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

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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

  • 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


The idea

The Idea


What does the cardiologist want

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?


Analysis of need

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


The current implementation

Inlet

Outlet

Channel

Plexiglass Plates

PDMS

Nano Coating

The Current Implementation


Fabrication of channels

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


Flow experiment

Flow Experiment


Early images of platelet adhesion on fibrinogen

Early Images of Platelet Adhesion on Fibrinogen

147/s

385/s

2091/s

3990/s

6000/s

7000/s


Platelet coverage vs shear

Platelet Coverage vs. Shear


Adhesion patterns at 20 dynes cm 2

Adhesion Patterns at 20 dynes/cm2

Fibronectin

Fibrinogen

vWf


Conclusions

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.


Future work

Future Work

  • Other substrates

  • Varieties of platelets

  • Quantification of adhesion patterns

  • In vivo testing


Acknowledgements

Acknowledgements

  • Sachin Sah

  • Kanvasri Jonnalaggada

  • Ameya Kantak

  • Bruce Gale

  • David Mills

  • James Spaulding

  • Mike McShane

  • Hua Ai

  • IfM Staff


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