Guangya ZHOU

Department of Mechanical Engineering

Faculty of Engineering
National University of Singapore
10 Kent Ridge Crescent
Singapore 119260
 Outline
• Basic concepts
• Micro fluidic elements
Micro valves, micro pumps, micro channels
Micro flow sensors
Mixers, filters
• Systems and examples
• Summary

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 Microfluidic devices
• Identified by the fact that one or more channels are less than 1mm
in dimension

• First developed in the early 1990s

• Why is it so appealing?
Small amounts of reagents
Easily automated
Mass production possibility
Multiple functions per device
Purification
Labeling
Reaction
Separation
Detection

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 Basic concepts
• Density : mass per volume

• Viscosity : a measure of how resistant a fluid is to flow (Temperature

dependent)
• Laminar flow: a flow in which the velocity of a given point in the fluid
does not change with time (well-defined, stream-lines)

• Turbulent flow: the velocity of a given point in the fluid change with time

• Volume flow rate: Q = Av A: cross-sectional area of the flow channel

v: average velocity of the fluid

• Mass flow rate: product of volume flow rate and the density of the fluid
Laminar flow : Re < 2300 Turbulent flow : Re > 4000

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 Basic concepts
• Newtonian fluids: shear stress is linearly proportional to shear rate
v y
v(y)
 =
y No slip
at wall
• Reynolds number:
 vDh
Re =

4  Crosssection Area
• Hydraulic diameter Dh: Dh =
Wetted Perimeter
Cross section Formula Variables

Circle Dh = D D: diameter
Annulus Dh = D − d D: diameter
d: inner diameter
Rectangular 2ab a & b: sides
Dh =
( a + b)
Triangle 3 a: side
Dh = a
(equilateral) 3
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 Pressure driven flow
In pressure driven flow, the fluid is pumped through the device via positive
displacement pumps, such as syringe pumps.

No-slip boundary condition: the fluid velocity at the walls must be zero.

A parabolic velocity profile within the channel. (laminar flow)

Source: Washington Univ. Example: water in a 100 µm square

channel, v = 0.17 m/s. (corresponds to
volume rate of 100 µL/min)

ηwater = 8.91 × 10-4 Ns/m2

water = 1000 kg/m3

 vDh (1000kg/m 3 )(0.17m/s )(100 10−6 m )

Re = =
 8.9110-4 Ns/m2

Use 1 N = 1 kgm/s2
Re = 19 << 2300
Microchannel flow is almost always laminar

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 Pressure driven flow
Effect of entrance length:
• Critical Re of 2300 assumes fully developed flow
• Not fully developed if channel length L < entrance length
• May not be fully developed in microchannel systems
For a pipe with diameter D:
Entrance length = 0.06Re D

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 Electrical Fluidic

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 Pressure driven flow
Electric-Fluid Analogs:
• Pressure  Voltage; Volume  Charge; Volume rate  Current
• Fluidic resistance: ratio of pressure drop over flow rate

Fluidic resistance P Pressure drop (unit: N/m2)

R=
(unit: Ns/m5) Q Volume rate (unit: m3/s)

Cross section Formula Variables

Circle 8 L r: radius
R=
r4 L: channel length
Rectangular 12 L w: width (w >> h)
R=
wh 3 h: depth
L: length
Triangle
2a
17.4 L a: one-half of the
R=
a4 width of the channel
L: length
54.740

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 Pressure driven flow
• Fluidic capacitance: Pressure-dependent volume change
Fluidic capacitance dV Volume change (unit: m3)
5
C=
(unit: N/m ) dP Pressure change (unit: N/m2)
Analog to electrical capacitance.
Storage of volume/mass by fluid and surrounding geometry (elastic
walls, membranes, etc.)
Flexible
membrane

• Fluidic inductance: Storing kinetic energy in fluidic systems

Analog to electrical electrical inductance.

Flow inertia by fluid and surrounding geometry.
Very little inductance in microfluidics.

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 Pressure driven flow
Microfluidic logic and oscillators:

Microfluidic Microfluidic
Tesla’s fluidic rectifier AND gate Oscillator
Output 1 Output 2
Input A Input B
Feedback
channel

Vent Vent

Out = A•B
Inlet Control
Differential fluidic chamber
resistance requires a
relative high fluid velocity

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 Electroosmotically driven flow
When silica is in contact with an aqueoussolution, its surface hydrolyzes to form
silanol surface groups (Weinberger, 1993). Thesegroups may be positively charged as
SiOH2+, neutral as SiOH or negatively charged as SiO-, depending on the pH value of
the surrounding electrolyte solution.

● strongly attracted cations form Stern and shear layer (electric double layer)
● cations in shear layer move along the electric field lines to the cathode
● bulk is accelerated by the moving shear layer via viscous forces
Source: TU Delft
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 Electrophoretic Separation
Principle of electrophoresis:
Velocity of an ion of charge Zi, in a homogeneous medium is
zi e Mobility of the ion species
vi = E
6 ri Unit: cm2/(Vs)
e: charge on electron 1.60210-19 C; ri: radius of the ion; : viscosity
Basic setup:
Detection mechanism: Sample
Buffer
• fluorescence
• mass spec.
• conductivity
Separation
Sample column
+V GND Slower Faster
component component
Injected sample +V GND
plug

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 Surface tension driven flow
Hydrophilic: 0 <  < 900 Surface tension force:

F = 2 r cos( )
: Interfacial surface tension, unit N/m
h r: Channel radius

Vertical capillary:
2 r cos( ) =  g  r 2 h
Hydrophobic: 900 <  < 1800
Surface tension force Gravitational force

2  cos( )
h=
g r

Horizontal capillary:
Very long micro fluidic channels can be filled
with liquid using surface tension along.

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 Bubbles in microfluidic structures
• Large bubbles with diameters greater than a few millimeters will generally
not adhere to surfaces, but smaller bubbles will.
Buoyant Force
4
Fbuoyant =  g  r 3 & Fsurface = 2 r
3
If Fbuoyant > FSurface, bubbles leave the surface.
If Fbuoyant < FSurface, bubbles adhere to the surface. Surface
tension force

• Disadvantages of bubbles: often must exert huge pressures to move

bubbles, tend to accumulate around dead volumes, produce large fluidic
capacitances, can wreak havoc with cells/samples.
• Advantages of bubbles: thermally produced bubbles for micro pumps.

• Solution to the bubble problem in microfluidics: Priming a micro fluidic

system with a gas that is highly soluble in water. (CO2, NH3, SO2, etc.)

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 Electrowetting
Electrowetting:
A voltage is used to modify the wetting properties of a solid material.

Electrode

Water
Droplet Hydrophobic
insulator
V

Electrode

Lippman equation: (Nobel Prize winner Gabriel Lippman in 1908)

1
 (V ) =  0 − CV 2
2
: Surface tension, C: Capacitance per unit area, V: applied voltage
In the last decade, electrowetting has been utilised for an increasing number of
applications. These include pixelated optical filters, fiber optics, adaptive lenses, lab-
on-a-chip.
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 Electrowetting
Digital microfluidics:
Micromanipulation of discrete droplets
Liquid flows towards regions of lower surface tension – physically because it
“attempts to wet more” the areas of lower surface tension

Source: Duke Univ. & National Central Univ.

Merging droplet Separating droplet

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 Electrowetting
Digital microfluidic lab-on-a-chip:
Unit-sized packets of fluid which are transported, stored, mixed, reacted, or
analyzed in a discrete manner.

Droplet dispensing
Digital Microfluidic Chips
Source: Duke Univ.
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 Continuous electrowetting
Continuous electrowetting effect:
A flow motion of liquid metal can be induced by a surface tension gradient
along the surface of the liquid metal as a result of the electrowetting effect.

Mercury & initial surface charge Electrically varied surface tension

Source: JOURNAL OF MICROELECTROMECHANICAL SYSTEMS, VOL. 9, NO. 2, p.171 – 180, JUNE 2000
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 Continuous electrowetting
Continuous electrowetting applications:

Long-distance travel linear

liquid micromotor Liquid micromotor

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 Microchannels
Overview of microchannels:
Silicon-based: bulk, buried, surface microchannels
Glass-based: bonding
Metal-based: electroplating
Polymer-based: spin on, soft-lithography
Simulation software:
CFD, ANASYS, Coventorware, …
Geometry to reducing broadening of injected samples

Conventional Improved geometry

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 Fabrication of microchannels
Bulk micromachining Processing:
Example 1: Example 2:
Isotropic Sealing with
DRIE Etch Mask Anisotropic plasma deposition thin
etch etch film layer

(1) (2)
(1) (3)

SEM:

(2) (4)

Sidewall mask Sealing with

fabrication deposited thin
film layer

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 Fabrication of microchannels
Bulk micromachining Processing:

(1) Silicon (3) Glass

(2) (4)

Microfluidic channel

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 Fabrication of microchannels
Surface micromachining Processing:
Channel
etch hole Si3N4
Si3N4 p++ Boron SiO2
diffusion

(1) (3)

LTO Sealed with

Si3N4
PSG Flow channel

(2) (4) EDP Etch

Silicon
microfabricated
microneedles

Source: Lin. L (UCB)

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 Fabrication of microchannels
Bulk Polymer Processing:
Injection molding (like CDs)

Plastic microfabrication
technology enables:

Design flexibility
Massive parallelism
Low-cost manufacturing

Fabrication sequence takes cues

from compact disc manufacture

Source: www.aclara.com

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 Fabrication of microchannels
Bulk Polymer Processing:
Soft-lithography

• Fabricate silicon, metal, or thick PR mold

(SU8)

• Apply uncured PDMS

(polydimethylsiloxane)

• No elevated pressure or temperatures

• Allow PDMS to cure

• Peel off PDMS replica

• Cured PDMS readily bonds to itself,

making multiple layered structures.

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 Fabrication of microchannels
Bulk Polymer Processing: Microchannels with round cross-section

(a) (b)

(c) (d)

(e) (f)

Silicon SU-8

PDMS (mold-part ) PDMS (mold-part )

PDMS (device) PDMS or glass

(g)

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 Fabrication of microchannels
Bulk Polymer Processing: Microchannels with round cross-section

ii). Pressure: 8kPa iii). Pressure: 5kPa

Depth: 22.85µm Depth: 13.586µm

i). Pressure: 15kPa

Depth: 35.569µm

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 Microvalves
Check valves:

SU8 Check valve

Fixed geometry valves:

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 Microvalves
Active valves:

• Current travels down platinum wires,

heating the coil
• The coils boil water to produce bubbles
• Bubbles push on the cross’s arms and
force it away from the main channel
• Bubbles generated on the other side of
the arms close the gate valve
Source: The University of Utah Source: Redwood Tech.
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 Micropumps
Categorization by pumping principle:
• Displacement pumps
In all positive displacement pumps, a cavity or
cavities are alternately filled and emptied by the
pump action causing fluid to move in a forward-
only fashion.

• Centrifugal pumps
A centrifugal pump consists of an impeller with
blades rotating inside a casing. The impeller
rotation reduces the pressure at the pump inlet
causing fluid to flow into the pump. The fluid is
then accelerated outward along the blades and
exits the pump.

• Other pumps

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 Displacement micropumps
• Consists of following components: Microactuator, pumping chamber,
flow rectifier (valves)

• Actuation methods in micro pumps

♦ Piezoelectric
Fast response time, very large force (stack type), not integrable
♦ Electrostatic
Very fast response time, very small force, very small strokes, integrable, low
power consumption, high reliability
♦ Electromagnetic
Fast response time, large size, not integrable, high power consumption
♦ Pneumatic
Very slow response time, very large strokes
♦ Thermopneumatic
Large pressure, large strokes, integrable, high power consumption
♦ Thermomechanic
Large pressure, large strokes, integrable, high power consumption

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 Displacement micropumps
Check-valve micropumps:

Design considerations:
• Compression ratio
V
=
V0
To achieve self-priming in a micro-pump, i.e. to be able to pump as
much gas and gas bubbles out of the micro-pump, the compression
ratio needs to be maximized.
• Critical pressure difference pcrit (check-valves start to be opened)
p − p in   p crit & p − pout   pcrit

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 Displacement micropumps
Check-valve micropumps: (Continued)
General design rules for check-valve micropumps:

• Minimize the critical pressure pcrit by using more flexural valve design or
valve material with small Young’s modulus.

Parylene check valve:

• Maximize the stroke volume V by using actuators with large stroke or

more flexible pump membrane.

• Minimize the dead volume V0 by using thinner spacer or wafer.

• Maximize the pump pressure p by using actuators with large forces.

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 Displacement micropumps
Check-valve micropumps: (Continued)
Examples of Check-valve micropumps:
Piezoelectric-driven:

Electrostatically-driven: Thermopneumatically driven

Driving electrodes Heating element

Action Action
unit unit

Si membrabe Si membrabe

Valve Valve
unit unit

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 Displacement micropumps
Piezoelectric driven Diffuser pumps:
• Valve-less pumping
• Reduces the complexity of the fabrication process and the possibility of
particle clogging

A. Olsson, “Valve-less Diffuser Micropumps”, Dissertation, Stockholm 1998

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 Displacement micropumps
Bubble-driven Diffuser pumps:

Diffuser pump
using Tesla’s
rectifier

JOURNAL OF MICROELECTROMECHANICAL SYSTEMS, VOL. 11, NO. 6, p. 665, DECEMBER 2002

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 Centrifugal micropumps
Micro centrifugal pumps:
• Fast moving blades or rotating channel systems add mechanical work to
the fluid by means of centrifugal force.
• No flow pulsation.

C. H. Ahn, M. G. Allen: “Fluid Micropumps Based on Rotary Magnetic Actuators”, Proceedings of

MEMS '95, Amsterdam, Jan 29. – Feb. 01. 1995, 408-412

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 Other micropumps
Ultrasonic pumping:
• With no moving parts

• Flexural plate wave (Momentum transferred to fluid by friction between

wall and fluid).
• Acoustic wave (Momentum transferred to fluid by damping of high intensity
sound waves).

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 Other micropumps
Electric field mediated pumping:
• No moving parts
• Static fields (electroosmosis & static electrohydrodynamic EHD)
• Traveling fields (travelling wave EHD pumping)

Electroosmosis micropump
♦ pumping electrolytes, like acids
♦ deep, narrow slots deep etched into silicon
♦ slot witdh: 3 µm; slot distance: 20 µm
♦ 1000 slots generate a flow rate of up to 30 µl/min
♦ 400 V operating voltage

Source: D. J. Laser, Stanford University

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 Other micropumps
Electric field mediated pumping: (Continued)
Injection-type electrohydrodynamic (EHD) pumping
● A pair of grid electrodes create a strong electric field
● An insulating fluid is partly ionized at the emitter
● Coulomb force accelerates bulk fluid in the electric field

♦ working fluids such as ethanol, propanol, acetone and deionized water

♦ 350 µm grid separation
♦ operation voltage between 40 and 700 V

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 Micro mixers
● Controlled mixing is necessary for many chemical/biochemical applications,
including chemical analysis/synthesis, drug dosing and compound labeling
● Mixing difficult on microscale – laminar flow

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 Micro mixers
Passive Mixing:
Based on channel geometry
Geometrically splitting and recombining substreams
1. Splitting /
recombining

2. Using obstacles

Resource: Smart Mater. Struct.11, 662–667 (2002)

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 Micro mixers
Passive Mixing: (Continued)
Chaotic Mixer

Resource: Science295, 647-651 (2002)

Altering flow direction

Changes in flow direction enhanced

mixing

Mixing was strongly dependent on

channel width and length

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Active Mixing:
Micro mixers
Micro stirrer Electrohydrodynamic Mixing

E = 0 V/m

E = 4 105 V/m

E = 6 105 V/m
Journal of MicroelectromechanicalSystems, 11(5),
462-470 (2002). Lab on a Chip3, 273-280 (2003)
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 H-Filter
• Flow is laminar
• Large particles in blood do not diffuse
• H+, Na+ and small molecules (high diffusion coefficient) diffuse rapidly
between streams

Source: Bruce K. Gale, Univ. of Utah

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 Micro flow sensors
How to measure flow rate?

• Pressure distribution measurement

􀂃 Dry fluid flow sensor
􀂃 Wet fluid flow sensor
……

• Shear stress measurement

􀂃 Skin friction flow sensor
……

• Thermal measurement
Anemometers
Calorimetric flow sensors
Time of flight flow sensors

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 Dry fluid flow sensors
In Dry fluid flow sensors, kinetic energy of the fluid plays a important role,
and viscosity not.
Cantilever design Prandtl’s flow sensor
Cantilever
Piezoresistor Orifice
Plate

Electrodes

Pyrex glass
Stagnation
Flexible
Orifice design Orifice
point
membrane
Piezoresistor

Silicon boss

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 Dry fluid flow sensors
Lift force flow sensor
• Small angle  small project area
• Dual plate structure  acceleration insensitive
Bending due to
force gradient
Torsional bar Flexible plate Flow over the plate

Piezoresistors

Support

Fixed
Frame

deflection
Front foil

Foil

Rear foil
Strain gauge
Flow velocity (m/s)

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 Wet fluid flow sensors
In wet fluid flow sensors, viscosity of the fluid plays a important role, and
kinetic energy not.
Analogous to Ohm’s law for electric conductors, in fluidic devices, volume
flow rate can be obtained by calculating the ratio of pressure drop over fluidic
resistance. Piezoresistors

p1 p2
Silicon
Package Capacitive
pressure sensor
Pyrex glass

Electrodes
Silicon Capacitive pressure sensors

Pyrex glass Pyrex glass

p1 p2
Silicon

Pyrex glass

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 Skin friction flow sensors
Measures skin friction (or shear force) on a suspended floating plate.
Basic structure Electrostatic skin friction flow sensor
(Analog Device design)
• Can apply force feedback
Etch
holes
Flow

A A Piezoresistors
Flow
Anchor

A-A Cross-
sectional view: Floating plate Poly-Si

Sacrificial
SiO 2
Silicon substrate

Suspension
spring

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 Thermal flow sensors
Electrothermal Sensing:
1. Thermocouples:
When two dissimilar metals (e.g. copper and iron) are brought together in a
circuit, and the junctions are held at different temperatures, then a small voltage
is generated and an electrical current flows between them.
VAB = ABT = (A - B)(Thot – Tcold)
A , B : Seebeck coefficients of the metal A and B

Seebeck effect : Temperature sensor based on Seebeck effect :

‘Cold’ Junction
at ambient T0
Temperature
to be
measured Metal A Output
Metal A
signal
Cold Hot Electronics
Current

Metal B
Metal B
Copper
wires
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 Thermal flow sensors
2. Thermoresistive effects:
Resistance (or resistivity) of most materials changes with temperature.
 = 0(1+T+T 2)
For metals and moderate temperature excursion:
RT = R0[1+(T-T0)]
 : Temperature coefficient of resistivity (TCR)
Metal Resistivity [Ωcm] TCR [10-4 / K]
Pt 10.6  10-6 39.2
Ni 6.84  10-6 68.1
Al 2.83  10-6 38
Au 2.4  10-6 40
Cr 1.26  10-5 30
Ti 3.84  10-5 38
W 4.9  10-6 45
Cu 1.72  10-6 41
Fe 9.71  10-6 65.1
Poly-Si 10.6  10-6 -12 to 12

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 Thermal flow sensors
2. Thermoresistive effects: (Continued)
• Poly-Si can be used, but low TCR and doping-dependent
• Wheatstone bridge circuit for signal processing
 RAl 1 
Vout =  −  Vsupply
R +R 2 
 Al Poly

Rpoly dVout Vout dRAl Vout dRPoly

Rploy = +
VSupply dT R Al dT RPoly dT
+
- dRPoly
Assuming: = R0 Poly
RAl Vout at initial temperature T0 dT
RPoly
RAl = Rpoly = R0 dRAl
= R0 Al
dT

dVout Vsupply
= ( Al −  Poly )
dT 4

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 Thermal flow sensors
Anemometer type flow sensors:
• Anemometers consist of a single element which is heated and the
temperature of which is measured.
• Thermoresistive temperature sensing.
• Anemometer can be operated in two modes: constant power and
constant temperature.
Schematic Constant Power mode Constant Temperature
mode (requires feedback
Flow control)

Power supply

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 Thermal flow sensors
Anemometer type flow sensors: (Continued)
• Sensitivity issues: Minimize the heat conduction to the support.

Q =   T +   Re  T Heat loss due to

forced convection
Total heat loss Conductive heat
flux to support
• Response time issues: Minimize the heat capacity of sensing element.
Thermal
Heater / isolation Heater /
temperature temperature
sensor sensor

Reference
temperature
sensor

Micromachined
Si3N4 thin
bridge

 The micromachined element carrying the resistor is thermally isolated from the
substrate using a material with low heat conductivity.
 The resistor is placed on a thin membrane, bridge, or cantilever with low heat
conductivity.
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 Thermal flow sensors
Anemometer type flow sensors: (Continued)
• Angular sensitivity issues:
The sensitivity of a hot wire anemometer depends on the orientation of
the flow velocity vector with respect to the direction of the wire.
For a wire whose length is more than 250 times longer than its
thickness/ width:
Q =   T +   Re  T  cos( )
Aluminium
Silicon nitride 3D hot wire anemometer
membrane


Flow

Polysilicon
Wire

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 Thermal flow sensors
Calorimetric flow sensors:
• Calorimetric sensors measure the displacement of temperature profile
around the heater, which is modulated by the fluid flow.
• Standard configuration consists of a heater surrounded by temperature
sensitive elements arranged symmetrically downstream and upstream.
• Downstream sensor is heated and upstream sensor is cooled.
• Output signal (the temperature difference upstream and downstream) is
a function of flow velocity.

Flow Temperature
sensor

Upstream Heater Downstream

temperature temperature
Heater
sensor sensor

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 Thermal flow sensors
Time-of-flight flow sensors:
• Time-of-flight sensors measure the passage time of a heat pulse over a
known distance.
• Distortion of signal by diffusion. Serious at small velocities.
Flow

Temperature
Heater sensor

Heat Large
Pulse flow
velocity
Small
Temperature

flow
velocity

Time
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 Systems and examples
Lab-on-a-chip:

Example application areas

• Biotechnology, drug discovery

• Diagnostics and biochemical analysis
• Forensics
• Environmental monitoring

Miniaturization Advantages
integration
• Very small sample volumes
• Parallel processing
• Disposable
• Portability

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 Systems and examples
Lab-on-a-chip: (Continued)

Common components
& Sub systems

• plumbing (pumping, valving,

channels/chambers or wells)
• sample preparation
• filtering
• separation
• mixing
• sorting
• DNA amplification (PCR)

Source: J. Evans, D. Liepmann, and A. Pisano (BSAC/UCB)

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 Systems and examples
Lab-on-a-chip: (Continued)
DNA analysis

Integrated DNA Analysis

Source: C. Mastrangelo, U. Michigan

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 Systems and examples
Drug Delivery/Biofluid Extraction:
Future targeted improvements in
drug delivery
• Improved efficacy
• Reduced side effects
• Continuous dosing
• Reduced pain
• Increased ease of use
• Increased use compliance
• Improved mobility

Microneedles
• Size and shape variable
• Reduced insertion pain for patient
• Reduced tissue damage
• Capable of targeting a specific insertion depth
• Can incorporate micro filters for excluding large
molecules
• Can integrate with other devices and processes

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 Systems and examples
Drug Delivery: (Continued)
Controlled-release microchip

• Anode is a gold membrane that is dissolved when 1V is

applied, releasing drug. Chip can be controlled remotely.
• Up to 1000 reservoirs on a dime-size chip.
• Chips can be implanted, swallowed, or integrated into
an intravenous delivery system.
Source: NATURE, VOL
• Biocompatible material will be need for “pharmacy-on- 397, p. 335, JANUARY
a-chip” 1999

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 Summary

• Basics of microfluidics
• Micro fluidic devices and sub-systems
• Examples of micro fluidic systems

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