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Literature on microfluidics

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Artificial cilia for active micro-fluidic mixing, Jaap den Toonder et al. (2008) Title Artificial cilia for active micro-fluidic mixing Authors Jaap den Toonder, Femke Bos, Dick Broer, Laura Filippini, Murray Gillies, Judith de Goede, Titie Mol, Mireille Reijme, Wim Talen, Hans Wilderbeek, Vinayak Khatavkar, Patrick Anderson Publication Lab on a Chip Volume 8 Issue 4 Pages 533-541 Date April 2008 Abstract In lab-on-chip devices, on which complete (bio-)chemical analysis laboratories are miniaturized and integrated, it is essential to manipulate fluids in sub-millimetre channels and sub-microlitre chambers. A special challenge in these small micro-fluidic systems is to create good mixing flows, since it is almost impossible to generate turbulence. We propose an active micro-fluidic mixing concept inspired by nature, namely by micro-organisms that swim through a liquid by oscillating microscopic hairs, cilia, that cover their surface. We have fabricated artificial cilia consisting of electro-statically actuated polymer structures, and have integrated these in a micro-fluidic channel. Flow visualization experiments show that the cilia can generate substantial fluid velocities, up to 0.6 mm s-1. In addition, very efficient mixing is obtained using specially designed geometrical cilia configurations in a micro-channel. Since the artificial cilia can be actively controlled using electrical signals, they have exciting applications in micro-fluidic devices. DOI 10.1039/b717681c A microfluidic processor for gene expression profiling of single human embryonic stem cells, Jiang F. Zhong et al. (2008) Title A microfluidic processor for gene expression profiling of single human embryonic stem cells Authors Jiang F. Zhong, Yan Chen, Joshua S. Marcus, Axel Scherer, Stephen R. Quake, Clive R. Taylor, Leslie P. Weiner Publication Lab on a Chip Volume 8 Issue 1 Pages 68-74 Date 2008 Abstract The gene expression of human embryonic stem cells (hESC) is a critical aspect for understanding the normal and pathological development of human cells and tissues. Current bulk gene expression assays rely on RNA extracted from cell and tissue samples with various degree of cellular heterogeneity. These 'cell population averaging' data are difficult to interpret, especially for the purpose of understanding the regulatory relationship of genes in the earliest phases of development and differentiation of individual cells. Here, we report a microfluidic approach that can extract total mRNA from individual single-cells and synthesize cDNA on the same device with high mRNA-to-cDNA efficiency. This feature makes large-scale single-cell gene expression profiling possible. Using this microfluidic device, we measured the absolute numbers of mRNA molecules of three genes (B2M, Nodal and Fzd4) in a single hESC. Our results indicate that gene expression data measured from cDNA of a cell population is not a good representation of the expression levels in individual single cells. Within the G0/G1 phase pluripotent hESC population, some individual cells did not express all of the 3 interrogated genes in detectable levels. Consequently, the relative expression levels, which are broadly used in gene expression studies, are very different between measurements from population cDNA and single-cell cDNA. The results underscore the importance of discrete single-cell analysis, and the advantages of a microfluidic approach in stem cell gene expression studies. DOI 10.1039/b712116d Recent advances in microscale pumping technologies: a review and evaluation, Iverson et al. (2008) Title Recent advances in microscale pumping technologies: a review and evaluation Authors Iverson, Garimella Publication Microfluidics and Nanofluidics Date 2008 Abstract Micropumping has emerged as a critical research area for many electronics and biological applications. A significant driving force underlying this research has been the integration of pumping mechanisms in micro total analysis systems and other multi-functional analysis techniques. Uses in electronics packaging and micromixing and microdosing systems have also capitalized on novel pumping concepts. The present work builds upon a number of existing reviews of micropumping strategies by focusing on the large body of micropump advances reported in the very recent literature. Critical selection criteria are included for pumps and valves to aid in determining the pumping mechanism that is most appropriate for a given application. Important limitations or incompatibilities are also addressed. Quantitative comparisons are provided in graphical and tabular forms. DOI 10.1007/s10404-008-0266-8 A bistable electromagnetically actuated rotary gate microvalve, Rajesh Luharuka et al. (2008) Title A bistable electromagnetically actuated rotary gate microvalve Authors Rajesh Luharuka, Peter J. Hesketh Publication Journal of Micromechanics and Microengineering Volume 18 Issue 3 Pages 035015 Date 2008 Abstract Two types of rotary gate microvalves are developed for flow modulation in microfluidic systems. These microvalves have been tested for an open flow rate of up to 100 sccm and operate under a differential pressure of 6 psig with flow modulation of up to 100. The microvalve consists of a suspended gate that rotates in the plane of the chip to regulate flow through the orifice. The gate is suspended by a novel fully compliant in-plane rotary bistable micromechanism (IPRBM) that advantageously constrains the gate in all degrees of freedom except for in-plane rotational motion. Multiple inlet/outlet orifices provide flexibility of operating the microvalve in three different flow configurations. The rotary gate microvalve is switched with an external electromagnetic actuator. The suspended gate is made of a soft magnetic material and its electromagnetic actuation is based on the operating principle of a variable-reluctance stepper motor. DOI 10.1088/0960-1317/18/3/035015 A MEMS-based valveless impedance pump utilizing electromagnetic actuation, Chia-Yen Lee et al. (2008) Title A MEMS-based valveless impedance pump utilizing electromagnetic actuation Authors Chia-Yen Lee, Hsien-Tsung Chang, Chih-Yung Wen Publication Journal of Micromechanics and Microengineering Volume 18 Issue 3 Pages 035044 Date 2008 Abstract This study presents a planar valveless impedance-based micro pump for biomedical applications. The micro pump comprises four major components, namely a lower glass substrate containing a copper micro coil, a microchannel, an upper glass cover plate and a PDMS diaphragm with a magnet mounted on its upper surface. When a current is passed through the micro coil, an electromagnetic force is established between the coil and the magnet. The resulting deflection of the PDMS diaphragm creates an acoustic impedance mismatch within the microchannel, which results in a net flow. The performance of the micro pump is characterized both experimentally and numerically using Ansoft/Maxwell3D FEA software. The results show that the mechanical integrity of the micro pump is assured provided that the diaphragm deflection does not exceed 110 µm. This deflection is obtained by supplying the micro coil with an input current of 0.6 A, and results in a flow rate of 7.2 ml min[?]1 when the PDMS membrane is driven by an actuating frequency of 200 Hz. DOI 10.1088/0960-1317/18/3/035044 Fabrication of a peristaltic micro pump with novel cascaded actuators, Ok Chan Jeong et al. (2008) Title Fabrication of a peristaltic micro pump with novel cascaded actuators Authors Ok Chan Jeong, Satoshi Konishi Publication Journal of Micromechanics and Microengineering Volume 18 Issue 2 Pages 025022 Date 2008 Abstract This paper presents the fabrication of an all-PDMS (polydimethylsiloxane) micro pump with novel cascaded actuators as dynamic valves. The micro pump consists of three pneumatic actuators in series and a micro fluidic channel connecting two fluidic inlet and outlet ports. The three-layer bonded pump structure is fabricated through a typical moulding process of PDMS and a simple heating process for the PDMS-to-PDMS bonding. The total size of the micro pump is 5 mm × 5 mm. The dynamic valve pattern of the single actuator is observed under various operational conditions of the square-wave input signal for the estimation of its volume stroke. The maximum volume stroke of the pneumatic actuator for liquid is about 85% of the volume of the liquid chamber. Three types of liquid-pumping tests are performed for characterization of the micro pump such as backpressure, frequency and viscous liquids. The flow rate of the de-ionized (DI) water is about 73.9 nl min[?]1 at zero backpressure. As the hydraulic difference between inlet and outlet ports increases, the flow rate gradually decreases. In the case of the frequency responses, the micro pump has the maximum flow rate of the DI water at 2 Hz. The viscosity-dependent flow rate of the working fluids is also observed. DOI 10.1088/0960-1317/18/2/025022 Highly parallel mix-and-match fabrication of nanopillar arrays integrated in microfluidic channels for long DNA molecule separation, J. Shi et al. (2007) Title Highly parallel mix-and-match fabrication of nanopillar arrays integrated in microfluidic channels for long DNA molecule separation Authors J. Shi, A. P. Fang, L. Malaquin, A. Pepin, D. Decanini, J. L. Viovy, Y. Chen Publication Applied Physics Letters Volume 91 Issue 15 Pages 153114-3 Date October 08, 2007 Abstract We report on a mix-and-match method based on a combination of soft UV nanoimprint lithography, contact optical lithography, and reactive-ion-etch techniques, which is applicable for high throughput manufacturing of nanostructure integrated microfluidic devices. We demonstrate the integration of high density and high aspect ratio nanopillars into microfluidic channels as electrophoresis sieving matrices. As a result, lambda DNA and T4 DNA can be separated within a few minutes. By changing the pattern design, the device could be used for separation of other types of molecules. URL http://link.aip.org/link/?APL/91/153114/1 Magnetically controlled valve for flow manipulation in polymer microfluidic devices, Gaspar et al. (2007) Title Magnetically controlled valve for flow manipulation in polymer microfluidic devices Authors Gaspar, Piyasena, Daroczi, Gomez Publication Microfluidics and Nanofluidics Date 15 August 2007 Abstract A simple, external in-line valve for use in microfluidic devices constructed of polydimethylsiloxane (PDMS) is described. The actuation of the valve is based on the principle that flexible polymer walls of a liquid channel can be pressed together by the aid of a permanent magnet and a small metal bar. In the presence of a small NdFeB magnet lying below the channel of interest, the metal bar is pulled downward simultaneously pushing the thin layer of PDMS down thereby closing the channel stopping any flow of fluid. The operation of the valve is dependent on the thickness of the PDMS layer, the height of the channel, the gap between the chip and the magnet and the strength of the magnet. The microfluidic channels are completely closed to fluid flows ranging from 0.1 to 1.0 μL/min commonly used in microfluidic applications. DOI 10.1007/s10404-007-0204-1 Construction of individual addressable PDMS slabs for microfluidic mixing, Maarten Hermans (2007) Title Construction of individual addressable PDMS slabs for microfluidic mixing Author Maarten Hermans Date August, 2007 Abstract In this report a method has been investigated to fabricate active mixing elements in a microfluidic system. Mixing is performed in this method by means of flexible, individual addressable PDMS slabs, containing dispersed superparamagnetic particles. These slabs are set into motion by placing them in a magnetic field gradient. The best way to disperse the magnetic particles in the PDMS is by first solving the magnetic particles together with the PDMS base in the solvent tetrahydrofuran (THF), letting the THF evaporate and finally add the PDMS curing agent. Up to a volume percentage magnetic content of 5 % is achieved in this report. As a result of the dispersed particles, the Young modulus of the magnetic PDMS decreases with an increase of the volume percentage of magnetic content. By making use of a double mould process, a method to fabricate a channel with slabs into PDMS with superparamagnetic particles dispersed in it is studied. The resulting slabs have dimensions about 13 mu x 70 mu and contain a volume percentage of magnetic content of 5 %. Finally, a first insight on the production and the properties of the current wires used to induce the magnetic field gradient is performed. Gold current wires with dimensions 15 mu x 300 nm are fabricated. The maximum current they can handle is about 200 mA. Chaotic mixing using periodic and aperiodic sequences of mixing protocols in a micromixer, Kang et al. (2007) Title Chaotic mixing using periodic and aperiodic sequences of mixing protocols in a micromixer Authors Kang, Singh, Kwon, Anderson Publication Microfluidics and Nanofluidics Date August 2007 Abstract We conducted a numerical study on mixing in a barrier embedded micromixer with an emphasis on the effect of periodic and aperiodic sequences of mixing protocols on mixing performance. A mapping method was employed to investigate mixing in various sequences, enabling us to qualitatively observe the progress of mixing and also to quantify both the rate and the final state of mixing. First, we introduce the design concept of the four mixing protocols and the route to achieve chaotic mixing of the mixer. Then, several periodic sequences consisting of the four mixing protocols are used to investigate the mixing performance depending on the sequence. Chaotic mixing was observed, but with different mixing rates and different final mixing states significantly influenced by the specific sequence of mixing protocols and inertia. As for the effect of inertia, the higher the Reynolds number the larger the rotational motion of the fluid leading to faster mixing. We found that a sequence showing the best mixing performance at a certain Reynolds number is not always superior to other sequences in a different Reynolds number regime. A properly chosen aperiodic sequence results in faster and more uniform mixing than periodic sequences. DOI 10.1007/s10404-007-0206-z A rapid magnetic particle driven micromixer, Wang et al. (2007) Title A rapid magnetic particle driven micromixer Authors Wang, Zhe, Chung, Dutta Publication Microfluidics and Nanofluidics Date 2007/06 Abstract Performances of a magnetic particle driven micromixer are predicted numerically. This micromixer takes advantages of mixing enhancements induced by alternating actuation of magnetic particles suspended in the fluid. Effects of magnetic actuation force, switching frequency and channel’s lateral dimension have been investigated. Numerical results show that the magnetic particle actuation at an appropriate frequency causes effective mixing and the optimum switching frequency depends on the channel’s lateral dimension and the applied magnetic force. The maximum efficiency is obtained at a relatively high operating frequency for large magnetic actuation forces and narrow microchannels. If the magnetic particles are actuated with a much higher or lower frequency than the optimum switching frequency, they tend to add limited agitation to the fluid flow and do not enhance the mixing significantly. The optimum switching frequency obtained from the present numerical prediction is in good agreement with the theoretical analysis. The proposed mixing scheme not only provides an excellent mixing, even in simple microchannel, but also can be easily applied to lab-on-a-chip applications with a pair of external electromagnets. DOI 10.1007/s10404-007-0188-x Magnetically Driven Colloidal Microstirrer, P. Tierno et al. (2007) Title Magnetically Driven Colloidal Microstirrer Authors P. Tierno, T.H. Johansen, T.M. Fischer Publication Journal of Physical Chemistry B Volume 111 Issue 12 Pages 3077-3080 Date March 29, 2007 Abstract Paramagnetic colloidal particles dispersed in water and deposited above magnetic bubble domains of a uniaxial ferrimagnetic garnet film are used as microscopic stirrer when subjected to external rotating magnetic fields. The hydrodynamic flow field above the stirrer is detected by tracking of nonmagnetic microspheres. The vorticity of the flow falls off inversely proportionally to the distance from the bubble center and is proportional to the field frequency. The device provides complete control over the mixing capability. This alternative method of active mixing might be used for microfluidics applications where mechanical stirring cannot be achieved easily with other machinery parts. URL http://pubs3.acs.org/acs/journals/doilookup?in_doi=10.1021/jp070579o Determining refractive index of single living cell using an integrated microchip, X.J. Liang et al. (2007) Title Determining refractive index of single living cell using an integrated microchip Authors X.J. Liang, A.Q. Liu, C.S. Lim, T.C. Ayi, P.H. Yap Publication Sensors and Actuators A: Physical Volume 133 Issue 2 Pages 349-354 Date February 12, 2007 Abstract We report a novel method for measuring the effective refractive index (RI) of single living cell using a small integrated chip, which might be an efficient approach for diseases diagnosis. This microchip is able to determine the refractive index of single living cell in real time without any extra cell treatments such as fluorescence labelling, chemical modification and so forth, meanwhile, providing low cost, small size, easy operation and high accuracy. The measurement system integrates an external cavity laser, a microlens, and some microfluidic channels onto a monolithic chip. In the experiments, two standard polystyrene beads with nominal RI are utilized to calibrate the measurement system and five different types of cancerous cells are subsequently measured in the chip. The experimental results show that the refractive indices of the cancerous cells tested ranges from 1.392 to 1.401, which is larger than typical value of normal cell of 1.35-1.37. This integrated chip potentially has a serial of applications on biodefense, disease diagnosis, biomedical and biochemical analysis. DOI 10.1016/j.sna.2006.06.045 URL http://www.sciencedirect.com/science/article/B6THG-4KFMM8C-6/1/6bbd0286d856e3df1a403b7a91c9d0f4 Magnetic separation in microfluidic systems, K. Smistrup (2007) Title Magnetic separation in microfluidic systems Author K. Smistrup Date January 31, 2007 Abstract This Ph.D. thesis presents theory, modeling, design, fabrication, experiments and results for microfluidic magnetic separators. A model for magnetic bead movement in a microfluidic channel is presented, and the limits of the model are discussed. The effective magnetic field gradient is defined, and it is argued that it is a good measure, when comparing the performance of magnetic bead separators. It is described how numeric modelling is used to aid the design of microfluidic magnetic separation systems. An example of a design optimization study is given. A robust fabrication scheme has been developed for fabrication of silicon based systems. This fabrication scheme is explained, and it is shown how, it is applied with variations for several designs of magnetic separators. An experimental setup for magnetic separation experiments has been developed. It has been coupled with an image analysis program to facilitate real-time monitoring of the experiments. The set-up and experimental protocol are described in detail. Results are presented for ’active’ magnetic bead separators, where on-chip microfabricated electromagnets supply the magnetic field and field gradients necessary for magnetic bead separation. It is shown conceptually how such a system can be applied for parallel biochemical processing in a microfluidic system. ’Passive’ magnetic separators are presented, where on-chip soft magnetic elements are magnetized by an external magnetic field and create strong magnetic fields and gradients inside a microfluidic channel. Systems with the elements placed beside the microfluidic channel is combined with hydrodynamic focusing to demonstrate a magnetic bead microarray inside a microfluidic channel. Systems where the on-chip magnetic material is placed underneath the microfluidic channel are also presented. One of these designs feature multiple magnetic length scales, and it is shown that this enhances bead capture ability. A ’hybrid’ magnetic separator design, where the magnetic field from on-chip current lines couples with an externally applied homogenous field to create strong fields and gradients is demonstrated. This gives extra magnetic bead manipulation possibilities compared to the passive designs. It is demonstrated how this can be used for magnetic bead microarrays. Finally, it is discussed, based on the research presented in this thesis, how to further develop magnetic separation systems in microfluidic systems, and recommendations are given for the choice of magnetic design based on the desired application. URL http://www.mic.dtu.dk/upload/institutter/mic/forskning/magnetic_systems/thesis_final_w_papers_2.pdf A review of passive and active mixing systems in microfluidic devices, James Green et al. (2007) Title A review of passive and active mixing systems in microfluidic devices Authors James Green, Arne E Holdo, Aman Khan Publication The International Journal of Multiphysics Volume 1 Issue 1 Pages 1-32 Date 2007/01 Abstract A review of mixing elements and devices for microscale fluidic devices is presented. The application, principles and characterisation of these devices is discussed, and the classifications based on these factors highlighted. A review of published works relating both experimental and simulation profiling of both passive and active mixing systems is presented. Each mixing principle upon which a design is based is discussed with regard to the fundamental physics that governs fluid behaviour. Passive systems covered include multi-lamination, split/recombination, chaotic advection, jet based, recirculation and droplet internal convection. Active systems covered include longitudinal and transverse pulsing, micro-stirrers, electro-kinetic methods, and acoustic/ultrasonic excitation. The review shows that the majority of devices have been designed within the past five years. Furthermore, at present, devices based on the multi-laminate method appear to outperform most other systems. DOI 10.1260/175095407780130544 URL http://www.ingentaconnect.com/content/mscp/mphys/2007/00000001/00000001/art00001 A chaotic micromixer modulated by constructive vortex agitation, Jing-Tang Yang et al. (2007) Title A chaotic micromixer modulated by constructive vortex agitation Authors Jing-Tang Yang, Ker-Jer Huang, Kai-Yang Tung, I.-Chen Hu, Ping-Chiang Lyu Publication Journal of Micromechanics and Microengineering Volume 17 Issue 10 Pages 2084-2092 Date 2007 Abstract A novel design for vortex modulation of a passive micromixer, named as the circulation-disturbance micromixer (CDM), has been achieved and analyzed experimentally and numerically. The micromixer consists of slanted grooves on the bottom and a zigzag barrier on the top. In this micromixer, the fluid produces a transverse motion perpendicular to the main field, and two modulated and hyperbolic vortices of disparate size are induced. The active-like agitation produced by the constructive interference of these two vortices induces increased flow through the grooves and the mixing efficiency is hence improved significantly. The 3D flow structure in CDM has been analyzed through both numerical simulation (CFD-ACE+) and two methods of visualization--using dyes and using micro laser-induced fluorescence (m-LIF, B-phycoerythrin (BPE) and Allophycocyanin alpha subunit (ApcA)) with a confocal microscope. Our results contribute to an understanding of the resulting enhanced hyperbolic flow mixing and provide also a superior microfluidic element for a 'lab on a chip'. Compared with a slanted groove micromixer, the mixing index of the designed CDM-2T increases 132%, whereas CDM-4T and CDM-8T respectively increase 183% and 280% at Reynolds number 10. DOI 10.1088/0960-1317/17/10/021 Microfluidic logic gates and timers, Michael W. Toepke et al. (2007) Title Microfluidic logic gates and timers Authors Michael W. Toepke, Vinay V. Abhyankar, David J. Beebe Publication Lab on a Chip Date 2007 Abstract We use surface tension-based passive pumping and fluidic resistance to create a number of microfluidic analogs to electronic circuit components. Three classes of components are demonstrated: (1) OR/AND, NOR/NAND, and XNOR digital microfluidic logic gates; (2) programmable, autonomous timers; and (3) slow, perfusive flow rheostats. The components can be implemented with standard pipettes and provide a means of non-electronic and autonomous preprogrammed control with potential utility in cell studies and high throughput screening applications. DOI 10.1039/b708764k Design and analysis of a high pressure piezoelectric actuated microvalve, I. Fazal et al. (2007) Title Design and analysis of a high pressure piezoelectric actuated microvalve Authors I. Fazal, M. C. Elwenspoek Publication Journal of Micromechanics and Microengineering Volume 17 Issue 11 Pages 2366-2379 Date 2007 Abstract A normally open piezoelectric actuated microvalve which modulates a gas flow is fabricated and tested. This work is based on the novel concept of combining micro-machining- and fine machining. The microvalve was tested for air flow. It is shown that a flow rate of 250 ml min[?]1 for a pressure difference of 4 bars can be achieved. The continuous and controlled flow of gas at any stage of valve operation can be obtained. Additionally, it has been shown that almost no hysteresis occurs during the valve operation and the power consumption is very low. URL http://www.iop.org/EJ/abstract/0960-1317/17/11/026/ Quantification of chaotic strength and mixing in a micro fluidic system, Ho Jun Kim et al. (2007) Title Quantification of chaotic strength and mixing in a micro fluidic system Authors Ho Jun Kim, Ali Beskok Publication Journal of Micromechanics and Microengineering Volume 17 Issue 11 Pages 2197-2210 Date 2007 Abstract Comparative studies of five different techniques commonly employed to identify the chaotic strength and mixing efficiency in micro fluidic systems are presented to demonstrate the competitive advantages and shortcomings of each method. The 'chaotic electroosmotic stirrer' of Qian and Bau (2002 Anal. Chem. 74 3616-25) is utilized as the benchmark case due to its well-defined flow kinematics. Lagrangian particle tracking methods are utilized to study particle dispersion in the conceptual device using spectral element and fourth-order Runge-Kutta discretizations in space and time, respectively. Stirring efficiency is predicted using the stirring index based on the box counting method, and Poincaré sections are utilized to identify the chaotic and regular regions under various actuation conditions. Finite time Lyapunov exponents are calculated to quantify the chaotic strength, while the probability density function of the stretching field is utilized as an alternative method to demonstrate the statistical analysis of chaotic and partially chaotic cases. Mixing index inverse, based on the standard deviation of scalar species distribution, is utilized as a metric to quantify the mixing efficiency. Series of numerical simulations are performed by varying the Peclet number (Pe) at fixed kinematic conditions. The mixing time (tm) is characterized as a function of the Pe number, and tm [?] ln(Pe) scaling is demonstrated for fully chaotic cases, while tm [?] Pea scaling with a [?] 0.33 and a = 0.5 are observed for partially chaotic and regular cases, respectively. Employing the aforementioned techniques, optimum kinematic conditions and the actuation frequency of the stirrer that result in the highest mixing/stirring efficiency are identified. A Bidirectional Electrostatic Microvalve With Microsecond Switching Performance, B. Bae et al. (2007) Title A Bidirectional Electrostatic Microvalve With Microsecond Switching Performance Authors B. Bae, J. Han, R. I. Masel Publication Journal of Microelectromechanical Systems Volume 16 Issue 6 Pages 1461-1471 Date 2007 Abstract This paper describes a new bidirectional high-pressure gas electrostatic microvalve that opens and closes in 50 $muhboxs$ or less. The microvalve consists of a valve-closing electrode, a flexible movable membrane, and a valve-opening electrode that is directly opposed to the valve-closing electrode. The membrane contains an embedded electrode, so the valve can zip closed when a potential is applied between the membrane and the valve-closing electrode. The valve-opening electrode allows the valve to open again in a rapid discontinuous motion, without requiring a large applied potential. A pressure-balance port is used to enhance the microvalve switching speed and to allow the valve to close against applied pressures greater than 8.3 atm (840 kPa). The gas conductance through the valve is 2.8 nl/Pa $ cdot$ s (17 sccm/atm), and the fluid leakage measured zero over the entire pressure range up to a burst pressure of 10.8 atm (1.1 MPa). Measurements show that the valve can open or close in 50 $muhboxs$ or less for applied pressures up to 126 kPa. In an extended lifetime test, a sample microvalve has been opened and closed 47 million times before failure. $hfill$[2007-0037] DOI 10.1109/JMEMS.2007.907782 A Magnetically Driven Micro-Mixing Device and its Numerical Analysis, A.M. Morega et al. (2007) Title A Magnetically Driven Micro-Mixing Device and its Numerical Analysis Authors A.M. Morega, J.C. Ordonez, M. Morega Date 2007 Conference Name COMSOL Users Conference 2007 Place Grenoble Publisher COMSOL Abstract In this paper, we present a FEM model of a mixing MEMS μTAS device. A quasistatic magnetic field, produced by sequentially switched DC currents advected through conductors embedded in the device substrate beneath the flow channel, is used to mix the working magnetic fluid, while it is forced to flow through a rib walled channel. The body forces in the magnetized fluid perturb the otherwise laminar flow, into a mixing flow. The study is also concerned with the heat transfer problem posed by the Joule effect produced by the electric currents. For the assumed working conditions, the temperature profile within the structure exhibits moderate levels of Joule heating, hence there is no stringent need to consider the temperature dependence of the fluid’s magnetization. Microfluidic platforms for lab-on-a-chip applications, Stefan Haeberle et al. (2007) Title Microfluidic platforms for lab-on-a-chip applications Authors Stefan Haeberle, Roland Zengerle Publication Lab on a Chip Volume 7 Issue 9 Pages 1094-1110 Date 2007 Abstract We review microfluidic platforms that enable the miniaturization, integration and automation of biochemical assays. Nowadays nearly an unmanageable variety of alternative approaches exists that can do this in principle. Here we focus on those kinds of platforms only that allow performance of a set of microfluidic functions-defined as microfluidic unit operations-which can be easily combined within a well defined and consistent fabrication technology to implement application specific biochemical assays in an easy, flexible and ideally monolithically way. The microfluidic platforms discussed in the following are capillary test strips, also known as lateral flow assays, the "microfluidic large scale integration" approach, centrifugal microfluidics, the electrokinetic platform, pressure driven droplet based microfluidics, electrowetting based microfluidics, SAW driven microfluidics and, last but not least, "free scalable non-contact dispensing". The microfluidic unit operations discussed within those platforms are fluid transport, metering, mixing, switching, incubation, separation, droplet formation, droplet splitting, nL and pL dispensing, and detection. URL http://dx.doi.org/10.1039/b706364b A review of some current research in microelectromechanical systems (MEMS) with defence applications, A. White (2006) Title A review of some current research in microelectromechanical systems (MEMS) with defence applications Author A. White Date 2006-11-22 Abstract This reviews reviews some research in microelectromechanical systems (MEMS) published during the period 1999-2000. Research in defence applications of MEMS or MEMS research with potential applications for the Australian Defence Organisation are also discussed. URL http://hdl.handle.net/1947/3799 Spatio-temporally-complex concentration profiles using a tunable chaotic micromixer, Chia-Hsien Hsu et al. (2006) Title Spatio-temporally-complex concentration profiles using a tunable chaotic micromixer Authors Chia-Hsien Hsu, Albert Folch Publication Applied Physics Letters Volume 89 Issue 14 Pages 144102-3 Date October 02, 2006 DOI 10.1063/1.2358194 URL http://link.aip.org/link/?APL/89/144102/1 The origins and the future of microfluidics, George M. Whitesides (2006) Title The origins and the future of microfluidics Author George M. Whitesides Publication Nature Volume 442 Issue 7101 Pages 368-373 Date 2006/06/27 Abstract The manipulation of fluids in channels with dimensions of tens of micrometres — microfluidics — has emerged as a distinct new field. Microfluidics has the potential to influence subject areas from chemical synthesis and biological analysis to optics and information technology. But the field is still at an early stage of development. Even as the basic science and technological demonstrations develop, other problems must be addressed: choosing and focusing on initial applications, and developing strategies to complete the cycle of development, including commercialization. The solutions to these problems will require imagination and ingenuity. DOI 10.1038/nature05058 Magnetically actuated micropumps using an Fe-PDMS composite membrane, J.J. Nagel et al. (2006) Title Magnetically actuated micropumps using an Fe-PDMS composite membrane Authors J.J. Nagel, G. Mikhail, H. Noh, J. Koo Publication Proceedings of SPIE, the International Society for Optical Engineering Volume 6172 Issue 1 Pages 617213-617222 Date 2006/03 Abstract In this paper we describe a novel Fe-PDMS composite that can be used to create magnetically actuated polymeric microstructures. The composite is formed by suspending <10µm iron (Fe) particles in polydimethylsiloxane (PDMS) at concentrations ranging from 25-75% by weight. Material properties and processing capabilities have been examined, and to demonstrate material's usefulness we have designed, fabricated, and tested two prototypical micropumps that utilize an Fe-PDMS actuator membrane. DOI 10.1117/12.658012 URL http://link.aip.org/link/?PSI/6172/617213/1 `Microfluidic' chips may accelerate biomedical research, David Orenstein (2006) Title `Microfluidic' chips may accelerate biomedical research Author David Orenstein Publication Stanford Report Date January 18, 2006 URL http://news-service.stanford.edu/news/2006/january18/fluidics-011806.html A review of microvalves, Kwang W. Oh et al. (2006) Title A review of microvalves Authors Kwang W. Oh, Chong H. Ahn Publication Journal of Micromechanics and Microengineering Volume 16 Issue 5 Pages R13-R39 Date 2006 Abstract This review gives a brief overview of microvalves, and focuses on the actuation mechanisms and their applications. One of the stumbling blocks for successful miniaturization and commercialization of fully integrated microfluidic systems was the development of reliable microvalves. Applications of the microvalves include flow regulation, on/off switching and sealing of liquids, gases or vacuums. Microvalves have been developed in the form of active or passive microvalves employing mechanical, non-mechanical and external systems. Even though great progress has been made during the last 20 years, there is plenty of room for further improving the performance of existing microvalves. DOI 10.1088/0960-1317/16/5/R01 URL http://www.iop.org/EJ/abstract/0960-1317/16/5/R01/ A split and recombination micromixer fabricated in a PDMS three-dimensional structure, Seok Woo Lee et al. (2006) Title A split and recombination micromixer fabricated in a PDMS three-dimensional structure Authors Seok Woo Lee, Dong Sung Kim, Seung S. Lee, Tai Hun Kwon Publication Journal of Micromechanics and Microengineering Volume 16 Issue 5 Pages 1067-1072 Date 2006 Abstract In this paper we propose a new split and recombination (SAR) micromixer that is compatible with the microfabrication process of polydimethylsiloxane (PDMS). We evaluate the mixing efficiency of the fabricated SAR micromixer and find that it increases interfaces exponentially. Simulation using CFD-ACE+ shows a cross-sectional view of the flow and estimates the mixing efficiency of the SAR micromixer and the pressure drop for a unit of the SAR micromixer. A mixing experiment involving phenolphthalein and NaOH solutions shows that interfaces, represented as red lines, are increased by SAR mixing. The result of our mixing experiment involving blue dye and water is evaluated to determine the mixing efficiency by calculating the standard deviation (stdev) of the pixel intensity of the observed image. After the seventh unit of the SAR micromixer, solutions are mixed to 90% at Re 0.6. The number of units needed to reach a mixed state in which the stdev is lower than 0.05, a 90% mixed state, increases from 5 to 10 for a flow rate ranging from 0.1 µ min[?]1 (Re 0.012) to 1000 µ min[?]1 (Re 120) including numerical analysis results. The pressure drop increases proportionally from 2.8 Pa to 35 000 Pa when the flow rate increases from 0.1 µ min[?]1 (Re 0.012) to 1000 µ min[?]1 (Re 120) in the numerical analysis results. DOI 10.1088/0960-1317/16/5/027 URL http://www.iop.org/EJ/abstract/0960-1317/16/5/027/ Magnetism and microfluidics, Nicole Pamme (2006) Title Magnetism and microfluidics Author Nicole Pamme Publication Lab on a Chip Volume 6 Issue 1 Pages 24-38 Date 2006 Abstract Magnetic forces are now being utilised in an amazing variety of microfluidic applications. Magnetohydrodynamic flow has been applied to the pumping of fluids through microchannels. Magnetic materials such as ferrofluids or magnetically doped PDMS have been used as valves. Magnetic microparticles have been employed for mixing of fluid streams. Magnetic particles have also been used as solid supports for bioreactions in microchannels. Trapping and transport of single cells are being investigated and recently, advances have been made towards the detection of magnetic material on-chip. The aim of this review is to introduce and discuss the various developments within the field of magnetism and microfluidics. DOI 10.1039/b513005k Long-Term Monitoring of Bacteria Undergoing Programmed Population Control in a Microchemostat, Frederick K. Balagadde et al. (2005) Title Long-Term Monitoring of Bacteria Undergoing Programmed Population Control in a Microchemostat Authors Frederick K. Balagadde, Lingchong You, Carl L. Hansen, Frances H. Arnold, Stephen R. Quake Publication Science Volume 309 Issue 5731 Pages 137-140 Date July 1, 2005 Abstract Using an active approach to preventing biofilm formation, we implemented a microfluidic bioreactor that enables long-term culture and monitoring of extremely small populations of bacteria with single-cell resolution. We used this device to observe the dynamics of Escherichia coli carrying a synthetic "population control" circuit that regulates cell density through a feedback mechanism based on quorum sensing. The microfluidic bioreactor enabled long-term monitoring of unnatural behavior programmed by the synthetic circuit, which included sustained oscillations in cell density and associated morphological changes, over hundreds of hours. DOI 10.1126/science.1109173 URL http://www.sciencemag.org/cgi/content/abstract/309/5731/137 A PMMA valveless micropump using electromagnetic actuation, C. Yamahata et al. (2005) Title A PMMA valveless micropump using electromagnetic actuation Authors C. Yamahata, C. Lotto, E. Al-Assaf, M. A. M. Gijs Publication Microfluidics and Nanofluidics Volume 1 Issue 3 Pages 197-207 Date July 01, 2005 Abstract We have fabricated and characterized a polymethylmethacrylate (PMMA) valveless micropump. The pump consists of two diffuser elements and a polydimethylsiloxane (PDMS) membrane with an integrated composite magnet made of NdFeB magnetic powder. A large-stroke membrane deflection (~200 µm) is obtained using external actuation by an electromagnet. We present a detailed analysis of the magnetic actuation force and the flow rate of the micropump. Water is pumped at flow rates of up to 400 µl/min and backpressures of up to 12 mbar. We study the frequency-dependent flow rate and determine a resonance frequency of 12 and 200 Hz for pumping of water and air, respectively. Our experiments show that the models for valveless micropumps of A. Olsson et al. (J Micromech Microeng 9:34, 1999) and L.S. Pan et al. (J Micromech Microeng 13:390, 2003) correctly predict the resonance frequency, although additional modeling of losses is necessary. DOI 10.1007/s10404-004-0007-6 Automated chip-based device for simple and fast nucleic acid amplification, Gotz Munchow et al. (2005) Title Automated chip-based device for simple and fast nucleic acid amplification Authors Gotz Munchow, Dalibor Dadic, Frank Doffing, Steffen Hardt, Klaus-Stefan Drese Publication Expert Review of Molecular Diagnostics Volume 5 Issue 4 Pages 613-620 Date July 2005 Abstract A chip-based PCR device is presented that is capable of rapid temperature ramping and handling sample volumes in the microliter range. The PCR chip comprises a microchannel thermally connected to three temperature zones. Inside this microchannel, the PCR sample plug is driven and precisely positioned by a ferrofluidic actuator for more than 40cycles within 5 min. Computer simulations predict that the sample plugs are thermally equilibrated on a time scale of some 10ms when transported to a different temperature zone. Hence, the thermal limitations on the cycle speed of the system are considerably reduced compared with conventional cyclers. The system was developed on a modular platform suitable for handling further microfluidic tasks such as DNA extraction and preparation of the PCR mix. Thus, the aspired chip-based platform represents not only a PCR system but a complete analysis system, from the injection of a patient’s blood sample to its final appraisal. DOI 10.1586/14737159.5.4.613 Microfluidics: Fluid physics at the nanoliter scale, Todd M. Squires et al. (2005) Title Microfluidics: Fluid physics at the nanoliter scale Authors Todd M. Squires, Stephen R. Quake Publication Reviews of Modern Physics Volume 77 Issue 3 Pages 977-1027 Date 2005/07 Abstract Microfabricated integrated circuits revolutionized computation by vastly reducing the space, labor, and time required for calculations. Microfluidic systems hold similar promise for the large-scale automation of chemistry and biology, suggesting the possibility of numerous experiments performed rapidly and in parallel, while consuming little reagent. While it is too early to tell whether such a vision will be realized, significant progress has been achieved, and various applications of significant scientific and practical interest have been developed. Here a review of the physics of small volumes (nanoliters) of fluids is presented, as parametrized by a series of dimensionless numbers expressing the relative importance of various physical phenomena. Specifically, this review explores the Reynolds number Re, addressing inertial effects; the Péclet number Pe, which concerns convective and diffusive transport; the capillary number Ca expressing the importance of interfacial tension; the Deborah, Weissenberg, and elasticity numbers De, Wi, and El, describing elastic effects due to deformable microstructural elements like polymers; the Grashof and Rayleigh numbers Gr and Ra, describing density-driven flows; and the Knudsen number, describing the importance of noncontinuum molecular effects. Furthermore, the long-range nature of viscous flows and the small device dimensions inherent in microfluidics mean that the influence of boundaries is typically significant. A variety of strategies have been developed to manipulate fluids by exploiting boundary effects; among these are electrokinetic effects, acoustic streaming, and fluid-structure interactions. The goal is to describe the physics behind the rich variety of fluid phenomena occurring on the nanoliter scale using simple scaling arguments, with the hopes of developing an intuitive sense for this occasionally counterintuitive world. DOI 10.1103/RevModPhys.77.977 URL http://link.aps.org/abstract/RMP/v77/p977 Glass valveless micropump using electromagnetic actuation, Christophe Yamahata et al. (2005) Title Glass valveless micropump using electromagnetic actuation Authors Christophe Yamahata, Frédéric Lacharme, Martin A.M. Gijs Publication Microelectronic Engineering Volume 78-79 Pages 132-137 Date March 2005 Abstract We present a valveless micropump in glass, which is magnetically actuated using the sinusoidal current of an external electromagnet. We employ a powder blasting microerosion process for microstructuring the glass substrates and fusion bonding for assembly of the multi-layered microfluidic chip. The reciprocating type micropump contains two nozzle/diffuser elements and a poly(dimethylsiloxane) membrane with embedded permanent magnet. The micropump is self-priming and exhibits a backpressure of 50 mbar and water flow rates up to 1 mL/min. The flow resonance frequency is in excellent agreement with the model of Olsson et al. [Journal of Micromechanics and Microengineering 9 (1999) 34]. DOI 10.1016/j.mee.2004.12.018 URL http://www.sciencedirect.com/science/article/B6V0W-4F4WXP5-8/1/19980eeddf61802f6f555940d4a73ebd TITAN: a conducting polymer based microfluidic pump, Y. Wu et al. (2005) Title TITAN: a conducting polymer based microfluidic pump Authors Y. Wu, D. Zhou, G. M. Spinks, P. C. Innis, W. M. Megill, G. G. Wallace Publication Smart Materials and Structures Volume 14 Issue 6 Pages 1511-1516 Date 2005 Abstract The electromechanical actuation properties of polypyrrole have been utilized in the design and development of a low voltage fluid movement system for microfluidic channels. A confined concentric arrangement of polypyrrole actuators is used to induce fluid movement through an inner channel in a single unit. Series connection of these units and appropriate electrical connection/stimulation induces a novel peristaltic action that enables fluids to be pumped in a predetermined direction. Flow rates of up to 2.5 µl min[?]1 can be achieved against a back pressure of 50 mbar, which is sufficient to enable fluid movement in a glass capillary channel (diameter: 266 µm, length: 12.8 cm). The mechanism of fluid movement enables the use of low voltage devices (1 V) to drive fluid with an average power requirement of 8.7 mW. DOI 10.1088/0964-1726/14/6/043 Control of microfluidic systems: two examples, results, and challenges, M. Armani et al. (2005) Title Control of microfluidic systems: two examples, results, and challenges Authors M. Armani, S. Chaudhary, R. Probst, S. Walker, B. Shapiro Publication International Journal of Robust and Nonlinear Control Volume 15 Pages 785-803 Date 2005 Abstract This paper describes results and challenges in feedback control of microfluidic systems. Results are provided for two representative examples: control of liquid droplets by electrically actuated surface tension forces and steering of many particles at once by micro flow control. Common themes and challenges are outlined based on the authors\textquoteright research programs and on the results of the March 2004 NSF workshop on ?Control and System Integration of Micro- and Nano-Scale Systems? organized by the author. Copyright ? 2005 John Wiley & Sons, Ltd. DOI 10.1002/rnc.1024 Micromixing with Linked Chains of Paramagnetic Particles, S.L. Biswal et al. (2004) Title Micromixing with Linked Chains of Paramagnetic Particles Authors S.L. Biswal, A.P. Gast Publication Analytical Chemistry Volume 76 Issue 21 Pages 6448-6455 Date November 1, 2004 Abstract Paramagnetic colloidal particles aggregate into linear chains under an applied external magnetic field. These particles can be chemically linked to create chains that can be magnetically actuated to manipulate microscopic fluid flow. The flexibility of the chain can be adjusted by varying the length of the linker molecule. In this paper, we describe the use of a suspension of linked paramagnetic chains in a rotating magnetic field to perform microscale mixing. The effect of chain rotation and flexibility on the diffusion of molecules is studied by observing the mixing of an acid and base in a microchannel. We show that, as the chain rotation frequency increases, there is marked increase in the effective mixing between fluid streams; however, a maximum frequency exists and above this frequency the chains are no longer effective in mixing. More flexible chains are more effective at mixing over a larger range of frequencies. DOI 10.1021/ac0494580 URL http://pubs3.acs.org/acs/journals/doilookup?in_doi=10.1021/ac0494580 A Robust Low-Cost PDMS Peristaltic Micropump With Magnetic Drive, E. Kai et al. (2004) Title A Robust Low-Cost PDMS Peristaltic Micropump With Magnetic Drive Authors E. Kai, T. Pan, B. Ziaie Date 2004/06 Publisher University of Minnesota Abstract In this paper, we present a low-cost PDMS peristaltic micropump with magnetic drive. The fabrication process is based on soft molding and bonding of three PDMS layers. A base layer incorporates the microchannels while a middle actuating layer houses three miniature permanent magnets covered by a top flat layer. A small DC motor (6mm in diameter and 15mm in length) with three permanent magnets (NdFeB) stagger-mounted on its shaft is used to pull down and actuate the membrane-mounted magnets. A maximum flow rate of about 24 muL/min at the speed of 4000rpm with power consumption of 14mW was demonstrated. URL http://mtlweb.mit.edu/researchgroups/mems-salon/thomas_Kai_Ziaie_2004.pdf Introduction: mixing in microfluidics, Julio M. Ottino et al. (2004) Title Introduction: mixing in microfluidics Authors Julio M. Ottino, Stephen Wiggins Publication Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences Volume 362 Issue 1818 Pages 923-935 Date May 15, 2004 Abstract In this paper we briefly review the main issues associated with mixing at the microscale and introduce the papers comprising the Theme Issue. DOI 10.1098/rsta.2003.1355 Ferrofluid-based microchip pump and valve, Herb Hartshorne et al. (2004) Title Ferrofluid-based microchip pump and valve Authors Herb Hartshorne, Christopher J. Backhouse, William E. Lee Publication Sensors and Actuators B: Chemical Volume 99 Issue 2-3 Pages 592-600 Date May 1, 2004 Abstract Fluid control is a key element in the performance of microfluidic "lab-on-a-chip" devices. The development of integrated multi-function micro-chemical reactors and analysis platforms depends upon on-chip valving and pumping. In this work, microfluidic valves and pumps were fabricated from etched glass substrates each bonded to a second glass substrate lid that had ultrasonically drilled access holes. The devices contained ferrofluid plugs of approximately 10 mm in length that were actuated by external magnets. The ferrofluid used in the devices was a colloidal suspension of ferromagnetic particles in a hydrophobic fluorocarbon carrier and was immiscible in water. With air in the channels, ferrofluid devices could withstand pressures of 12 kPa and could be opened and closed against pressures of 8.5 and 5.0 kPa, respectively, under a magnetic field of 2.8 kG. A ferrofluid pump comprising a ferrofluid piston and two ferrofluid valves was able to generate air pressures in excess of 5 kPa. In untreated glass channels, leakage of water around ferrofluid seals was significant. However, when the portions of the channel network that contained the ferrofluid were coated with a hydrophobic organo-silane, leakage was not detectable. DOI 10.1016/j.snb.2004.01.016 URL http://www.sciencedirect.com/science/article/B6THH-4C1NG07-2/2/22b21ba5fac95325ffc5104fc83ec228 Micropump based on PZT unimorph and one-way parylene valves, Guo-Hua Feng et al. (2004) Title Micropump based on PZT unimorph and one-way parylene valves Authors Guo-Hua Feng, Eun Sok Kim Publication Journal of Micromechanics and Microengineering Volume 14 Issue 4 Pages 429-435 Date 2004 Abstract This paper describes a micropump composed of a piezoelectric PZT unimorph and one-way parylene valves. Two different designs of the valves (cantilever- and bridge-type) are studied, fabricated and tested. The micropump (13 × 13 × 1.2 mm3 in size) is capable of pumping liquid up to 700 mL min[?]1 with its pumping speed being insensitive to a backpressure up to 2.5 kPa. The flow rate of 700 mL min[?]1 is obtained when the micropump is driven with square pulses at 6 kHz with 50% duty cycle and 100 V peak-to-peak. The maximum static pumping pressure is measured to be 4 kPa. DOI 10.1088/0960-1317/14/4/001 URL http://www.iop.org/EJ/abstract/0960-1317/14/4/001/ Disposable smart lab on a chip for point-of-care clinical diagnostics, C.H. Ahn et al. (2004) Title Disposable smart lab on a chip for point-of-care clinical diagnostics Authors C.H. Ahn, Jin-Woo Choi, G. Beaucage, J.H. Nevin, Jeong-Bong Lee, A. Puntambekar, J.Y. Lee Publication Proceedings of the IEEE Volume 92 Issue 1 Pages 154-173 Date 2004 Abstract This paper presents the development of a disposable plastic biochip incorporating smart passive microfluidics with embedded on-chip power sources and integrated biosensor array for applications in clinical diagnostics and point-of-care testing. The fully integrated disposable biochip is capable of precise volume control with smart microfluidic manipulation without costly on-chip microfluidic components. The biochip has a unique power source using on-chip pressurized air reservoirs, for microfluidic manipulation, avoiding the need for complex microfluidic pumps. In addition, the disposable plastic biochip has successfully been tested for the measurements of partial oxygen concentration, glucose, and lactate level in human blood using an integrated biosensor array. This paper presents details of the smart passive microfluidic system, the on-chip power source, and the biosensor array together with a detailed discussion of the plastic micromachining techniques used for chip fabrication. A handheld analyzer capable of multiparameter detection of clinically relevant parameters has also been developed to detect the signals from the cartridge type disposable biochip. The handheld analyzer developed in this work is currently the smallest analyzer capable of multiparameter detection for point-of-care testing. DOI 10.1109/JPROC.2003.820548 URL http://ieeexplore.ieee.org/search/wrapper.jsp?arnumber=1258178 Plastic micropumps using ferrofluid and magnetic membrane actuation, C. Yamahata et al. (2004) Title Plastic micropumps using ferrofluid and magnetic membrane actuation Authors C. Yamahata, M.A.M. Gijs Pages 458-461 Date 2004 Conference Name 17th IEEE International Conference on Micro Electro Mechanical Systems, 2004 Abstract This paper presents a simple and low-cost prototyping technology for the realization of integrated micropumps in polymethylmethacrylate (PMMA). The three-dimensional (3D) micropumps consist of stacks of structured PMMA layers, which are either realised with precision milling tools for the more complex parts, or fabricated using the powder blasting technique for channel-type structures. We integrate silicone membranes into the chip to realize check-valves or use dynamic diffuser valves. We use two different types of magnetic actuation external to the micropump: (i) an external magnet displaces a ferrofluid liquid plug that plays the role of a piston in a channel; (ii) an external coil actuates an integrated magnetic membrane, consisting of NdFeB magnetic powder in a polydimethylsiloxane (PDMS) matrix. DOI 10.1109/MEMS.2004.1290621 Microfluidic mixers: from microfabricated to self-assembling devices, C. J Campbell et al. (2004) Title Microfluidic mixers: from microfabricated to self-assembling devices Authors C. J Campbell, B. A Grzybowski Publication Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences Volume 362 Pages 1069-1086 Date 2004 Abstract This paper begins with a survey of both passive and active microfluidic mixers that have been implemented in recent years. It then describes a micromixing device based on dynamic self-assembly. This device is easy to fabricate and has excellent working characteristics in the continuous-flow mode. The paper concludes with a brief discussion of possible applications of self-assembly in microfluidics. DOI 10.1098/rsta.2003.1363 Micro magnetic stir-bar mixer integrated with parylene microfluidic channels, Kee Suk Ryu et al. (2004) Title Micro magnetic stir-bar mixer integrated with parylene microfluidic channels Authors Kee Suk Ryu, Kashan Shaikh, Edgar Goluch, Zhifang Fan, Chang Liu Publication Lab on a Chip Volume 4 Issue 6 Pages 608-613 Date 2004 Abstract Previously, we reported a micro magnetic stir-bar mixer driven by an external rotating magnetic field and its rapid mixing performance in polydimethyl-siloxane (PDMS) channels. The PDMS piece with embedded fluid channels were manually aligned to a glass substrate and assembled. In this paper, we report the fabrication and testing results of a micro magnetic stir-bar monolithically integrated in parylene surface-micromachined channels with improved design features, including small tolerance of the stir-bar to channel wall (10 [micro sign]m). Using of parylene based microchannels with improved design not only provides improved mixing, but also eliminates certain problems associated with PDMS-based channels. For example, porosity of PDMS causes evaporation and absorption of chemicals and thus channels made of PDMS are prone to cross-contamination. We have also demonstrated that the magnetic stir-bar can be used to pump liquid in micro channels. DOI 10.1039/b403305a A review of micropumps, D. J. Laser et al. (2004) Title A review of micropumps Authors D. J. Laser, J. G. Santiago Publication Journal of Micromechanics and Microengineering Volume 14 Issue 6 Pages R35-R64 Date 2004 Abstract We survey progress over the past 25 years in the development of microscale devices for pumping fluids. We attempt to provide both a reference for micropump researchers and a resource for those outside the field who wish to identify the best micropump for a particular application. Reciprocating displacement micropumps have been the subject of extensive research in both academia and the private sector and have been produced with a wide range of actuators, valve configurations and materials. Aperiodic displacement micropumps based on mechanisms such as localized phase change have been shown to be suitable for specialized applications. Electroosmotic micropumps exhibit favorable scaling and are promising for a variety of applications requiring high flow rates and pressures. Dynamic micropumps based on electrohydrodynamic and magnetohydrodynamic effects have also been developed. Much progress has been made, but with micropumps suitable for important applications still not available, this remains a fertile area for future research. DOI 10.1088/0960-1317/14/6/R01 An AC Magnetohydrodynamic Microfluidic Switch for Micro Total Analysis Systems, Lemoff et al. (2003) Title An AC Magnetohydrodynamic Microfluidic Switch for Micro Total Analysis Systems Authors Lemoff, Lee Publication Biomedical Microdevices Volume 5 Issue 1 Pages 55-60 Date March 01, 2003 Abstract In this paper, a magnetohydrodynamic (MHD) microfluidic switch, which could form the basis for general microfluidic circuits, is reported. The switch uses an AC MHD pumping mechanism in which the Lorentz force is used to pump electrolytic solutions. By integrating two AC MHD pumps into different arms of a Y-shaped fluidic circuit, flow can be switched between the two arms by activating one of the micropumps and setting the other one at a counteracting pressure to prevent flow. Flow could be switched from one microchannel to another at a velocity of 0.3 mm/sec. This type of switch is easily integrated with other biochips and can be used to produce complex fluidic routing, which may have multiple applications in micro total analysis systems (µTAS). Examples of applications include on-chip combinatorial chemistry for drug discovery and drug testing, connectors for routing samples to different detectors, and general reconfigurable assays. DOI 10.1023/A:1024415400633 A magneto-hydrodynamically controlled fluidic network, Haim H. Bau et al. (2003) Title A magneto-hydrodynamically controlled fluidic network Authors Haim H. Bau, Jianzhong Zhu, Shizhi Qian, Yu Xiang Publication Sensors and Actuators B: Chemical Volume 88 Issue 2 Pages 205-216 Date January 15, 2003 Abstract The paper describes fluidic networks consisting of individually controlled branches. The networks' basic building blocks are conduits equipped with two electrodes positioned on opposing walls. The entire device is either subjected to an external uniform magnetic field or fabricated within a magnetic material. When a prescribed potential difference is applied across each electrode pair, it induces current in the liquid (assumed to be at least weakly conductive solution). Analogously with electric circuits, by judicious application of the potential differences at various branches, one can direct liquid flow in any desired way without a need for mechanical pumps or valves. Equipped with additional, internally located electrodes, the network branches double as stirrers capable of generating chaotic advection. The paper describes the basic building blocks for such a network, the operation of these branches as stirrers, a general linear graph-based theory for the analysis and optimal control of fluidic magneto-hydrodynamic (MHD) networks, an example of a network fabricated with low temperature, co-fired ceramic tapes, and preliminary experimental observations that illustrate that the ideas described in this paper can, indeed, be implemented in practice. DOI 10.1016/S0925-4005(02)00325-8 URL http://www.sciencedirect.com/science/article/B6THH-479KD4W-3/2/793b37f7655aba1452e1233ff369420b Microfluidic Device for Single-Cell Analysis, A. R Wheeler et al. (2003) Title Microfluidic Device for Single-Cell Analysis Authors A. R Wheeler, W. R Throndset, R. J Whelan, A. M Leach, R. N Zare, Y. H Liao, K. Farrell, I. D Manger, A. Daridon Publication Analytical Chemistry Volume 75 Issue 14 Pages 3581-3586 Date 2003 Abstract We have developed a novel microfluidic device constructed from poly(dimethylsiloxane) using multilayer soft lithography technology for the analysis of single cells. The microfluidic network enables the passive and gentle separation of a single cell from the bulk cell suspension, and integrated valves and pumps enable the precise delivery of nanoliter volumes of reagents to that cell. Various applications are demonstrated, including cell viability assays, ionophore-mediated intracellular Ca2+ flux measurements, and multistep receptor-mediated Ca2+ measurements. These assays, and others, are achieved with significant improvements in reagent consumption, analysis time, and temporal resolution over macroscale alternatives. DOI 10.1021/ac0340758 URL http://pubs3.acs.org/acs/journals/doilookup?in_doi=10.1021/ac0340758 Microfluidic technologies in clinical diagnostics, Thomas H. Schulte et al. (2002) Title Microfluidic technologies in clinical diagnostics Authors Thomas H. Schulte, Ron L. Bardell, Bernhard H. Weigl Publication Clinica Chimica Acta Volume 321 Issue 1-2 Pages 1-10 Date July 2002 Abstract Background: Laboratory instrumentation and analytical devices are becoming smaller, simpler, and smarter. This trend to miniaturization extends to fluid handling and fluid analysis. However, fluid behavior undergoes significant changes as geometric scale decreases. The laminar flow behavior of fluids in microfluidic devices must be accommodated in the design and development of clinical and bio-clinical miniaturized systems. Conclusion: The scale of chemical and clinical analysis systems will continue to decrease. The capability to manufacture smaller fluidic devices and to quantitatively monitor smaller volumes of liquids bring this process of miniaturization into the domain of laminar flow. New and enabling technologies are being developed using the unique diffusion-based characteristics of the laminar flow domain for sample preparation and analysis. These new analytical systems will have a significant impact on the future of clinical diagnostics. DOI 10.1016/S0009-8981(02)00093-1 URL http://www.sciencedirect.com/science/article/B6T57-45KSY6Y-4/1/3161d841d323ec2ed1a765d53337f43a Chaotic Mixer for Microchannels, Abraham D. Stroock et al. (2002) Title Chaotic Mixer for Microchannels Authors Abraham D. Stroock, Stephan K. W. Dertinger, Armand Ajdari, Igor Mezic, Howard A. Stone, George M. Whitesides Publication Science Volume 295 Issue 5555 Pages 647-651 Date January 25, 2002 DOI 10.1126/science.1066238 URL http://www.sciencemag.org/cgi/content/abstract/295/5555/647 A magnetic microstirrer and array for microfluidic mixing, Liang-Hsuan Lu et al. (2002) Title A magnetic microstirrer and array for microfluidic mixing Authors Liang-Hsuan Lu, Kee Suk Ryu, Chang Liu Publication Journal of Microelectromechanical Systems Volume 11 Issue 5 Pages 462-469 Date 2002 Abstract We report the development of a micromachined magnetic-bar micromixer for microscale fluid mixing in biological laboratory-on-a-chip applications. The mixer design is inspired by large scale magnetic bar mixers. A rotating magnetic field causes a single magnetic bar or an array of them to rotate rapidly within a fluid environment. A fabrication process of the magnetic bar mixer is developed. Results of fluid mixing in micro channels and chambers are investigated using experimental means and computer-aided fluid simulation. DOI 10.1109/JMEMS.2002.802899 A Microfabricated Rotary Pump, Chou et al. (2001) Title A Microfabricated Rotary Pump Authors Chou, Unger, Quake Publication Biomedical Microdevices Volume 3 Issue 4 Pages 323-330 Date December 01, 2001 Abstract Because microfluidic devices operate at low Reynolds number, many fluidic operations are limited by diffusion. We have developed a microfabricated rotary pump and demonstrated that active mixing can be used to overcome the slow diffusion process in two applications. First, we showed that mixing of reagents could be efficiently accomplished for objects of a wide range of diffusion constants. Second, we showed how reaction kinetics of a surface-binding assay can be enhanced by nearly two orders of magnitude. DOI 10.1023/A:1012412916446 Micro magnetic silicone elastomer membrane actuator, Melvin Khoo et al. (2001) Title Micro magnetic silicone elastomer membrane actuator Authors Melvin Khoo, Chang Liu Publication Sensors and Actuators A: Physical Volume 89 Issue 3 Pages 259-266 Date April 15, 2001 Abstract We present results of the design, fabrication, and testing of a microfabricated, membrane-type magnetic actuator. Magnetic pieces made of electroplated Permalloy (Ni80Fe20) are embedded in a thin flexible membrane made of silicone elastomer. When an external magnetic field is applied, a torque generated on the magnetic pieces produces membrane displacement. Permalloy pieces that are 100-[mu]m-wide, 870-[mu]m-long, and 22-[mu]m-thick are strategically positioned in a 2-mm-square, 40-[mu]m-thick polydimethylsiloxane (PDMS) membrane (Sylgard 184). This design, produced through numerical simulations, is optimized to realize large membrane displacements. Tests performed on this membrane actuator showed displacements >80 [mu]m in the presence of a 2.85x105 A/m external magnetic field. Larger displacements are possible with greater magnetization fields. This type of membrane actuator can be applied to the fabrication of tetherless micropumps for use in microfluidic systems. DOI 10.1016/S0924-4247(00)00559-8 URL http://www.sciencedirect.com/science/article/B6THG-42K5HH2-C/2/2b675284e6bfaebbe166673d23ae43b7 Rapid prototyping of active microfluidic components based on magnetically modified elastomeric materials, William C. Jackson et al. (2001) Title Rapid prototyping of active microfluidic components based on magnetically modified elastomeric materials Authors William C. Jackson, Hy D. Tran, Michael J. O'Brien, Emmanuil Rabinovich, Gabriel P. Lopez Publication Journal of Vacuum Science & Technology B: Microelectronics and Nanometer Structures Volume 19 Issue 2 Pages 596-599 Date 2001/03 Abstract Replica molding of elastomeric materials has proven to be an extremely useful new technology for the formation of complex microfluidic systems. Recent demonstrations of convenient methods for production of such systems by simple, rapid methods that do not require expensive fabrication facilities have enabled the extensive use of microsystems in research and development into a host of new application fields. This report describes a simple new method for fabricating active elastomeric components in microfluidic systems that is based on deformation of elastic materials that have been impregnated or coated with magnetic materials. Computer controlled miniature electromagnets are used to activate switching valves within microfluidics systems. Similar fabrication techniques can be easily extended to construct complex, and potentially completely integrated, microfluidic systems containing active valves, pumps, injectors, mixers, and flow controllers. Preliminary results indicate fabrication of channels approximately 200 µm in width, with valves approximately 5 mm in size (including both valve chamber and valve actuator). The fabrication cycle time is on the order of one day using readily available benchtop equipment, and the valves seal hermetically against a 1.5 kPa back pressure. ©2001 American Vacuum Society. DOI 10.1116/1.1350840 URL http://link.aip.org/link/?JVB/19/596/1 From Micro- to Nanofabrication with Soft Materials, Stephen R. Quake et al. (2000) Title From Micro- to Nanofabrication with Soft Materials Authors Stephen R. Quake, Axel Scherer Publication Science Volume 290 Issue 5496 Pages 1536-1540 Date November 24, 2000 DOI 10.1126/science.290.5496.1536 URL http://www.sciencemag.org/cgi/content/abstract/290/5496/1536 Fluidic Microchannel Arrays for the Electrophoretic Separation and Detection of Bioanalytes using Electrochemiluminescence, Yan et al. (2000) Title Fluidic Microchannel Arrays for the Electrophoretic Separation and Detection of Bioanalytes using Electrochemiluminescence Authors Yan, Smith, Collins Publication Biomedical Microdevices Volume 2 Issue 3 Pages 221-229 Date June 01, 2000 Abstract In this paper a low cost, multi-channel separation and detection system is reported for use in fast, high throughput screening of bioanalytes. Applications include genetic engineering and drug discovery, particularly combinatorial chemistry. A prototype detection system is presented which is comprised of an array of 50 microchannels fabricated on 25 mm×75 mm glass substrates with planar, thin film metal electrodes for electrophoresis and electrochemiluminescence excitation. Fluidic interconnects to the microchannels via standard tubing provide quick and facile interfacing to external macro components, controllers and/or other microsystems. The fabrication process is readily scalable to higher density arrays. DOI 10.1023/A:1009944832192 Monolithic Microfabricated Valves and Pumps by Multilayer Soft Lithography, Marc A. Unger et al. (2000) Title Monolithic Microfabricated Valves and Pumps by Multilayer Soft Lithography Authors Marc A. Unger, Hou-Pu Chou, Todd Thorsen, Axel Scherer, Stephen R. Quake Publication Science Volume 288 Issue 5463 Pages 113-116 Date April 7, 2000 DOI 10.1126/science.288.5463.113 URL http://www.sciencemag.org/cgi/content/abstract/288/5463/113 A novel micromachined magnetic membrane microfluid pump, M. Khoo et al. (2000) Title A novel micromachined magnetic membrane microfluid pump Authors M. Khoo, C. Liu Volume 3 Pages 2394-2397 vol.3 Date 2000 Conference Name Engineering in Medicine and Biology Society, 2000. Proceedings of the 22nd Annual International Conference of the IEEE Abstract We present results on the design, fabrication, and testing of a new, micromachined magnetic pump for integrated microfluidic systems. Structurally, the pump consists of a magnetic microactuator and two polymer-based one-way diffuser valves. The microactuator is based on a thin membrane made of polydimethylsiloxane (PDMS), a soft silicone elastomer. Membrane displacement is caused by the interaction between ferromagnetic pieces (embedded within the thickness of the membrane) and an external magnet. This novel mechanism reduces fabrication and packaging complexity, and allows for remote operation of the micropump without any tether wires for power input. The operation is simple as no precise alignment is required between the external magnet and the pump. PDMS is biocompatible compared to silicon. One future application of this tetherless micropump is implanted biomedical microfluidic systems. We developed a novel micromachining process for embedding ferromagnetic materials within a thin, spin-cast PDMS membrane. Unique pump and diffuser mechanisms that allow for continuous pumping are also developed. Diffuser elements containing no moving parts are fabricated using polymer micromachining techniques. Micro Permalloy pieces are strategically positioned within a 2×2 mm2, 40-μm-thick PDMS membrane. Dimensions and locations of the membrane and the Permalloy pieces are optimized for maximum membrane vertical displacement under a given magnetic field. Experimentally, we have demonstrated successful on-chip fluid pumping. In the presence of an oscillating 2.85×105-A/m external magnetic field, a 1.2-μl/min flow rate was measured for an actuation frequency of 2.9-Hz. The flow rate can be easily varied by the frequency DOI 10.1109/IEMBS.2000.900628 URL http://ieeexplore.ieee.org/xpls/abs_all.jsp?arnumber=900628 An integrated liquid mixer/valve, J. Voldman et al. (2000) Title An integrated liquid mixer/valve Authors J. Voldman, M.L. Gray, M.A. Schmidt Publication Journal of Microelectromechanical Systems Volume 9 Issue 3 Pages 295-302 Date 2000 Abstract We present an integrated liquid mixer/valve to be used for sample preparation for bioscience analysis systems. The mixer/valve is a glass-silicon bonded structure with a wafer-bonded cantilever-plate flapper valve and deep reactive-ion etched ports. It is passively pressure actuated and is distinguished by the fact that it can perform both a mixing and valving function simultaneously to mix two liquids noncontinuously. We present the design and fabrication of the mixer/valve and show that it successfully performs both its valving and mixing functions, including the discontinuous mixing of two liquids. We propose a method for characterizing mixing in this device using fluorescence microscopy and the pH dependence of fluorescein fluorescence. This method aims to allow one to extract the mixing length from a quantifiable observable. We present modeling and results of mixing length measurements using this method DOI 10.1109/84.870054 A microfabricated device for sizing and sorting DNA molecules, Hou-Pu Chou et al. (1999) Title A microfabricated device for sizing and sorting DNA molecules Authors Hou-Pu Chou, Charles Spence, Axel Scherer, Stephen Quake Publication Proceedings of the National Academy of Sciences of the United States of America Volume 96 Issue 1 Pages 11-13 Date 1999-01-05 Abstract We have demonstrated a microfabricated single-molecule DNA sizing device. This device does not depend on mobility to measure molecule size, is 100 times faster than pulsed-field gel electrophoresis, and has a resolution that improves with increasing DNA length. It also requires a million times less sample than pulsed-field gel electrophoresis and has comparable resolution for large molecules. Here we describe the fabrication and use of the single-molecule DNA sizing device for sizing and sorting DNA restriction digests and ladders spanning 2–200 kbp. URL http://www.pnas.org/content/96/1/11 Magnetic microactuators based on polymer magnets, L.K. Lagorce et al. (1999) Title Magnetic microactuators based on polymer magnets Authors L.K. Lagorce, O. Brand, M.G. Allen Publication Journal of Microelectromechanical Systems Volume 8 Issue 1 Pages 2-9 Date 1999 Abstract Integrated permanent magnet microactuators have been fabricated using micromachined polymer magnets. The hard magnetic material utilized is a polymer composite, consisting of magnetically hard ceramic ferrite powder imbedded in a commercial epoxy resin to a volume loading of 80%. The magnets have the form of thin disks approximately 4 mm in diameter and 90 μm in thickness. These disks have been magnetized in the thickness direction, and even in this geometrically unfavorable direction showed typical permanent magnet behavior with an intrinsic coercivity Hci of 4000 Oe (320 kA/m) and a residual induction Br of 600 Gauss (60 mT). Cantilever beam-type magnetic actuators carrying a screen-printed disk magnet on their free ends have been fabricated on an epoxy board. A planar coil on the opposite side of the substrate is used to drive the beams vertically. The actuators exhibit hard magnetic behavior allowing both attraction and repulsion by reversing the current direction. Static and dynamic testing of the magnetic actuators have been performed. The experimental data are compared with theoretical results obtained from both finite element simulations and analytical models. Good agreement is obtained between simulation and experiment DOI 10.1109/84.749396

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