Introduc)on

 to  Microfluidics  
Fluid  Flow  in  Small  Length  Scales  
 

With input from Turgut Fettah Kosar

 What  is  Microfluidics?  
“Microfluidics  is  the  field  studying  the  science  and  
engineering  of  any  system,  sub-­‐system  or  device  
that  incorporates  fluids  being  manipulated  in  
micrometer  length  scale  in  at  least  one  
dimension.”  
 
A  box  of  useful  tools  for  research  and  engineering  
than  a  discipline  in  itself!  

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 What  is  Microfluidics?  
•  Study  of  fluid  flows  and  design  of  components  such  
as  conduits,  valves,  pumps,  mixers,  interconnects  on  
micrometer  (micron,  µm)  length  scales  
•  One  dimension  between  1µm  and  999µm  
 (1inch  =  25,400µm;  diameter  of  hair  ≈  50µm)  
•  Interdisciplinary  field:  engineering,  physics,  
chemistry,  biology,  materials  science,  biotechnology  
•  Took  off  early  1990s  
•  Commercial  products  

3  
Example:  PCR  from  Fluidigm  Chip  
9216 dynamic qPCR
reactions on one chip!

http://www.fluidigm.com/chips-kits.html
4  
 Why  Microfluidics?  
Small volume Reduced cost

Repeating units Less waste

Parallel measurements Faster assays

Batch fabrication Higher data quality

Modularity Better statistics

MEMS integration Convenient packaging

Automation Compact footprint

Unobserved phenomena Single cell/molecule assays

Subcellular domains Mimic in vivo µ-environment

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 Why  Microfluidics?  

1.  High-­‐Throughput  Benefits  

2.  Quan)ta)ve  Benefits  
3.  Small-­‐Scale  Benefits  
–  Microscale  Phenomena  

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 Why  Microfluidics?  
Example:  Miniaturiza)on  in  Cell  Biology  

Manual  Labor  
Lab  and  Bench  Space   Large  Number  of  Cells  

Expensive  Equipment  
Reagents  and  Supplies  
Microfluidic  Device   7  
 Things  you  cannot  do  in  macro!  

•  Example:  Manipula)on  of  individual  cells  by  

dielectrophoresis  (DEP)  

http://www.youtube.com/watch?v=_nJCLxbiiNs&feature=related 8  
 Things  you  cannot  do  in  macro!  

•  Example:  Digital  Microfluidics  

–  Westervelt  Group  –  Harvard  University  

http://www.youtube.com/watch?v=nXnmvG6Lxyg (Lab Chip, 2008, 8, 81-87) 9  

Digital Microfluidics

hlp://www.youtube.com/watch?
v=nXnmvG6Lxyg  
 
Manipula)on  of  individual  cells  by  
dielectrophoresis    
hlp://www.youtube.com/watch?
v=_nJCLxbiiNs&feature=related  
 
 
  10  
 Things  you  cannot  do  in  macro!  

•  Example:  Droplet  Generator  

WATER

OIL OIL

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 Applica)ons  of  Microfluidics  
•  Biological  Assays  
•  Chemical  Analysis  
•  Chemical  Sensing  
•  Biochemical  and  Drug  Delivery  
•  Cellular  and  Molecular  Separa)on  
•  Material  Synthesis  
•  Op)cs  

Dynamically reconfigurable liquid-core liquid-cladding lens in a microfluidic channel” Sindy K. Y. Tang,

Claudiu A. Stan and George M. Whitesides, Lab Chip, 2008, 8, 395–401
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 Applica)ons  of  Microfluidics  
Microfluidics  

Lab-­‐on-­‐a-­‐Chip   Sensing  and   Cell  and   Biomedical  and  

Systems   Detec)on   Molecular  Biology   Clinical  

Microanalysis  in   Sensors/Detectors   Cells,  Proteins,  and   Clinical  Monitoring,  

Chemistry  and  Biology   •  Physical  sensing:  resis)ve,   Nucleic  Acids   Implants  
•  Sample  Pretreatment:   capaci)ve,  induc)ve,   •  Cells:  micro  cultures,   •  Monitoring:  diagnos)c  
resonant  
filtra)on,  extrac)on   adhesion,  manipula)on,   assays,  flow  cytometry,  
•  Biological  sensing:  
•  Sample  Introduc)on:   electropora)on,  lysis,   microdialysis,  catheter-­‐
bioreceptors  (an)bodies,  
hydrodynamic,   proteins,  nucleic  acids,   cell-­‐based  sensors   based  sensors,  point-­‐of-­‐
electrokine)c   enzymes)   •  Proteins:  immunoassays,   care  diagnos)cs  
•  Separa)ons:   •  Chemical  sensing:   enzyma)c  assays   •  Implants  and  bioelectric  
chromatography,   electrochemical   •  Nucleic  acids:   interfaces:  implantable  
electrophoresis   (amperometry,   purifica)on,   MEMS  devices,  drug  
voltammetry,   hybridiza)on,   delivery,  implantable  
conductometry),  op)cal   amplifica)on,   sensors,  )ssue  
(absorbance,  fluorescence,   sequencing   enginering  
chemiluminescence,  
colorimetric),  mass  
spectrometry  

Good references: “Introduction to BioMEMS” by Albert Folch and “Biomedical Microsystems” by Ellis Meng
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 Why  are  surfaces  important?  

1.  Small  number  of  atoms/molecules:  bulk  vs.  

surface  
2.  Enhanced  mobility:  
   Dsurf  >>Dbulk  
3.  Higher  energy  state  due  to  dangling  
(unsa)sfied)  or  strained  bonds.  
–  Higher  reac)vity  

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 Macroscale  versus  Microscale  

Diameter: 1 10-1 10-2 10-3

Surface Area: 1 10-2 10-4 10-6
Volume: 1 10-3 10-6 10-9
Weight: 1kg 1gr 1mg 1µg

Surface/Volume: 1 10 102 103

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 Macroscale  versus  Microscale  

Diameter: 1d 10-1d 10-2d 10-3d

Surface Area: 1A 10-2A 10-4A 10-6A
Volume: 1V 10-3V 10-6V 10-9V
Weight: 1kg 1gr 1mg 1µg

Surface/Volume: 1 10 102 103

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 Scaling  Laws  
Smaller  Length  Scales  –  Different  Physics  
•  Things  start  behaving  differently  as  we  gradually  
shrink  their  sizes.  
•  Forces:  body,  surface  and  line  
•  Forces,  quan))es  and  phenomena  propor)onal  to:  
–  volume  (L³)  become  less  significant.  
–  area  (L²)  become  more  important.  
–  length  (L)  start  to  dominate.  
L³   L²   L  
  gravity,   drag    (viscous),   surface  tension  
  iner)al  forces,   surface  charge,   “capillary  ac)on”  
  buoyancy   fric)on  
Examples:  
•  S)c)on:  electrosta)c  or  Van  der  Waals  over  gravity/
iner)a  
•  Capillary  ac)on:  surface  tension  over  gravity  
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Passive  Pumping  by  
Surface  Tension  

18  
 Passive  Pumping  by  
Surface  Tension  
Laplace Pressure
(Young-Laplace Equation):

1 1
ΔP ≡ Pin − Pout = γ ( + )
R1 R2
For bubbles and droplets:
R1=R2=R

2γ
ΔP =
R

(From: Young and Beebe, Chem. Soc. Rev., 2010, 39, 1036–1048)
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 Channel  Transi)ons  
•  Try  to  make  smooth  transi)ons  when  channel  
width  changes  (unless  the  sharp  transi)on  has  
a  func)onal  purpose).  

Good Transition too sharp!

May create eddies.
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 Peclet  Number:  Pe  
vw v: average fluid velocity
Pe = w: characteristic width of channel
D D: mass diffusion coefficient

•  Compares  transport  of  a  certain  species  in  

the  liquid  by  advec)on  (mo)on  of  liquid)  to  
that  by  diffusion.  
•  Approximately,  Pe  indicates  the  minimum  
length  of  channel  in  “w”  units  for  the  two   w

streams  to  be  completely  mixed:  

•  The  higher  Pe,  the  longer  the  channel  needs   Pe·w

to  be  for  complete  mixing.  

21  
 Ac)ve  Mixing  Example  
Microstirrer: a piece of ferromagnetic wire

(Video taken during the 2014 Microfluidics Workshop at University of Notre Dame) 22