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Microfluidics MICROFLUIDICS Sandip Ghosal Department of Mechanical Engineering, Northwestern University 2145 Sheridan Road, Evanston, IL 60208 1 Article Outline Glossary 1. Definition of the Subject and its Importance. 2. Introduction 3. Physics of Microfluidics 4. Future Directions 5. Bibliography GLOSSARY 1. Reynolds number: A characteristic dimensionless number that determines the nature of fluid flow in a given set up. 2. Stokes approximation: A simplifying approximation often made in fluid mechanics where the terms arising due to the inertia of fluid elements is neglected. This is justified if the Reynolds number is small, a situation that arises for example in the slow flow of viscous liquids; an example is pouring honey from a jar. 3. Ion mobility: Velocity acquired by an ion per unit applied force. 4. Electrophoretic mobility: Velocity acquired by an ion per unit applied electric field. 5. Zeta-potential: The electric potential at the interface of an electrolyte and substrate due to the presence of interfacial charge. Usually indicated by the Greek letter zeta (ζ). 1 6. Debye layer: A thin layer of ions next to charged interfaces (predominantly of the opposite sign to the interfacial charge) due to a balance between electrostatic attraction and random thermal fluctuations. 7. Debye Length: A measure of the thickness of the Debye layer. 8. Debye-H¨uckel approximation: The process of linearizing the equation for the electric potential; valid if the potential energy of ions is small compared to their average kinetic energy due to thermal motion. 9. Electric Double Layer (EDL): The Debye layer together with the set of fixed charges on the substrate constitute an EDL. It may be thought of as a parallel plate capacitor or a layer of dipoles . 10. Electrophoresis: The motion of charged objects in a fluid due to an imposed electric field. 11. Dielectrophoresis: The phenomenon that results in a polarizable dielectric medium experiencing a force in a non-uniform electric field. 12. Electroosmosis: The motion of an ionic liquid relative to a fixed charged substrate due to an imposed electric field. 13. AC Electroosmosis aka Induced Charge Electroosmosis (ICEO): Fluid flow caused by an electric field in an ionic medium containing embedded polarizable objects (such as metal cylinders). The effect is non-linear in the electric field and can result in unidirectional flow even with an AC voltage. 14. Thermocapillary Effect: Motion of fluid or object in fluid due to spatial inhomo- geneities in surface tension caused by variations in the temperature field. 15. Marangoni Effect: Same as the Thermocapillary effect except that the variation of sur- face tension is caused by inhomogeneities in the concentration of a dissolved chemical species such as a surfactant. 16. Electrowetting: The phenomenon that results in changes of contact angle of a conduct- ing liquid drop placed on a conducting plate when the electric potential of the plate is changed. 17. Electrowetting on Dielectric (EWOD) The same phenomenon as Electrowetting, ex- cept a thin dielectric coating is applied on the metal plate so that the liquid and the plate are not in electrical contact. 2 Definition of the Subject and its Importance Microfluidics is the science of manipulating fluids on spatial scales anywhere between one to a hundred micron. In SI units a micro-meter (µm) or micron refers to a millionth of a meter. 2 To put this in perspective, the average width of a human hair is about 80 microns and the diameter of a hydrogen atom is 0:00005 micron. Thus, microfluidics involves engineering structures for manipulating fluids on scales that are microscopic in comparison to human di- mensions but that are nevertheless much larger than atomic dimensions so that the systems can still be treated in the continuum approximation. Microfluidic devices are commonplace in the world of living things; for example, the narrowest capillaries in the human circula- tory system are of the order of 5 − 10 microns and the diameter of a swimming bacteria maybe about 10 microns. However, devices engineered by humans that can be considered microfluidic is of much recent vintage. The methods as well as the motivation for designing microfluidic devices entered an era of rapid development in the last ten years or so, a trend that has continued to accelerate to this date. The primary driving force behind this trend has come from Molecular Biology and the Life Sciences where progress has become dependent upon the ability to perform analytical chemistry at heretofore unprecedented speeds. As of 2006 there were about sixty companies in the US engaged in marketing microfluidic prod- ucts. Revenues from such products reached 1.7 billion US dollars in 2003 and is projected to reach 2.7 billion US dollars in 2008. 3 Introduction The idea of a microfluidic chip is derived from the concept of a microelectronic chip. The difference is, channels through which fluids flow take the place of conducting pathways for electrons. The transistors and other micro-electronic elements are replaced by mixers, separators and other micro-fluidic elements designed to perform the basic tasks of analytical chemistry. 3.1 The Case for Microfluidics The technology of microelectronics was invented and developed to fulfill a specific need: pro- cessing of digital information in devices that are smaller, cheaper and faster. The evolution of microfluidics is being driven by exactly the same considerations except that the function that needs to be performed is related to analytical chemistry. Applications in modern biol- ogy and medicine such as drug testing, gene sequencing and gene expression studies require the performance of extremely large numbers of repetitive steps. For example, large banks of robots were employed in the Human Genome Project which nevertheless took eleven years and over three billion dollars to complete. An analogy can be drawn with the Manhattan project where large scale numerical calculations were laboriously performed by rooms full of human `calculators'. However, large scale automated laboratories for such functions as gene sequencing can only be a temporary measure. The ultimate enabling technology for `super- chemistry' must be minaturization, as it was for `super-computing'. This is because (a) as device size shrinks, the time needed to perform a specific operation (such as electrophoretic 3 Figure 1: Left panel: Chipsets for the Agilent 2100 Bioanalyzer for performing various bio- analytical procedures Right panel: an example of a microfluidic chip contained within the package. (Image: courtesy of Agilent Technologies). separation) becomes smaller (b) a large number of identical steps can be run in parallel on a small device (c) the amount of sample and reagents consumed becomes much smaller (d) the devices themselves can be mass produced lowering the unit cost. 3.2 A Brief History of Microfluidics Unlike microelectronics, which by now must be considered a mature technology, microfluidics is still in its infancy. In fact microfluidics draws heavily from many of the same technological breakthroughs that led to the current sophistication in the manufacture of computer chips. It is difficult to say when microfluidics really began or what the first “microfluidic device" was. If one uses the definition of microfluidics given in the introductory paragraph as something that involves a device that manipulates fluid on a 1 − 100 micron scale, then perhaps the ink jet printer should qualify as one of the earliest microfluidic devices. The first inkjet printer was patented by Siemens in 1951 and subsequently went through many stages of innovations and improvement through the efforts of companies such as HP, Xerox, IBM, Cannon, Epson and others. The fluid mechanical principles involved are rich in complexity and there are excellent reviews available on the subject [1]. An early example of a microfluidic chip is due to Jacobson and Ramsey who demonstrated DNA Restriction Fragment Analysis on a single chip under computer control [2]. The first commercial \Lab on a Chip" was the AGILENT 2100 Bioanalyzer introduced in 1999. The number of patents issued per year for inventions related to some aspect of commercial microfluidic applications has grown from a handful per year in the nineties to more than 350 patents a year. 4 Figure 2: Examples of Microfluidic systems in the living world (A) the Stenocara beetle from Namibia (left) that harvests water droplets from fog using a textured surface with alternating hydrophobic/hydrophillic areas as seen in the microscope image (middle) (B) the African \Bombardier Beetle" (Stenaptinus insignis) discharging a boiling toxic liquid jet (right) through steerable micro-nozzles (Images reprinted with permission from Nature and Proc. Natl. Acad. Sci. USA { full citations in text). 3.3 Natural Microfluidic Systems Microfluidic systems of beautifully elegant design are commonplace in the natural world. A stunning example is the fog harvesting Stenocara beetle of the Kalahari desert in Namibia. The shell of this beetle is a patterned substrate of alternating hydrophillic and hydrophobic areas [3]. The beetle positions itself on top of sand dunes with its head down and facing the ocean wind that blows in the early morning fog. The surface patterning is designed to catch the water droplets, grow them to a critical size and then detach them. This size selection is important, for the droplets need to be large enough to roll down by gravity against the prevailing headwind and not be blown off the beetle's back. The African bombardier beetle (Stenaptinus insignis)
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