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Investigation of Fluid Behavior in Bifurcated Microfluidic Chambers

Investigation of Fluid Behavior in Bifurcated Microfluidic Chambers. Joel Ramey Advisor: Dr. David Schmidtke. Outline. Motivation Making the apparatus Experiments Results Implications Future work. 8um diameter. http://www.ladinfo.org/wbc-rbc-large-B.jpg. Motivation. Monocytes.

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Investigation of Fluid Behavior in Bifurcated Microfluidic Chambers

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  1. Investigation of Fluid Behavior in Bifurcated Microfluidic Chambers Joel Ramey Advisor: Dr. David Schmidtke

  2. Outline • Motivation • Making the apparatus • Experiments • Results • Implications • Future work 8um diameter http://www.ladinfo.org/wbc-rbc-large-B.jpg

  3. Motivation Monocytes Endothelial cells Pool of fat Smooth muscle cells • 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/Image:Carotid_Plaque.jpg

  4. How do monocytes penetrate Ley et al…Immunology 2007

  5. Why bifurcations Fox & Hugh, Heart 1966 Ku et al. Atherosclerosis. 1985

  6. 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

  7. 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

  8. PDMS stamps • Clean pattern • Pour PDMS over over pattern • Cure PDMS • Peal from pattern http://faculty.washington.edu/afolch/images/Project_3DPDMS0.jpg

  9. 1st semester • Created new masks • Initially transparencies • Inherent limitations • Flow experiments • Bead adhesion shows promise • More new masks • Chrome

  10. 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

  11. Investigation of flow • Ran initial flow experiments with 6um beads • Ran with 30º and 120º bifurcations • Analyze flow Sarvepalli

  12. 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

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

  14. Questions?

  15. Atherosclerosis Monocytes Endothelial cells Pool of fat Smooth muscle cells 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.

  16. 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

  17. How do monocytes penetrate Ley et al…Immunology 2007

  18. 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

  19. 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.

  20. 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

  21. Malek et al. J.A.M.A 1999 Skilbeck et al. Biorheology 2001 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

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

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