Introduction to Microfluidics: Basics and Applicationsmnm.physics.mcgill.ca/.../Protected_files/2013Microfluidics.pdf · Micro & Nanobioengineering Lab ... McGill, Nov 2005 Introduction

© 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

[email protected]

wikisites.mcgill.ca/djgroup

Optional slide number: 10pt Arial Bold, white

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§ 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


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Outline


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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) .

A microfluidic channel is about the same width as a human hair, 70 µm


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Outline


Advantages of Microfluidics §  Low sample and reagent consumption; fluid volumes (µl; 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 .

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P.J. Lee et al. (2007). Biotech. Bioeng. 97: 1340-6.


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Right: Quake lab group, Stanford, http://thebigone.stanford.edu/ Left: Juncker lab group, McGill, http://wikisites.mcgill.ca/djgroup/

Advantages of Microfluidics

§  Low sample and reagent consumption; fluid volumes (µl; nl; pl; fl) §  Small physical and economic footprint


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Advantages of Microfluidics: Lab on a Chip §  Parallelization and high throughput experimentation


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Outline


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Fluid Mechanics

§  Law: Conservation of mass

§  Law: Conservation of momentum

§  Assumption: Incompressibility

§  Assumption: No-slip boundary condition, i.e. velocity of the fluid flow at a surface is zero


No-slip Boundary Condition

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Basic Properties §  Types of fluids:

§  Newtonian fluids §  Non-Newtonian fluids

§  Types of fluid flow:

§  Laminar §  Turbulent


Shea

ring

stre

ss, τ

Rate of shearing strain, dv/dy

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Newtonian Fluids §  Linear relationship between stress and strain, i.e. viscosity is

independent of stress and velocity

v + dv v


Substance Viscosity (mPa·s) Air 0.017

Acetone 0.3 Water 0.9

Mercury 1.5 Olive oil 80 Honey 2,000 – 10,000

Viscosity

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§  Viscosity is a measure of internal friction (resistance) to flow


Non-Newtonian Fluids

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§  Non-linear relationship between shear stress and shear strain

§  Examples: paint, blood, ketchup, cornstarch solution

Rate of shearing strain, dv/dy

Shea

ring

stre

ss, τ

Newtonian Non-Newtonian shear thickening

Non-Newtonian shear thinning


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Laminar and Turbulent Flow §  Laminar flow:

§  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

ρ: fluid density A: cross-sectional v: fluid velocity area of channel L: characteristic length P: wetted perimeter µ: viscosity


Laminar and Turbulent Flow

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Couette Flow (Laminar)

§  Couette flow: §  One of the plates moves parallel to the other §  Steady flow between plates §  No-slip condition applies


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Poiseuille Flow (Laminar)

§  Poiseuille flow: §  Pressure-driven flow §  No-slip condition applies


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Outline


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Outline


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Laminar Flow

Right: P. Yager et al. (2006). Nature 442: 412-18.

Left: P.J.A. Kenis et al. (1999). Science 285: 83-5.


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

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For an antibody, D ≈ 40 µm2 s-1

For urea, D ≈ 1400 µm2 s-1

For X = 100 µm, the time becomes: Antibody: 125 s; Urea: 3.6 s


Diffusion and Mixing

University of Hertfordshire, STRI, http://www.herts.ac.uk/research/stri.html

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Direction of Flow


Generating Biochemical Gradients

N.L. Jeon et al. (2000). Langmuir 16: 8311–16.

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Generating Biochemical Gradients

N. L. Jeon et al., Langmuir, 2000, 16, 8311–16.

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Outline


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Capillary Phenomenon and Liquid Transport


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Capillary Phenomenon and Liquid Transport


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Capillary Phenomenon

r

h

θ

Pressure of the liquid column:

Capillary pressure:

Height of liquid column:

ghP ρ=Δ

rP γ2

−=Δ

grh

ρθγ cos2

=

: Surface tension γ

: Contact angle θ


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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


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Wettability §  Adhesion vs. cohesion

§  Contact angles are a way to measure liquid-surface interactions

Hydrophobic Hydrophilic


Capillary Systems

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Capillary Systems

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Outline


Microfluidic and Lab-on-a-Chip Devices

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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


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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


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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.


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Capture 1

Capture 2


Detection


Reading Signal

Sample Loading


Immobilization



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Capture 1

Capture 2


Detection


Reading Signal

Sample Loading


Immobilization



Droplet-Based Microfluidics

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A.S. Utada et al. (2005). Science 22: 537-41.


Isolation/Detection of Rare Cells

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S. Nagrath et al. (2007). Nature 450: 1235-39.


Recapitulating Organ Function on a Chip

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D. Huh et al. (2010). Science 25: 1662-68.


Microfluidic Probe for Perfusion of Brain Slices

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a b

c d

Technology developed in our laboratory

A. Queval et al. (2010). Lab Chip 10: 326-34.


Thank You!

QUESTIONS?

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Microfluidics advantages § Parallelization and high throughout experimentation

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Source: The National Institute of Standards and Technology (NIST)


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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


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Surface energy of various liquids


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Surface energy of various solids


Autonomous control with hydrogels

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D. J. Beebe, Nature 404, 588-590 (2000).


• 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

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Documents

Introduction to Microfluidics: Basics and Applicationsmnm.physics.mcgill.ca/.../Protected_files/2013Microfluidics.pdf · Micro & Nanobioengineering Lab ... McGill, Nov 2005 Introduction