Introduction to Microfluidics: Basics and Applications

1 2002 IBM Corporation Micro & Nanobioengineering Lab Biomedical Engineering Department McGill University | McGill, Nov 2005 Introduction to Microfluidics: Basics and Applications Kate Turner Hands-on Workshop in Micro and Nanobiotechnology 4th March 2013 Optional slide number: 10pt Arial Bold, white 2 What is microfluidics? Why microfluidics? Basics of fluid mechanics Special phenomena associated with the micro-scale Laminar flow Diffusion and mixing Capillary phenomena Surface energy Microfluidics and lab-on-a-chip devices Outline Optional slide number: 10pt Arial Bold, white 3 What is microfluidics? Why microfluidics? Basics of fluid mechanics Special phenomena associated with the micro-scale Laminar flow Diffusion and mixing Capillary phenomena Surface energy Microfluidics and lab-on-a-chip devices Outline Optional slide number: 10pt Arial Bold, white 4 Microfluidics Fluidics: handling of liquids and/or gases Micro: has at least one of the following features: Small volumes Small size Low energy consumption Use of special phenomena (we ll talk more about this later).

2 A microfluidic channel is about the same width as a human hair, 70 m Optional slide number: 10pt Arial Bold, white 5 What is microfluidics? Why microfluidics? Basics of fluid mechanics Special phenomena associated with the micro-scale Laminar flow Diffusion and mixing Capillary phenomena Surface energy Microfluidics and lab-on-a-chip devices Outline Optional slide number: 10pt Arial Bold, white Advantages of Microfluidics Low sample and reagent consumption; fluid volumes ( l; nl; pl; fl) Small physical and economic footprint Parallelization and high throughput experimentation Unique physical phenomena: use of effects in the micro-domain: Laminar flow Capillary forces Diffusion . 6 Lee et al. (2007). Biotech. Bioeng. 97: 1340-6. Optional slide number: 10pt Arial Bold, white 7 Right: Quake lab group, Stanford, Left: Juncker lab group, McGill, Advantages of Microfluidics Low sample and reagent consumption; fluid volumes ( l; nl; pl; fl) Small physical and economic footprint Optional slide number: 10pt Arial Bold, white 8 Advantages of Microfluidics: Lab on a Chip Parallelization and high throughput experimentation Optional slide number: 10pt Arial Bold, white 9 What is microfluidics?

3 Why microfluidics? Basics of fluid mechanics Special phenomena associated with the micro-scale Laminar flow Diffusion and mixing Capillary phenomena Surface energy Microfluidics and lab-on-a-chip devices Outline Optional slide number: 10pt Arial Bold, white 10 Fluid Mechanics Law: Conservation of mass Law: Conservation of momentum Assumption: Incompressibility Assumption: No-slip boundary condition, velocity of the fluid flow at a surface is zero Optional slide number: 10pt Arial Bold, white No-slip Boundary Condition 11 Optional slide number: 10pt Arial Bold, white 12 Basic Properties Types of fluids: Newtonian fluids Non-Newtonian fluids Types of fluid flow: Laminar Turbulent Optional slide number: 10pt Arial Bold, white Shearing stress, Rate of shearing strain, dv/dy 13 Newtonian Fluids Linear relationship between stress and strain, viscosity is independent of stress and velocity v + dv vOptional slide number: 10pt Arial Bold, white Substance Viscosity (mPa s) Air Acetone Water Mercury Olive oil 80 Honey 2,000 10,000 Viscosity 14 Viscosity is a measure of internal friction (resistance) to flow Optional slide number: 10pt Arial Bold, white Non-Newtonian Fluids 15 Non-linear relationship between shear stress and shear strain Examples: paint, blood, ketchup, cornstarch solution Rate of shearing strain, dv/dy Shearing stress, Newtonian Non-Newtonian shear thickening Non-Newtonian shear thinning Optional slide number: 10pt Arial Bold, white 16 Laminar and Turbulent Flow Laminar flow.

4 Fluid particles move along smooth paths in layers Most of energy losses are due to viscous effects Viscous forces are the key players and inertial forces are negligible Turbulent flow: An unsteady flow where fluid particles move along irregular paths Inertial forces are the key players and viscous forces are negligible Reynolds number: Measure of flow turbulence Re < 2000 for laminar Due to small dimensions Re < 1 in microfluidic systems where : fluid density A: cross-sectional v: fluid velocity area of channel L: characteristic length P: wetted perimeter : viscosity Optional slide number: 10pt Arial Bold, white Laminar and Turbulent Flow 17 Optional slide number: 10pt Arial Bold, white 18 Couette Flow (Laminar) Couette flow: One of the plates moves parallel to the other Steady flow between plates No-slip condition applies Optional slide number: 10pt Arial Bold, white 19 Poiseuille Flow (Laminar) Poiseuille flow: Pressure-driven flow No-slip condition applies Optional slide number: 10pt Arial Bold, white 20 What is microfluidics?

5 Why microfluidics? Basics of fluid mechanics Special phenomena associated with the micro-scale Laminar flow Diffusion and mixing Capillary phenomena Surface energy Microfluidics and lab-on-a-chip devices Outline Optional slide number: 10pt Arial Bold, white 21 What is microfluidics? Why microfluidics? Basics of fluid mechanics Special phenomena associated with the micro-scale Laminar flow Diffusion and mixing Capillary phenomena Surface energy Microfluidics and lab-on-a-chip devices Outline Optional slide number: 10pt Arial Bold, white 22 Laminar Flow Right: P. Yager et al. (2006). Nature 442: 412-18. Left: Kenis et al. (1999). Science 285: 83-5. Optional slide number: 10pt Arial Bold, white Diffusion Diffusion is the transport of particles from a region of higher concentration to one of lower concentration by random motion. X: diffusion length D: diffusion constant t: time 23 For an antibody, D 40 m2 s-1 For urea, D 1400 m2 s-1 For X = 100 m, the time becomes: Antibody: 125 s; Urea: s Optional slide number: 10pt Arial Bold, white Diffusion and Mixing University of Hertfordshire, STRI, 24 Direction of Flow Optional slide number: 10pt Arial Bold, white Generating Biochemical Gradients Jeon et al.

6 (2000). Langmuir 16: 8311 16. 25 Optional slide number: 10pt Arial Bold, white Generating Biochemical Gradients N. L. Jeon et al., Langmuir, 2000, 16, 8311 16. 26 Optional slide number: 10pt Arial Bold, white 27 What is microfluidics? Why microfluidics? Basics of fluid mechanics Special phenomena associated with the micro-scale Laminar flow Diffusion and mixing Capillary phenomena Surface energy Microfluidics and lab-on-a-chip devices Outline Optional slide number: 10pt Arial Bold, white 28 Capillary Phenomenon and Liquid Transport Optional slide number: 10pt Arial Bold, white 29 Capillary Phenomenon and Liquid Transport Optional slide number: 10pt Arial Bold, white 30 Capillary Phenomenon r h Pressure of the liquid column: Capillary pressure: Height of liquid column: ghP = rP 2 = grh cos2=: Surface tension : Contact angle Optional slide number: 10pt Arial Bold, white 31 Surface Tension Floating razor blades Surface tension is a property of cohesion (the attraction of molecules to like molecules) When an interface is created, the distribution of cohesive forces is asymmetric Molecules at the surface may be pulled on more strongly by bulk molecules Optional slide number: 10pt Arial Bold, white 32 Wettability Adhesion vs.

7 Cohesion Contact angles are a way to measure liquid-surface interactions Hydrophobic Hydrophilic Optional slide number: 10pt Arial Bold, white Capillary Systems 33 Optional slide number: 10pt Arial Bold, white Capillary Systems 34 Optional slide number: 10pt Arial Bold, white 35 What is microfluidics? Why microfluidics? Basics of fluid mechanics Special phenomena associated with the micro-scale Laminar flow Diffusion and mixing Capillary phenomena Surface energy Microfluidics and lab-on-a-chip devices Outline Optional slide number: 10pt Arial Bold, white microfluidic and Lab-on-a-Chip Devices 36 microfluidic Devices Closed chips Continuous flow Droplet-based Digital microfluidics Open Chips microfluidic probes (MFP) Micro-arrays External pressure Capillary effect Electrokinetic mechanisms Electrowetting-on-dielectirc Surface acoustic waves Optoelectrowetting Ink-jet printing Pin-printing technology Microcontact printing Optional slide number.

8 10pt Arial Bold, white 37 Immunoassay A biochemical test that measures the concentration of a substance in a biological liquid Enzyme-Linked ImmunoSorbent Assay (ELISA) Sandwich assays Immobilized capture antibody Captured antigen from the sample Fluorescently labelled detection antibody Optional slide number: 10pt Arial Bold, white 38 Capture 1 Capture 2 Fluorescently-labelled Detection Antibodies Detection Immobilization Recognition Reading Signal Sample Loading Micromosaic Immunoassay Immobilization M. Pla-Roca, D. Juncker. (2011). Biological Microarrays, Humana Press, USA. Optional slide number: 10pt Arial Bold, white 39 Capture 1 Capture 2 Fluorescently-labelled Detection Antibodies Detection Immobilization Recognition Reading Signal Sample Loading Micromosaic Immunoassay Immobilization M. Pla-Roca, D. Juncker. (2011). Biological Microarrays, Humana Press, USA. Optional slide number: 10pt Arial Bold, white 40 Capture 1 Capture 2 Fluorescently-labelled Detection Antibodies Detection Immobilization Recognition Reading Signal Sample Loading Micromosaic Immunoassay Immobilization M.

9 Pla-Roca, D. Juncker. (2011). Biological Microarrays, Humana Press, USA. Optional slide number: 10pt Arial Bold, white Droplet-Based Microfluidics 41 Utada et al. (2005). Science 22: 537-41. Optional slide number: 10pt Arial Bold, white Isolation/Detection of Rare Cells 42 S. Nagrath et al. (2007). Nature 450: 1235-39. Optional slide number: 10pt Arial Bold, white Recapitulating Organ Function on a Chip 43 D. Huh et al. (2010). Science 25: 1662-68. Optional slide number: 10pt Arial Bold, white microfluidic Probe for Perfusion of Brain Slices 44 a b c d Technology developed in our laboratory A. Queval et al. (2010). Lab Chip 10: 326-34. Optional slide number: 10pt Arial Bold, white Thank You! QUESTIONS? 45 Optional slide number: 10pt Arial Bold, white Microfluidics advantages Parallelization and high throughout experimentation 46 Source: The National Institute of Standards and Technology (NIST) Optional slide number: 10pt Arial Bold, white 47 Incompressible vs compressible: Source: The Nucleus Learning website Gas particles are very spread out, so can be compressed Liquid particles are not spread out, so hard to be compressed Optional slide number: 10pt Arial Bold, white 48 Surface energy of various liquids Optional slide number: 10pt Arial Bold, white 49 Surface energy of various solids Optional slide number: 10pt Arial Bold, white Autonomous control with hydrogels 50 D.

10 J. Beebe, Nature 404, 588-590 (2000). Optional slide number: 10pt Arial Bold, white Superhydrophobic Surfaces: Hydrophobic surface having nano- scale roughness. water superhydrophobic Hydrophobic Surfaces: Water- fearing surface Water tries to minimize contact with surface. water hydrophobic Hydrophilic Surfaces: Water- loving surface Water tries to maximize contact with surface. water hydrophilic Surface energy CONTACT ANGLE 0 5 40 35 100 160 115 Plasma Cleaned Glass Glass Polyethylene Glycol SAM Polystyrene PTFE (Teflon) Superhydrophobic IsotacWc Polypropylene 51