Microfluidics basics

1. Micro & Nanobioengineering Lab
Biomedical Engineering Department
McGill University
| McGill, Nov 2005 © 2002 IBM Corporation
Introduction to Microfluidics:
Basics and Applications
Kate Turner
Hands-on Workshop in Micro and Nanobiotechnology
4th March 2013
katherine.turner2@mail.mcgill.ca
wikisites.mcgill.ca/djgroup

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
2
Outline

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
3
Outline

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)
.
A microfluidic channel is about the
same width as a human hair, 70 µm
4

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
5
Outline

6. 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

7. Right: Quake lab group, Stanford, http://thebigone.stanford.edu/
Left: Juncker lab group, McGill, http://wikisites.mcgill.ca/djgroup/
7
Advantages of Microfluidics


Low sample and reagent consumption; fluid volumes (µl; nl; pl; fl)


Small physical and economic footprint

8. Advantages of Microfluidics: Lab on a Chip
8


Parallelization and high throughput experimentation

9. 

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
9
Outline

10. 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

11. No-slip Boundary Condition
11

12. Basic Properties


Types of fluids:


Newtonian fluids


Non-Newtonian fluids


Types of fluid flow:

Laminar

Turbulent
12

13. Shearing
stress,

Rate of shearing strain, dv/dy
Newtonian Fluids


Linear relationship between stress and strain, i.e. viscosity is
independent of stress and velocity
v + dv
v
13

14. 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
Viscosity


Viscosity is a measure of internal friction (resistance) to flow

15. Non-Newtonian Fluids


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
15

16. 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
16

17. Laminar and Turbulent Flow
17

18. Couette Flow (Laminar)


Couette flow:


One of the plates moves parallel to the other


Steady flow between plates


No-slip condition applies
18

19. Poiseuille Flow (Laminar)


Poiseuille flow:


Pressure-driven flow


No-slip condition applies
19

20. 

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
Outline

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
21
Outline

22. 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

23. 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

24. Diffusion and Mixing
University of Hertfordshire, STRI, http://www.herts.ac.uk/research/stri.html
Direction
of Flow
24

25. Generating Biochemical Gradients
N.L. Jeon et al. (2000). Langmuir 16: 8311–16.
25

26. Generating Biochemical Gradients
N. L. Jeon et al., Langmuir, 2000, 16, 8311–16.
26

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
27
Outline

28. Capillary Phenomenon and Liquid Transport
28

29. Capillary Phenomenon and Liquid Transport
29

30. Capillary Phenomenon
r
h
θ
30
Pressure of the liquid column:
Capillary pressure:

P gh
2

P  
r
2cos
gr
h
: Surfacetension
Height of liquid column:
: Contact angle

31. Surface Tension


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
31

32. Wettability

 Adhesion vs. cohesion

 Contact angles are a way to measure liquid-surface interactions
Hydrophobic Hydrophilic
32

33. Capillary Systems
33

34. Capillary Systems
34

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
35
Outline

36. Microfluidic and Lab-on-a-Chip Devices
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
36

37. Immunoassay
Immobilized capture
antibody
Captured antigen
from the sample


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
37

38. Detection
Recognition
Capture 1
Capture 2
Sample Loading
38
Micromosaic Immunoassay
Immobilization
Reading Signal
Fluorescently-labelled
Detection Antibodies
M. Pla-Roca, D. Juncker. (2011). Biological Microarrays, Humana Press, USA.

39. Reading Sig
oading
Micromosaic Immunoassay
Immobilization Recognition
Capture 1
Capture 2
Sample L
Detection
nal
Fluoresce
Detection
ntly-labelled
Antibodies
M. Pla-Roca, D. Juncker. (2011). Biological Microarrays, Humana Press, USA.
39

40. Reading Sig
oading
Micromosaic Immunoassay
Immobilization Recognition
Capture 1
Capture 2
Sample L
Detection
nal
Fluoresce
Detection
ntly-labelled
Antibodies
M. Pla-Roca, D. Juncker. (2011). Biological Microarrays, Humana Press, USA.
40

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

42. Isolation/Detection of Rare Cells
S. Nagrath et al. (2007). Nature 450: 1235-39.
42

43. Recapitulating Organ Function on a Chip
D. Huh et al. (2010). Science 25: 1662-68.
43

44. 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

45. Thank You!
QUESTIONS?
45

46. Microfluidics advantages


Parallelization and high throughout experimentation
Source: The National Institute of Standards and Technology (NIST)
46

47. Incompressible vs compressible:
Source: The Nucleus Learning website
Gas particles are very spread out, so
can be compressed
47
Liquid particles are not spread out, so
hard to be compressed

48. Surface energy of various liquids
48

49. Surface energy of various solids
49

50. Autonomous control with hydrogels
D. J. Beebe, Nature 404, 588-590 (2000).
50

51. •Superhydrophobic Surfaces:
Hydrophobic surfacehaving
nano-‐scaleroughness.
water
superhydrophobic
water
hydrophobic
• Hydrophilic Surfaces:
“Water-‐lovingsurface”
Water tries tomaximize
contact withsurface.
water
hydrophilic
Surface energy
• Hydrophobic Surfaces:
“Water-‐fearingsurface”
Water tries tominimize
contact withsurface.
CONTACTANGLE
0° 5° 40°
35° 160°
100° 115°
Plasma
Cleaned
Glass
Glass
Polyethylene
Glycol
SAM
Polystyrene
PTFE
(Teflon
)
Superhydrophobic
Isotactic
Polypropylene
51