Proceedings Volume 4982

Microfluidics, BioMEMS, and Medical Microsystems

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Proceedings Volume 4982

Microfluidics, BioMEMS, and Medical Microsystems

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Volume Details

Date Published: 17 January 2003
Contents: 8 Sessions, 41 Papers, 0 Presentations
Conference: Micromachining and Microfabrication 2003
Volume Number: 4982

Table of Contents

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Table of Contents

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  • Biological and Medical Applications
  • Polymeric Devices
  • BioMEMS Materials and Nanofabrication
  • Biosensors and DNA
  • Microfluidic Applications I
  • Microfluidic Applications II
  • Microfluidic Applications III
  • Poster Session
Biological and Medical Applications
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Microsystem technologies for ophthalmological implants
Wilfried Mokwa
Due to the low power consumption CMOS electronics is ideal for the use in implanted systems. This paper presents two projects working on ophthalmological implants. Both systems are powered by an external RF-field. One system has been developed to measure the intraocular pressure continuously which is important for the therapy of glaucoma patients. The system consists of a micro coil and an integrated pressure transponder chip built into an artificial soft lens. A second example is a very complex system for epiretinal stimulation of the nerve cells of the retina. With such a system it might be possible to give blind people that are suffering from retinitis pigmentosa some visual contact to their surrounding.
Single-cell manipulation and fluorescence detection in benchtop flow cytometry system with disposable plastic microfluidic chip
Jung Kyung Kim, Hyunwoo Bang, Seok Chung, et al.
Flow cytometry and microfluidic system are versatile tools to study the functional genomics at the single-cell level in the postgenomic era. We have developed a microfluidics-based benchtop flow cytometry system incorporating a disposable plastic microchip and low-power diode lasers. The plastic microfluidic chip is designed and fabricated using soft lithography which enables the development of inexpensive and flexible miniaturized fluidic devices. The microchip contains the hydrodyamic focusing chamber where the sample and sheath fluids are driven by a pressure difference. The performance of the combined fluidics and optics is studied systematically to evaluate the detection accuracy and efficiency of our flow cytometry system. The interactions of the biological particles with surrounding squeezed flow and focused laser beam are investigated to optimize the design of the microchannel network as well as the optical characteristics of the instrument for efficient single-cell manipulation and detection.
Resonant mass biosensor for ultrasensitive detection of bacterial cells
Amit Gupta, Demir Akin, Rashid Bashir
This paper describes a surface micromachined cantilever beam based oscillator detector for biological applications. This study used a novel microfabrication technique of merged epitaxial lateral overgrowth (MELO) and chemical mechanical polishing (CMP) to fabricate thin, low stress, single-crystal silicon cantilever beams. Vibration spectra of the cantilever beams, excited by thermal and ambient noise, was measured in air using a Digital Instrument Dimension 3100 Series scanning probe microscope (SPM). The cantilever beams were calibrated by obtaining the spring constant using the added-mass method. The sensors were used to detect the presence of Listeria innocua bacteria by applying increasing concentration of bacteria suspension on the same cantilever beam and measuring the resonant frequency changes in air. Cantilever beams were also used to detect the mass of the adsorbed antibodies and used to show selective capture of bacterial cells. The results indicate that the developed biosensor is capable of rapid and ultra-sensitive detection of bacteria and promises significant potential for enhancement of microbiological research and diagnostics.
Single-cell analysis on a microchip platform using optical tweezers and optical scissors
Microfluidic devices, or "lab-on-a-chip" systems for single cell analysis represent a new field of micro-total analysis systems (μTAS) that could not only perform a task quicker, and more accurately than conventional methods, but could also incorporate additional tools to the study of biological variability in a population by allowing researchers to directly examine the contents of a multitude of single cells from the population under study. Realizing such a device, presents several engineering challenges to the fields of micro-machining, micromanipulation and analytical bio-chemistry. The device needs to be able to accurately and efficiently select, manipulate and analyze volumes represented by a single cell without diluting the contents. For this purpose, optical tweezers and scissors were implemented to select single cells on a microchip, bring the cell to a desired location, and lyse the cell using the optical scissors. Channels were engineered in the device using a molecular fluorine (F2) laser. Each channel’s cross-section is approximately the size of an individual cell (10μm wide and deep). This paper, describes the manipulation of cells on a microchip using optical tweezers and the injection of the cellular contents by optical scissors from a single cell into 10μm channels.
Micro-array development for cell secretion studies
We are focusing on the development of a biochip which will enable massively parallel amperometric measurements on single cells for exocytosis studies. Initial prototypes have been fabricated with picoliter-sized wells which roughly conform to the shape of the cells. The electrochemical measurement using the prototype devices can capture a large fraction, approximately 80%, of the catecholamine release with millisecond temporal resolution. With this prototype device, cells must be manually positioned into the micro-wells by a micromanipulator. Therefore, two new designs incorporating three dimensional microfluidic structures have been developed for automatic cell positioning. One design is based on thin silicon diaphragms with picoliter-sized well arrays, while another has 1μm silicon nitride membranes. Both designs have through-membrane holes and are designed in such a way that the cells will be automatically positioned onto electrodes once a suitable pressure differential is applied between the two sides of the thin diaphragms. Details of the microfabrication process for both designs will be presented in this paper as well as results of automatic cell positioning tests.
Micromachined conformal electrode array for retinal prosthesis application
Murat Okandan, Kurt O. Wessendorf, Todd R. Christenson, et al.
Retinal prosthesis projects around the world have been pursuing a functional replacement system for those with retinal degeneration. In this paper, we will outline the concept for a micromachined conformal electrode array and present preliminary fabrication results. Individual electrodes are designed to float on micromachined springs on a substrate that will enable the adjustment of spring constants and therefore contact force by adjusting the dimensions of the springs at each electrode. This will also allow us to accommodate the varying curvature/topography of the retina. We believe that this approach will provide several advantages by improving the electrode/tissue interface as well as generating some new options for in-situ measurements and overall system design.
Polymeric Devices
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Polymer-based microfluidic devices for biomedical applications
Mateusz L. Hupert, Malgorzata A. Witek, Yun Wang, et al.
Two types of Microfluidic bioanalytical systems were designed and fabricated in polymer substrates using the LIGA process. A continuous flow polymerase chain reaction (CFPCR) Microfluidic device was fabricated in polycarbonate (PC), which utilized isothermal zone and shuttling the sample through each zone to achieve amplification. A 20-cycle PCR amplification of a fragment of a plasmid DNA template was achieved in 5.3 min. The results were comparable to those obtained in commercial laboratory-scale PCR system. The second system consisted of a microchip contating a low-density array assembled into the Microfluidic channel, which was hot-embossed in poly(methyl methacrylate) (PMMA). The detection of low-abundant mutations in gene fragments (K-ras) that carry point mutations with high diagnostic value for colorectal cancer was successfully performed. The array accessed microfluidics in order to enhance the kinetic associated with hybridization.
Molded multilevel modular microfluidic devices
In this paper, we present a quasi-three-dimensional micro-fluidic device that has been constructed using the LIGA technology at CAMD. The idea is centered in the modular construction of molded plastic devices. A primary master template was patterned into SU-8 and PMMA, from which we made a reversed insertion mold by electroplating Nickel on it. Chips were patterned by hot embossing and the complex structure was obtained by stacking one layer on top of the other. Alignment marks were placed in each different layer to allow the accurate positioning of the structures. Each layer is a 2-dimensional micro-fluidic system and liquids can go from one level to another level, back and forth, producing this almost three-dimensional behavior. This work aims to introduce concepts and features that will be a step towards a complete modularization of micro-fluidic devices.
Laser-based fabrication of microfluidic components and systems
Diffuser micro-pumps are commonly fabricated with the standard lithography techniques using silicon as the base material. The important components of this kind of micro-pump are flow directing diffusers and a moving diaphragm. Different diffuser designs show various flow rates and pump efficiency. In this work, polymer is used as its base material instead of silicon. Polymer is cost-effective and relatively easy to be machined with an Excimer laser. Moreover, the flexibility of the material gives a much better performance compared with the silicon based micro-pumps. The measured flow rate of this pump is 10 to 20 times higher than that of the silicon based micro-pumps. In addition, the performance of the diffuser polymer micro-pump is simulated with FLUENT and the calculated result at low frequency is in good agreement with the experimental result.
Modeling and validation of a molded polycarbonate continuous-flow polymerase chain reaction device
Michael W. Mitchell, Xuezhu Liu, Yannick Bejat, et al.
A continuous flow polymerase chain reaction (CFPCR) system was designed, fabricated from molded polycarbonate, and tested. Finite element modeling was used to simulate the thermal and Microfluidic response of the system. The mold insert for the initial prototypes was fabricated using the X-ray LIGA microfabrication process and device components produced by hot embossing polycarbonate. Commercial thin film heaters under PID control were used to supply the necessary heat flux to maintain the steady-state temperatures in the PCR. The simulated transient temperature response at start up was compared to the experimental response. The simulated steady state temperature profile along the channel generated by the finite element analysis was compared to the experimental temperature profile displayed by liquid crystals. Experimental and simulated results were within 5% of each other, validating the thermal design of the CFPCR device.
Polymer based microfluidic devices: examples for fluidic interfaces and standardization concepts
Claudia Gaertner, Holger Becker, Birgit Anton, et al.
Although microfluidic devices have been used in research and are increasingly available on a commercial scale, most available systems are custom-made. Despite the progress made in the miniaturization of the devices and their biological or chemical application, only little attention went into the interfacing of the devices to the macroworld, particularly the adaptation of existing standards in the application fields. In this paper we present some concepts and methods of interfacing miniaturized devices with the macroworld, e.g for sample introduction. We have thereby made use of existing (semi-) standards, particularly in the biotechnology community and for biomedical applications.
BioMEMS Materials and Nanofabrication
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The Stanford Nanofabrication Facility and the National Nanofabrication Users' Network: the ultimate sandbox for bioMEMS and bioengineering R&D
As cutting-edge research becomes more multidisciplinary, it becomes increasingly difficult to find experimental and laboratory resources that can support such broadly defined research. The five, founding-member university facilities of the Nanofabrication Users' Network (NNUN) have been providing such broad-based resources for nine years. The goal of the NNUN is not only to develop micro- and nanotechnology fabrication resources and expertise across a broad range of disciplines, but also to encourage researchers from industry as well as academia outside the network to make use of our facilities. All NNUN sites are shared-equipment, open-use laboratories featuring a broad range of micro- and nanofabrication equipment. The NNUN is comprised of two main "hub" facilities at Stanford and Cornell Universities, and three "satellite" facilities at the University of California, Santa Barbara, Penn State University, and Howard University. Based on the academic traditions of openness and sharing, these facilities comprise a vibrant, dynamic community of researchers. Our lab members come from a wide variety of disciplines, with research in areas of optics, MEMS, biology, and chemistry, as well as process characterization and fabrication of more traditional electronics devices. We are especially committed to supporting use of micro- and nanofabrication technologies in non-traditional research applications. The NNUN is supported by the National Science Foundation under cooperative agreements ECS-9731293 and ECS-9731294.
Rapid fabrication of hot embossing tools using PDMS
In this paper, we present a simple method of fabricating the hot embossing tools using polydimethylsiloxane (PDMS). The tools are then used to fabricate microfluidic systems in polymethylmethacrylate (PMMA) of various aspect ratios. A negative photoepoxy (SU-8) or thick positive (AZ4620) photoresist on silicon is used as a molding template for the casting process to obtain a negative of the desired features in PDMS. The fabrication time of these PDMS tools is typically less and remains the same for realizing low as well as high aspect ratio features. This processing technique was used to fabricate microchannels over a wide range of aspect ratios in PMMA. This approach offers many advantages compared to the conventional methods of fabricating hot embossing tools including rapid processing, reduction in complexity and cost. This technique can also be extended to create orthogonal 3-D microfluidic systems in various thermoplastics.
Investigation of hard magnetic silicone elastomer thin films
Zhongmei Yao, Ji Fang, Jackie C. Chen, et al.
The hard magnetic materials with a high remnant magnetic moment, Mr, have the unique advantages that can achieve bi-directional (push-pull) movement in an external magnetic field. This paper presents the results on fabrication and testing of the novel hard magnetic silicone elastomer thin films. The micro-size hard ferrite powder, NdFeB powder and different silicone elastomers have been used to fabricate the various large elongation hard magnetic thin films. The uniform thin films range from 40 μm to 216 μm and they are successfully fabricated. Three different fabrication processing have been investigated and the mechanical properties, like Young’s modulus and deflection force, have been evaluated. The simulation results with ANSYS match the experimental data. In comparison to electrostatic or piezoelectric actuation, the magnetic actuation can provide stronger forces and larger deflections. The large elongation hard magnetic thin film provides an excellent diaphragm material, which plays an important role in the micro pump or valve. This film movement has been tested in the external magnetic field, and proved to have large deflections and high performances.
Shrinkage of polyurethane molecular stamp fixed on epoxy resin modified glass substrate
Zhengchun Liu, Quanguo He, Pengfeng Xiao, et al.
The shrinkage of polyurethane stamps used for the in situ synthesis of DNA microarrays via molecular stamping method was studied with Micron XYZ Scope. It was found that the polyurethane stamp fixed on the epoxy resin modified glass strongly and showed minimum linear shrinkage. The linear shrinkage of the whole polyurethane stamp and that of each feature of polyurethane stamp were controlled within 0.0341% and 0.309%, respectively, which were due to the strong van der Waals forces and hydrogen bonds between polyurethane and epoxy resin. It was also confirmed by scanning electron microscope that the polyurethane stamp fixed on the epoxy resin modified glass replicated the patterns of motherboard with a high fidelity. All these underlay the synthesis of DNA microarray through molecular stamping method.
Laser processing of microfluidic components and bioMEMS
Elizabeth K. Illy, Graham Rutterford, Andrew I. Bell, et al.
Micro-processing with lasers is an enabling technology for microfluidics and bioMEMS due to the high precision, accuracy and resolution achievable using laser sources. Visible micromachining of metals and ceramics has proved an efficient and precise way of producing spotting pins for high-throughput screening applications. UV micromachining of the polymer materials often used in metered dose inhalers (MDI) and other medical devices is efficient due to the high absorption properties of these polymers. Key to these types of devices is the accuracy and reproducibility. This paper describes the use of copper vapour lasers to produce micro-fluidic and bioMEMS type components.
Biosensors and DNA
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BioMEMS for multiparameter clinical monitoring
For diabetes patients glucose monitoring means an important improvement of their life quality and additionally it is a $3-billion-a-year business. Continuous glucose monitoring provides gapless glucose level control, an early warning of hypoglycemia, and is intended to control insulin pumps. An upgrading to multi-parameter monitoring would not only benefit patients with severe metabolism defects but also the metabolism of diabetes patient could be better controlled by monitoring an additional parameter like lactate. Multi-parameter monitoring devices are not commercially available, one of the complications in the integration of different biosensors using the same detecting molecule for all analytes is chemical cross talk between adjacent amperometric biosensors. Recently some integrated biosensors were published but either they were not mass producible or they were realized in an expensive silicon based technology. In addition to it most of them were not tested under monitoring conditions but their integration principles will be discussed. As an example a low cost multi- parameter microsystem and some applications of it in clinical diagnosis will be presented. Also an overlook of non-invasive methods and (minimal) invasive methods will be given with a focus on microdialysis.
Real-time DNA biosensor using passive microfluidic structures
An evanescent field waveguide DNA biosensor coupled with a microfluidic sample delivery system is the platform for our studies. By employing microfluidics our aim is to reduce sample size and scale to large arrays, thereby increasing the efficiency of the sensor. We are studying the hybridization rate in small sensing zones under flow conditions, with a capture oligonucleotide immobilized on the surface of the waveguide. We are also investigating what effect passive mixing structures placed in the sensing zone have on the hybridization kinetics of the system.
High-throughput integration of optoelectronics devices for biochip fluorescent detection
Evan P. Thrush, Ofer Levi, Ke Wang, et al.
Miniaturized, portable and robust sensing systems are required for the development of integrated biological analysis systems and their application to clinical diagnostics. This work uses vertical cavity surface emitting lasers (VCSELs), optical emission filters and PIN photodetectors to realize monolithically integrated, near infrared, fluorescence detection systems. The integration of these micro technologies with biochip applications will drastically reduce cost and allow for parallel sensing architectures, which is particularly useful for flow channel arrays such as in capillary array electrophoresis. This paper focuses on the fabrication of integrated fluorescence sensors. Fabrication procedures have been developed to realize intracavity contacted VCSELs and low noise photodetectors, such as selective AlGaAs wet etching and via planarization. A reflow process with positive photoresist has been developed to provide via electrical contacts and to optically isolate the photodetector from the light source. Three-dimensional microstructures can be simply made by this reflow technique. Optical simulations predict that a detection sensitivity lower than 10000 molecules per 104μm2 sample area. Single molecule detection may be possible in certain sensing architectures.
Use of molecular beacons for the detection of bacteria in microfluidic devices
Chuanwu Xi, Stephen A. Boppart, Lutgarde Raskin
We present the use of DNA and peptide nucleic acid (PNA) molecular beacons (MBs) as sensitive indicators in microfluidic bioMEM devices. DNA and PNA MBs can be used to quantitatively study hybridization kinetics in real time in a polydimethyl siloxane (PDMS) microfluidic device. PNA MBs perform better than DNA MBs for the study of hybridization kinetics of rRNA targets in real time in microfluidic channels. We also demonstrate the use of PNA MBs for fast detection of bacterial cells in microfluidic channels. Using PNA MBs as detection probes will enable us to develop an integrated biosensor for the rapid and on-site detection and quantification of microbial pathogens in environmental and clinical samples.
Porous-Si-based bioreactors for glucose monitoring and drug production
Biosensors are a very useful tool to produce drugs or to monitor chemical species through their product of reaction. The sensor is fabricated bounding on its surface specific enzymes that can accomplish the synthesis function. We studied the possibility to fabricate Si-based micro-biosensors to detect glucose in water solutions. We used porous Si (PS) as surface to bound the glucose oxidase enzyme. We ideated an fabricated a novel biosensor structure based on a PS membrane that can be used for glucose monitoring and for drug production, by properly choosing the enzyme to immobilize in the reactor. The fabrication details of the structure, having a suspended and auto-supporting PS membrane, through surface micromachining processes, ULSI compatible, are shown. Micro channels localised below the membrane will allow the buffer solution flow through the porous matrix. Moreover, in this work we acquired the know-how on the enzyme manipulation, bonding and detection on Si-based surfaces. The glucose oxidase was deposited in PS, on bulk Si and on glass to perform photoluminescence, absorbance and optical microscopy measurements.
Integrated optical biochemical sensor fabricated using rapid-prototyping techniques
This paper details the design and fabrication of an integrated optical biochemical sensor using a select oxygen-sensitive fluorescent dye, tris(2,2’-bipyridyl) dichlororuthenium(II) hexahydrate, combined with polymeric waveguides that are fabricated on a glass substrate. The sensor uses evanescent interaction of light confined within the waveguide with the dye that is immobilized on the waveguide surface. Adhesion of the dye to the integrated waveguide surface is accomplished using a unique process of spin-coating/electrostatic layer-by-layer formation. Exposure of the dye molecules to the analyte and subsequent chemical interaction is achieved by directly coupling the fluid channel to the integrated waveguide. A unique fabrication aspect of this sensor is the inherent simplicity of the design, and the resulting rapidity of fabrication, while maintaining a high degree of functionality and flexibility.
Microfluidic Applications I
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An answer in the palm of your hand: microfluidics for analytical applications
Yolanda Fintschenko, Wen-Yee Choi, Eric B. Cummings, et al.
We have applied CZE and CEC in microfluidic devices to a number of analytical problems including the analysis of chemical warfare agents, polycyclic aromatic hydrocarbons, and proteins. In addition to developments in the areas of separations, we are also heavily involved in the "front-end" of analytical systems particularly in the area of sample preconcentration. We have a particular interest in the concentration of a wide range of molecules including small molecules, biopolymers, and cells. Our current toolbox includes a microfluidic platform known as Liquid Phase μChemLab developed by a team at Sandia for protein analysis. This platform has been demonstrated with protein biotoxins, CW agent degradation products, protein preconcentration, and is suitable for other targets. Additionally, electrodeless dielectrophoresis technology developed at Sandia is an attractive alternative to filters for cell concentration.
Fabrication of a hybrid plastic-silicon microfluidic device for high-throughput genotyping
Isabelle Chartier, J. Sudor, Yves Fouillet, et al.
The lab-on-a-chip approach has been increasingly present in biological research over the last ten years, high-throughput analyses being one of the promising utilization. The work presented here has consisted in developing an automated genotyping system based on a continuous flow analysis which integrates all the steps of the genotyping process (PCR, purification and sequencing). The genotyping device consists of a disposable hybrid silicon-plastic microfluidic chip, equipped with a permanent external, heating/cooling system, syringe-pumps based injection systems and on-line fluorescence detection. High throughput is obtained by performing the reaction in a continuous flow (1 reaction every 6min per channel) and in parallel (48 channels). We are presenting here the technical solutions developed to fabricate the hybrid silicon-plastic microfluidic device. It includes a polycarbonate substrate having 48 parallel grooves sealed by film lamination techniques to create the channels. Two different solutions for the sealing of the channels are compared in relation to their biocompatibility, fluidic behavior and fabrication process yield. Surface roughness of the surface of the channels is the key point of this step. Silicon fluidic chips are used for thermo-cycled reactions. A specific bonding technique has been developed to bond silicon chips onto the plastic part which ensures alignment and hermetic fluidic connexion. Surface coatings are studied to enhance the PCR biocompatibility and fluidic behavior of the two-phase liquid flow. We then demonstrate continuous operation over more than 20 hours of the component and validate PCR protocol on microliter samples in a continuous flow reaction.
Microfluidic system incorporating layer-by-layer nanofabricated capsules
Michelle Prevot, A. L. Cordeiro, Gleb B. Sukhorukov, et al.
A microfluidic system was designed, fabricated and implemented to study the behavior of polyelectrolyte capsules flowing in microscale channels. The silicon component of the system contains microchannels that leads into constrictions, which were fabricated using lithography techniques. Polyelectrolyte microcapsules were also fabricated with well-known layer-by-layer assembly technique, on a spherical template. Once the template was removed, the resulting hollow capsules were introduced into the system. The behavior of the capsules at the constrictions was visualized and the properties of the capsules were investigated. Capsules recovered from the system appear to have a undergone a plastic deformation.
Construction of an integrated biomodule composed of microfluidics and digitally controlled microelectrodes for processing biomolecules
Patrick F. Wagler, Uwe Tangen, Thomas Maeke, et al.
This work focuses on the development of an online programmable microfluidic bioprocessing unit (BioModule) using digital logic microelectrodes for rapid pipelined selection and transfer of DNA molecules and other charged biopolymers. The design and construction technique for this hybrid programmable biopolymer processing device is presented along with the first proof of principle functionality. The electronically controlled collection, separation and channel transfer of the biomolecules is monitored by a sensitive fluorescence setup. This hybrid reconfigurable architecture couples electronic and biomolecular information processing via a single module combination of fluidics and electronics and opens new fields of applications not only in DNA computing and molecular diagnostics but also in applications of combinatorial chemistry and lab-on-a-chip biotechnology to the drug discovery process. Fundamentals of the design and silicon-PDMS-based construction of these electronic microfluidic devices and their functions are described as well as the experimental results.
Microfluidic Applications II
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Flat fluidics: a new route toward programmable biochips
Achim Wixforth, Christoph Gauer, Juergen Scriba, et al.
The miniaturization of chemical and biological processes has made enormous progress driven mainly by genomics and proteomics. Microfluidics is the core technology to realize miniaturized laboratories with feature sizes on a submillimeter scale. Here, we report on a novel microfluidic technology which allows biochips to be programmed so that different biological assays can be performed with only one chip layout. Interdigital transducers integrated on piezoelectric substrates excite surface acoustic waves (SAW) which drive reagents on the surface of the biochip. The reagents can be placed on any desired spot on the chip’s surface, they can be merged, split and brought to reaction. SAW technology can also be used to efficiently agitate small volumes of liquids accelerating diffusion limited reactions considerably.
Ultrasonic temperature control and measurement in microfluidic channels
Hemanth Jagannathan, Goeksenin G. Yaralioglu, A. Sanli Ergun, et al.
This paper describes the design and operation of a system used for the accurate control and measurement of temperature in micro-fluidic channels. Ultrasonic transducers are used for both heating and measuring the temperature of fluids inside the channel. Heating is performed by exciting the transducer with a tone burst at a single frequency. The temperature measurement is done through non-invasive means by monitoring the velocity of a sound propagating through the channel. The whole system is automated for data collection using Labview. The system developed has the advantages of easy integration, simple operation and design along with a wide application domain. The same ultrasonic transducer can be used for both heating and temperature measurement leading to possibilities of closed loop temperature control in micro-channels. The system requires milli-watts of power for heating and has a nano-second response time for temperature measurement with an accuracy of 0.1 degrees.
Novel design and fabrication of a microcentrifuge for biomedical and biochemical applications
In this paper, modeling and simulation of a novel micro-centrifuge for biomedical and biochemical applications is described. The micro-centrifuge that we designed can work not only as a shaker but also as a detector of cell growth, which has great potential applications in bioanalysis. The initial design contains four channels for mixing or collecting of samples by centrifugal force. The rotor, the key component of this device, is actuated using electrostatic force. There are four electrodes on the substrate to actuate the micro-centrifuge rotation around the X-axis (lateral in plane) and the Y-axis (vertical in plane) respectively, and eight pairs of comb drives are used to actuate the micro-centrifuge rotation around the Z-axis (perpendicular to the XY plane). The multiple axis actuation design makes it very flexible to control the micro-centrifuge. Because of its small feature size, the cost of the reagent used for the micro-centrifuge will be greatly reduced. An array of micro-centrifuges will be designed to achieve a fast cycling time. A Finite Element Analysis (FEA) has been completed to analyze the static and dynamic performance of the micro-centrifuge, such as the natural frequencies, tilt angle, and driving voltage. A novel fabrication process using SOI technology has been proposed which is now being developed.
Design and development of application-specific microfluidic components for flow control
Bai Xu, James Castracane, Bruce Altemus, et al.
There has been a growing interest in the research of microfluidic management systems, e.g., for DNA sequencing devices, biological cell manipulation systems, chemical analysis systems and microdosage systems. microfluidic management is crucial capability in most biomedical nanodevices and micro fuel cells using methanol as fuel. It involves the manipulation of fluids ranging from a scale of nano to millimeters. Basic building components for a microfluidic management system are microvalves and micropump s together with the interconnect fluidic channels . Micropumps can have passive and/or active valve. Because of the increasing functionality in portable electronic devices and systems, the micropumps and mic rovalves should be compact, reliable, long-lifetime and high energy efficient. In this report, the design, fabrication and modeling of a low power, low voltage, leak proof microfluidic management systems will be discussed.
Electrochemical micropump and its application in a DNA mixing and analysis system
Dong Eun Lee, Hang-Ping Chen, Steven A. Soper, et al.
The research work reported in this paper focuses on developing an electrochemical micropump and a DNA mixing and analysis system using the electrochemical pumps for actuation. The micropum consists of two swing-door check valves and an electrochemical pumping chamber. In the prototype system, two micropumps were used to deliver the reagents and DNA samples respectively. The SU-8 based UV-lithography process was used to fabricate the system on a glass substrate.
Microfluidic Applications III
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Numerical simulation of free jet formation and breakdown by the volume-of-fluid method
This paper deals with the formation and breakdown of liquid jets from different nozzle designs with square cross section. The jet formation is quantitatively examined in terms of a scaled viscosity and pressure transient for a convergent nozzle design. The study also shows, that a divergent nozzle outlet should be avoided, because it may cause asymmetric disturbances on the jet. Two different mechanisms of jet breakdown occur in dependence on the nozzle geometry. Curves of the critical Weber number vs. Reynolds number are calculated.
Passive mixing in microchannels by applying geometric variations
Hengzi Wang, Pio Iovenitti, Erol C. Harvey, et al.
Passive mixing by applying geometric variations were studied in this research. In respect to the nature of laminar flow in a microchannel, the geometric variations were designed to try to improve the lateral convection. By doing this, the dispersion of solute was not only contributed by diffusion, but also, and more importantly, the convection in the lateral direction. Geometric parameters versus the mixing performance were investigated systematically in T-type channels, by applying a known computational fluidic dynamic (CFD) solver for microfluidics. Various obstacle shapes, sizes and layouts were studied. As the ratio of the height to obstacles to the depth of channel became negative, it was the special case that obstacles became grooves. The mechanism for obstacles to enhance mixing was to create convective effects. However, the asymmetric arrangement of grooves applied a different mechanism to enhance mixing by create helical shaped recirculation of fluids. The stretching and folding of fluids of this mixing mechanism provided a efficient way to reduce the diffusion path in microchannels. The mixing performance of mixers with obstacles were evaluated by mass fraction, and mixers with grooved surfaces were evaluated by particle tracing techniques. The results illustrated that both of the strategies provided potential solutions to microfluidic mixing.
Emulsions on demand using microstructured devices
Christian Mahe, Jean Francois Tranchant, Melanie Tromeur, et al.
Emulsions are very common in the field of cosmetics. Unfortunately, most emulsions contain ineffective substances to increase the stability of the products for a long time. These stabilizers can cause some severe healthy problems in several cases. One possible solution is the production of emulsions on demand to prevent the use of stabilizers. Stable emulsion can be achieved if the diameters of the droplets of one solution surrounded by a second solution are smaller than 1μm. Microstructured devices are suited in principle to generate such droplet distributions. Basic task of the development was a micro emulsifier that can be integrated into cosmetic flacons and that can deliver emulsions on demand by pressing a human fingertip onto a part of the flacon. Standardized cosmetic flacons have been used as basic devices. They consist of two separate glass bottles for two different liquid phases and two mechanical pumps integrated in a multifunctional cap. Regarding the viscosity ranges of the two liquids different microemulsifier structures have been developed. External dimensions and connections of the device have been chosen in a way that allows an integration of the devices into the cap. The second design conists of several streaming paths in parallel that allow a reduction of the pressure drop. Furthermore, it consists of three structured silicon chips bonded together. Emulsions with a stability of about 15-30 min have been achieved without any stabilizers. External forces of less than 10N were sufficient to generate emulsions on demand.
Poster Session
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Flow regimes and mass transfer characteristics in static micromixers
The design and calculation of micro mixers is done by conventional analytical and numerical calculations. Due to the small dimensions, laminar flow is expected and the mass transfer is supposed to be dominated by diffusion. A detailed CFD-study by CFDRC-ACE+ of simple static mixers shows a deviation from strictly laminar flow in a wide range of Re numbers and channel dimensions. The static mixers under test have a T-Profile with rectangular cross sections and characteristic dimensions of 50 to 400 μm. The mean flow velocity is varied from 0,01 m/s to 5 m/s, which are typical values for chemical and biological applications, chemical analysis, and microfluidics with acceptable pressure losses. With increasing flow velocity and increasing Re numbers the flow starts to develop a vortex at the entrance of the mixing channel. With further increasing velocity the flow tends to instabilities, which causes the break up of the flow symmetry. With the onset of the vortex formation and with the occurrence of the flow instabilities the mass transfer is enhanced by the exchange of fluid elements. The laminar diffusion model cannot describe this mixing effect. A simple analytical model for first calculations is proposed.
Flexible microreactor system for chemical research at moderate temperatures
Miniaturization is fast gaining attention in chemical processes that are conventionally carried out on a lab-scale or larger. Major progress and landmarks has been made during the last five years. A microreactor system has been developed for fast catalyst development and process optimization. This paper focuses on the issues of microreactor system design and characterization for fast and accurate reaction analysis.
Magnetically driven assembly of superparamagnetic colloidal particles
Benjamin B. Yellen, Gary Friedman, Alan D. Feinerman
Thin ferromagnetic film patterned into isolated islands is used to direct assembly of superparamagnetic colloidal particles into two-dimensional arrays. Ferromagnetic islands positioned under a template of micro-wells are shown to promote highly regular 2D arrays, while external uniform magnetic field is used to bias the particles to attract or repel from the exposed end of the ferromagnetic islands. A theoretical analysis on the interactions between superparamagnetic colloidal particles with the template and external uniform magnetic fields is also presented.
Active silicon support for DNA diagnostics
Heated liquid cavities have been studied. Microlitre scale liquid cavities were etched to the surface of a silicon wafer. Liquid cavities were sealed with a glass cover. Integration of active components to the silicon support is also possible. A heater and a thermistor element are integrated into the silicon support. A pole structure was used within the wells for thermal optimization and self-feeding. The pole structure increases the surface area between silicon and liquid, which enhances thermal transport between silicon and liquid. The temperature of the water is also more uniform. The pole structure also makes the liquid cavity semiporous, enabling the self-feeding of samples due to capillary force. Active silicon support could be used in diagnostics and in biotechnology. Silicon supports were tested in PCR (Polymerace Chain Reaction). The construction of the temperature controlling setup for the silicon support is described. Temperature controlling setup is an independent measuring setup. Interface to the silicon support is made with a printed board to a microscope glass slide format. It is possible to use the printed board interface in a microarray reader. The contruction of a fluorescence measurement setup based on a microarray reader is described.
Development of a microfluidic drug delivery neural prosthesis using a wide-bandgap semiconductor waveguide structure
Mona R. Safadi, Gregory W. Auner, Raymond Iezzi, et al.
We have developed a microfluidic retinal prosthesis, using wide bandgap optical wavelength semiconductor thin film waveguides, to facilitate spatial and quantitative photactivation of “caged” neurotransmitter to microfluidic channels. Novel waveguide materials and micromachining technology are necessary to fabricate 360 nanometer capable waveguides for the microfluidic device. Single crystal wide bandgap semiconductor thin films are grown on sapphire by plasma source molecular beam epitaxy (PSMBE). 248 nanometer KrF Excimer laser micromachining technology is employed to micro-fabricate wave-guiding channels and microfluidic structures. A waveguide that allows for spatial and temporal drug delivery within the retina was fabricated. In addition, there is a need for a waveguide structure that may be used in physiological drug delivery systems. A device that may deliver ultraviolet light in precise intensities and to selective areas of a microfluidic implant without direct ultraviolet exposure to the biological cells is needed in retinal and cortical implants. Results of a prototype microfluidic waveguide system will be presented.
Noninvasive biosensor for hypoglycemia
Vijay K. Varadan, Ashwin K. Whitchurch, Karunakaran Sarukesi
Hypoglycemia-abnormal decrease in blood sugar- is a major obstacle in the management of diabetes and prevention of long-term complications, and it may impose serious effects on the brain, including impairment of memory and other cognitive functions. This is especially a concern in early childhood years when the nervous system is still developing. Hypoglycemic unawareness (in which the body’s normal ability to signal low blood sugar doesn’t work and an oncoming low blood sugar episode proceeds undetected) is a particularly frightening problem for many people with diabetes. Researchers have now uncovered evidence that repeated bouts of insulin-induced hypoglycemia can harm the brain over time, causing confusion, abnormal behavior, loss of consciousness, and seizures. Extreme cases have resulted in coma and death. In this paper, a non-invasive biosensor in a wrist watch along with a wireless data downloading system is proposed.
Low-voltage-driven miniaturized pump with high back pressure
Chengxun Liu, Min Guo, Xiaofang Chen, et al.
A novel micro peristaltic pump with two separate parts is presented. One part of the pump was integrated into a small disposable cartridge and the other was made reusable as an integrated part in the analytical device. Regarding the first part, three identical chambers were fabricated in the cartridge and actuated in peristaltic mode by strong permanent magnetic forces as well as restoring forces. The peristaltic timing was generated by the second part which is a reusable rotating permanent sector magnet. A maximal flow rate of 3.1 mL/min and backpressure of 20 kPa were achieved with this pump.