Details of Grant 

EPSRC Reference:	EP/C52845X/1
Title:	Flow, Margination and Adhesive Interaction of Blood Cells with the Vessel Wall - an Interdisciplinary Approach
Principal Investigator:	Barigou, Professor M
Other Investigators:	Nash, Professor G Thornton, Dr C
Researcher Co-Investigators:
Project Partners:
Department:	Chemical Engineering
Organisation:	University of Birmingham
Scheme:	Standard Research (Pre-FEC)
Starts:	01 September 2005	Ends:	30 November 2008	Value (£):	475,679
EPSRC Research Topic Classifications:	Medical science & disease
EPSRC Industrial Sector Classifications:	Healthcare
Related Grants:
Panel History:
Summary on Grant Application Form
Blood is a complex mixture of particles (red blood cells, white blood cells, platelets) suspended in a liquid called plasma. While red blood cells circulate continually to deliver oxygen to all parts of the body, the white blood cells and platelets have to stick to the wall of blood vessels to carry out their protective functions. White cells do this so they can crawl into tissue and protect us against invading bacteria, viruses and fungi. Platelets stick to the wall of injured blood vessels to help stop bleeding. Effective adhesion is thus essential for our health. Unfortunately, these adhesive interactions can become disorganised in a number of diseases, and instead of being protective, they can cause blockage and damage in blood vessels. This happens, for example, in the build up to a heart attack. Given the importance of adhesion, it may be surprising that we lack understanding of key stages in its initiation: (i) the motion of white cells and platelets as they move from the blood stream to contact the vessel wall; (ii) the effects of the flowing blood on the efficiency with which they attach to the wall; (iii) how these interactions are influenced by the properties and local flow conditions of the blood. Because of the important roles of blood particle deposition in the initiation and progression of blood vessel diseases, hard data and efficient computational models are needed to effectively identify the key physical properties of the circulation which influence adhesion in its different regions.This research proposal seeks to develop novel theoretical approaches to predict the motion of white blood cells and platelets in the bloodstream and their adhesive interaction with the vessel wall, and to test the predictions made by the theory using realistic experiments. The project proposes to address the problem at the micro-level using the novel approach of Discrete Element Modelling (DEM). Currently, this is the most suitable approach for the simulation of the highly discontinuous phenomena found in flowing liquids which contain many particles. However, it has only seen very limited application to blood flow. The DEM method deduces the overall behaviour of the particles in suspension not by considering it as a whole, but by observing the individual behaviour of each particle, in particular, localizing collisions among the particles and modelling the actual contact between two particles. Because of the computational difficulties of resolving millions of deforming cellular interfaces, no one to date has simulated realistic blood flows at such a microstructural level.Experimentally, we will observe the detailed microscopic structure of blood flow in small glass channels using a new generation of micro-Particle Imaging Velocimetery (micro-PIV) which can measure the position of particles (or cells) and how fast they are moving in model vessels with a diameter less than a millimetre, with accuracy at the micron (one-millionth of a metre) level. This is the most appropriate and most accurate technique in space and time currently available for probing blood flow in vessels as small as those where most adhesion occurs. It will yield detailed information on the flow field (velocities at any moment in any region, forces acting in the flow, particle collision velocities, particle flow regimes, particle-free layer near the wall etc.) that will allow the DEM simulations to be validated.This proposal is intended to be the first of a series of projects which seek to develop a complete theoretical description of the physical processes which underlie platelet and white cell adhesion in different regions of the circulation. Ultimately, we aim to arrive at a detailed understanding of the critical physical factors in initiation and expansion of disease processes, and thus to identify those responses which may be changed to improve health.
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Organisation Website:	http://www.bham.ac.uk