Novel prototyping method for microfluidic devices based on thermoplastic polyurethane microcapillary film

Thermoplastic polyurethane microcapillary film (TPU-MCF), as a novel extruded product, inherently contains an array of circular micron-sized capillaries embedded inside the polymer matrix. With the aid of simple laser cutting and conventional sealing technologies, a rapid prototyping method for microfluidic devices is proposed based on the ready-made microstructure of MCFs. Two functionalized microfluidic devices: serpentine micromixer and multi-droplet generator, are rapidly fabricated to demonstrate the advantages and potential of employing this new method. The whole proof-of-concept fabrication process can be completed in 8–10 min in a simple way; each procedure is repeatable with stable performance control of microfluidic devices; and the material cost can be as low as $0.01 for each device. The TPU-MCF and this novel method are expected to provide a new perspective and alternative in microfluidic community with particular requirements.     

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.

     

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.     

Effect of microstructure on blood cell clogging in blood separators based on capillary action

In this study, the blood cell clogging phenomenon occurring in blood separators based on capillary action is carefully investigated and how to minimize the reduction in plasma separation speed caused by clogging is discussed. Four different blood separators are fabricated on optically transparent glass substrates to clearly observe the blood plasma separation and the blood cell clogging in the microfluidic devices. Each separation experiment is captured by a high-speed video camera. The captured images are analyzed using a theoretical model proposed in this study to quantify the effect of the microstructure on the degree of blood cell clogging. Finally, design guidelines for the microstructure of the micro blood separator are discussed based on the analysis. D. Kim and J. Y. Yun contributed equally to this work.     

Damage and failure in silicon-glass-metal microfluidic joints for high-pressure MEMS devices

The design, fabrication, and testing of microfluidic joints consisting of Kovar metal tubes attached to silicon using borosilicate glass for high pressure microelectromechanical systems devices are presented. The MIT microrocket, which requires microfluidic joints to sustain pressures of at least 12.7 MPa and temperatures in excess of 700 K, is used to demonstrate the feasibility of the glass sealing methodology. A key concern in such joints is the occurrence of cracks due to residual stresses during fabrication, which can affect the load-carrying capability. To obtain a better understanding of the damage and failure characteristics, a hierarchical approach was taken. First, two types of joint configurations with several glass compositions and geometries were considered at the joint-level. Axial tension and pressure tests were performed, and finite element models were used to obtain the residual stress field and to predict failure loads based on linear elastic fracture mechanics. Subsequently, tests were performed on actual and dummy microrockets to validate the methodology at the device-level. Key observations include the importance of bonding between the Kovar tube and the silicon sidewall, which can help increase joint strength, and the detrimental effects of joint proximity under differential pressure loading and manufacturing defects in multiple joint specimens. In addition to specific experimental and analyses results that allow a physical understanding of the damage and failure mechanisms, another key contribution of this work is the overall insight of the design and analysis of reliable glass-sealed microfluidic packages. This insight will help one make better design and process selections for packages in other high-pressure silicon-based MEMS applications.     

Simulations of extensional flow in microrheometric devices

We present a detailed numerical study of the flow of a Newtonian fluid through microrheometric devices featuring a sudden contraction–expansion. This flow configuration is typically used to generate extensional deformations and high strain rates. The excess pressure drop resulting from the converging and diverging flow is an important dynamic measure to quantify if the device is intended to be used as a microfluidic extensional rheometer. To explore this idea, we examine the effect of the contraction length, aspect ratio and Reynolds number on the flow kinematics and resulting pressure field. Analysis of the computed velocity and pressure fields show that, for typical experimental conditions used in microfluidic devices, the steady flow is highly three-dimensional with open spiraling vortical structures in the stagnant corner regions. The numerical simulations of the local kinematics and global pressure drop are in good agreement with experimental results. The device aspect ratio is shown to have a strong impact on the flow and consequently on the excess pressure drop, which is quantified in terms of the dimensionless Couette and Bagley correction factors. We suggest an approach for calculating the Bagley correction which may be especially appropriate for planar microchannels. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

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.

     

Capillary flow-driven blood plasma separation and on-chip analyte detection in microfluidic devices

We report a comprehensive review on the capillary flow-driven blood plasma separation and on-chip analyte detection in microfluidic devices. Blood plasma separation is the primary sample preparation step prior to most biochemical assays. Conventionally, centrifugation is used for the sample preparation process. There are numerous works reporting blood plasma separation in microfluidic devices which aim at miniaturizing the sample preparation procedure. Capillary-based blood plasma separation shows promise in actualizing point-of-care diagnostic devices for applications in resource-limited settings including military camps and rural areas. In this review, the devices have been categorized based on active and passive plasma separation techniques used for the separation of plasma from capillary-driven blood sample. A comparison between different techniques used for blood plasma separation is outlined. On-chip detection of analytes present in the separated plasma obtained using some of these reported devices is also presented and discussed.     

Subdynamic asymptotic behavior of microfluidic valves

Decreasing the Reynolds number of microfluidic no-moving-part flow control valves considerably below the usual operating range leads to a distinct "subdynamic" regime of viscosity-dominated flow, usually entered through a clearly defined transition. In this regime, the dynamic effects on which the operation of large-scale no-moving-part fluidic valves is based, cease to be useful, but fluid may be driven through the valve (and any connected load) by an applied pressure difference, maintained by an external pressure regulator. Reynolds number ceases to characterize the valve operation, but the driving pressure effect is usefully characterized by a newly introduced dimensionless number and it is this parameter which determines the valve behavior. This summary paper presents information about the subdynamic regime using data (otherwise difficult to access) obtained for several recently developed flow control valves. The purely subdynamic regime is an extreme. Most present-day microfluidic valves are operated at higher Re, but the paper shows that the laws governing subdynamic flows provide relations useful as an asymptotic reference.     

No more bonding,no more clamping,magnetically assisted membrane integration in microfluidic devices

The integration of porous membranes with microfluidic devices allows a simple but high-throughput mass transport control for numerous microfluidic applications, such as single-cell separation, sample analysis, and purification. In this study, we demonstrate a novel integration process of porous membranes into microfluidic devices by applying a magnetic field and hydrodynamically stabilizing them. This new approach simplifies the integration process by removing physicochemical bonding between membranes and microfluidic devices, but overcomes many practical issues observed in current methods, such as device leakage, membrane replacement, and membrane material selection. More importantly, our approach allows us to install membranes with diverse physicochemical features and spatial configurations into a single microfluidic device. This additional ability can significantly improve its performance and capability in applications. Finally, we successfully demonstrate the utilization of our membrane device for simple particle separation.     

Circuit model for microfluidic bubble generation under controlled pressure

We explore the microfluidic generation of bubbles in a flow-focusing junction using a pressure-controlled device rather than the more common flow rate-controlled devices. This device is a prototype for extending microfluidic drop generation methods to molten polymers. We show that the bubble generation process is highly sensitive to pressure: small changes in pressure induce large changes in bubble size and bubble formation frequency. A simple resistance circuit model can explain this pressure dependence. Briefly, we show that bubble generation is possible only within a finite pressure range. Near the ends of this pressure range, the ratio of the flow rates of the dispersed to continuous phase is highly sensitive to pressure, and therefore so also is the bubble generation process. The circuit model offers a way to use existing models of drop generation (which are based on flow rate-controlled operation) to predict pressure-controlled operation. We also examine drop formation using a highly viscous polymer as the dispersed phase. Drops are formed far downstream of the flow-focusing junction, and they are far smaller than the microfluidic channel dimensions. These results suggest that existing microfluidic drop generation methods may be exploited to make complex particles from thermoplastic polymers.     

Nonlinear ceramics for tunable microwave devices

The research on materials and systems for tunable microwave devices has gained attraction within the last years. The radio frequency characterization and the component design of tunable microwave components based on dielectric ceramics especially barium-strontium-titanate (BST) are presented in this second part, whereas the basic material properties are discussed in detail in the first part. After a short introduction to the processing technology used for the fabrication of tunable components based on a BST thick film, the relations between microwave properties and material properties as well as the microstructure are presented in detail. The design process for tunable microwave components based on BST thick films is described. Especially the considerations related to micro- and macrostructure and their connection are highlighted. The paper closes with two different application examples: a reconfigurable array antenna for satellite communication and varactors for high power applications.     

Investigation and improvement of reversible microfluidic devices based on glass–PDMS–glass sandwich configuration

Reversibly assembled microfluidic devices are dismountable and reusable, which is useful for a number of applications such as micro- and nano-device fabrication, surface functionalization, complex cell patterning, and other biological analysis by means of spatial–temporal pattern. However, reversible microfluidic devices fabricated with current standard procedures can only be used for low-pressure applications. Assembling technology based on glass–PDMS–glass sandwich configuration provides an alternative sealing method for reversible microfluidic devices, which can drastically increase the sealing strength of reversibly adhered devices. The improvement mechanism of sealing properties of microfluidic devices based on the sandwich technique has not been fully characterized, hindering further improvement and broad use of this technique. Here, we characterize, for the first time, the effect of various parameters on the sealing strength of reversible PDMS/glass hybrid microfluidic devices, including contact area, PDMS thickness, assembling mode, and external force. To further improve the reversible sealing of glass–PDMS–glass microfluidic devices, we propose a new scheme which exploits mechanical clamping elements to reinforce the sealing strength of glass–PDMS–glass sandwich structures. Using our scheme, the glass–PDMS–glass microchips can survive a pressure up to 400 kPa, which is comparable to the irreversibly bonded PDMS microdevices. We believe that this bonding method may find use in lab-on-a-chip devices, particularly in active high-pressure-driven microfluidic devices.     

A post-bonding-free fabrication of integrated microfluidic devices for mass spectrometry applications

This paper presents a novel process for fabricating integrated microfluidic devices with embedded electrodes which utilizes low-cost UV curable resins. Commercial UV glue is sandwiched between two substrates and is used for both the structural material and the bonding adhesive. During the exposure procedure, the pattern of micro-fluidic channels is defined using a standard lithography process while the two substrates are bonded. The un-cured UV glue is then removed by vacuum suction to form the sealed microfluidic channel. With this simple approach, conventional high-temperature bonding processes can be excluded in the fabrication of sealed microfluidic structures such that the developed method is highly advantageous for fabricating microchip devices with embedded electrodes. The overall time required to fabricate the sealed microchip device is less than 10 min since no time-consuming etching and bonding process is necessary. An innovative micro-reactor integrated with an in-channel micro-plasma generator for real-time chemical reaction analysis is fabricated using the developed process. On-line mass-spectrum (MS) detection of an esterification reaction is successfully demonstrated, which results in a fast, label-free, preparation-free analysis of chemical samples. The developed process can thus show its potential for rapid and low-cost microdevice manufacturing.     

Mathematical analysis of oxygen transfer through polydimethylsiloxane membrane between double layers of cell culture channel and gas chamber in microfluidic oxygenator

For successful cell culture in microfluidic devices, precise control of the microenvironment, including gas transfer between the cells and the surrounding medium, is exceptionally important. The work is motivated by a polydimethylsiloxane (PDMS) microfluidic oxygenator chip for mammalian cell culture suggesting that the speed of the oxygen transfer may vary depending on the thickness of a PDMS membrane or the height of a fluid channel. In this paper, a model is presented to describe the oxygen transfer dynamics in the PDMS microfluidic oxygenator chip for mammalian cell culture. Theoretical studies were carried out to evaluate the oxygen profile within the multilayer device, consisting of a gas reservoir, a PDMS membrane, a fluid channel containing growth media, and a cell culture layer. The corresponding semi-analytical solution was derived to evaluate dissolved oxygen concentration within the heterogeneous materials, and was found to be in good agreement with the numerical solution. In addition, a separate analytical solution was obtained to investigate the oxygen pressure drop (OPD) along the cell layer due to oxygen uptake of cells, with experimental validation of the OPD model carried out using human umbilical vein endothelial cells cultured in a PDMS microfluidic oxygenator. Within the theoretical framework, the effects of several microfluidic oxygenator design parameters were studied, including cell type and critical device dimensions.     

Electrokinetic and aspect ratio effects on secondary flow of viscoelastic fluids in rectangular microchannels

The secondary flow of PTT fluids in rectangular cross-sectional plane of microchannels under combined effects of electroosmotic and pressure driving forces is the subject of the present study. Employing second-order central finite difference method in a very refined grid network, we investigate the effect of electrokinetic and geometric parameters on the pattern, strength and the average of the secondary flow. In this regard, we try to illustrate the deformations of recirculating vortices due to change in the dimensionless Debye–Hückel and zeta potential parameters as well as channel aspect ratio. We demonstrate that, in the presence of thick electric double layers, significant alteration occurs in the secondary flow pattern by transition from favorable to adverse pressure gradients. Moreover, it is found that for polymer-electrolyte solutions with large Debye lengths, the secondary flow pattern and the shape of vortices are generally dependent upon the width-to-height ratio of the channel cross section. Also, the inspections of strength and average of secondary flow reveal that the sensitivity of these quantities with respect to the electrokinetic, geometric and rheological parameters increases by increasing the absolute value of velocity scale ratio. In this regard, utilizing the curve fitting of the results, several empirical expressions are presented for the strength and average of the secondary flow under various parametric conditions. The obtained relations with the other predictions for secondary flow are of high practical importance when dealing with the design of microfluidic devices that manipulate viscoelastic fluids.     

A versatile technology platform for microfluidic handling systems,part II: channel design and technology

Microfluidic devices often require channels of a specific size and shape. These devices are then made in a fabrication process that is often specialized to produce only those (and very similar) channels. As a result, devices requiring channels of different size and shape cannot easily be integrated on the same chip. This paper presents a method to fabricate microfluidic channels in a wide range of shape and size on the same chip by using a slit pattern through which the channels are etched. The fabrication process to fabricate these channels is discussed in detail, and an empirical model is presented to find the optimal slit pattern for a required size and shape. This part of the paper focusses on the channel design and fabrication. Details on the whole fabrication process and optional functionalization of the channels are presented in part I of this paper.     

Visualization of fluid mixing in microchannels

The development of a microchannel for fluid-mixing applications comes from the recent interest in microfluidic device applications in biology. Microfluidics refers to fluid flow and transport phenomena associated with these devices. The basic idea of developing microfluidic devices is to shrink the physical dimensions of most commonly used processors - that is, using miniaturization and function integration to create the so-called lab on a chip. The development of microfabrication procedures and the associated fundamental theories requires computer analysis and simulation techniques. Computer modeling not only reduces the experiment costs - such as data acquisition devices and control - but also expedites a certain design concept's evaluation process. More importantly, computer modeling results will help gain a better understanding of the flow field through flow visualization, and the information drawn from the results of computer simulations will in turn improve the design. This is especially important during the conceptual design phase.     

Predictive model on micro droplet generation through mechanical cutting

We describe the step-by-step formation process of picoliter to femtoliter volume of microdroplets by using a mechanical valve. An experiment-based theoretical model has been proposed through a parametric study of droplet formation in a microchannel with variations of the channel height, the working pressure to drive the liquids in the microchannels, and the viscosity of the dispensed phase. Three steps in the process of droplet generation have been depicted. The present study provides a clear understanding of the droplet generation process based on physical cutting method by using a mechanical valve and could be applied to advanced design for highly flexible droplet-based microfluidic systems. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. W. S. Lee, S. Jambovane and D. Kim contributed equally to this work.     

Low-cost origami fabrication of 3D self-aligned hybrid microfluidic structures

3D microfluidic device fabrication methods are normally quite expensive and tedious. In this paper, we present an easy and cheap alternative wherein thin cyclic olefin polymer (COP) sheets and pressure sensitive adhesive (PSA) were used to fabricate hybrid 3D microfluidic structures, by the Origami technique, which enables the fabrication of microfluidic devices without the need of any alignment tool. The COP and PSA layers were both cut simultaneously using a portable, low-cost plotter allowing for rapid prototyping of a large variety of designs in a single production step. The devices were then manually assembled using the Origami technique by simply combining COP and PSA layers and mild pressure. This fast fabrication method was applied, as proof of concept, to the generation of a micromixer with a 3D-stepped serpentine design made of ten layers in less than 8 min. Moreover, the micromixer was characterized as a function of its pressure failure, achieving pressures of up to 1000 mbar. This fabrication method is readily accessible across a large range of potential end users, such as educational agencies (schools, universities), low-income/developing world research and industry or any laboratory without access to clean room facilities, enabling the fabrication of robust, reproducible microfluidic devices.