Engineered hydrophobicity of discrete microfluidic elements for double emulsion generation

Microfluidic device fabrication has classically utilized methods that have limited devices to specific applications. More recently, discrete microfluidic elements have reimagined the design process of microfluidic device fabrication to that of building blocks that can be constructed in various forms to produce devices of many applications. Here, surface modification of discrete microfluidic elements via initiated chemical vapor deposition is demonstrated. Coated modular elements can quickly assemble to form complex 2-D or 3-D structures with step-like surface energy gradients for applications requiring discrete control of channel surface wettability. This platform is applied toward the generation of double emulsions to show the ease of design and manufacturing over existing methods developed to manage two-phase flows.     

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.

     

Bonding of thermoplastic polymer microfluidics

Thermoplastics are highly attractive substrate materials for microfluidic systems, with important benefits in the development of low cost disposable devices for a host of bioanalytical applications. While significant research activity has been directed towards the formation of microfluidic components in a wide range of thermoplastics, sealing of these components is required for the formation of enclosed microchannels and other microfluidic elements, and thus bonding remains a critical step in any thermoplastic microfabrication process. Unlike silicon and glass, the diverse material properties of thermoplastics opens the door to an extensive array of substrate bonding options, together with a set of unique challenges which must be addressed to achieve optimal sealing results. In this paper we review the range of techniques developed for sealing thermoplastic microfluidics and discuss a number of practical issues surrounding these various bonding methods.     

Advances and applications on microfluidic velocimetry techniques

The development and analysis of the performance of microfluidic components for lab-on-a-chip devices are becoming increasingly important because microfluidic applications are continuing to expand in the fields of biology, nanotechnology, and manufacturing. Therefore, the characterization of fluid behavior at the scales of micro- and nanometer levels is essential. A variety of microfluidic velocimetry techniques like micron-resolution Particle Image Velocimetry (μPIV), particle-tracking velocimetry (PTV), and others have been developed to characterize such microfluidic systems with spatial resolutions on the order of micrometers or less. This article discusses the fundamentals of established velocimetry techniques as well as the technical applications found in literature.     

Single-cell microfluidic impedance cytometry: a review

Lab-on-chip technologies are being developed for multiplexed single cell assays. Impedance offers a simple non-invasive method for counting, identifying and monitoring cellular function. A number of different microfluidic devices for single cell impedance have been developed. These have potential applications ranging from simple cell counting and label-free identification of different cell types or detecting changes in cell morphology after invasion by parasites. Devices have also been developed that trap single cells and continuously record impedance data. This technology has applications in basic research, diagnostics, or non-invasively probing cell function at the single-cell level. This review will describe the underlying principles of impedance analysis of particles. It then describes the state-of-the-art in the field of microfluidic impedance flow cytometry. Finally, future directions and challenges are discussed.     

Suction-enhanced siphon valves for centrifugal microfluidic platforms

In traditional centrifugal microfluidic platforms pumping is restricted to outward fluid flow, resulting in potential real estate issues for embedding complex microsystems. To overcome the limitation, researchers utilize hydrophilic channels to force liquids short distances back toward the disk center. However, most polymers used for CD fabrication are natively hydrophobic, and creating hydrophilic conditions requires surface treatments/specialized materials that pose unique challenges to manufacturing and use. This work describes a novel technology that enjoys the advantages of hydrophilic fluidics on a hydrophobic disk device constructed from untreated polycarbonate plastic. The method, termed suction-enhanced siphoning, is based on exploiting the non-linear hydrostatic pressure profile and related pressure drop created along the length of a rotating microchannel. Theoretical analysis as well as experimental validation of the system is provided. In addition, we demonstrate the use of the hydrostatic pressure pump as a new method for priming hydrophobic-based siphon structures. The development of such techniques for hydrophobic fluidics advances the capabilities of the centrifugal microfluidic platform while remaining true to the goal of creating disposable polymer devices using feasible manufacturing schemes.     

Investigation of wax and paper materials for the fabrication of paper-based microfluidic devices

Paper-based microfluidic devices hold great potential in today’s microfluidic applications. They offer low costs, simple and quick fabrication processes, ease of uses, etc. In this work, several wax and paper materials are investigated for the fabrication of paper-based microfluidic devices. A novel method of using wax as a suitable backing to a paper-based analytical device has been demonstrated. Governing equations for the mechanics of the fluid flow in paper-based channels with constant widths have been experimentally validated. Experimental results showing deviations from the governing equations have been verified using fluidic channels with varying widths. There lies the possibility of manipulation of the fluid flow in paper-based microfluidic devices solely using geometric factors. This opens up many potential applications that may require sequential delivery of reagents or samples. Lastly, properties of paper such as the average pore diameter and permeability can be deduced from experimental results.     

Highly integrated polymeric microliquid flow controller for droplet microfluidics

Microfluidic applications demand accurate control and measurement of small fluid flows and volumes, and the majority of approaches found in the literature involve materials and fabrication methods not suitable for a monolithic integration of different microcomponents needed to make a complex Lab-on-a-Chip (LoC) system. The present work leads to a design and manufacturing approach for problem-free monolithic integration of components on thermoplastics, allowing the production of excellent quality devices either as stand-alone components or combined in a complex structures. In particular, a polymeric liquid flow controlling system (LFCS) at microscale is presented, which is composed of a pneumatic microvalve and an on-chip microflow sensor. It enables flow regulation between 30 and 230 μl/min with excellent reproducibility and accuracy (error lower than 5%). The device is made of a single Cyclic Olefin Polymer (COP) piece, where the channels and cavities are hot-embossed, sealed with a single COP membrane by solvent bonding and metalized, after sealing, to render a fully functional microfluidic control system that features on-chip flow sensing. In contrast with commercially available flow control systems, the device can be used for high-quality flow modulation in disposable LoC devices, since the microfluidic chip is low cost and replaceable from the external electronic and pneumatic actuators box. Functionality of the LFCS is tested by connecting it to a microfluidic droplet generator, rendering highly stable flow rates and allowing generation of monodisperse droplets over a wide range of flow rates. The results indicate the successful performance of the LFCS with significant improvements over existing LFCS devices, facing the possibility of using the system for biological applications such as generating distinct perfusion modes in cell culture, novel digital microfluidics. Moreover, the integration capabilities and the reproducible fabrication method enable straightforward transition from prototype to product in a way that is lean, cost-effective and with reduced risk.     

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.     

Spiral-shaped inertial stem cell device for high-throughput enrichment of iPSC-derived neural stem cells

Stem cell enrichment plays a critical role in both research and clinical applications. The typical method for stem cell enrichment may use invasive processes and takes a long period of time. Spiral-shaped microfluidic devices, which combine lift and Dean drag forces to direct cells of different sizes into separate trajectories, can be used to noninvasively process samples at a rate of milliliters per minute. This paper presents a simple 2-loop spiral-shaped inertial microfluidic devices with the aid of sheath flow to enrich neural stem cells (NSCs), derived from induced pluripotent stem cells. NSCs and spontaneously differentiated non-neural cells were mixed and flowed through the spiral-shaped devices. Samples collected at the outlets were analyzed for purity and recovery. It was found that the device focused the NSCs into a narrow trajectory, which could then be collected in two out of the eight outlets. The device was tested at different flow rates and found that the most highly enriched fractions (2.1×) with NSCs recovery 93% were achieved at the flow rate (3 ml/min). Next, we extended our investigation from 2-loop design to 10-loop design to eliminate the use of sheath flow. NSCs were enriched to 2.5×, but only 38% of the NSCs were recovered from the most enriched fractions. Spiral-shaped microfluidic devices are capable of rapid, label-free enrichment of target stem cells, and have great potential in point-of-care tissue preparation.     

Polymer microfabrication technologies

 The need for low-cost microfabrication technologies in modern life-sciences is described. The article compares the replication technologies, hot embossing and micro-injection moulding and gives an overview over the technologies used for fabrication of the replication masters. The back-end processes transforming the replicated plastic part into a complete microsystem are described. Some manufacturing issues of mass production are discussed. Received: 22 June 2001/Accepted: 18 July 2001     

The development of two-component micro powder injection moulding and sinter joining

Two-component micro powder injection moulding experienced significant progress in the recent past. Starting as a manufacturing method for integrating two different plastics, the extension of two-component injection moulding (2C-IM) from pure plastics to more resistant materials like ceramics or metals (2C-PIM) provided sophisticated and challenging applications. With the transfer of 2C-PIM to micro systems, two-component micro powder injection moulding (2C-MicroPIM) was established. Up to a certain extend sinter joining is an alternative to 2C-PIM. It allows for component assemblies to be moulded as separate low-complexity parts which are then joined into complex assemblies. This procedure considerably reduces the time and cost required to manufacture the injection moulding tools. This article gives an overview of the development of 2C-MicroPIM—from two component plastic devices to the production of complex two-component micro assemblies made of two ceramic or metallic materials and the state-of-the-art of science and technology of sinter joining.

     

The development of two-component micro powder injection moulding and sinter joining

Two-component micro powder injection moulding experienced significant progress in the recent past. Starting as a manufacturing method for integrating two different plastics, the extension of two-component injection moulding (2C-IM) from pure plastics to more resistant materials like ceramics or metals (2C-PIM) provided sophisticated and challenging applications. With the transfer of 2C-PIM to micro systems, two-component micro powder injection moulding (2C-MicroPIM) was established. Up to a certain extend sinter joining is an alternative to 2C-PIM. It allows for component assemblies to be moulded as separate low-complexity parts which are then joined into complex assemblies. This procedure considerably reduces the time and cost required to manufacture the injection moulding tools. This article gives an overview of the development of 2C-MicroPIM??from two component plastic devices to the production of complex two-component micro assemblies made of two ceramic or metallic materials and the state-of-the-art of science and technology of sinter joining.     

Disposable microfluidic chip for rapid pathogen identification with DNA microarrays

This work presents the combination and acceleration of PCR and fluorescent labelling within a disposable microfluidic chip. The utilised geometry consists of a spiral meander with 40 turns, representing a cyclic-flow PCR system. The used reaction chemistry includes Cy3-conjugated primers leading to a one-step process accelerated by cyclic-flow PCR. DNA of three different bacterial samples (Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa) was processed and successfully amplified and labelled with detection limits down to 10² cells per reaction. The specificity of species identification was comparable to the approach of separate PCR and labelling. The overall processing time was decreased from 6 to 1.5 h. We showed that a disposable polycarbonate chip, fabricated by injection moulding is suitable for the significant acceleration of DNA microarray assays. The reaction output led to high-sensitivity bacterial identification in a short time, which is crucial for an early and targeted therapy against infectious diseases.     

A dry film technology for the manufacturing of 3-D multi-layered microstructures and buried channels for lab-on-chip

The development of innovative and reliable techniques for devices miniaturization are enabling the massive growth of lab on chip (LOC) applications. In this article, we briefly review the technological options for LOC microfabrication, then we present the optimization of a process for the realization of tridimensional multi-layered structures and buried channels in a microfluidic network using a photo-patternable dry film, with a potential for LOC manufacturing. The tuning of all the fabrication parameters is widely discussed and micrographs and optical profiler images are reported to show fabrication results. The fabrication process is used for a Split-flow-thin (SPLITT) fractionation cell configuration. SPLITT is a particle fractionation technique based on the combined effect of two laminar streams (the sample containing the particles and a carrier) flowing inside a thin microchannel and the action of a vertical driving force for particle displacement. Since the SPLITT implemented in this work is electrically driven, patterned electrodes (thickness: 100 nm) are also integrated in the flow cell walls. The functionality of the cell was tested first verifying the presence of proper flow conditions for microfluidic SPLITT (absence of mixing between the streams) and then proving electrical fractionation with two different proteins (BSA and β-lactoglobulin) at different levels of ionic strength. The flow of the streams within the microfluidic channel was also simulated by a numerical 2-D model exactly reproducing the cell geometry, with a good accordance with experimental results.

     

Modular component design for portable microfluidic devices

A new modular design concept for microfluidic devices is proposed and demonstrated in this study. We designed three key modular microfluidic components: pumps, valves, and reservoirs, and demonstrated that a microfluidic device with specific functions can be easily assembled with those key modular components. Our pumps are man-powerable so that the assembled microfluidic devices require no any other power sources like expensive syringe pumps or air compressors. This feature makes the assembled microfluidic devices completely portable. We also combined our assembled device with other existing mixing microchannels to serve as the mixing and loading system in polymerase chain reaction experiment to amplify DNA successfully. This result shows that those modular components can be integrated into other microchannels, implying great potential applications of the modular design.     

Application of polydopamine in biomedical microfluidic devices

Polydopamine (PDA) is a bioinspired material with tremendous potential for applications involving surface modifications. By simply immersing the substrate in the dopamine monomer solution, we are able to apply a hydrophilic and biofunctional PDA coating that adheres strongly to any surface, including (super)hydrophobic surface, with unprecedented ease. Using PDA, almost any materials can be immobilized on the surface in a single step by mixing them with the dopamine monomer solution. This review provides a comprehensive coverage of the applications of PDA in the device fabrication, surface modification, and biofunctionalization of biomedical microfluidic devices. While discussing the advantages and limitations of PDA, we pay special attention to its unique properties that specifically benefit biomedical microfluidic devices. We also discuss other potential applications of PDA beyond the current development. Through this review, we hope to promote PDA and encourage a broader adoption of PDA by the microfluidic community.     

Safe and cost-effective rapid-prototyping of multilayer PMMA microfluidic devices

The rapid translation of research from bench to bedside, as well as the generation of commercial impact, has never been more important for both academic and industrial researchers. It is therefore unsurprising that more and more microfluidic groups are investigating research using a wide range of thermoplastics which can be readily translated to large-scale manufacturing, if the technology is taken to commercialisation. While structuring, via additive or subtractive manufacturing, is becoming relatively easy through the use of commercial-grade devices, reliable and fast assembly remains a challenge. In this article, we propose an innocuous and cost-effective, under 2-min technique which enables the bonding of multiple poly(methyl methacrylate) layers. This bonding technique relies on the application of small amounts (10 µl/cm²) of ethanol, low temperatures (70 °C) and relatively low pressures (~1.6 MPa). Our characterisation analysis shows that using a bonding time of 2 min is enough to produce a strong bond able to withstand pressures always above 6.2 MPa (with mean of 8 MPa, highest reported in the literature), with minimal channel deformation (<5%). This technique, which we demonstrate on assembly comprising up to 19 layers, presents an exciting improvement in the field of rapid prototyping of microfluidic devices, enabling extremely fast design cycles in microfluidic research with a material compatible with mass manufacturing, thus allowing a smoother transition from the laboratory to the market. Beyond the research community, this robust prototyping technique has the potential to impact on the deliverability of other scientific endeavours including educational projects and will directly fuel the fluidic maker movement.     

Integration of impedance spectroscopy sensors in a digital microfluidic platform

Digital microfluidics combines the advantages of a low consumption of reagents with a high flexibility of processing fluid samples. For applications in life sciences not only the processing but also the characterization of fluids is crucial. In this contribution, a microfluidic platform, combining the actuation principle of electrowetting on dielectrics for droplet manipulations and the sensor principle of impedance spectroscopy for the characterization of the fluid composition and condition, is presented. The fabrication process of the microfluidic platform comprises physical vapor deposition and structuring of the metal electrodes onto a substrate, the deposition of a dielectric isolator and a hydrophobic top coating. The key advantage of this microfluidic chip is the common electric nature of the sensor and the actuation principle. This allows for fabricating digital microfluidic devices with a minimal number of process steps. Multiple measurements on fluids of different composition (including rigid particles) and of different conditions (temperature, sedimentation) were performed and process parameters were monitored online. These sample applications demonstrate the versatile applications of this combined technology.     

基于无纺布检测浓度的微流控装置

目前微流控器件主要由玻璃或聚合物材料制成,而无纺布具有成本低、易加工、一次性等优点,为微流体材料提供了一种新的选择。本研究把蜡印染在无纺布上制备微流控器件,可以形成有效的蜡印通道,控制流体在内部通道扩散和流动。并把不同浓度的红色水溶性染料滴到通道中,利用图像处理算法检测其灰度值做浓度比对,发现在特定浓度下,灰度值呈现近似线性规律,可将其推广到生物医学现场检测等领域。