Implementation of a Device for Assessing Dosage for Platelet Glycoprotein Inhibitors

1. Implementation of a Device for Assessing Dosage for Platelet Glycoprotein Inhibitors Steven A. Jones, Yuri Lvov, Tianhong Cui, Bruce Walters Sachin Sah, Kanvasri Jonnalagada, Jeremy Klein

2. PLATELETS • Blood Coagulation • Vasoconstriction, vessel repair, immune response • Defects lead to bleeding disorders • Can enhance atherosclerosis, heart attack, unstable angina, diabetes, stroke, eclampsia

3. Platelet Anatomy

4. The Idea

5. What Does the Cardiologist Want? • Glycoprotein Inhibitors (e.g. abciximab). • What is the proper dose for this heart patient? • Has an appropriate dose been reached? • Does this patient need GP Inhibitors?

6. Analysis of Need • "It is not possible to use in vitro assays for more direct measurement of platelet viability and hemostatic function on a regular basis, because they are difficult to perform, expensive, and time-consuming” Holme et al., Transfusion, V. 38, 1998

7. Inlet Outlet Channel Plexiglass Plates PDMS Nano Coating The Current Implementation

8. Fabrication of channels Thermal Oxide Silicon Substrate UV Mask Negative Photoresist Silicon Oxide Develop Etch Silicon Oxide Etch Silicon to 150 μm Cast PDMS mold

9. Flow Experiment

10. Early Images of Platelet Adhesion on Fibrinogen 147/s 385/s 2091/s 3990/s 6000/s 7000/s

11. Platelet Coverage vs. Shear

12. Adhesion Patterns at 20 dynes/cm2 Fibronectin Fibrinogen vWf

14. Conclusions • Adhesion over various proteins can be observed. • LbL Assembly • Fluorescent Staining/Microscopy • Adhesion is shear dependent. • Adhesion patterns depend on the protein substrate used.

15. Future Work • Other substrates • Varieties of platelets • Quantification of adhesion patterns • In vivo testing

16. Acknowledgements • Sachin Sah • Kanvasri Jonnalaggada • Ameya Kantak • Bruce Gale • David Mills • James Spaulding • Mike McShane • Hua Ai • IfM Staff