Investigation of Fluid Behavior in Bifurcated Microfluidic Chambers

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Investigation of Fluid Behavior in Bifurcated
Microfluidic Chambers

• Joel Ramey
• Advisor Dr. David Schmidtke

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Outline

• Motivation
• Making the apparatus
• Experiments
• Results
• Implications
• Future work

8um diameter
http//www.ladinfo.org/wbc-rbc-large-B.jpg
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Motivation

• What is a Leukocyte?
• White blood cell
• Why is adhesion important?
• Inflammation
• Thrombosis
• Atherosclerosis
• 1 million deaths/year

David W. Schmidtke
http//en.wikipedia.org/wiki/ImageCarotid_Plaque.
jpg
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How do monocytes penetrate
Ley et alImmunology 2007
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Why bifurcations
Fox Hugh, Heart 1966
Ku et al. Atherosclerosis. 1985
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Research Aim

• Take advantage of established microfabrication
  techniques to study fluid dynamics with different
  geometries.
• Easy to implement
• Plethora of available geometries

David W. Schmidtke
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Photolithography Procedure
Transfer of a geometric shape from a photomask to
a substrate

• Substrate Cleaning (glass slide)

• Layer of Photoresist
• (negative photoresist)

• Aligning the Mask

• UV Exposure

• Develop

David W. Schmidtke
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PDMS stamps

• Clean pattern
• Pour PDMS over
• over pattern
• Cure PDMS
• Peal from pattern

http//faculty.washington.edu/afolch/images/Projec
t_3DPDMS0.jpg
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1st semester

• Created new masks
• Initially transparencies
• Inherent limitations
• Flow experiments
• Bead adhesion shows
• promise
• More new masks
• Chrome

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Apparatus
Bead suspension (100 x 103 beads/mL)
Polystyrene beads. 6, 10, 20 um diameters
Flow chamber
Syringe Pump Controls shear stress
Video Camera
Microscope
VCR
Monitor
Computer
Schmidtke
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Investigation of flow

• Ran initial flow experiments with 6um beads
• Ran with 30º and 120º bifurcations
• Analyze flow

Sarvepalli
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Future

• Look more closely at fluid dynamics in main
  branch
• Run computational fluid dynamics for actual
  pattern
• Analyze flow with beads at apex
• Run experiments with leukocytes
• Look into using pulsatile flow

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Acknowledgments

• Dr. Schmidtke
• Travis Spain
• Phillip Coghill
• Alex
• Dr. Johnson
• Dr. Keay

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Questions?
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Atherosclerosis
Disorder of the large arteries.
Atheroma formation accumulation of fatty
substances, cholesterol and cellular waste
products.

• Major cause of morbidity in the United States
• Affects close to 60 million Americans
• Contributes to 33 of all deaths in U.S each
  year.

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In vitro

• Advantages
• Watch experiment in real time
• Process has high degree repeatability
• Control over variables
• Disadvantages
• Geometric constraints
• Not an actual artery
• Different surfaces

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How do monocytes penetrate
Ley et alImmunology 2007
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Predominant human anatomic sites for the
localization of atherosclerotic lesions
High Shear Region (15-50dyn/cm2)
Low Shear Region (0-4dyn/cm2)
Cross section of the carotid sinus
Carotid artery
Stagnation Point
DeBakey et al. Ann. Surg. 1985
Ku et al. Atherosclerosis. 1985
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Schematic sudden expansion flow chamber. H,
chamber height downstream of expansion h chamber
height upstream of expansion S, gasket
thickness x coordinate parallel to glass slide
y, coordinate normal to glass slide.
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Research Aim
Take advantage of the microfabrication
technologies to study the pattern of cell
adhesion and rolling at bifurcated geometries

• Techniques easy to implement

• Many different geometries are available

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Previous Studies

• In vivo Models

Ramos et al. Circ Res. 1999 Westrick et al.
Circulation 2001

• Computational simulation

Malek et al. J.A.M.A 1999 Berger et al. Ann. Rev.
Fluid Mech. 2000

• Glass models of bifurcations

Karino et al. J. Biomechanics 1990 Pedersen et
al. Biomechanics 1992 Malinauskas et al.
Atherosclerosis 1998

• Sudden Expansion Flow Chambers

Barber et al. Am. J. Physiology 1998 Skilbeck et
al. Biorheology 2001 Skilbeck et al. Arterioscler
Thromb Vasc Biol. 2001
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In vivo

• Uses mice to study adhesion
• Advantages
• Genetically tailored
• Real results
• Disadvantages
• Cannot watch in real
• time
• Fluid mechanics not
• observed
• More variability