System Integration - A Major Step toward Lab on a Chip

Microfluidics holds great promise to revolutionize various areas of biological engineering, such as single cell analysis, environmental monitoring, regenerative medicine, and point-of-care diagnostics. Despite the fact that intensive efforts have been devoted into the field in the past decades, microfluidics has not yet been adopted widely. It is increasingly realized that an effective system integration strategy that is low cost and broadly applicable to various biological engineering situations is required to fully realize the potential of microfluidics. In this article, we review several promising system integration approaches for microfluidics and discuss their advantages, limitations, and applications. Future advancements of these microfluidic strategies will lead toward translational lab-on-a-chip systems for a wide spectrum of biological engineering applications

Electrostatic Elastomer Devices for Reconfigurable High-Density Microfluidics.

Components and systems for the scalable, very large-scale integration (VLSI) of thousands of microfluidic devices into Micro Total Analysis Systems (μTAS) are the fo-cus of much ongoing research. Most solutions to date have focused on either a) the scal-ing and modification of conventional pneumatically-driven elastomer microfluidics or b) the development of electrically or magnetically addressable fluidic components and sys-tems. Although these technologies have each solved the integration problem partially, they still leave something to be desired such as lack of on-chip power or degradation in chip performance due to cross contamination. This thesis presents the design, fabrication, and characterization of an electrostati-cally actuated user-reconfigurable elastomer microfluidic system intended for VLSI mi-crofluidics. Capacitor plates form top (deformable) and bottom of the micro chan-nel/chamber, facilitating gap-closing actuation. Device fabrication followed standard mi-cromaching process. We also present experimental results of flow and pressure data for valves, pumps and demonstrate various multi-component configurations of the system. The presented technology is compatible with standard polydimethylsiloxane (PDMS) mi-crofluidics, has actuation voltages low enough to be driven by commercial CMOS IC’s and can be used to displace aqueous, gaseous and lipid phases. By adding thin film metal flexures into the PDMS polymer, individual elastomer channels were made to self-close without the use of pneumatics via the application of 10 – 20 V, 5 MHz signals synthesized digitally by a microcontroller and a radio-frequency amplifier IC. These valves were integrated into discrete micro valve and three-valve peristaltic micro pumps. A single valve was able to hold 6 psi pressure, and the peristaltic pump had a flow rate 4.4 valve-volume/min (1 - 2 nL/min), depending on the actuation frequency and device configuration. Further, these valves were arranged into hexagonal or quadricular arrays with 75% fill factor. During use, valves were selected to be permanently closed, permanently open or addressable; this allowed for the on-the-fly determination of channels, valves and pumps. We demonstrated various multi-component configurations of the system: distributed valving, fluid switching, flow splitting and mix-ing. The primary contribution of this technology is to provide a scalable reconfigurable liquid manipulation platform for the very large scale integration of μTAS.Ph.D.Mechanical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/61769/1/mpchang_1.pd

Three-phase Contact Line Phenomena In Droplets On Solid And Liquid Surfaces: Electrocapillary, Pinning, Wetting Line Velocity Effect, And Free Liquid Surface Deformation

In this dissertation physical phenomena relevant to (i) an interface formed between two fluids and a solid phase (wetting line) and (ii) an interface between three fluids (triple contact line) were investigated. In the former case, the wetting line (WL) phenomena which encompass the wetting line energy (WLE) or pinning, the wetting line velocity (WLV), and the contact angle hysteresis, were studied using a micropump based on electrowetting on dielectric (EWOD). In the latter case, the interfacial phenomena such as the air film lubrication effect and the liquid free surface deformation were taken into account to explain the dual equilibrium states of water droplets on liquid free surfaces. EWOD was implemented to devise a pumping method for a continuous flow in a microchannel. An active micropump with a simple layout and no moving parts is designed and fabricated which has on demand flow on/off capability. The micropump is based on droplet/meniscus pressure gradient generated by EWOD. By altering the contact angle between liquid and solid using an electric field a pressure gradient was induced and a small droplet was pumped into the channel via a uniform flow rate. A surface tension based propellant method was introduced as a low power consumption actuation method in microfluidic devices. For an initial droplet volume of 0.3µL and a power of 12nW a constant flow rate of 0.02µL/sec was demonstrated. Sample loading on-demand could be achieved by regulating an electric potential. Unexpectedly, the flow rate of the pump was found to be constant in spite of the changes in the droplet’s radius, which directly affects the pump’s driving pressure. iv The WL phenomena were studied in details to unravel the physical concept behind the micropump constant flow rate during the operation. An interesting observation was that the shrinking input droplet changes its shape in two modes in time sequence: (i) in the first mode its contact angle decreases while its wetting area remains constant due to the pinning, (ii) in the second mode the droplet’s WL starts to move while its contact angle changes as a function of its velocity. Contact angles were measured for the droplet advancing and receding WLs at different velocities to capture a full picture of contact angle behavior due to pinning and WLV effects. These results are also relevant to the meniscus inside the channel. The changes on the contact angle caused by the presence of EWOD at the bottom of the channel were studied in detail. The EWOD based micropump was used as a platform to study the contribution of the pinning and WLV effects on its constant flow rate. The effects of the WLE on the static contact angle and the WLV on the dynamic contact angle in the pump operation were investigated. Also the effect of EWOD voltage on the magnitude and uniformity of the micropump flow rate was studied. Dynamic contact angles (as a function of pinning and WLV) were used to accurately calculate the pressure gradient between the droplet and the meniscus and estimate the flow rate. It was shown that neglecting either of these effects not only results in a considerable gap between the predicted and the measured flow rates but also in an unphysical instability in the flow rate analysis. However, when the WLE and WLV effects were fully taken into account, an excellent agreement between the predicted and the measured flow rates was obtained. v For the study of the TCL between three fluids, aqueous droplets were formed at oil-air interface and two stable configurations of (i) non-coalescent droplet and (ii) cap/bead droplet were observed. General solutions for energy and force analysis were obtained and were shown to be in good agreement with the experimental observations. Further the energy barrier obtained for transition from configuration (i) to (ii), was correlated to the droplet release height and the probability of non-coalescent droplet formation. Droplets formed on the solid surfaces and on the free surface of immiscible liquids have various applications in droplet-based microfluidic devices. This research provides an insight into their formation and manipulation

Micro Electromechanical Systems (MEMS) Based Microfluidic Devices for Biomedical Applications

Micro Electromechanical Systems (MEMS) based microfluidic devices have gained popularity in biomedicine field over the last few years. In this paper, a comprehensive overview of microfluidic devices such as micropumps and microneedles has been presented for biomedical applications. The aim of this paper is to present the major features and issues related to micropumps and microneedles, e.g., working principles, actuation methods, fabrication techniques, construction, performance parameters, failure analysis, testing, safety issues, applications, commercialization issues and future prospects. Based on the actuation mechanisms, the micropumps are classified into two main types, i.e., mechanical and non-mechanical micropumps. Microneedles can be categorized according to their structure, fabrication process, material, overall shape, tip shape, size, array density and application. The presented literature review on micropumps and microneedles will provide comprehensive information for researchers working on design and development of microfluidic devices for biomedical applications

Modular integration and on-chip sensing approaches for tunable fluid control polymer microdevices

228 p.Doktore tesi honetan mikroemariak kontrolatzeko elementuak diseinatu eta garatuko dira, mikrobalbula eta mikrosentsore bat zehazki. Ondoren, gailu horiek batera integratuko dira likido emari kontrolatzaile bat sortzeko asmotan. Helburu nagusia gailuen fabrikazio arkitektura modular bat frogatzea da, non Lab-on-a-Chip prototipoak garatzeko beharrezko fase guztiak harmonizatuz, Cyclic-Olefin-Polymer termoplastikozko mikrogailu merkeak pausu gutxi batzuetan garatuko diren, hauen kalitate industriala bermatuz. Ildo horretan, mikrogailuak prototipotik produkturako trantsizio azkar, erraz, errentagarri eta arriskurik gabeen bidez lortu daitezkeenetz frogatuko da

MULTIPHYSICS ANALYSIS OF HIGH DIFFERENTIAL PRESSURE ELECTROZIPPER PERISTALTIC MICROPUMP

The problem investigated in this dissertation is that of designing and developing a micropump for on-chip applications that have requirements for simultaneous high differential pressures and high flow rates, particularly for gas flow applications. In the literature, there are designs that provide high differential pressures at low flow rates and there are designs that provide for high flow rates at low differential pressures. Developing on-chip design solutions for both simultaneously is currently a wide open research area. It is a challenging research area in nanotechnology and microelectromechanical systems (MEMS) to develop on-chip micropump solutions that provide for simultaneous high differential pressures and high flow rates. The research in this dissertation considered this interesting and challenging research problem and focused its thesis on developing such performance requirementsfor peristaltic micropumps using the so-called "electrozipper" mechanism approach. The electrozipper mechanism uses electrostatic forces to bring two surfaces together for pumping fluids by zippering them together by starting at one end and finishing up at the far end, not dissimilar from the result of squeezing out toothpaste from a tube by rolling the tube up. The main pursuit of the research in this dissertation is to derive designs that yield high differential pressures and high flow rates simultaneously, particularly, differential pressures greater than 1 atm (one atmospheric pressure) with flow rates in the range 1-1000 SCCM (cubic centimeters per minute at standard atmospheric conditions).A critical parameter that limits the performance of electrozipper-based mechanisms is the voltage dielectric breakdown factor of the semiconductor dielectric material used to insulate the voltage potential differences between the two electrozippering surfaces. Silicon dioxide (SiO2) is selected as the dielectric material that has a voltage dielectric breakdown factor greater than 1 volt per nanometer (nm). All micropump designs of this dissertation are limited to 1 volt per nanometer to stay below the voltage dielectric breakdown factor of Silicon dioxide. The baseline value for the dielectric thickness is taken to be 200 nm. As a result, the applied voltage is limited to a maximum of 200 volts.Baseline design parameters of the micropump chamber geometry include micropump plate radius = 1 mm and chamber height = 20 microns. Micropump plate thicknesses of 2, 4, 6, 8, and 10 microns are considered throughout the investigation. Extensive multiphysics 2D simulations are performed on the baseline configuration for intake and outlet power strokes. One of the contributions of the research work is the development of simulation models for simulating the multiphysics interactions of electrostatics, structures, fluid flow, and moving boundaries of the micropump. Another contribution is the derivation of analytical models for the intake and outlet power strokes. The results from the multiphysics simulations and that from the analytical models are shown to agree within a few per cent for all cases treated.Another contribution is that of considering preloaded tension (i.e., preloaded residual stresses) in the micropump plate as an additional baseline design parameter and showing that micropump performance (i.e., higher differential pressures and flow rates) is significantly improved under such preloaded conditions. It is shown that preloaded tension in the plate can be used as stored energy to balance out the applied voltage requirements of the intake and power strokes and thereby increase micropump performance and reduce power requirements. With the employment of preloaded residual stress, differential pumping pressures greater than 1.5 atm are shown to be achievable for a 10 micron plate thickness and, for such cases, it is shown that fatigue safety limits are satisfied for multimillions life-cycles.The new vacuum micropump concept is proposed for the sensor industry to handle large differential pressures (1 atm) at the outlet and achieving very low absolute pressures at the inlet reservoir. The baseline design is shown to provide 10-3Torr vacuum pressures in the presence of leak back rates for plate surface roughness height factors in the range from 1-10 nm. And, it is shown that high vacuum pressures (e.g., 10-6 to 10-9Torr) are achievable by cascading two such micropumps. A detailed method is provided to study different design alternatives for vacuum micropump applications.Non-dimensional ratios in the analytical equations are used to extrapolate the performance of designs beyond that of the baseline configuration and tailor designs for particular differential pressure/flow rate performances and size requirements. This design approach saves the enormous computational time required by multiphysics simulations. Two designs applications are considered to meet high flow rates with high differential pressures. One is pumping down a 1 Torr inlet reservoir to a 1 atm outlet reservoir and the second application considered is that of pumping a 1 atm inlet reservoir to a 2 atm outlet reservoir. Designs with flow rates in the range 1-1000 SCCM are shown to be achievabl

Finite element modeling in the design and optimization of portable instrumentation

Finite element modeling method (FEM) is a powerful numerical analysis method that is widely used in various engineering and scientific domains. In this thesis, we have utilized FEM to study structural analysis, heat transfer, and fluid flow in the instrumentation design and optimization. In particular, we have designed and optimized a portable micro-dispenser for bio-medical applications and a portable enclosure device for industrial applications. In the micro-dispenser study, our proposed model is comprised of a permanent mainframe and a disposable main tank, which can hold a bulk volume of sample fluid as an off-chip reservoir. The height of the micro-dispenser and the diameter of the passive valve have been analytically designed upon the physical properties of the fluid sample. A Peltier thermoelectric device supported by a fuzzy logic controller is dedicated to controlling the temperature within the micro-dispenser. As an extension, we have also explored another piezoelectric-based actuator, which is further optimized by genetic algorithm and verified by FEM simulations. Furthermore, in the enclosure study, we have proposed a design and optimization methodology for the self-heating portable enclosures, which can warm up the inner space from -55°C for encasing the low-cost industrial-class electronic devices instead of expensive military-class ones to work reliably within their allowed operating temperature limit. By considering various factors (including hardness, thermal conductivity, cost, and lifetime), we have determined to mainly use polycarbonate as the manufacturing material of the enclosure. The placement of the thermal resistors is studied with the aid of FEM-based thermal modeling. In summary, despite the distinct specialties and diverse applications in this multi-disciplinary research, we have proposed our design methodologies based on FEM. The design efficacy has been not only demonstrated by the FEM simulations, but also validated by our experimental measurements of the corresponding prototypes fabricated with a 3D printer

Lab-on-PCB Devices

Lab-on-PCB devices can be considered an emerging technology. In fact, most of the contributions have been published during the last 5 years. It is mainly focussed on both biomedical and electronic applications. The book includes an interesting guide for using the different layers of the Printed Circuit Boards for developing new devices; guidelines for fabricating PCB-based electrochemical biosensors, and an overview of fluid manipulation devices fabricated using Printed Circuit Boards. In addition, current PCB-based devices are reported, and studies for several aspects of research and development of lab-on-PCB devices are described

Self-contained microfluidic platform for general purpose lab-on-chip using pcb-mems technology.

El presente trabajo está centrado en la investigación de una nueva plataforma microfluídica autónoma para propósito general fabricada en PCBMEMS. En la vista de la proliferación en los últimos años de los sistemas microfluídicos Lab on Chip (LoC) y la multitud de aplicaciones en las que tienen cabida, surge la necesidad de creación de un sistema portable, autónomo y con una fabricación orientada hacia la producción masiva. En este contexto, se presenta el trabajo de esta tesis dentro de los proyectos de investigación de financiación nacional ISILAB (TEC2011-29045-C04-02) y BIOLOP (TEC2014-54449-C3-2- R). La tesis se encuentra organizada para cubrir los aspectos previamente propuestos. Primeramente, se presenta una introducción donde se explican los motivos para el desarrollo de este trabajo y cuáles son los objetivos específicos que se quieren cumplir. Seguidamente, se hace un breve estudio del arte. En este estudio se presenta la tecnología MEMS, los principios básicos de la microfluídica, que son los fundamentos de los sistemas LOCs y por último, se detalla un estudio de los principales elementos activos en la literatura que componen una plataforma microfluídica. Después de la introducción y revisión literaria del marco de esta tesis, se explican los resultados obtenidos. Esta tesis está desarrollada en dos fases principales: el desarrollo de todos los componentes que hacen un lab on chip autónomo de propósito general y el desarrollo de una tecnología basada en estándares para una producción masiva. En la primera fase se detallan los principales componentes que forman parte de una plataforma autónoma multifunción: microválvula, sistema de impulsión, circuito microfluídico y plataforma de sensado. Todos estos componentes son diseñados como un prototipo y están fabricados en SU-8 y PCBMEMS. El PCB permanece como sustrato y los canales y cámaras microfluídicas están fabricados en SU-8. La microválvula diseñada presenta una activación termoeléctrica, es de un solo uso y tiene una rápida activación y un consumo bajo de energía. Además, el diseño está pensado para ser altamente integrable en una plataforma microfluídica. El siguiente componente descrito es una sistema de impulsión basado en cámaras presurizadas, este sistema está integrado con la microválvula y su principal característica es la activación en el momento de uso, asegurando la ausencia de pérdidas. Para probar la validez de los componentes anteriores, se desarrolla un circuito microfluídico de propósito general. El circuito está diseñado para mezclar dos muestras y transportarlas a una cámara de detección. Finalmente, se desarrolla una plataforma para la detección de glucosa, integrable en el circuito microfluídico. Una vez desarrollado el prototipo, el siguiente objetivo de la tesis es el paso de la tecnología de prototipado hacía una de producción masiva. Para ello los materiales utilizados son el PMMA y el PCB. La tecnología PCBMEMS es conocida por su versatilidad para la integración de la electrónica, por lo que lo hace idóneo para la conexión con el exterior. El PMMA es un material también muy extendido en las aplicaciones microfluídicas, debido a su transparencia, bio compatibilidad y su fácil modelado. La unión de los dos componentes representa un desafío en el desarrollo de la tesis, debido a sus diferentes propiedades químicas. El proceso de fabricación se desarrolla integrando la microválvula y el sistema de impulsión, como partes de una plataforma microfluídica. Para terminar, se ha diseñado un pequeño circuito microfluídico para probar la viabilidad del sistema propuesto hacia una tecnología de gran escala. Finalmente, se exponen las conclusiones de la investigación, las posibles líneas futuras de este trabajo y los apéndices que complementan el trabajo de la tesis.The work presented is focused on the investigation of a new autonomous microfluidic platform manufactured using PCBMEMS technology for general purpose. With the proliferation of the microfluidic platforms, Lab on Chip (LoC), and the multitude of applications which have placed in the market, there is a need to create a self-contained microfluidic platform for general purpose with mass production-oriented manufacturing. Within this framework, the work of this thesis is presented. This is part of two national research project ISILAB (TEC2011-29045-C04-02) and BIOLOP (TEC2014-54449-C3-2- R). The thesis is organized to cover the aspects previously explained. Firstly, an introduction is presented with the motivation and objectives of this work. Subsequently, a study of the art is done. This study presents theMEMS technology, the basics principles of microfluidics, which are the pillars of the lab on chips and finally, a study of the main active elements presented in the literature. After the introduction and the literary revision of the framework of this thesis, the results obtained are presented. This thesis is developed in two main phases: the development of all components that make an autonomous general purpose lab on chip and the development of a standards-based technology for mass production. The first phase details the main components of an autonomous multifunction platform: microvalve, impulsion system, microfluidic circuit and sensing platform. All of these components are designed as a prototype and are manufactured in SU- 8 and PCBMEMS. The PCB remains as a substrate, and the microfluidic channels and chambers are manufactured in SU-8. The microvalve developed is a single use thermoelectrical microvalve with fast activation and low power consumption. In addition, the design is thought to be highly integrable in a microfluidic plat-form. The next component is a impulsion system based on pressurized chambers. The system is integrated with the microvalve and its main characteristic is the activation at the moment of use, ensuring the absence of losses. To test the validity of the above components, a general purpose microfluidic circuit is developed. The circuit is designed to mix two samples and transport those to a detection chamber. Finally, a platform for the detection of glucose, integrable in the microfluidic circuit, is developed. Once the prototype is achieved, the next objective of the thesis is the migration from prototyping technology to mass production. To this end, the materials used are PMMA and PCB. PCBMEMS technology is known for its versatility for the integration of electronics, making it suitable for electrical connection. PMMA is also widely used in microfluidic applications due to its transparency, bio compatibility and easy modeling. The union of the two components represents a challenge in the development of the thesis due to its different chemical properties. The manufacturing process is developed by integrating the microvalve and the drive system, as parts of a microfluidic platform. In conclusion, a small microfluidic circuit is designed by testing the feasibility of the proposed system towards large-scale technology. Finally, the conclusions of the research, the possible future lines of this work and the appendices that complement the work of the thesis are presented