Frontal photopolymerization for microfluidic applications

Frontal photopolymerization (FPP) offers numerous advantages for the rapid prototyping of microfluidic devices. Quantitative utilization of this method, however, requires a control of the vertical dimensions of the patterned resist material. To address this fundamental problem, we study the ultraviolet (UV) photopolymerization of a series of multifunctional thiolene resists through a combination of experiments and analytical modeling of the polymerization fronts. We describe this nonlinear spatio-temporal growth process in terms of a "minimal" model involving an order parameter phi(x, t) characterizing the extent of monomer-to-polymer conversion, the optical attenuation T(x, t), and the solid front position h(t). The latter exhibits an induction time (or equivalent critical UV dose) characterizing the onset of frontal propagation. We also observe a novel transition between two logarithmic rates of growth, determined by the Beer-Lambert attenuation constants mu(0) and mu(infinity) of the monomer and fully polymerized material, respectively. The measured frontal kinetics and optical transmission of the thiolene resist materials are consistent with our photopolymerization model, exhibiting both "photodarkening" and "photoinvariant" polymerization. This is apparently the first observation of photodarkening reported in FPP. On the basis of these results, multilevel fluidic devices with controlled height are readily fabricated with modulated illumination. A representative two-level microfluidic device, incorporating a chaotic mixer, a T junction, and a series of controlled flow constrictions, illustrates the practical versatility of this fabrication method.     

Electrochemical techniques for microfluidic applications

Electrochemical principles provide key techniques to promote the construction of bio/chemical microsystems of the next generation. There is a wealth of technology for the microfabrication of bio/chemical sensors. In addition, microfluidic transport in a network of flow channels, pH regulation, and automatic switching can be realized by electrochemical principles. Since the basic components of the devices are electrode patterns, the integration of different components is easily achieved. With these techniques, bio/chemical assays that require the exchange of solutions can be conducted on a chip. Furthermore, autonomous microanalysis systems that can carry out necessary procedures are beginning to be realized. In this article, techniques developed in our group will be comprehensively introduced.     

Laser-induced thermal bubbles for microfluidic applications

We present a unique bubble generation technique in microfluidic chips using continuous-wave laser-induced heat and demonstrate its application by creating micro-valves and micro-pumps. In this work, efficient generation of thermal bubbles of controllable sizes has been achieved using different geometries of chromium pads immersed in various types of fluid. Effective blocking of microfluidic channels (cross-section 500 × 40 μm(2)) and direct pumping of fluid at a flow rate of 7.2-28.8 μl h(-1) with selectable direction have also been demonstrated. A particular advantage of this technique is that it allows the generation of bubbles at almost any location in the microchannel and thus enables microfluidic control at any point of interest. It can be readily integrated into lab-on-a-chip systems to improve functionality.     

A water-activated pump for portable microfluidic applications

An on-chip micropump for portable microfluidic applications was investigated using mathematical modeling and experimental testing. This micropump is activated by the addition of water, via a dropper, to ionic polymer particles that swell due to osmotic effects when wetted. The resulting particle volume increase deflects a membrane, forcing a separate fluid from an adjacent reservoir. The micropump components, along with the microfluidic components, are fabricated using the contact liquid photolithographic polymerization (CLiPP) method. The maximum flow rate achieved with this pump is 17 microL per minute per mg of dry polymer particles of 355-425 microm in diameter. The pump flow rate may be controlled by adjusting the particle size and amount, the membrane properties, and the channel dimensions. The experimental results demonstrate good agreement with an analytical model describing the particle swelling and its coupling with resistive forces from the bending membrane, viscous flow in the microchannel, and interfacial effects. Key features of this micropump are that it can be placed directly on a microdevice, and that it requires only a small amount of water and no external power supply to function. Therefore, this pumping system is useful for applications in which a highly portable device is required.     

Fuel cell-powered microfluidic platform for lab-on-a-chip applications

The achievement of a higher degree of integration of components--especially micropumps and power sources--is a challenge currently being pursued to obtain portable and totally autonomous microfluidic devices. This paper presents the integration of a micro direct methanol fuel cell (μDMFC) in a microfluidic platform as a smart solution to provide both electrical and pumping power to a Lab-on-a-Chip system. In this system the electric power produced by the fuel cell is available to enable most of the functionalites required by the microfluidic chip, while the generated CO(2) from the electrochemical reaction produces a pressure capable of pumping a liquid volume through a microchannel. The control of the fuel cell operating conditions allows regulation of the flow rate of a liquid sample through a microfluidic network. The relation between sample flow rate and the current generated by the fuel cell is practically linear, achieving values in the range of 4-18 μL min(-1) while having an available power between 1-4 mW. This permits adjusting the desired flow rate for a given application by controlling the fuel cell output conditions and foresees a fully autonomous analytical Lab-on-a-Chip in which the same device would provide the electrical power to a detection module and at the same time use the CO(2) pumping action to flow the required analytes through a particular microfluidic design.     

Polyurethane-based microfluidic devices for blood contacting applications

Protein adsorption on PDMS surfaces poses a significant challenge in microfluidic devices that come into contact with biofluids such as blood. Polyurethane (PU) is often used for the construction of medical devices, but despite having several attractive properties for biointerfacing, it has not been widely used in microfluidic devices. In this work we developed two new fabrication processes for making thin, transparent and flexible PU-based microfluidic devices. Methods for the fabrication and bonding of microchannels, the integration of fluidic interconnections and surface modification with hydrophilic polyethylene oxide (PEO) to reduce protein adsorption are detailed. Using these processes, microchannels were produced having high transparency (96% that of glass in visible light), high bond strength (326.4 kPa) and low protein adsorption (80% reduction in fibrinogen adsorption vs. unmodified PDMS), which is critical for prevention of fouling. Our findings indicate that PEO modified PU could serve as an effective alternative to PDMS in blood contacting microfluidic applications.     

Polymer microfabrication methods for microfluidic analytical applications

A growing number of microsystem technology (MST) applications, particularly in the field of microfluidics with its applications in the life sciences, have a need for novel fabrication methods which account for substrates other than silicon or glass. We present in this paper an overview of existing polymer microfabrication technologies for microfluidic applications, namely replication methods such as hot embossing, injection molding and casting, and the technologies necessary to fabricate the molding masters. In addition, techniques such as laser ablation and layering techniques are examined. Methods for bonding and dicing of polymer materials, which are necessary for complete systems, are evaluated.     

Multi-layer microfluidic glass chips for microanalytical applications

A new, versatile architecture is presented for microfluidic devices made entirely from glass, for use with reagents which would prove highly corrosive for silicon. Chips consist of three layers of glass wafers bonded together by fusion bonding. On the inside wafer faces a network of microfluidic channels is created by photolithography and wet chemical etching. Low dead-volume fluidic connections between the layers are fabricated by spark-assisted etching (SAE), a computer numerical controlled (CNC)-like machining technique new to microfluidic system fabrication. This method is also used to form a vertical, long path-length, optical cuvette through the middle wafer for optical absorbance detection of low-concentration compounds. Advantages of this technique compared with other, more standard, methods are discussed. When the new glass-based device for flow-injection analysis of ammonia was compared with our first-generation chips based on silicon micromachining, concentration sensitivity was higher, because of the longer path-length of the optical cuvette. The dependence of dispersion on velocity profile and on channel cross-sectional geometry is discussed. The rapid implementation of the devices for an organic synthesis reaction, the Wittig reaction, is also briefly described.     

Characterization of SU-8 for electrokinetic microfluidic applications

The characterization of SU-8 microchannels for electrokinetic microfluidic applications is reported. The electroosmotic (EO) mobility in SU-8 microchannels was determined with respect to pH and ionic strength by the current monitoring method. Extensive electroosmotic flow (EOF), equal to that for glass microchannels, was observed at pH > or =4. The highest EO mobility was detected at pH > or =7 and was of the order of 5.8 x 10(-4) cm(2) V(-1) s(-1) in 10 mM phosphate buffer. At pH < or =3 the electroosmotic flow was shown to reverse towards the anode and to reach a magnitude of 1.8 x 10(-4) cm(2) V(-1) s(-1) in 10 mM phosphate buffer (pH 2). Also the zeta-potential on the SU-8 surface was determined, employing lithographically defined SU-8 microparticles for which a similar pH dependence was observed. SU-8 microchannels were shown to perform repeateably from day to day and no aging effects were observed in long-term use.     

Fibre optic coupler as a detector for microfluidic applications

A new construction of a fibre optic coupler is presented in the paper. Two polymer optical fibres were used to build a coupler in which coupling efficiency of optical power depends on the refractive index of liquid delivered to a microchannel formed by the fibres. The coupler was tested as a detector in saccharose concentration measurements, and was used in absorbance measurements. A red light emitting diode and a spectrometer were used as a light source and a photodetector, respectively. Experiments confirmed that the coupler can be used for the real time monitoring of the changes in the refractive index of a saccharose solution exhibiting repeatable changes in the signal, with no hysteresis. Absorbance tests were performed with a solution of bromothymol blue at different pH.     

A miniaturized high-voltage integrated power supply for portable microfluidic applications

In this work a portable microfluidic device with a reusable integrated high voltage power supply is presented, which allows for quick exchange of inexpensive disposable poly(dimethylsiloxane)(PDMS) microfluidic chips on a carrier only slightly larger than a microscope slide. The device is powered by an onboard MN21 cell battery (5 mm radius, 30 mm long) and is demonstrated through the rapid and controlled transport of a fluorescent dye through an expansion chamber geometry. Power consumption experiments demonstrate the device's ability to complete over 40 dispense-flushing cycles on a single battery.     

Biofunctionalization of electrowetting-on-dielectric digital microfluidic chips for miniaturized cell-based applications

In this paper we report on the controlled biofunctionalization of the hydrophobic layer of electrowetting-on-dielectric (EWOD) based microfluidic chips with the aim to execute (adherent) cell-based assays. The biofunctionalization technique involves a dry lift-off method with an easy to remove Parylene-C mask and allows the creation of spatially controlled micropatches of biomolecules in the Teflon-AF(?) layer of the chip. Compared to conventional methods, this method (i) is fully biocompatible; and (ii) leaves the hydrophobicity of the chip surface unaffected by the fabrication process, which is a crucial feature for digital microfluidic chips. In addition, full control of the geometry and the dimensions of the micropatches is achieved, allowing cells to be arrayed as cell clusters or as single cells on the digital microfluidic chip surface. The dry Parylene-C lift-off technique proves to have great potential for precise biofunctionalization of digital microfluidic chips, and can enhance their use for heterogeneous bio-assays that are of interest in various biomedical applications.     

Silicon photonic sensors incorporated in a digital microfluidic system

Label-free biosensing with silicon nanophotonic microring resonator sensors has proven to be an excellent sensing technique for achieving high-throughput and high sensitivity, comparing favorably with other labeled and label-free sensing techniques. However, as in any biosensing platform, silicon nanophotonic microring resonator sensors require a fluidic component which allows the continuous delivery of the sample to the sensor surface. This component is typically based on microchannels in polydimethylsiloxane or other materials, which add cost and complexity to the system. The use of microdroplets in a digital microfluidic system, instead of continuous flows, is one of the recent trends in the field, where microliter- to picoliter-sized droplets are generated, transported, mixed, and split, thereby creating miniaturized reaction chambers which can be controlled individually in time and space. This avoids cross talk between samples or reagents and allows fluid plugs to be manipulated on reconfigurable paths, which cannot be achieved using the more established and more complex technology of microfluidic channels where droplets are controlled in series. It has great potential for high-throughput liquid handling, while avoiding on-chip cross-contamination. We present the integration of two miniaturized technologies: label-free silicon nanophotonic microring resonator sensors and digital microfluidics, providing an alternative to the typical microfluidic system based on microchannels. The performance of this combined system is demonstrated by performing proof-of-principle measurements of glucose, sodium chloride, and ethanol concentrations. These results show that multiplexed real-time detection and analysis, great flexibility, and portability make the combination of these technologies an ideal platform for easy and fast use in any laboratory.

Integration of polymeric membranes with microfluidic networks for bioanalytical applications.

The concept of microfluidics has significantly influenced the design and the implementation of modern bioanalytical systems due to the fact that these miniaturized devices can handle and manipulate samples in a much more efficient way than conventional instruments. In an analogy to the development of microelectronics, increasingly sophisticated devices with greater functionalities have become one of the major goals being pursued in the area of micrototal analysis systems. The incorporation of polymeric membranes into microfluidic networks has therefore been employed in an effort to enhance the functionalities of these microfabricated devices. These commercially available membranes are porous, flexible, mechanically robust and compatible with plastic microfluidic networks. The large surface area-to-volume ratio of porous membrane media is particularly important for achieving rapid buffer exchange during microdialysis and obtaining ultrahigh concentration of adsorbed enzymes for various biochemical reactions. Furthermore, the membrane pore diameter in the sub-microm range eliminates the constraints of diffusional mass-transfer resistance for performing chiral separation using adsorbed protein as the chiral stationary phase. A review on the recent advancement in the integration of polymeric membranes with microfluidic networks is presented for their widespread applications in bioanalytical chemistry.     

基于微流控芯片的色谱系统的研究进展及其应用

近年来,基于微流控芯片的色谱技术研究取得了快速发展。本文对微流控芯片上色谱柱的加工方法、泵阀驱动控制装置的设计、集成及联用色谱系统的研制及其应用等方面予以综述,涉及文献66篇。     

Trends in the bioanalytical applications of microfluidic electrocapture

Downscaled analytical tools for sample preparation have offered benefits such as higher throughput, easier automation and lower sample/reagent consumption. Microfluidic electrocapture, which is a newly developed sample preparation/manipulation system, uses an electric field to trap and separate charged species without using any solid sorbent. The feasibility of using microfluidic electrocapture is reported for separation, clean-up, concentration, microreactions and complexation studies of proteins, peptides and other biologically important biomolecules. The instrumentation and applications of microfluidic electrocapture are reviewed and an overview is provided of future perspectives offered by the current and envisaged platforms.     

A light writable microfluidic "flash memory": optically addressed actuator array with latched operation for microfluidic applications

This paper presents a novel optically addressed microactuator array (microfluidic "flash memory") with latched operation. Analogous to the address-data bus mediated memory address protocol in electronics, the microactuator array consists of individual phase-change based actuators addressed by localized heating through focused light patterns (address bus), which can be provided by a modified projector or high power laser pointer. A common pressure manifold (data bus) for the entire array is used to generate large deflections of the phase change actuators in the molten phase. The use of phase change material as the working media enables latched operation of the actuator array. After the initial light "writing" during which the phase is temporarily changed to molten, the actuated status is self-maintained by the solid phase of the actuator without power and pressure inputs. The microfluidic flash memory can be re-configured by a new light illumination pattern and common pressure signal. The proposed approach can achieve actuation of arbitrary units in a large-scale array without the need for complex external equipment such as solenoid valves and electrical modules, which leads to significantly simplified system implementation and compact system size. The proposed work therefore provides a flexible, energy-efficient, and low cost multiplexing solution for microfluidic applications based on physical displacements. As an example, the use of the latched microactuator array as "normally closed" or "normally open" microvalves is demonstrated. The phase-change wax is fully encapsulated and thus immune from contamination issues in fluidic environments.     

In-channel atom-transfer radical polymerization of thermoset polyester microfluidic devices for bioanalytical applications

A new technique for polymer microchannel surface modification, called in-channel atom-transfer radical polymerization, has been developed and applied in the surface derivatization of thermoset polyester (TPE) microdevices with poly(ethylene glycol) (PEG). X-ray photoelectron spectroscopy, electroosmotic flow (EOF), and contact angle measurements indicate that PEG has been grafted on the TPE surface. Moreover, PEG-modified microchannels have much lower and more pH-stable EOF, more hydrophilic surfaces and reduced nonspecific protein adsorption. Capillary electrophoresis separation of amino acid and peptide mixtures in these PEG-modified TPE microchips had good reproducibility. Phosducin-like protein and phosphorylated phosducin-like protein were also separated to measure the phosphorylation efficiency. Our results indicate that PEG-grafted TPE microchips have broad potential application in biomolecular analysis.     

Recent advances in direct current electrokinetic manipulation of particles for microfluidic applications

Microfluidic devices have been extensively used to achieve precise transport and placement of a variety of particles for numerous applications. A range of force fields have thus far been demonstrated to control the motion of particles in microchannels. Among them, electric field‐driven particle manipulation may be the most popular and versatile technique because of its general applicability and adaptability as well as the ease of operation and integration into lab‐on‐a‐chip systems. This article is aimed to review the recent advances in direct current (DC) (and as well DC‐biased alternating current) electrokinetic manipulation of particles for microfluidic applications. The electric voltages are applied through electrodes that are positioned into the distant channel‐end reservoirs for a concurrent transport of the suspending fluid and manipulation of the suspended particles. The focus of this review is upon the cross‐stream nonlinear electrokinetic motions of particles in the linear electroosmotic flow of fluids, which enable the diverse control of particle transport in microchannels via the wall‐induced electrical lift and/or the insulating structure‐induced dielectrophoretic force.     

How to embed three-dimensional flexible electrodes in microfluidic devices for cell culture applications

This communication describes a simple, rapid and cost effective method of embedding a conductive and flexible material within microfluidic devices as a means to realize uniform electric fields within cellular microenvironments. Fluidic channels and electrodes are fabricated by traditional soft-lithography in conjunction with chemical etching of PDMS. Devices can be deformable (thus allowing for a combination of electro-mechanical stimulation), they are made from inexpensive materials and easily assembled by hand; this method is thus accessible to a wide range of laboratories and budgets.