Implementation of a device for assessing dosage for platelet glycoprotein inhibitors
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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. PLATELETS. Blood Coagulation Vasoconstriction, vessel repair, immune response

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Implementation of a device for assessing dosage for platelet glycoprotein inhibitors
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


Platelets
PLATELETS Glycoprotein Inhibitors

  • Blood Coagulation

  • Vasoconstriction, vessel repair, immune response

  • Defects lead to bleeding disorders

  • Can enhance atherosclerosis, heart attack, unstable angina, diabetes, stroke, eclampsia


Platelet anatomy
Platelet Anatomy Glycoprotein Inhibitors


The idea
The Idea Glycoprotein Inhibitors


What does the cardiologist want
What Does the Cardiologist Want? Glycoprotein Inhibitors

  • 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?


Analysis of need
Analysis of Need Glycoprotein Inhibitors

  • "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


The current implementation

Inlet Glycoprotein Inhibitors

Outlet

Channel

Plexiglass Plates

PDMS

Nano Coating

The Current Implementation


Fabrication of channels
Fabrication of channels Glycoprotein Inhibitors

Thermal Oxide

Silicon Substrate

UV Mask

Negative Photoresist

Silicon Oxide

Develop

Etch Silicon Oxide

Etch Silicon to 150 μm

Cast PDMS mold


Flow experiment
Flow Experiment Glycoprotein Inhibitors


Early images of platelet adhesion on fibrinogen
Early Images of Platelet Adhesion on Fibrinogen Glycoprotein Inhibitors

147/s

385/s

2091/s

3990/s

6000/s

7000/s


Platelet coverage vs shear
Platelet Coverage vs. Shear Glycoprotein Inhibitors


Adhesion patterns at 20 dynes cm 2
Adhesion Patterns at 20 dynes/cm Glycoprotein Inhibitors2

Fibronectin

Fibrinogen

vWf


Conclusions
Conclusions Glycoprotein Inhibitors

  • Adhesion over various proteins can be observed.

    • LbL Assembly

    • Fluorescent Staining/Microscopy

  • Adhesion is shear dependent.

  • Adhesion patterns depend on the protein substrate used.


Future work
Future Work Glycoprotein Inhibitors

  • Other substrates

  • Varieties of platelets

  • Quantification of adhesion patterns

  • In vivo testing


Acknowledgements
Acknowledgements Glycoprotein Inhibitors

  • Sachin Sah

  • Kanvasri Jonnalaggada

  • Ameya Kantak

  • Bruce Gale

  • David Mills

  • James Spaulding

  • Mike McShane

  • Hua Ai

  • IfM Staff


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