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An Overview of Microfluidics

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Presentation on
MICROFLUIDICS
and its applications
by Rajan Arora

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Contents
1. What is Microfluidics?
2. Typical Microfluidic systems
3. Where Microfluidics lies
4. Origins, history & miles...

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What is Microfluidics?
• It is the science and technology of systems that
process or manipulate small (10–9 to 10–18 litre...

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An Overview of Microfluidics

  1. 1. Presentation on MICROFLUIDICS and its applications by Rajan Arora
  2. 2. Contents 1. What is Microfluidics? 2. Typical Microfluidic systems 3. Where Microfluidics lies 4. Origins, history & milestones 5. Typical components of Microfluidic systems 6. Physics of Microfluidics 7. Differences between micro and macro scale fluidics 8. Flow mechanisms 9. Branches of Microfluidics 10. Applications of Microfluidics 11. Lab on a chip 12. Low cost microfluidics – Paper, Plastic and Textile based microfluidics 13. Other emerging applications 14. Growth 15. References
  3. 3. What is Microfluidics? • It is the science and technology of systems that process or manipulate small (10–9 to 10–18 litres) amounts of fluids, using channels with dimensions of tens to hundreds of micrometres  Microfluidics in nature: Lung alveoli
  4. 4. A typical microfluidic system DNA separation system • From Agilent- Caliper • Allow to characterize DNA Fragments with excellent resolution, and in a small time
  5. 5. Another example • An elementary lab-on-a-chip: Diagnoses heart attack within 10 minutes
  6. 6. Microfluidics Engineering Physics Chemistry Biochemistry Nanotechnology Biotechnology Where microfluidics lies
  7. 7. How it all started “There’s Plenty of Room at the Bottom” I would like to describe a field, in which little has been done, but in which an enormous amount can be done in principle. This field is not quite the same as the others in that it will not tell us much of fundamental physics (in the sense of, ``What are the strange particles?'') but it is more like solid-state physics in the sense that it might tell us much of great interest about the strange phenomena that occur in complex situations. Furthermore, a point that is most important is that it would have an enormous number of technical applications.
  8. 8. How microfluidics came to be • Molecular analysis • Biodefence • Molecular biology • Microelectronics Much of the exploratory research in microfluidic systems has been carried out in a polymer — poly(dimethylsiloxane), or PDMS, an optically transparent, soft elastomer.
  9. 9. Motivation for miniaturization • Micro scale = laminar flow • Laminar flow allows controlled mixing • Low thermal mass • Efficient mass transport (speedy diffusion) • Good (large) ratio of channel surface area: channel volume • Single cell and molecule manipulations • Protection against contamination and evaporation • Kinetics easy to study
  10. 10. Benefits of size reduction 1. Decreased reagent consumption 2. Small economic footprint 3. Rapid heat transfer and catalysis 4. Fast diffusive mixing 5. Automation and integration
  11. 11. History of Microfluidics • 1958 Jack Kilby & Robert Norton Noyce (IC) • 1959 Richard Feynman: “There’s Plenty of Room at the Bottom” • 1960s Microelectronic IC • 1970s MEMS • 1980s Microflow sensor, Microvalves, Micropumps • 1990s Microfluidics
  12. 12. Milestones • 1970 - 1990 : Essentially nothing (apart from the Stanford gas chromatographer) • 1990 : First liquid chromatograph (Manz et al) μTAS concept (Manz, Graber, Widmer, Sens.Actuator, 1991) • 1990 -1998 : First elementary microfluidic systems (micromixers, microreactors, separation systems,..) • 1998-2004 : Appearance of soft lithography technology, which fostered the domain. All sorts of microfluidic systems with various levels of complexity are made, using different technologies
  13. 13. Generic components of a microfluidic system • a method of introducing reagents and samples (as fluids) • methods for moving these fluids around on the chip, and for combining and mixing them • methods for moving these fluids around on the chip, and for combining and mixing them
  14. 14. Typical components
  15. 15. • Common fluids used in microfluidic devices include whole blood samples, bacterial cell suspensions, protein or antibody solutions and various buffers • Microfluidic devices can be used to obtain a variety of interesting measurements including molecular diffusion coefficients, fluid viscosity, pH, chemical binding coefficients and enzyme reaction kinetics
  16. 16. Physics of microfluidics • Knudsen Number = d/L Ratio of the molecular mean free path length to a representative physical length scale
  17. 17. • Length-scale ratios dictate approach for understanding flow • Continuum flow region is traditional Chem Engg fluid mechanics • For microfluidics, Knudsen number is of the order 10-7 How does a small L influence things in the continuum flow region? Viscous Forces tend to dominate Inertial Forces  Re << 1
  18. 18. Major differences between micro- and macro- fluidics • Turbulence (or its absence: laminar flow) -inertia vs viscosity; convective mixing • Electro-osmotic flow (EOF) -When an ion-containing fluid placed in a microchannel that has fixed charges on its surface and an electrical potential is applied along the channel, the fluid moves as a plug rather than with the parabolic-flow -allows very high resolution separations of ionic species. It is a key contributor to electrophoretic separations of DNA in microchannels
  19. 19. Flow mechanisms 1. Pressure Driven Flow (image on next slide) -Via positive displacement pumps, such as syringe pumps -No-slip boundary condition states that the fluid velocity at the walls must be zero. This produces a parabolic velocity profile within the channel -The parabolic velocity profile has significant implications for the distribution of molecules transported within a channel -Relative inexpensive and quite reproducible
  20. 20. Flow mechanisms 2. Electrokinetic Flow (image on next slide) -If the walls of a microchannel have an electric charge, as most surfaces do, an electric double layer of counter ions will form at the walls. When an electric field is applied across the channel, the ions in the double layer move towards the electrode of opposite polarity. This creates motion of the fluid near the walls and transfers via viscous forces into convective motion of the bulk fluid. If the channel is open at the electrodes, as is most often the case, the velocity profile is uniform across the entire width of the channel
  21. 21. Electrokinetic flow
  22. 22. Branches of microfluidics 1. CONTINUOUS FLOW MICROFLUIDICS Continuous flow microfluidics enables to manipulate continuous flow of liquid through micro-channels thanks to devices such as external pressure pumps or integrated mechanical micro-pumps. Continuous flow processes are used in a wide range of applications like in bioanalytical, chemical, energy and environmental fields.
  23. 23. 2. DIGITAL MICROFLUIDICS Also called droplet microfluidics or emulsion science, digital microfluidics is one of the main application field of microfluidics. It enables to manipulate autonomous droplets on a substrate using electro-wetting. This allow to generate and control uniform, reproducible droplets over the experiments’ parameters. Droplets generation can be used in a large scale of applications like in synthesis of nanoparticles, single cell analysis, and encapsulation of biological entities. This technology will probably become an important tool for drug delivery and biosensing, by providing new solutions for state-of-the-art diagnostics and therapeutics.
  24. 24. 3. OPTOFLUIDICS AND MICROFLUIDICS Optfluidics is an emerging fast-growing science resulting from the combination of three fields of science: microphotonics, optics and microfluidics. Optofluidics merges light and liquids into miniaturized optical devices that take advantage of the properties of fluids to generate high precision and flexibility. Optofluidic applications include lab-on-chip devices, fluid waveguides, deformable lenses, microdroplets lasers, displays, biosensors, optical switches or molecular imaging tools and energy.
  25. 25. 4. ACOUSTOFLUIDICS Acoustofluidics deals with the use of acoustic fields, mainly ultrasonics onto fluids within microfluidic channels allowing to manipulate cells and particles. It refers to the study and manipulation of acoustic waves on microscale to nanoscale fluidic environments.
  26. 26. 5. ELECTROPHORESIS AND MICROFLUIDICS Electrophoresis is a technique used in clinical and research laboratories in order to separate molecules based on their size, electrical charge and shape. An electric current flows through a medium holding the mixture of molecules. Positively-charged ions (cations) proceed towards a negative electrode whereas negatively-charged ions (anions) proceed towards a positive electrode. This method is used for both DNA and RNA analysis.
  27. 27. Microfluidic Applications
  28. 28. Key Application Areas • Polymerase Chain Reactions • Immunoassays • Drug Screening • Electrophoretic separations • Analysis of unpurified blood samples • DNA sequencing • Single Cell manipulation • Screens for protein crystallization conditions • Cell culture studies
  29. 29. Lab-on-a-chip: Start-to-finish systems based on microfluidics • A lab-on-a-chip is a miniaturized device that integrates onto a single chip one or several analyses which are usually done in a laboratory • Mainly focuses on human diagnostics and DNA analysis. Less often, on the synthesis of chemicals • Microfluidic technologies used in lab-on-a-chip devices enable the fabrication of millions of microchannels, each measuring mere micrometers, on a single chip that fits in the palm of your hand. • Eg. Commerically available chips for glucose monitoring, HIV detection or heart attack diagnostics, A chip which enables security forces to detect as soon as possible biological threats towards troops and civilians.
  30. 30. Lab-on-a-chip Advantages Disadvantages • Low cost • High parallelization • Ease of use and compactness • Reduction of human error • Faster response time and diagnosis • Low volume samples • Real time process control and monitoring increase sensitivity • Expendable: Due to their low price, automation and low energy consumption • Not yet ready for industrialization • Miniaturization increases the signal/noise ratio • Untrained diagnoses • May enable anyone to sequence the DNA of others using a drop of saliva
  31. 31. LAB-ON-A-CHIP: CURRENT RESEARCH FOCUS • The industrialization of lab-on-a-chip technologies to make them ready for commercialization • The increase in the maximum number of biological operations on the same chip and the increase in parallelization to achieve the detection of hundreds of pathogens in the same microfluidic cartridge • Fundamental research on certain technologies with a high potential impact, such as DNA reading through nanopore, which requires more investigation in order to be applicable.
  32. 32. Next for lab-on-a-chip  Integration with smartphones
  33. 33. Potential impact on healthcare services In a near future, lab-on-a-chip devices, with their ability to perform complete diagnosis can change our way of practicing medicine. • Diagnosis will be done by people with lower qualifications, thus enabling doctors to focus only on treatment. • Real time diagnosis will increase the chances of survival for patients • A complete diagnosis will greatly reduce antibio- resistance, which is currently one of the biggest challenges • In developing countries, lab-on-a-chip will enable healthcare providers to open diagnostics to a wider population
  34. 34. Low-cost and high-impact Microfluidics
  35. 35. Low-cost and high impact microfluidics 1. Paper-based Microfluidics • Available everywhere and cheap • Low fabrication cost • Passive fluid transport through capillary action • Thin, lightweight • Easy to stack, store, and transport • Disposable and Biodegradable
  36. 36. APPLICATIONS Paper-based Microfluidics
  37. 37. Bacterial detection in water using paper-based microfluidics
  38. 38. Bacterial detection in water using paper-based microfluidics Methods for Result-analysis
  39. 39. • Use of materials such as Polydymethilsiloxane (PDMS), acrylic(PMMA), Polystyrene, Cycloolefin • For variety of applications that cannot be achieved with paper -Able to pattern microstructure, microvalves, etc -Able to transfer bulk liquid in a micro channel -Can be used for cell works (separation, cell culture) -Can be used repetitively Low-cost and high impact microfluidics 2. Plastic-based Microfluidics
  40. 40. Application of plastic-based microfluidics Acrylic-based Electrochemical Detection of Nitrate in Water Current methods
  41. 41. Application of plastic-based microfluidics Acrylic-based Electrochemical Detection of Nitrate in Water
  42. 42. Other applications of plastic- based microfluidics • Rapid Genotyping of Malaria-Transmitting Mosquitoes • Circulating Tumor Cells Separation
  43. 43. • Sports performance measurement such as real-time sweat pH monitoring -Connection via Bluetooth for real-time analysis on smartphones • Smart shirts, esp for security forces Low-cost and high impact microfluidics 3. Textile-based Microfluidics
  44. 44. Other Emerging Applications of Microfluidics #1
  45. 45. #2
  46. 46. #3
  47. 47. Growth Source: Yole Development Report 2015
  48. 48. References • George M. Whitesides, The origins and the future of microfluidics, NATURE|Vol 442|27 July 2006 • Lab-on-chip technologies: making a microfluidic network and coupling it into a complete microsystem—a review, P Abgrall and A-M Gue, J. Micromech. Microeng. 17 (2007) R15–R49 • Yole Development Report 2015, Yole Développement, Villeurbanne, France
  49. 49. Thanks

Hinweis der Redaktion

  • The control of tiny amounts of gases or liquids in a miniaturized system of channels, pumps, valves, and sensors.
  • Multo-disciplinary
  • A talk given by Richard Feynman at Caltech, 1959
  • gas-phase chromatography (GPC), high-pressure liquid chromatography (HPLC) and capillary electrophoresis (CE) - new, more compact and more versatile formats
    major military and terrorist threats-US DoD-detectors for chemical and biological threats
    The explosion of genomics in the 1980s, followed by the advent of other areas of microanalysis related to molecular biology, such as high-throughput DNA sequencing, required analytical methods with much greater throughput, and higher sensitivity and resolution than had previously been contemplated in biology.
  • Speed: diffusion: 1mm -> 15 min, 10μm -> 100ms)
  • 3. High S-to-V ratio, Precise temperature control
    4. Speed and accuracy of reaction, repeatability

    A single chip can do processing from beginning to end, integrating multiple operations
    Automation increases throughput,efficiency; Reduction in human error
  • On large scales, fluids mix convectively: for example, the mixing of milk when it is swirled into coffee, or smoke, leaving a chimney, with air. This type of mixing reflects the fact that in macroscopic fluids, inertia is often more important than viscosity. In microsystems, with water as a fluid, the opposite is true: fluids do not mix convectively — when two fluid streams come together in a microchannel, they flow in parallel, without eddies or turbulence, and the only mixing that occurs is the result of diffusion of molecules across the interface between the fluids.
  • Examples: Urinalysis, bacterial detection
  • Detection of nitrate in water is essential because excess nitrate can cause various health problems, most famously Blue-baby syndrome (methanoglobinemia)
  • Mosquito leg is inserted in a plastic-based microfluidic device and blue-LED light is used for visual amplification. Detection using a call-phone camera.
  • 4 billion dollar industry

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