Micro & Nanobioengineering Lab

Biomedical Engineering Department

McGill University

Introduction to Microfluidics:
Basics and Applications
Kate Turner

Hands-on Workshop in Micro and Nanobiotechnology

4th March 2013

katherine.turner2@mail.mcgill.ca
| McGill, Nov 2005 © 2002 IBM Corporation
wikisites.mcgill.ca/djgroup
Outline
§  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

Optional slide number:

Outline
§  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

Optional slide number:

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

Optional slide number:

Outline
§  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

Optional slide number:

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
.

P.J. Lee et al. (2007).

Biotech. Bioeng. 97: 1340-6.
6

Optional slide number:

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

Right: Quake lab group, Stanford, http://thebigone.stanford.edu/

Left: Juncker lab group, McGill, http://wikisites.mcgill.ca/djgroup/
7

Optional slide number:

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

Optional slide number:

Outline
§  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

Optional slide number:

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

10

Optional slide number:

No-slip Boundary Condition

11

Optional slide number:

Basic Properties
§  Types of fluids: §  Types of fluid flow:
§  Newtonian fluids §  Laminar
§  Non-Newtonian fluids §  Turbulent

12

Optional slide number:

Newtonian Fluids
§  Linear relationship between stress and strain, i.e. viscosity is
independent of stress and velocity

Shearing stress, τ
v + dv
v

Rate of shearing strain, dv/dy

13

Optional slide number:

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

Substance Viscosity (mPa·s)

Air 0.017
Acetone 0.3
Water 0.9
Mercury 1.5
Olive oil 80
Honey 2,000 – 10,000

14

Optional slide number:

Non-Newtonian Fluids
§  Non-linear relationship between shear stress and shear strain
§  Examples: paint, blood, ketchup, cornstarch solution

Non-Newtonian
shear thickening Newtonian
Shearing stress, τ

Non-Newtonian
shear thinning

Rate of shearing strain, dv/dy

15

Optional slide number:

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 where
§  Due to small dimensions
Re < 1 in microfluidic
systems

16

Optional slide number:

Laminar and Turbulent Flow

17

Optional slide number:

Couette Flow (Laminar)

§  Couette flow:

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

18

Optional slide number:

Poiseuille Flow (Laminar)

§  Poiseuille flow:

§  Pressure-driven flow
§  No-slip condition applies

19

Optional slide number:

Outline
§  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

20

Optional slide number:

Outline
§  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

21

Optional slide number:

Laminar Flow

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

412-18.
Left: P.J.A. Kenis et al. (1999). Science
285: 83-5.

22

Optional slide number:

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
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

23

Optional slide number:

Diffusion and Mixing

Direction
of Flow

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

24

Optional slide number:

Generating Biochemical Gradients

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

25

Optional slide number:

Generating Biochemical Gradients

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

26

Optional slide number:

Outline
§  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

27

Optional slide number:

Capillary Phenomenon and Liquid Transport

28

Optional slide number:

Capillary Phenomenon and Liquid Transport

29

Optional slide number:

Capillary Phenomenon

θ
Pressure of the liquid column: ΔP = ρgh
r
2γ
Capillary pressure: ΔP = −
r
γ : Surface tension
h
2γ cosθ
Height of liquid column: h =
θ : Contact angle ρgr

30

Optional slide number:

Surface Tension
§  Surface tension is a property of cohesion (the attraction of molecules
to like molecules) Floating razor blades
§  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

31

Optional slide number:

Wettability
§  Adhesion vs. cohesion
§  Contact angles are a way to measure liquid-surface interactions

Hydrophobic Hydrophilic

32

Optional slide number:

Capillary Systems

33

Optional slide number:

Capillary Systems

34

Optional slide number:

Outline
§  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

35

Optional slide number:

Microfluidic and Lab-on-a-Chip Devices
Microfluidic
Devices

Open
Closed chips Chips

Droplet-based Microfluidic
Continuous flow probes (MFP) Micro-arrays

Digital microfluidics Ink-jet printing

External pressure

Capillary effect
Electrowetting-on-
Pin-printing
dielectirc
Electrokinetic mechanisms technology
Surface acoustic
waves
Microcontact
Optoelectrowetting printing

36

Optional slide number:

Immunoassay
§  A biochemical test that measures the concentration of a
substance in a biological liquid
§  Enzyme-Linked ImmunoSorbent Assay (ELISA)
§  Sandwich assays
Fluorescently labelled
detection antibody
Captured antigen
Immobilized capture from the sample
antibody

37

Optional slide number:

Micromosaic Immunoassay

Immobilization Recognition
Immobilization
Capture 1
Capture 2
Sample Loading

Detection
Reading Signal

Fluorescently-labelled
Detection Antibodies
M. Pla-Roca, D. Juncker. (2011). Biological Microarrays, Humana Press, USA.
38

Optional slide number:

Micromosaic Immunoassay

Immobilization Recognition
Immobilization
Capture 1
Capture 2
Sample Loading

Detection
Reading Signal

Fluorescently-labelled
Detection Antibodies
M. Pla-Roca, D. Juncker. (2011). Biological Microarrays, Humana Press, USA.
39

Optional slide number:

Micromosaic Immunoassay

Immobilization Recognition
Immobilization
Capture 1
Capture 2
Sample Loading

Detection
Reading Signal

Fluorescently-labelled
Detection Antibodies
M. Pla-Roca, D. Juncker. (2011). Biological Microarrays, Humana Press, USA.
40

Optional slide number:

Droplet-Based Microfluidics

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

41

Optional slide number:

Isolation/Detection of Rare Cells

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

42

Optional slide number:

Recapitulating Organ Function on a Chip

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

43

Optional slide number:

Microfluidic Probe for Perfusion of Brain Slices
a b

c d

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

Technology developed in our laboratory
44

Optional slide number:

 Thank You!

QUESTIONS?

45

Optional slide number:

Microfluidics advantages
§  Parallelization and high throughout experimentation

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

46

Optional slide number:

Incompressible vs compressible:

Gas particles are very spread out, so Liquid particles are not spread out, so
can be compressed hard to be compressed

Source: The Nucleus Learning website

47

Optional slide number:

Surface energy of various liquids

48

Optional slide number:

Surface energy of various solids

49

Optional slide number:

Autonomous control with hydrogels

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

50

Optional slide number:

 Surface  energy  

water  
water
water  
hydrophilic   hydrophobic   superhydrophobic  
• Hydrophilic  Surfaces:   • Hydrophobic  Surfaces:   • Superhydrophobic  Surfaces:  

 “Water-­‐loving  surface”   “Water-­‐fearing  surface”   Hydrophobic  surface  having  

Water  tries  to  maximize   Water  tries  to  minimize   nano-­‐scale  roughness.  
contact  with  surface.     contact  with  surface.  
CONTACT  ANGLE  
0°   5°   35°   40°   100°   115°   160°  

Plasma   Polyethylene     Polystyrene   Superhydrophobic  

PTFE     IsotacWc    
Cleaned   Glass     Glycol    
Glass     SAM   (Teflon Polypropylene    
)  
51

Optional slide number: