Fabrication of microfluidic structures in quartz via micro machining technologies

Microfluidic channels have been created for quartz material using micromechanical manufacturing technologies such as micro laser machining, micro ultrasonic machining, and ultra-precision machining. Ultra-precision machining has been used to manufacture cross-junction channels 14 µm wide and 28 µm deep with a three-dimensional triangle cross-section. Micro laser machining has been used to manufacture U-shaped and -shaped microfluidic channels. Deep holes and microfluidic channels with a high slenderness ratio (width/depth) can be obtained by using micro ultrasonic machining technology. These three machining techniques are compared with respect to surface profiles and machining quality.

     

Recognition of thin, flat microelectromechanical structures for automation of the assembly process

Visual recognition of microelectromechanical parts is necessary for automation of the assembly process. The visual recognition system that we have developed is based partly on neural networks and partly on digital image-processing techniques. The system takes grey-level microscope images and produces recognition code as the output as well as information about micropart position. The recognition procedure is not sensitive to micropart position. This is ensured by preprocessing based on calculation of the image moment properties. For the recognition, a supervised feedforward neural network is utilized. A combination of standard backpropagation and resilient propagation is chosen for learning the network. The performance of the system is tested on recognition of the parts of a microvalve system. The results are satisfactory with respect to recognition accuracy and recognition time.     

聚二甲基硅氧烷微流控芯片的制备

采用印刷电路板技术加工出芯片模具,以聚二甲基硅氧烷(PDMS)为材料制作出微流控芯片。该芯片由基片和盖片组成,微流控沟道位于基片上,深度和宽度分别为75μm和100μm,由盖片对其进行密封。考察了有绝缘漆模具和无绝缘漆模具制作的芯片的电泳分离情况。在该PDMS微流控芯片上对用异硫氰酸酯荧光素标记的氨基酸进行了电泳分离,当信噪比S/N=3时,最小检测浓度达到0.8×10-11mol/L。     

EWOD microfluidic systems for biomedical applications

As the technology advances, a growing number of biomedical microelectromechanical systems (bio-MEMS) research involves development of lab-on-a-chip devices and micrototal analysis systems. For example, a portable instrument capable of biomedical analyses (e.g., blood sample analysis) and immediate recording, whether the patients are in the hospital or home, would be a considerable benefit to human health with an excellent commercial viability. Digital microfluidic (DMF) system based on the electrowetting-on-dielectric (EWOD) mechanism is an especially promising candidate for such point-of-care systems. The EWOD-based DMF system processes droplets in a thin space or on an open surface, unlike the usual microfluidic systems that process liquids by pumping them in microchannels. Droplets can be generated and manipulated on EWOD chip only with electric signals without the use of pumps or valves, simplifying the chip fabrication and the system construction. Microfluidic operations by EWOD actuation feature precise droplet actuation, less contamination risk, reduced reagents volume, better reagents mixing efficiency, shorter reaction time, and flexibility for integration with other elements. In addition, the simplicity and portability make the EWOD-based DMF system widely popular in biomedical or chemical fields as a powerful sample preparation platform. Many chemical and biomedical researches, such as DNA assays, proteomics, cell assays, and immunoassays, have been reported using the technology. In this paper, we have reviewed the recent developments and studies of EWOD-based DMF systems for biomedical applications published mostly during the last 5 years.     

Multi-scale,multi-depth lithography using optical fibers for microfluidic applications

This paper proposes and demonstrates a method for multi-scale, multi-depth three-dimensional (3D) lithography. In this method, 3D molds for replicating microchannels are fabricated by passing a non-focused laser beam through an optical fiber, whose tip is immersed in a droplet of photopolymer. Line width is adjustable from 1 to 980 µm using eight kinds of optical fibers with different core diameters. The height of line drawing can be controlled by adjusting the distance between the tip of the optical fiber and a substrate. The surface roughness (R_a, R_z) of a single line and plane was evaluated. The method was employed to fabricate a 3D mold of a microchannel containing tandem chambers, which was then successfully replicated in PDMS. Multi-scale, multi-depth 3D lithography can provide a simple, flexible tool for producing PDMS microfluidic devices.     

Self-optimizing, thermally adaptive microfluidic flow structures

Although microfluidic devices offer many benefits, high fluid shear stresses in such devices are an undesirable consequence of miniaturization. In the present study, we present an adaptive “smart” design that mitigates the effects of high shear stresses in microfluidic-based devices by autonomously optimizing its internal flow structure. This concept was demonstrated by testing a prototype microscale thermal-fluid device that responded to changes in the local thermal environment. The autonomous, self-optimizing functionality was achieved using poly(N-isopropylacrylamide) hydrogel actuated microvalves, which independently controlled the flow to four distinct regions within the device. The experimental results showed that the device optimized its internal topological flow arrangement such that fluid was delivered only to regions where cooling was required. As a result, a series of spatially distributed thermal loads were dissipated with minimal pumping power consumption.     

Au–Sn flip-chip solder bump for microelectronic and optoelectronic applications

As an alternative to the time-consuming solder pre-forms and pastes currently used, a co-electroplating method of eutectic Au–Sn alloy was used in this study. Using a co-electroplating process, it was possible to plate the Au–Sn solder directly onto a wafer at or near the eutectic composition from a single solution. Two distinct phases, Au₅Sn (ζ-phase) and AuSn (δ-phase), were deposited at a composition of 30 at.%Sn. The Au–Sn flip-chip joints were formed at 300 and 400°C without using any flux. In the case where the samples were reflowed at 300°C, only an (Au,Ni)₃Sn₂ IMC layer formed at the interface between the Au–Sn solder and Ni UBM. On the other hand, two IMC layers, (Au,Ni)₃Sn₂ and (Au,Ni)₃Sn, were found at the interfaces of the samples reflowed at 400°C. As the reflow time increased, the thickness of the (Au,Ni)₃Sn₂ and (Au,Ni)₃Sn IMC layers formed at the interface increased and the eutectic lamellae in the bulk solder coarsened.     

聚二甲基硅氧烷微流体芯片的制作技术

基于MEMS技术的微流体芯片在分析化学和生物医学领域显示了巨大的应用潜力。作为构建微流体芯片的基底材料———聚二甲基硅氧烷(PDMS)已经表现出了许多的优点:良好的电绝缘性、较高的热稳定性、优良的光学特性以及简单的加工工艺等。采用浇注法制作了PDMS电泳微芯片,对PDMS微流体芯片的加工工艺、封装方法和结构特征进行了探讨,并提出了相应的解决方案。     

Methods for counting particles in microfluidic applications

Microfluidic particle counters are important tools in biomedical diagnostic applications such as flow cytometry analysis. Major methods of counting particles in microfluidic devices are reviewed in this paper. The microfluidic resistive pulse sensor advances in sensitivity over the traditional Coulter counter by improving signal amplification and noise reduction techniques. Nanopore-based methods are used for single DNA molecule analysis and the capacitance counter is useful in liquids of low electrical conductivity and in sensing the changes of cell contents. Light-scattering and light-blocking counters are better for detecting larger particles or concentrated particles. Methods of using fluorescence detection have the capability for differentiating particles of similar sizes but different types that are labeled with different fluorescent dyes. The micro particle image velocimetry method has also been used for detecting and analyzing particles in a flow field. The general limitation of microfluidic particle counters is the low throughput which needs to be improved in the future. The integration of two or more existing microfluidic particle counting techniques is required for many practical on-chip applications.     

Deep microstructuring in glass for microfluidic applications

Glass is widely used as a structural and functional material in micro-total-analysis-systems. Two low-cost techniques have been used to produce deep and vertical microstructures into glass. A commercially available photosensitive glass (Foturan™) is patterned by photolithography and etched in an HF solution for the construction of a microfluidic component. Channels and reservoirs were bonded to a poly(dimethylsiloxane) cover. A two-level structure with various depths (reservoirs and channels) was also made by a double exposure through two different masks. The other technique uses micro-ultra-sonic machining to form channels by erosion into borosilicate glass (Pyrex 7740). The two structuring techniques are compared with respect to surface profiles and surface states.     

Positioning system for particles in microfluidic structures

Fast continuous flow detection of biomolecules in lab-on-a-chip structures is a challenging task. Combining these molecules with small magnetic particles, the interaction between their stray field and, e.g., magneto-resistive sensors can be used to indirectly prove the biomolecules. To position the particles on top of a sensor array at the bottom of the flow channel, we propose a microfluidic structure of changing channel height combining hydrodynamic and gravitational effects. We present numerical calculations predicting an increase in the capture rate by more than 100% in comparison to a straight channel. We experimentally realize an optical analysis of the specific binding of biotin-functionalized Chemagen beads on a streptavidin-coated surface. To prove the binding is not due to the surface effects, a second uncoated bead species is employed.     

A micromechanical flow sensor for microfluidic applications

We fabricated a microfluidic flow meter and measured its response to fluid flow in a microfluidic channel. The flow meter consisted of a micromechanical plate, coupled to a laser deflection system to measure the deflection of the plate during fluid flow. The 100 /spl mu/m square plate was clamped on three sides and elevated 3 /spl mu/m above the bottom surface of the channel. The response of the flow meter was measured for flow rates, ranging from 2.1 to 41.7 /spl mu/L/min. Several fluids, with dynamic viscosities ranging from 0.8 to 4.5/spl times/10/sup -3/ N/m, were flowed through the channels. Flow was established in the microfluidic channel by means of a syringe pump, and the angular deflection of the plate monitored. The response of the plate to flow of a fluid with a viscosity of 4.5/spl times/10/sup -3/ N/m was linear for all flow rates, while the plate responded linearly to flow rates less than 4.2 /spl mu/L/min of solutions with lower dynamic viscosities. The sensitivity of the deflection of the plate to fluid flow was 12.5/spl plusmn/0.2 /spl mu/rad/(/spl mu/L/min), for a fluid with a viscosity of 4.5/spl times/10/sup -3/ N/m. The encapsulated plate provided local flow information along the length of a microfluidic channel.     

Integratable magnetic shape memory micropump for high-pressure,precision microfluidic applications

Precisely controlling the flow of fluids on a microscopic scale has been a technological challenge in the field of microfluidics. Active microfluidics, where a defined manipulation of the working fluid is necessary, requires active components such as micropumps or microvalves. We report on an optimized design of an integratable, wireless micropump made from the magnetic shape memory (MSM) alloy Ni–Mn–Ga. An external magnetic field generates a shape change in the MSM material, which drives the fluid in a similar fashion as a peristaltic pump. Thus, the pump does not need electrical contacts and avoids the mechanical parts found in traditional pumping technologies, decreasing the complexity of the micropump. With a discrete pumping resolution of 50–150 nL per pumping cycle, which is further scalable, and a pumping pressure well exceeding 2 bar, the MSM micropump is capable of accurately delivering the fluids needed for microfluidic devices. The MSM micropump is self-priming, pumping both liquid and gas, and demonstrates repeatable performance across a range of pumping frequencies. Furthermore, it operates simultaneously as both a valve and reversible micropump, offering superior possibilities compared to existing technologies within the flow rate range of 0–2000 µL/min. Due to its simplicity, this technology can be scaled down easily, which lends itself for future integration into lab-on-a-chips and microreactors for life science and chemistry applications.     

Fabrication of microfluidic devices for packaging CMOS MEMS impedance sensors

This work presents a polydimethylsiloxane (PDMS) microfluidic device for packaging CMOS MEMS impedance sensors. The wrinkle electrodes are fabricated on PDMS substrates to ensure a connection between the pads of the sensor and the impedance instrument. The PDMS device can tolerate an injection speed of 27.12 ml/h supplied by a pump. The corresponding pressure is 643.35 Pa. The bonding strength of the device is 32.44 g/mm². In order to demonstrate the feasibility of the device, the short circuit test and impedance measurements for air, de-ionized water, phosphate buffered saline (PBS) at four concentrations (1, 2 × 10⁻⁴, 1 × 10⁻⁴, and 6.7 × 10⁻⁵ M) were performed. The experimental results show that the developed device integrated with a sensor can differentiate various samples.     

Fabrication of microchannels in single crystal diamond for microfluidic systems

A growth of single crystal diamond (SCD) microchannels on HPHT diamond substrate has been carried out successfully by a simple and novel method. Firstly, aluminum film was patterned on SCD diamond substrate surface by magnetron sputtering, photolithography and dry etching techniques. Secondly, the aluminum patterns were transferred onto diamond substrate via inductively coupled plasma etching to form grooves on diamond surface. Finally, microchannels were achieved by epitaxial lateral overgrowth of SCD on the surface of prepared substrate by microwave plasma chemical vapor deposition system. After that, fluorescent liquid was introduced to check hollowness of the microchannels. This work provides a simple and time saving method to fabricate SCD microchannels for microfluidic system, which offers a great potential for hard environment applications.     

玻璃-PDMS薄膜-玻璃夹心微流控芯片制作

聚二甲基硅氧烷(PDMS)是目前微流控芯片中应用的最广泛的基质材料,但基于PDMS材料的微流控芯片在应用中存在溶剂易挥发、难以进行较长时间检测分析的问题.针对这些问题,发展了一种简便高效的“玻璃-PDMS薄膜-玻璃”(G-P-G)夹心式微流控芯片的制作方法.该方法巧妙利用聚酯(PET)胶片作为载体转移处理脆弱的结构化PDMS膜,然后通过等离子体处理将结构化PDMS膜夹在两个玻璃基板的中间,形成“玻璃-PDMS薄膜-玻璃”夹心结构芯片,由于玻璃材料的低通透性,使得芯片具有低溶剂挥发特性.该夹心式芯片的低溶剂挥发特性通过蛋白质结晶实验得到了验证.     

Fabrication of microfluidic networks with integrated electrodes

In this paper a method is presented for the fabrication of micro-channel networks in glass with integrated and insulated gate electrodes to control the zeta-potential at the insulator surface and therewith the electro-osmotic flow (EOF). The fabrication of the electrodes is a sequence of photolithography, etching and thin film deposition steps on a glass substrate, followed by chemical mechanical polishing (CMP) and subsequently direct thermal bonding to a second glass plate to form closed micro-channels. Plasma enhanced chemical vapor deposition (PECVD) SiO₂-layers as insulating material between the electrodes and micro-channels and different electrode materials are examined with respect to a high bonding temperature to obtain an optimal insulating result. A CMP process for the reduction of the SiO₂ topography and roughness is studied and optimized in order to obtain a surface that is smooth enough to be directly bondable to a second glass plate.     

Engineering microfluidic concentration gradient generators for biological applications

This paper reviews the latest developments in the design and fabrication of concentration gradient generators for microfluidics-based biological applications. New gradient generator designs and their underlying mass transport principles are discussed. The review provides a blueprint for design considerations of concentration gradients in different applications, specifically biological studies. The paper discusses the basic phenomena associated with microfluidic gradient generation and the different gradient generation modes used in static and dynamic biological assays. Finally, the paper summarizes all factors to consider when using concentration gradient generators and puts forward perspectives on the future development of these devices.     

Fabrication,simulations, and measurements of self-assembled millimeter-wave antennas for system-on-chip applications

A micro-electro-mechanical systems fabrication process has been developed to create self-assembled on-chip high efficiency antennas. The self-assembly creates out-of-plane antenna structures, which can have good radiation efficiency on low resistivity substrates. The structural material is SU-8 and the self-assembly curvatures are defined lithographically. The losses are reduced by having the antennas, transmission lines, and an isolating conducting ground plane placed on top of the supporting (and lossy) dielectric layer. The fabrication process includes deposition of a thick metal layer, which envelopes the antenna structure. This paper presents the fabrication process for a self-assembled monopole antenna, and numerical and physical experiments for the antenna pattern characteristics. The physical measurements show a realized gain (includes mismatch loss) of ?1.29 dBi at 59 GHz.