Bio-Nano/Micro Fluidic Systems · 2019. 7. 22. · NTHU ESS µ-Nano Bio & fluidics System Lab Prof....

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Prof. Fan-Gang Tsengµ-Nano Bio & fluidics System Lab

Bio-Nano/Micro Fluidic Systems

Prof. Fan-Gang TsengNational Tsing Hua University

Engineering and System Science Dept.

Part A Micro Fluidic Physics

Part B Bio-sample preparation

Part C Operation of Micro Fluidic Systems-Continuous and Digital Fluidic Systems

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Part A Micro Fluidic Physics

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outline

1.scaling law of micro/nano fluidics2. Sample collection3. Sample preparation4. Sample transportation/treatment

a. Continuous flow systemb. Digital flow system

5. examples

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Scaling law of micro/nano fluidics

• Microfluidics

Navier-Stokes Eq., Reynolds number, Peclet’s number, Capillary number, Knudsen’s number, Froude’s number

• Surface related phenomena

Diffusion, surface tension force

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Scaling with length scale

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Dimensional and Dimensionless

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Microfluidics

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uρCpL/k

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Part B Bio-sample preparation

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Sample collection

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120 µm

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Sample Preparation

• extraction• purification• separation• amplification• sorting

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Capillary Electrophoresis

D. N. Heiger, High Performance Capillary Electrophoresis - An Introduction, Hewlett-Packard Co.

Electrokinetic phenomena: electrophoresis and electro-osmosisP flow EOF

0 ms

60 ms

150 ms

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P DEP N DEP

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(magnetic beads)

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Part C Operation of Micro Fluidic Systems

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• Digital Fluidic Systems1. droplet generation2. droplet suspension3. droplet surface manipulation

Micro Fluidic Systems:

EWOD, CJ Kim, UCLAµTransducers sourcebook, 98

• Continuous Fluidic Systems1. micro channel2. mixing/reaction,3. flow logic, 4. flow detection5. fluid actuation (pump, valve)6. integration and package

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• Reagent: storage, reconstitution, sample volume• fluidic device: fabrication,micro flow

measurement, and characterization• Surface modification•Integration• Package: interconnects, filling/bubbles/ dead

volume, leakage• control algorithms, data processing,

and communicaiton• Power consumption/ effeciency• Passive or active• reusable or disposable

Challenges for Continuous Micro/nano fluidic system

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One example of Continuous Micro/nano fluidic system

Abe Lee, 2003

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Flow channels1. Mixers 2. Extractors3. Flow logics

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Flow channelsBulk micromachining Surface micromachining

Buried micro channels Polymer micro channelsµTransducers sourcebook, 98 µTransducers sourcebook, 98

µTransducers sourcebook, 98

Anti-reflection coating

SU-8

SubstrateStandard UV exposure

Partial UV exposure

(a)

(b)

(c)

Anti-reflection coating

Stacked channel

Channel release

(d)

(e)

(f)Chuang, Tseng, MEMS’02

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MixersSharp turn Flow lamination

Plume mixers Active mixers




CHAOTIC MICRO-MIXER

H. Suzuki, C.-M. Ho, MEMS 02

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Separation


Electrophoresis Extractors

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Flow logics

Flow rectifier

Coanda effect Flow oscillator


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Fluidic sensors

1. Flow sensors2. Viscosity/density

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Flow sensorsThermal flow sensors

Cantilever drag flow sensor Lift force flow sensorCaltech, UCLA


C. Lin, F. G. Tseng, Sensors J. 2002

Fiber Floating Element

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Viscosity/density sensors

Acoustic Wave Sensors, 97

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Thermal/Fluidic actuators

1. Valves

2. Pumps

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Micro valve

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ValvesCheck valves Active valves

(thermal pneumatic)


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Actuation Mechanisms for Microvalves

• Pneumatic-Large linear forces-Requires external force generation ad external interconnections

• Thermal Expansion-Larger linear forces-Relatively slow, may heat fluid, consume large amounts of power

• Peizolelectric-Very Large forces-Very small movements, large voltages

C. Rich and K. Wise, Proc. MEMS’99, 130-134

C. Grosiean et al, Proc. MEMS’99, 147-152

S. Shoji et al, Transducers 91, 1052-1055

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M.Huff etal, Transducers’93, 88-101

K. Yanagisawa et al, Transcucers’93, 102-105

• Electrostatic

-High but nonlinear forces, large movements

-requires high voltages

• Electromagnetic

-Large forces and movement, very fast, low power

-Complex fabrication process/difficult to integrate

• Shape Memory Alloy (SMA)

-Very large force

-Slow response, need heat upCarien & Mastrangelo, MEMS-00

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Carien & Mastrangelo, MEMS-00

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Micro pump (with or w/o moving part)

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(Ion drag)

(concentration difference)(suction force by high velocity/low pressure)

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Pressure driven pumpMembrane Pump

Rotary Pump

G. Kovacs, Micromachined Transducers Sourcebook, 1998

Diffuser Pump



Ultrasonic Pump

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Electro driven pump (ion drag)Electroosmotic Pump EHD Pump

MHD PumpCapillary Electrophoresis by Electroosmosis pumping

H. Chujo et al., MEMS’03

Lorentz Force pumps fluidF=I×B

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Filters

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Filters


Horizontal

Vertical

H. Sato et.al., MEMS’03

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Flow systems

1. Interconnects

2. Packaging and integration

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Interconnects

Single point Multi point


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Packaging and integration

Snap-together plastic package,injection mold, gluing sealing

Stacking method


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類比微流體系統:

1.Biomedical Sensing System

3. Drug delivery

4. Gas/liquid chromatography

5. Micro Power Generator

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Micro Total Analysis System (µTAS)or Lab on the chip (LOC)

i-STAT’s handheld clinical analyzer and disposable cartridge

Biologixs pH sensor cube and reader

Porton Diagnostic’s potassium sensor and reader


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Drug deliveryMicro needle array

needle+blood sensingASME IMECE’00MEMS’98 P. Griss and G. Stemme, µTAS’02

K. Oka et al., Transducers’01

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微系統科技的應用研究舉例(Bio-MEMS)

Insulin pump (Debiotech, Switzerland)


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Gas/liquid chromatography


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Micro Power GeneratorMicro Fuel cellMicro battery

Bial Fuel cellDirect Methonal Fuel cell

Y. Seo and Y.-H. Cho, MEMS,03 M. Chiao, K. B. Lam, and L. Lin, MEMS,03K. B. Lee, F. Sammoura, and L. Lin, MEMS,03

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Digital Micro Fluidic Systems

1. droplet generation

2. droplet suspension

3. droplet surface manipulation

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Droplet generatorsHP

Sharp, Inc, MEMS 96

Epson

E.S. Kim, USC, MEMS98

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液珠懸浮控制

(S. Nilsson, et. al., µTas’00)

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微液珠平面驅動方式

•微液珠驅動方式:1. 靜電及電潤濕 [2-4] 2. 光驅動法 [5] 4. 固態液體珠 [6]5. 非對稱結構 [8]6. 熱毛細力 [9]7. 結合Marangoni效應, 熱毛細力, 凝結及成核效應[7]

Most of them are employing surface tension gradient!!!

Lee. J, Sensors and Actuators 2002

K. Ichimura, Science, 2002

P. Ausslllous, Nature, 2001

O. Sandre, Physical Review E, 1999

J. C. Chen, Science, 2001

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Electrostatic

(Masao Washizu, IEEE 1998 ) (Altti Torkkeli, IEEE 2001 )

• Very high voltage, • electrolysis problem, • charged bio-molecules may be attracted by electrical field

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Electrowetting

(Sung Kwon Cho, IEEE 2002 )

EWOD (ElectroEetting on Dielectric)

CJ Kim, UCLA

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Moving

Creating

Separation

(Pei Yu Chiou, IEEE 2003)

OWE (Opto-Electrowetting)Electrowetting

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Photonic & SAMs

(K. Ichimura, Science 2000)

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0306090120150180210

0 1 2 3 4 5Distance(mm)

Temperature(℃

) 30V-Xdirection

1mm

0 s

0.5 s

1 s

1.5 s

2 s

4 s

0 s

0.5 s

1 s

1.5 s

2 s

4 s

1 µl 0.1 µl

2 mm 2 mm

•Droplets Moving Behavior

2.17mm

1 µl0.1 µl

Marangoni Effect

Marangoni flow

Capillary flow

TH TL

Temperature distribution

F. G. Tseng et al, Transducer’03

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(Susan Daniel, Science 2001)

Marangoni flow

Capillary flow

TH TL

Marangoni +capillary+ coalesces Effect

Droplet movement ~10 cm/s, 10 times faster

Hydrophilic Hydrophobic

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Surface Roughness

Wettability Switching by Surface Roghness Effect (Bo He, IEEE 2003 )

Winzelγsv

γlv

θ’γsl

Cassie

a b

Water

θγ

γγθ cos

)('cos rr

lv

slsv =−

=

1cos'cos −+= ff θθ

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Superhydrophobic & Gravity

Hydropphobic powder (20µm) coating (Pascale Aussillous, Nature 2001)

Water Droplet Weight 7mg with tilt angle of surface 1°˚ (Masashi Miwa, Langmuir 2000)

Liquid Marble (Powder coating)Superhydrophobic Surface (SAMs)

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(a). Au on glass side+ SAMs

θ＝110.7°˚Hydrophobic SAMs*

θ＝56.7°˚Hydrophilic SAMs (-COOH)

(b) Au on micro posts

θ＝109.9°˚dia: 60μm pitch:40μm

θ＝73.8°˚dia:80μmPitch: 180μm

(c) Au on micro posts+SAMs

θ＝143.6°˚Hydrophobic SAMs*dia: 60μm pitch:40μm

θ＝12.4°˚Hydrophilic SAMs(-COOH)dia:80μmPitch: 180μm

Fan-Gang Tseng, and Shu Chun Chien, “Droplet Movement Induced by Nano Assembled Molecules And Micro Textures “ Nanotech2004

+

SAMs*: CH3(CH2)17SH

Combination of surface roughness and SAM

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Comparasion

Principle Max. Velocity(mm/s)

Droplet Size(µl) Power

Electrstatic(Altti Torkkeli, IEEE 2001) 10 2 ~ 50 Yes(124VAC)

Electrowetting(S. K. Cho, IEEE 2002) 250 1 Yes(100VAC)

Optic(K. Ichimura, Science 2000) 0.035 2 Yes

Temperature Gradient(Susan Daneil, Science 2001) ~ 20 0.001 ~ 1 Yes

Roughness(Bo He, IEEE 2003) ？ 7 No

Gravity(P. Aussillous, Nature 2001) ？ 1 ~ 10 No

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Digital fluidic systems:

1. Biomolecule Micro Array

2. Micro Droplet Systems

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Micro ArraysDNA Micro arrays

Chemically synthesize

Mechanically spot

DNA array system:Standford University, Brown group

Capillary

Tip

Bio-reagent

Glass slideUltrasound wash bath

Petri dishPrintingTip array

Translation stage

(Affymetrix,USA,from transducers source book)

• High throughput• Low volume• High speed screening

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Microdroplet Drug Releasing

Open connection channle

Droplet Volume

B. de Heij et al, MEMS’02

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Digital µTAS or LOC

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Continuous vs. Digital Fluidic system

Continuous digital

1. Components versitle single2. Device complexity complex simple3. fabrication difficult depends4. integratability difficult easier5. Flow sesing/control complex depends6. Flow resistance high low7. Dead volume high low8. reuse difficult possible9. System cost high depends10.Fluid flow enclosure (half)open11.evaporation low high

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Reference

1. G. T. A. Kovacs, “Micromachined Transducers Sourcebook”, McGraw-Hill, 1998

2. Abe Lee, lecture notes UCI-BME 295, 20033. Proceedings of Micro Total Analysis Systems,

98, 00-044. Proceedings of IEEE MEMS conference, 96,98,

02, 035. Proceedings of IEEE Transducers’01, 036. Proceedings of ASME IMECE MEMS, 98, 99,

00.

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Bio-Nano/Micro Fluidic Systems · 2019. 7. 22. · NTHU ESS µ-Nano Bio & fluidics System Lab Prof....

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