications.

Two‐Photon Direct Laser Writing of pNIPAM Actuators in Microchannels for Dynamic Microfluidics

Microfluidic tools enable to investigate and manipulate various chemical and biological processes at small scales. As a result, it finds widespread applications in lab‐on‐chip devices, drug delivery systems, or miniaturized cell cultures. However, microfluidic devices are still limited in their flexibility and are often designed to fulfill a single functionality. Moreover, technologies to introduce dynamic functionalities with high precision and at high resolution after the development of a continuous phase microfluidic chip remain scarce. Herein, two‐photon polymerization direct laser writing is introduced as a suitable approach to equip continuous phase microfluidic chips with structurally defined thermoresponsive poly(N‐isopropyl‐acrylamide) (pNIPAM) microactuators. Harnessing the lower critical phase transition temperature of pNIPAM, and upon controlling specific design parameters, the efficient catch and release of polystyrene beads of different sizes using a pNIPAM micropillar brush array is demonstrated. Moreover, a biocompatible pNIPAM microgripper array is designed to subsequently capture and release differently sized (single) cell populations. Overall, the method offers great flexibility and a high degree of freedom toward the fabrication of dynamic microfluidic devices with great adaptability to experimental conditions in real time.

Effect of Mold Materials Used During Hot Embossing on Feature Fidelity for Microfabrication in Cyclic Olefin Polymer (COP) Substrate

During the transition from research to market, the fabrication of microfluidic devices in thermoplastic substrates is inevitable. For short production runs of several hundred products, hot embossing is the typical method before moving on to a typically more expensive injection molding process for higher production volumes. In this work, we investigated the effect of mold material used during hot embossing on feature fidelity for microfabrication in cyclic olefin polymer (COP) substrate. Specifically, we designed a simple flow-focusing microfluidic device and fabricated three different molds using silicon wafer by deep reactive ion etching (DRIE), aluminum filled high temperature epoxy by soft lithography and aluminum by CNC milling. We performed hot embossing experiments with 2mm thick COP substrates and these three different molds using automatic bench top Carver hot press. Finally, we characterized the hot embossed substrates by optical and scanning electron microscopy. Fabrication results demonstrate that the mold material plays a big role in feature fidelity. Among the mold materials used, silicon substrate performed the worst based on defects after demolding. Epoxy and aluminum molds were similar in terms of microfabricated feature defects in the substrate which could be mostly attributed to their coefficient of thermal expansion (CTE). A mold material with a CTE closer to the thermoplastic will result in much better feature fidelity.

Evolution of 3d printing technology in fabrication of microfluidic devices and biological applications: a comprehensive review

Lab-on-a-chip or LOC is a term that is used to describe microfluidic devices that integrate multiple analyte detection, which are normally carried out in a laboratory, into one micro-chip unit and may have applications in diverse fields such as electronics, medicine and biomedical domains. Even though microfluidics has advanced greatly during the past decade due to increased needs for portability, reduced sample requirement and multiple analyte detection capabilities biological research has not adopted the technology at the required pace. This may be owing to the time-consuming and expensive process involved in the microfabrication of biochips, the requirement of specialised setup facilities and the extremely high cost associated with microfluidics as compared to conventional technologies. In recent years, three-dimensional (3D) printing has piqued curiosity in the scientific community. It has the potential to create complex, high-resolution structures and that too in a short timeframe depending upon device complexity. This could inspire progressive research in microfluidics, particularly finding applications in biomedical engineering and point-of-care diagnostics. This article gives an overview of how 3D printing aids in the manufacture of microfluidic devices for biological applications, as well as the existing 3D printing methods which are utilised for fabrication and the future perspective in the development of microfluidic devices.

ADVANCES IN ULTRAPRECISION DIAMOND TURNING: TECHNIQUES, APPLICATIONS, AND FUTURE TRENDS

Advances in ultraprecision diamond turning have revolutionized manufacturing processes across various industries, offering unparalleled precision and surface quality in the fabrication of optical components, microfluidic devices, and advanced mechanical parts. This review delves into the techniques, applications, and future trends in ultraprecision diamond turning, highlighting recent advancements and potential trajectories. Techniques in ultraprecision diamond turning have evolved significantly, driven by innovations in machine design, tooling materials, and control systems. Diamond turning machines equipped with ultra-stiff structures, high-speed spindles, and advanced feedback mechanisms enable sub-nanometer level accuracy and surface finishes down to Angstrom levels. Additionally, advancements in single-point diamond turning (SPDT), fast tool servo (FTS), and deterministic microgrinding (DMG) techniques further enhance the versatility and precision of the process. Applications of ultraprecision diamond turning span a wide range of industries, including aerospace, automotive, biomedical, and telecommunications. In optics manufacturing, diamond turning facilitates the production of aspheric lenses, freeform optics, and diffractive optical elements with unprecedented accuracy, contributing to the development of high-performance imaging systems and laser applications. Moreover, in the biomedical field, diamond-turned microfluidic devices enable precise control over fluid flow and particle manipulation, empowering advancements in drug delivery systems and lab-on-a-chip technologies. Future trends in ultraprecision diamond turning are poised to address challenges related to scalability, multi-material processing, and in-situ metrology. Integration of adaptive control algorithms and machine learning techniques promises enhanced process stability and predictive maintenance, optimizing productivity and reducing downtime. Furthermore, the development of hybrid manufacturing approaches, combining diamond turning with additive manufacturing or laser processing, offers novel avenues for fabricating complex, multi-functional components with improved efficiency and cost-effectiveness. The ongoing advancements in ultraprecision diamond turning techniques, coupled with diverse applications across industries, underscore its pivotal role in advancing manufacturing capabilities. Anticipated future trends hold promise for further expanding the scope and impact of this technology, driving innovation and pushing the boundaries of precision engineering.
 Keywords: Ultraprecision, Diamond, Turning, Technique, Review.

Beyond 2D: Novel biomaterial approaches for modeling the placenta

This review considers fully three-dimensional biomaterial environments of varying complexity as these pertain to research on the placenta. The developments in placental cell sources are first considered, along with the corresponding maternal cells with which the trophoblast interact. We consider biomaterial sources, including hybrid and composite biomaterials. Properties and characterization of biomaterials are discussed in the context of material design for specific placental applications. The development of increasingly complicated three-dimensional structures includes examples of advanced fabrication methods such as microfluidic device fabrication and 3D bioprinting, as utilized in a placenta context. The review finishes with a discussion of the potential for in vitro, three-dimensional placenta research to address health disparities and sexual dimorphism, especially in light of the exciting recent changes in the regulatory environment for in vitro devices.

Characterization of Shrink Film Properties for Rapid Microfluidics Lab-on-Chip Fabrication.

Shrink film is a thin sheet of polystyrene plastic that shrinks to 25-40% of its original size when heated. This study investigated the shrinkage factor of the film at different temperatures and baking times to determine the optimal fabrication recipe for shrink film microfluidic device production. Additionally, this study characterized the properties of shrink film, including minimum possible feature size and cross-section geometries, using manual engraving and the CAMEO 4 automated cutting machine. The optimal shrinkage factor ranged from 1.7 to 2.9 at 150 °C and a baking time of 4 min, producing the ideal size for microfluidic device fabrication. The X- and Y-axes shrank ~2.5 times, while Z-axis thickened by a factor of ~5.8 times. This study achieved a minimum feature size of 200 microns, limited by the collapsing of channel sidewalls when shrunk, leading to blockages in the microchannel. These findings demonstrate the feasibility and versatility of using shrink film as a cost-effective and efficient material for the rapid fabrication of microfluidic devices. The potential applications of this material in various fields such as the medical and biomedical industries, bacteria and algae culture and enumeration are noteworthy.

Enhancing fabrication of hybrid microfluidic devices through silane‐based bonding: A focus on polydimethylsiloxane‐cyclic olefin copolymer and PDMS‐lithium niobate

AbstractEffective manipulation and control of fluids in microfluidic channels requires robust bonding between the different components. Polydimethylsiloxane (PDMS) is widely employed in microchannel fabrication due to its affordability, biocompatibility, and straightforward fabrication process. However, PDMS's low surface energy poses challenges in bonding with many organic and inorganic substrates, hindering the development of hybrid microfluidic devices. In this study, a simple and versatile three step process is presented for bonding PDMS microchannels with organic (cyclic olefin copolymer (COC)) and inorganic substrates (lithium niobate (LiNbO3)) using plasma activation and a silane coupling agent. Initially, the PDMS surface undergoes oxygen/argon plasma activation, followed by functionalization with (3‐aminopropyl) triethoxysilane (APTES). Subsequently, the COC or LiNbO3 is plasma activated and brought into contact with PDMS under a load at a specific temperature. Characterization by Fourier transform infrared, scanning electron microscopy, atomic force microscopy, and contact angle measurements confirmed the successful treatment of the substrates. In addition, bonding strength of the fabricated hybrid devices was assessed through leakage and tensile tests. Under optimized conditions (100°C and 4% v/v APTES), PDMS‐COC hybrid microchannels achieved a flow rate of 600 mL/h without leakage and a tensile strength of 562 kPa. Conversely, the PDMS‐ LiNbO3 assembly demonstrated a flow rate of 216 mL/h before leakage, with a tensile strength of 334 kPa. This bonding method exhibits significant potential and versatility for various materials in microfluidic applications, ranging from biomedical research to enhanced oil recovery.

Optimizing laser-based micro-cutting for PMMA microfluidic device fabrication: thermal analysis and parameter optimization

Abstract Laser processes have gained popularity in microfluidic device fabrication. This study aims to determine the optimal parameters for laser-based micro-cutting to achieve the desired width, depth, profile, and material removal, considering the thermal properties of PMMA. A CNC CO2 laser was used, and 29 trials tested various speed and power combinations. Two theoretical models based on trial results focused on depth and width. COMSOL Multiphysics FEA software estimated surface temperature. Theoretical depth estimation matched experimental data more accurately when the P/S ratio was below 0.15 and the scanning speed was set at 500 mm/s or 750 mm/s. At 500 mm/s, width estimation was most accurate, up to 30 W. At 750 mm/s, experimental width exceeded predictions. Material removal increased proportionally with increasing P/S ratio, but beyond a threshold of 0.15, material removal remained nearly constant despite rising heat input. Laser-cut track shape varied, resembling a ‘U’ at lower and a ‘V’ at higher ratios. The groove shape transitioned from ‘U’ to ‘V’ when the temperature surpassed 1200 K. A V-shaped groove required a temperature exceeding 1500 K. Optimization confirmed a microchannel depth of 0.197 mm, width of 0.256 mm, and ‘U–V’ channel shape achievable at 30 W and 200 mm/s scanning speed, with a surface temperature of 1325 K.

Development of a direct PMMA-PCB bonding method for low cost and rapid prototyping of microfluidic-based gas analysers.

Rapid prototyping of microfluidic devices requires low cost materials and simple fabrication methods. PMMA and PCB have been used separately for the fabrication of microfluidic devices in a wide range of applications. Although the combined use of PMMA and PCB can have considerable merits, few works have been reported on the direct bonding of these materials. In this work we have investigated the fabrication of microfluidic devices using PMMA and PCB for the analysis of gaseous samples. In order to yield a reliable direct bonding method, four parameters including temperature, pressure, solvent and patterned interface material were experimentally investigated. Results of testing various prototypes showed that a patterned interface of concentric rectangular copper rings exposed to solvent at room temperature and under moderate pressure provided better adhesion strength, sealing and durability. After successful development of the PMMA-PCB direct bonding process, sample prototypes were designed and fabricated to practically assess the combined advantages of two materials. Presented concepts include implementation of heater on a PCB, array of gas sensors coupled with microchannels, serpentine microchannel and fast evaporation of liquid sample using an SMD resistor. It has been shown that advantages of utilizing PMMA such as fabricating the channel easily and with low cost, can be combined with benefits of a PCB including simple sensor installation and the use of copper tracks and electronic components for gas flow modulation. Moreover, it is possible to implement channel, circuit and other electronic components such as microprocessors on a single device.