Micropillars for Direct Measurements of Blood Clot Formation (MEP)

Background

If we sustain a wound, an intricate blood clotting system acts to prevent bleeding by plugging the wound with an elastic network containing fibrin polymers and platelets. Proper regulation of the fibrin-platelet interaction is crucial to prevent bleeding disorders, however dysregulation can lead to thrombosis, the formation of a clot in a blood vessel which can block blood flow. Additionally, a piece of the clot can break off, known as embolisation, and travel through the bloodstream leading to issues such as ischaemic stroke. There is a particular risk of embolisation during revascularisation techniques which aim to remove the occluding blood clot.

Platelets exert large contractile forces during clot formation that govern the final structural and mechanical properties of thrombi. To date, no quantitative measurements have been made to measure these contractile forces; as such, there is little information on how these forces affect the final properties of the thrombus. The aim of this project is to develop a novel miniaturized device capable of time-resolved in situ measurements of the forces that the platelets exert during clot formation.

Objectives

The central questions this M.Sc. project will address are: 

  1. how does blood clot composition affect platelet-driven contraction during formation? 
  2. how does platelet-driven contraction affect the mechanical properties of the blood clot and its risk of embolisation? 

The answers to these questions will provide key insight into blood clot mechanics and will lead to improvements in revascularisation techniques to prevent stroke.

Proposed Approach
You will combine biochemical reconstitution of artificial, biomimetic thrombi with control over compositional parameters such as red blood cell, fibrin and platelet concentrations (TUD, 3ME), fabrication of PDMS micropillar devices to measure contractile forces (TUD, EWI), and biophysical characterization using a microscale-indentation device (TUD, TNW).

Supervision

This exciting multidisciplinary project that encompasses bioengineering, microfabrication and biophysics entails a close collaboration between three labs at TU Delft:

  • Gijsje Koenderink, Faculty of Applied Sciences (TNW), Bionanoscience Department
  • Frank Gijsen, 3ME, Department of Biomechanical Engineering
  • Massimo Mastrangeli, EWI, Department of Microelectronics

You will be supervised on a daily basis by Iain Muntz, a postdoc in the Koenderink lab and linking pin between the 3 groups. Additionally, Milica Dostanić from the Mastrangeli lab and Rachel Cahalane from the Gijsen lab will be involved in hands-on training and supervision.

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