A simple and cost-effective method for fabrication of integrated electronic-microfluidic devices using a laser-patterned PDMS layer

We report a simple and cost-effective method for fabricating integrated electronic-microfluidic devices with multilayer configurations. A CO₂ laser plotter was employed to directly write patterns on a transferred polydimethylsiloxane (PDMS) layer, which served as both a bonding and a working layer. The integration of electronics in microfluidic devices was achieved by an alignment bonding of top and bottom electrode-patterned substrates fabricated with conventional lithography, sputtering and lift-off techniques. Processes of the developed fabrication method were illustrated. Major issues associated with this method as PDMS surface treatment and characterization, thickness-control of the transferred PDMS layer, and laser parameters optimization were discussed, along with the examination and testing of bonding with two representative materials (glass and silicon). The capability of this method was further demonstrated by fabricating a microfluidic chip with sputter-coated electrodes on the top and bottom substrates. The device functioning as a microparticle focusing and trapping chip was experimentally verified. It is confirmed that the proposed method has many advantages, including simple and fast fabrication process, low cost, easy integration of electronics, strong bonding strength, chemical and biological compatibility, etc.     

A Rapid and Low-Cost Procedure for Fabrication of Glass Microfluidic Devices

In this paper, we present a simple, rapid, and low-cost procedure for fabricating glass microfluidic chips. This procedure uses commercially available microscopic slides as substrates and a thin layer of AZ 4620 positive photoresist (PR) as an etch mask for fabricating glass microfluidic components, rather than using expensive quartz glasses or Pyrex glasses as substrates and depositing an expensive metal or polysilicon/amorphous silicon layer as etch masks in conventional method. A long hard-baking process is proposed to realize the durable PR mask capable of withstanding a long etching process. In order to remove precipitated particles generated during the etching process, a new recipe of buffered oxide etching with addition of 20% HCl is also reported. A smooth surface microchannel with a depth of more than 110 mum is achieved after 2 h of etching. Meanwhile, a simple, fast, but reliable bonding process based on UV-curable glue has been developed which takes only 10 min to accomplish the efficient sealing of glass chips. The result shows that a high bonding yield (~ 100%) can be easily achieved without the requirement of clean room facilities and programmed high-temperature furnaces. The presented simple fabrication process is suitable for fast prototyping and manufacturing disposable microfluidic devices.     

SU-8 microchannels for live cell dielectrophoresis improvements

In this work a novel highly precise SU-8 fabrication technology is employed to construct microfluidic devices for sensitive dielectrophoretic (DEP) manipulation of budding yeast cells. A benchmark microfluidic live cell sorting system is presented, and the effect of microchannel misalignment above electrode topologies on live cell DEP is discussed in detail. Simplified model of budding Saccharomyces cerevisiae yeast cell is presented and validated experimentally in fabricated microfluidic devices. A novel fabrication process enabling rapid prototyping of microfluidic devices with well-aligned integrated electrodes is presented and the process flow is described. Identical devices were produced with standard soft-lithography processes. In comparison to standard PDMS based soft-lithography, an SU-8 layer was used to construct the microchannel walls sealed by a flat sheet of PDMS to obtain the microfluidic channels. Direct bonding of PDMS to SU-8 surface was achieved by efficient wet chemical silanization combined with oxygen plasma treatment of the contact surface. The presented fabrication process significantly improved the alignment of the microstructures. While, according to the benchmark study, the standard PDMS procedure fell well outside the range required for reasonable cell sorting efficiency. In addition, PDMS delamination above electrode topologies was significantly decreased over standard soft-lithography devices. The fabrication time and costs of the proposed methodology were found to be roughly the same.

     

Microfluidic chips for capillary electrophoresis with integrated electrodes for capacitively coupled conductivity detection based on printed circuit board technology

A simple and low budget microfabrication method compatible with mass production was developed for the integration of electrodes for capacitively coupled contactless conductivity detection (C4D) in Lab on a Chip devices. Electrodes were patterned on a printed circuit board using standard processing. This was followed by lamination-photolithography-lamination to cover the electrodes in dry film photoresist (DFR) using an office laminator. This resulted in a flush, smooth surface on top of the detection electrodes, enabling subsequent integration of a microfluidic network at a distance dictated by the thickness of the DFR (17 μm, 30 μm and 60 μm were used in this work). This process was applied to create two types of detectors, re-usable detectors to be used in combination with a separate microfluidic network and integrated detectors where the microfluidic network is irreversibly sealed to the detector. A poly(dimethylsiloxane) (PDMS) slab containing the microfluidic network was positioned on top of the re-usable detectors to create the PDMS hybrid devices. The integrated DFR devices were created by patterning and sealing the microchannel in DFR using subsequent lamination and lithographic steps. The sensitivity of the C4D made using this new technology for small inorganic cations was between 6 and 20 μM, which is comparable with devices made using significantly more advanced technologies. Where the 17 μm film slightly improved the sensitivity, the use of 30 μm thick insulating films was preferred as these did not impose significant restrictions on the applicable field strengths.     

Rapid,simple and low cost fabrication of a microfluidic direct methanol fuel cell based on polydimethylsiloxane

In this paper a simple and rapid fabrication method for a microfluidic direct methanol fuel cell using polydimethylsiloxane (PDMS) as substrate is demonstrated. A gold layer on PDMS substrate as seed layer was obtained by chemical plating instead of conventional metal evaporation or sputtering. The morphology of the gold layer can be controlled by adjusting the ratio of curing agent to the PDMS monomer. The chemical properties of the gold films were examined. Then catalyst nanoparticles were grown on the films either by cyclic voltammetry or electrophoretic deposition. The microfluidic fuel cell was assembled by simple oxygen plasma bonding between two PDMS substrates. The cell operated at room temperature with a maximum power density around 6.28 mW cm^?2. Such a fuel cell is low-cost and easy to construct, and is convenient to be integrated with other devices because of the viscosity of the PDMS. This work will facilitate the development of miniature on-chip power sources for portable electronic devices.     

Desktop micromilled microfluidics

Micromilling is a proven method for prototyping microfluidic devices; however, high overhead costs, large machine footprints, an esoteric software stack, and nonstandard device bonding protocols may be hampering the widespread adoption of micromilling in the greater microfluidics community. This research exploits a free design-to-device software chain and uses it to explore the applicability of a new class of inexpensive, desktop micromills for fabricating microfluidic devices out of polycarbonate. We present an analysis framework for stratifying micromill’s spatial accuracy and surface quality. Utilizing this we concluded milling geometries directly on the substrate is advantageous to making molds out of the substrate, in terms of accuracy and minimum feature size. Moreover, we proposed a general procedure to calculate feedrate and spindle-speed for any sub-millimeter endmill based on a recommended load percentage. We also established stepover is the major parameter in determining the surface quality rather than spindle-speed and feedrate, showing low-cost mills are able to deliver high-quality surface finishes. Ultimately, we clarified the suitability of low-cost micromills and a cost-efficient assembly method in the field of microfluidics by demonstrating rate- and size-controlled microfluidic droplet generation.     

Plastic LC/MS microchip with an embedded microstructured fibre having the dual role of a frit and a nanoelectrospray emitter

Integrating functionality on a microfluidic platform, such as a frit or electrospray emitter for coupling with a mass spectrometer, can be complicated, costly, and introduce dead volume deleterious to liquid chromatography (LC). Here, we demonstrate the fabrication of a LC/MS microchip device with an integrated nanoelectrospray emitter that also functions as a retaining frit. The integrated emitter effectively minimizes dead volume associated with coupling the device externally to MS with electrospray ionization and complications associated with frit microfabrication. The emitter is made of microstructured optical fibre, which has an array of equivalent parallel channels. The size and spacing of these channels make the fibre amenable to retaining chromatographic packing material while simultaneously performing as a nanoelectrospray emitter. The chromatographic chip is fashioned from cyclic olefin copolymer (Zeonor) using hot embossing and thermal/solvent bonding techniques. The device is fabricated in less than 3 h with simple technique and low-cost materials while maintaining sufficient solvent resistance and mechanical strength, withstanding pressure drops of up to 100 bar. This microchip was used to effectively separate small drug molecules by isocratic elution and larger peptides using gradient elution. Robustness of the plastic LC/MS devices was demonstrated by frequent use over several months with consistent results. Such devices represent a practical approach to the facile integration of a frit and/or an ESI emitter in a microfluidic device at low cost while minimizing dead volume associated with coupling the chip to MS.     

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.     

Micro-injection moulding of polymer microfluidic devices

Microfluidic devices have several applications in different fields, such as chemistry, medicine and biotechnology. Many research activities are currently investigating the manufacturing of integrated microfluidic devices on a mass-production scale with relatively low costs. This is especially important for applications where disposable devices are used for medical analysis. Micromoulding of thermoplastic polymers is a developing process with great potential for producing low-cost microfluidic devices. Among different micromoulding techniques, micro-injection moulding is one of the most promising processes suitable for manufacturing polymeric disposable microfluidic devices. This review paper aims at presenting the main significant developments that have been achieved in different aspects of micro-injection moulding of microfluidic devices. Aspects covered include device design, machine capabilities, mould manufacturing, material selection and process parameters. Problems, challenges and potential areas for research are highlighted.     

New production method of convex microlens arrays for integrated fluorescence microfluidic detection systems

A new method for producing microlens array with large sag heights is proposed for integrated fluorescence microfluidic detection systems. Three steps in this production technique are included for concave microlens array formations to be integrated into microfluidic systems. First, using the photoresist SU-8 to produce hexagonal microchannel array is required. Second, UV curable glue is injected into the hexagonal microchannel array. Third, the surplus glue is rotated by a spinner at high velocity and exposed to a UV lamp to harden the glue. The micro concave lens molds are then finished and ready to produce convex microlens in poly methsiloxane (PDMS) material. This convex microlens in PDMS can be used for detecting fluorescence in microfluidic channels because a convex microlens plays the light convergence role for optical fiber detection.     

New production method of convex microlens arrays for integrated fluorescence microfluidic detection systems

A new method for producing microlens array with large sag heights is proposed for integrated fluorescence microfluidic detection systems. Three steps in this production technique are included for concave microlens array formations to be integrated into microfluidic systems. First, using the photoresist SU-8 to produce hexagonal microchannel array is required. Second, UV curable glue is injected into the hexagonal microchannel array. Third, the surplus glue is rotated by a spinner at high velocity and exposed to a UV lamp to harden the glue. The micro concave lens molds are then finished and ready to produce convex microlens in poly methsiloxane (PDMS) material. This convex microlens in PDMS can be used for detecting fluorescence in microfluidic channels because a convex microlens plays the light convergence role for optical fiber detection.

     

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

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

Automating fluid delivery in a capillary microfluidic device using low-voltage electrowetting valves

A multilayer capillary polymeric microfluidic device integrated with three normally closed electrowetting valves for timed fluidic delivery was developed. The microfluidic channel consisted two flexible layers of poly (ethylene terephthalate) bonded by a pressure-sensitive adhesive spacer tape. Channels were patterned in the spacer tape using laser ablation. Each valve contained two inkjet-printed silver electrodes in series. Capillary flow within the microchannel was stopped at the second electrode which was modified with a hydrophobic monolayer (valve closed). When a potential was applied across the electrodes, the hydrophobic monolayer became hydrophilic and allowed flow to continue (valve opened). The relationship between the actuation voltage, the actuation time, and the distance between two electrodes was performed using a microfluidic chip containing a single microchannel design. The results showed that a low voltage (4.5 V) was able to open the valve within 1 s when the distance between two electrodes was 1 mm. Increased voltages were needed to open the valves when the distance between two electrodes was increased. Additionally, the actuation time required to open the valve increased when voltage was decreased. A multichannel device was fabricated to demonstrate timed fluid delivery between three solutions. Our electrowetting valve system was fabricated using low-cost materials and techniques, can be actuated by a battery, and can be integrated into portable microfluidic devices suitable for point-of-care analysis in resource-limited settings.     

Drop-on-demand printed microfluidics device with sensing electrodes using silver and PDMS reactive inks

For this work, a cure-in-place polydimethylsiloxane (PDMS) reactive ink was developed and its utility demonstrated by printing a complete microfluidic mixer with integrated electrodes to measure fluid conductivity, concentration, and mixing completeness. First, a parameter-space investigation was conducted to generate a set of PDMS inks and printing parameters compatible with drop-on-demand (DOD) printing constraints. Next, a microfluidic mixer was fabricated using DOD-printed silver reactive inks, PDMS reactive inks, and a low-temperature polyethylene glycol fugitive ink. Lastly, the device was calibrated and tested using NaCl solutions with concentrations ranging from 0.01 to 1.0 M to show that electrolyte concentration and mixing completeness can be accurately measured. Overall, this work demonstrates a set of reactive inks and processes to fabricate sophisticated microfluidic devices using low-cost inks and DOD printing techniques.     

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.

     

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

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

Fabrication of buried microfluidic channels with observation windows using femtosecond laser photoablation and parylene-C coating

We developed an advanced method for fabricating microfluidic structures comprising channels and inputs/outputs buried within a silicon wafer based on single level lithography. We etched trenches into a silicon substrate, covered these trenches with parylene-C, and selectively opened their bottoms using femtosecond laser photoablation, forming channels and inputs/outputs by isotropic etching of silicon by xenon difluoride vapors. We subsequently sealed the channels with a second parylene-C layer. Unlike in previously published works, this entire process is conducted at ambient temperature to allow for integration with complementary metal oxide semiconductor devices for smart readout electronics. We also demonstrated a method of chip cryo-cleaving with parylene presence that allows for monitoring of the process development. We also created an observation window for in situ visualization inside the opaque silicon substrate by forming a hole in the parylene layer at the silicon backside and with local silicon removal by xenon difluoride vapor etching. We verified the microfluidic chip performance by forming a segmented flow of a fluorescein solution in an oil stream. This proposed technique provides opportunities for forming simple microfluidic systems with buried channels at ambient temperature.     

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.     

A rapid polymerisation process realizing 3D biocompatible structures in a microfluidic channel suitable for genetic analysis

Surface probe immobilisation is a complex and time consuming task undertaken prior to microfluidic integration, this requires surface functionalisation, biomolecule spotting, incubation and blocking steps. Traditional bonding techniques (anodic, thermal, etc.) or adhesives (UV cured) used to seal fluidic systems may denature biomolecules due to high temperature or vapour effects, thus bonding techniques such as thin film laminate or PDMS are used to seal systems, with substrate-fluidic alignment required prior to bonding. We propose a technique allowing probe DNA molecules to be immobilised in a sealed microfluidic system using (3D) hydrogel structures without any alignment steps. A prepolymer solution is introduced to the channels where photo-polymerisation is undertaken forming 3D structures covalently attached to the channel surface. We use a photo-initiated prepolymer material poly-ethylene-glycol (PEG) to form structures containing probe DNA. This process is fast compared to conventional biomolecule immobilisation techniques and is also biocompatible, this direct write approach removes overnight immobilisation/incubation of the probe DNA, it also facilitates immobilisation within a sealed fluidic system where conventionally DNA probe spots must be immobilised prior to channel sealing. We consider the transport of target DNA from bulk analyte to the 3D gel structure and evaluate hybridisation within the microfluidic system.     

A universal approach for irreversible bonding of rigid substrate-based microfluidic devices at room temperature

We present a simple and universal method for irreversibly bonding rigid substrate-based microfluidic devices at room temperature. In this method, a pre-patterned self-adhesive film covers and seals the area of the rigid substrate containing microchannels to create a closed microfluidic system, and then an adhesive-assisted sandwich bonding is used to reinforce the strength of bonding. The bonding can be achieved in 10 min at room temperature without requiring cleanroom facilities, complex surface modification, or employing rigorous cleaning. Despite its simplicity, this bonding method can create high-performance microfluidic devices with burst pressures over 2 MPa, but without channel clogging or microstructure deformation. The universality of this bonding method is demonstrated by applying it to the production of microfluidic devices with various rigid substrates. The simplicity, low cost, and universality of our method should allow it to be adopted by researchers lacking access to cleanroom facilities.