Day 2

Microfluidic Design Principles

Intro to Microfluidics

22 November 2010

Microfluidic device fabrication
Course Instructors Stanford You the students

concept

CAD

photolithography

molding

finishing

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Intro to Microfluidics

2

Next: Hands on learning – Day 1
Multiplexed Mixer

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Intro to Microfluidics

3

Next: Hands on learning – Day 2
Addressable Array

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4

Designing your own chips

One size does not fit all

Microfludic chips are designed to suit specific needs
22 November 2010 Intro to Microfluidics 5

Microfluidics at a low level
Primary Tasks • Input Selection • Flow distribution • Mixing • Storage Primary elements • Channel • Valve • Chamber

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Course chip designs decomposed
Lines

Curves

Stars

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Part 1
Distribution: design of on-chip flow

Lines and Curves

The most important elements of a microfluidic device Channels for stuff

Color convention Flow Control

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Typical channel geometry

width
100um

Length
whatever you need it to be

IMPORTANT Height : Width = 1 : 10
(or larger)
Can create challenges for design 10um

Height/depth

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Challenging geometry
Large Flat Chambers
side

h w
w >> 10 h

top

Collapse zone

l

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Challenging geometry
Large Flat Chambers
side

h w
w >> 10 h

top

l

Solution: posts
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Typical channel geometry

width
100um

Length
whatever you need it to be

These dimensions are special
10um

Height/depth

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Fluid flow at the microscale
Governing Equation

ρ⎜

⎛ ∂v ⎞ + v ⋅ ∇ v ⎟ = ρg − ∇ p + μ∇ 2 v ⎝ ∂t ⎠
(make dimesionless)

(Navier-Stokes Equation)

∂v 1 + v ⋅ ∇v = g − ∇p + ∇2v ∂t N Re

The Reynolds Number

ρvh N Re = μ
NRe = 0.01

Inertial (turbulent) flow

Viscous (laminar) flow

For water flow at 1mm/s at 25°C through a channel 10µm deep:

Viscocity dominated flow

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Deriving further
Governing Equation

ρ⎜

⎛ ∂v ⎞ + v ⋅ ∇ v ⎟ = ρg − ∇ p + μ∇ 2 v ⎝ ∂t ⎠

Assumptions
• No local acceleration • Constant density • Incompressible Newtonian fluid • Velocity components only in direction of bulk flow

1 dp μ d 2 v x = ρ dx ρ dz 2
Forced by pressure

Speed depends only on depth/height

Fluid velocity profile in an infinitely wide channel
z

h P1 L

vx P2

x

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Laminar flow
Fluid velocity profile in an infinitely wide channel
z

h P1 L

vx P2

x

N Re << 1

Laminar fluid flow analogous to sliding sheets
v=4 v=2 v=0

How does this help microfluidic design?
22 November 2010 Intro to Microfluidics 16

Governing Equation

1 dp μ d v x = ρ dx ρ dz 2
2

z

h P1 L

vx P2

x

Solving for constant pressure drop:
Poiseuille (Laminar) flow

⎛ 8μ L ⎞ ΔP = Q ⋅ ⎜ 4 ⎟ ⎝ πr ⎠ ⎛ 12 μ L ⎞ ΔP = Q ⋅ ⎜ 3 ⎟ ⎝ wd ⎠
V = I ⋅R

Circular Channel

Does this look familiar?
Rectangular Channel

Ohm’s law

microfluidic systems can be designed like linear electrical circuits

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“Analog” microfluidic circuitry
Battery ≈ Pressure Resistor ≈ Channel length/geometry Increase flow/current ≈ Channel contraction Decrease flow/current ≈ Channel expansion

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Test case 1

A In Out

B

Which path will have higher flow?
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Test case 2

A

B

Which network has equal flow through branches?
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Part 2
Mixing

Laminar flow and lack of mixing

v=4 v=2 v=0

Chemical species in one plane are ‘ignorant’ of those in another

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Mixing in purely laminar flow is diffusive
v=4 v=2 v=0

Chemical species in one plane are ‘ignorant’ of those in another

Injection point

Molecular diffusion evident

w

Typical diffusion time: w2

t diff ≈

Over short distances concentrations negligibly mix
23

D

22 November 2010

Intro to Microfluidics

Speeding up diffusion
Solution 1: narrower channels

Diffusion path

Diffusion path

Restrictions?
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Speeding up diffusion
Solution 2: twisted flow

Stroock et. al. Science (2002)

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Part 3
Input selection

Simple flow selection
P1

P1 > P2
P2 P1

P1 < P2
P2
22 November 2010 Intro to Microfluidics

Reliable? Robust?
27

Input control using laminar flow
Laminar Interface Guidance
To Rest of Chip

To Aux. Waste To Aux. Waste

To Aux. Waste

Laminar flow interface is coerced across an output channel to generate mixing ratios Excess flow is collected by overflow/bypass channel and sent to waste
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Input control using laminar flow
Laminar Interface Guidance
To Rest of Chip

To Aux. Waste To Aux. Waste

To Aux. Waste

Laminar flow interface is coerced across an output channel to generate mixing ratios Excess flow is collected by overflow/bypass channel and sent to waste
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Input ratio control
A microfluidic ‘servo’: pressure to concentration translation

• switching can be binary (off/on) or graded (0, 0.1, 0.2, ... , 0.9, 1.0) • Down stream blending with chaotic mixers

Possible with more than 2 inputs?
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Integrated microvalves
“Push Down” Valve control Open Flow 0 psig flow glass substrate Valve membrane control Closed No Flow 30 psig flow glass substrate

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Electronic Analogy
Drain Qout

Pin Gate Qin Source
Microfluidic Valve
22 November 2010 Intro to Microfluidics

MOSFET
32

Valves: Up, down, or both

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Valve geometry
Control channel w Flow channel Valve Pad w (100um, typical)

Overhang ~ 20-30um Control channel >w Flow channel
Valve Pad

w

Larger valves better?
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Valve operation

dP = 10psi <=15um deep

dP = 5psi Up to 45um deep

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Crossing over
Need valve here

Need valve here Cannot route valve here Valves under same control

Impossible?
22 November 2010 Intro to Microfluidics 36

Valve geometry
Control channel w Flow channel Valve Pad w (100um, typical)

Overhang ~ 20-30um Control channel >w Flow channel
Valve Pad

w

What happens with smaller than “w” valves?
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Membrane deflection vs. width

30psi 100 x 100um Pad ~2000 uNewtons

Control Flow

30psi 100 x 20um Pad ~400 uNewtons

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Crossing over

“Cross-over”: does not produce valve

Cannot route valve here Valves under same control

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Crossing over

More robust “Cross-over”

Cannot route valve here Valves under same control

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Valve simplified selection
V1 = OFF

P1
V2 = ON

P1 = P2
P2
V1 = ON

P1
V2 = OFF

P1 = P2
P2
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Higher order selection
3 inputs 4 inputs 5 inputs 6 inputs • • • 16 inputs ⇒ ⇒ ⇒ ⇒ • • • ⇒ 3 valves 4 valves 5 valves 6 valves

16 valves?!

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Input Multiplexer (MUX)
N inputs selected by only 2*Log2 (N) control valves - Binary Addressing

Melin & Quake. Ann. Rev. Biophys. Biomol, Struct. (2007)

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Higher order multiplexing
N inputs selected by only N!/(N/2)!^2 control valves
(Note: N must be divisible by 2)

Melin & Quake. Ann. Rev. Biophys. Biomol, Struct. (2007)

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MUX cross contamination

Melin & Quake. Ann. Rev. Biophys. Biomol, Struct. (2007)

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Cleaner MUX

Melin & Quake. Ann. Rev. Biophys. Biomol, Struct. (2007)

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Cleaner MUX

Melin & Quake. Ann. Rev. Biophys. Biomol, Struct. (2007)

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Valves controlling valves - latching

Melin & Quake. Ann. Rev. Biophys. Biomol, Struct. (2007)

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Valves controlling valves - latching

Single source for 20 control valves (push down)

Latches (push-up) control valve state

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Part 4
Pumps, metering, and mixing

Macrofluidic pumping

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Microfluidic peristalsis

See “Noel’s Piano”
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Metering

Melin & Quake. Ann. Rev. Biophys. Biomol, Struct. (2007)

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Valve enhanced mixing

Melin & Quake. Ann. Rev. Biophys. Biomol, Struct. (2007)

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Part 5
Storage and filtering

A simple storage chamber

Chamber
(when valves are closed)

Issues - How do you: • controllably capture particles? • access contents without loosing them?

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A simple storage chamber

Chamber
(when valves are closed)

Solutions? • Filtering channels • Partially closed valves

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A chamber with filters
Chamber Filters Media

d

h h ~ 0.5*d

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Chamber with partial valve

Not quite a cross over
(and/or lower valve pressure)

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The sieve valve

control 0 psig flow glass substrate control 30 psig flow glass substrate
Sieve pore Allows flow/diffusion Blocks bigger objects Rectangular profile

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The sieve valve

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Summary
1:10 h:w aspect ratio Only laminar flow Fluidic networks designed using Ohm’s Law ⌧Mixing by diffusion Valves are fluidic transistors Core elements

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Other finer details

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Further Reading

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Further Reading

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