Microuidics for chemicaI and

bioIogicaI engineering
Jacinta C. Conrad
University of Houston
Chemical and Biomolecular Engineering
CHEE 1131
Fall 2013
1
Shepherd, Conrad, Lewis, et al., Langmuir 22, 86188622 (2006)
2
Two physical properties of fuids:
Viscosity: measure of fuid resistance to stress [mass/length-time]
Density: [mass/length
3
]
Fluid: physical defnition
A fuid is a material that fows under an applied stress
Liquid: constant volume Gas: volume of container
http://water.aiche.org http://sciencekids.co.nz
3
Macroscale fows
Characteristics:
Large length scales L
Fast fow speeds V
Turbulent fow
Many macroscale fows are characterized by large Reynolds number:
http://www.youtube.com/watch?v=IRrCKp_dMXY
=
V L

Reynolds number Re =
inertial force
viscous force
1: turbulent
Where do fows appear in a chemical plant?
4
http://www.photo-dictionary.com/photoIes/Iist/687/1097petrochemicaI_pIant.jpg
Flow examples in plants (unit operations)
5
Combination: mixing operation to create a homogeneous
system
- Requires control over mixing streams
Separation: separation of mixture components
- Emulsifcation: creation of a liquid-in-liquid suspension
- Distillation: separation of one liquid from another liquid
- Evaporation: removal of a gas from a mixture
Reaction: reaction among chemical species in a mixture
- Synthesis: e.g. creation of particles or chemicals
Flow examples in plants (unit operations)
Fluid fow processes: e.g. fltration, fuid transport
Heat transfer processes: e.g. evaporation, condensation
Mass transfer processes: e.g. gas absorption, distillation,
extraction, adsorption, drying
Thermodynamic processes: e.g. gas liquefaction, refrigeration
Mechanical processes: e.g. screening and sieving
X
Microfuidics: miniaturization of fows
6
Liu et al., J. Pharma. AnaI. 1, 175-183 (2011)
plant: meters to kilometers
piping: cm to m
device: mm to cm
channels: m to mm
The introduction of microfuidics or lab-on-a-chip devices allows unit
operations to be carried out in a small format:
"Miniaturization puts chemical plants where you want them": R. F. Service,
Science 202, 400 (1998)
Length scales for microfuidic fows
7
Nguyen and Wereley, Fundamentals and Applications of Microfuidics, 2nd ed. (2006)

1m 1mm 1 Pm 1nm
1000 L
1 PL
1 mL 1 L 1 nL
1
1 pL
Microanalysis systems
Microfilters/ microreactors
Micropumps/ valves/ flow sensors
Microneedles
MICROFLUIDIC DEVICES
OTHER OBJECTS
Molecules Smoke particles
Nanotechnology/ Nanodevices?
Bacteria
Viruses
Human hair Man
Conventional fluidic devices
Length scale
Volume scale
1 fL 1 aL































Materials for microfuidics: elastomers
8
Advantages:
Easy to prototype and replicate (via soft lithography)
Cheap materials (polydimethylsiloxane, commercially available)
Disadvantages:
Flexible and deformable (poor for high-pressure applications)
Poor resistance to organic solvents
http://farm6.staticickr.com/5022/5627347258_cd0e1b1920_z.jpg
Materials for microfuidics: rigid plastics
X
Mair et al., Lab Chip 6, 1346-1354 (2006)
Advantages:
Easy to prototype and replicate (via injection molding)
Cheap materials (polyolefns, commercially available)
Operate at high pressure
Disadvantages:
Poor resistance to organic solvents
Fabrication is more diffcult than lithographic-based techniques
Materials for microfuidics: glass
X
http://www.i-micronews.com/upIoad/Interviews/Micronit%20Lab-on-a-Chip%20Products-3.jpg
Advantages:
Excellent resistance to solvents
Rigid and non-deformable
Compatible with high-pressure and biological applications
Disadvantages:
Until recently, expensive to manufacture (new startups)
High costs for design prototypes in money and time
Materials for microfuidics: Tefon
X
Advantages:
Excellent resistance to organic solvents
Rigid and non-deformable
Minimal adsorption and fouling by biological molecules
Disadvantages:
Not transparent, precluding direct imaging using microscopy
Ren et al., Proc. Natl. Acad. Sci. USA 108, 8162-8166 (2011)
Microfuidic physics is different! 1
9
University of New Mexico (DeMoss and Cahill) (http://panda.unm.edu/fash/viscosity.phtml)
Critical fow properties in devices
10
=
V L

Reynolds number Re =
inertial force
viscous force
1: laminar fow
Physical meaning: fuid elements follow straight streamlines, and
fuid interfaces remain nearly parallel over long distances in
microfuidic devices
Microscale fow physics is different! 2
11
FoIch Iab (University of Washington) via YouTube
Critical fow properties in devices
12
=
V L

Reynolds number Re =
inertial force
viscous force
1: laminar fow
Physical meaning: diffusion is very slow compared to convection in
microfuidic devices, and thus mixing requires special device
designs
=
V L
D
0
Pclet number Pe =
time to diffuse
time to convect
1: fast convection
Physical meaning: fuid elements follow straight streamlines, and
fuid interfaces remain nearly parallel over long distances in
microfuidic devices
j = D
0
dc
dx
D
0
=
k
B
T
6a
Combination: diffusion in microfuidics
X

cm
2
/sec
10
-2
10
-4
10
-6
Gases Liquid Solid
10
-10
10
-8
10
0
Polymers
Glasses


























Nguyen and Wereley, Fundamentals and Applications of Microfuidics, 2nd ed. (2006)
The mixing rate in microfuidic devices is determined by the fux of diffusion:
species concentration [kg/m3] fux of diffusion
The diffusion coeffcient D
0
is inversely proportional to viscosity:
e.g. for a spherical particle of radius a:
Finally, the mixing time is proportional to the square of the channel length.
Combination: passive micromixer
X
Key idea: Increase the length of the fow channel
http://www.youtube.com/
watch?v=ZCMr1tHnGRs
Combination: passive planar micromixer
13











































Melin et al., Lab Chip 4, 214-219 (2004)
Key idea: Modify geometry to obtain mixing via changing fow pattern
Combination: parallel lamination mixer
14
Key idea: Split streams to increase surface area and hence mixing
Kamholz et al., Anal. Chem. 71, 5340-5347 (1999)
Schwesinger et al., J. Micromech. Microeng. 6, 99-102 (102)
Combination: 3-D serpentine mixers
X
Key idea: Add elements to "fold" fuid via three-dimensional structure
Liu et al., J. Microelectromech. Syst. 9, 190-197 (2000)













































b
a
c






Combination: 3-D microvascular networks
15
Key idea: Split streams in 3-d geometries to enhance mixing
Therriault et al., Nat. Mater. 2, 265-271 (2003)
Combination: herringbone micromixers
16
Key idea: Add elements to "fold" fuid via chaotic advection
Slanted ridges:
3-D herringbone:
Stroock et al., Science 295, 647-651 (2002)
Combination: herringbone mixer movie
17
FoIch Iab (University of Washington) via YouTube
X
=
D
L
2
mixing
Fourier number Fo =
rate of conduction
rate of energy storage
= 0.1-1
Combination: microfuidic valving
18
mold
flat
substrate
A







Key idea: Fabricate a plastic valve that is separately actuated with air

A B
C D
E F







Unger et al., Science 288 113-116 (2000)
on-off on-off
peristaltic pump valve grid
switching valve
Combination: colloid valves
19







Key idea: Incorporate micron-sized colloidal particles into devices
passive valve actuated valve
Terray et al., Science 296, 1841-1844 (2002)
Combination: in-situ piston
20
Key idea: Photopolymerize parts in place in microfuidic devices
Hasselbrink et al., Anal. Chem. 74 4913-4918 (2002)
Separation: emulsifcation ("droplets")
21
Key idea: Exploit the Rayleigh-Plateau instability to create emulsion drops
Thorsen et al., Phys. Rev. Lett. 86 4163-4166 (2001)
Wikipedia
Stress: elongates jet of liquid
Surface tension: minimizes surface area
Result: jet breaks up into drops
Emulsifcation: fow-focusing
22
Abate Iab (University of CaIifornia San Francisco) via YouTube
Anna et al., Anal. Chem. 74 4913-4918 (2002)


Key idea: "Pinch off" droplets using a fow-focusing geometry
Droplets + valving = adjustable sizes
23
Abate Iab (University of CaIifornia San Francisco) via YouTube
Emulsifcation: enhanced mixing in drops
24
Tice et al., Langmuir 19 9127-9133 (2003)
Key idea: Recirculation within drops enhances mixing rates
Emulsifcation: drops in drops (in drops...)
25
Key idea: Encapsulate drops in other drops to create multiple emulsions
Chu et al., Angew. Chem. Int. Ed. 46 8970-8974 (2007)
Utada et al., Science 308 537-541 (2005)
Drops in drops: tune fow rates
26
Abate Iab (University of CaIifornia San Francisco) via YouTube
i
n
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e
a
s
i
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g

i
n
n
e
r

f
u
i
d

f
o
w

r
a
t
e
Separation: cell sorting via optical forces
27
Waste Collection
Optical switch
Analysis region
Buffer Buffer
Sample input








Key idea: Use radiation pressure to sort cells in a microfuidic device



IR laser AOM
488-nm laser
PMT
Photodiode
Filter (525/40)
Filter
(488/10)
Sample
Output
wells
cartridge
Microfluidic
input
reservoir
Sheath
a
b
c





Wang et al., Nat. Biotechnol. 23 83-87 (2005)
Separation: particle sorting via gravity
X
Key idea: Use gravity to sort particles of different mass
Huh et al., Anal. Chem. 79 1369-1376 (2009)
Separation: deterministic lateral displacement
28
Key idea: Particles of different diameter follow different streamlines
Huang et al., Science 304 987-990 (2004)
Separation of parasites from blood
29
Holm et al., Lab Chip 304, 1326-1332 (2011)

















Separation: motile sperm sorter
30
Key idea: Live cells swim across laminar streamlines
Cho et al., Anal. Chem. 75 1671-1675 (2003)
Separation: distillation
31
















Key idea: Establish vapor-liquid equilibrium in segmented fow and separate
vapor using capillary forces
Hartman et al., Lab Chip 9, 1843-1849 (2009)
Reaction: drops as microreactors
32
Key idea: Drops increase reaction rates by increasing surface-to-volume
ratio, reducing diffusion distances, and enhance heat and mass transfer
Ahmed et al., Adv. Synth. Catal. 348 1043-1048 (2006)
Reaction: enzyme kinetics
33
Key idea: Design a droplet-based microfuidic system to extract kinetic
parameters of an enzymatic reaction
Text
Song and Ismagilov, J. Am. Chem. Soc. 125 14613-14619 (2003)
Reaction: nucleation
34
Chen et al., J. Am. Chem. Soc. 127 9672-9673 (2005)
Key idea: Design a droplet-based microfuidic system to study effect of
mixing on nucleation of protein crystals
Reaction: nanoparticle synthesis
35
Key idea: Use of gas slugs to separate small liquid reaction volumes
increases the monodispersity of microfuidically-produced particles
Khan et al., Langmuir 20 8604-8611 (2004)
Reaction: microfber synthesis
36
microtubules
microfbers
Khan et al., Lab Chip 4 576-580 (2004)
Key idea: Photopolymerize a fow-focused stream "on the fy"
Reaction: gradient etching
37
Key idea: Gradients in reactant composition generate differences in etching
rates through a surface
Jeon et al., Langmuir 16 8311-8316 (2000)
Applications of microfuidics
38
Chemical synthesis
- Especially for high-value components
Controlled release
- Pharmaceuticals
- Cosmetics
Biotechnology
- Genomics and sequencing
- Biodetection
- Directed evolution
Models of biological processes
- Microvasculature and veination
- Chemotaxis and chemical response
iii
i ii ii
iv iv
v vi
iii
i ii
iv
v
i
iii
Protein
Fluorinated
carrier uid
PDMS
Glass
capillary
Precipitant
Buer
a
Valve-based system
b
Droplet-based system
c
SlipChip (well-based) system
Open
Open
Valve
Load
precipitant
Load
protein
Close
Close
Close
Mix
1 mm
100 m
1 mm 1 mm
1 cm
100 m
1 mm
100 m
100 m
250 m
Load protein
Preloaded
precipitants
Mix protein
with precipitants
Slip
Slip
Protein
Slip
Slip into contact
Precipitants
Protein
Crystallization trials
250 m
Open
















Application: crystallization
X
Review article: Li and Ismagilov, Annu. Rev. Biophys. 39, 139-158 (2010)