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Micro-fluidic Biochips for trans-endothelial migration of eosinophils for the study of asthma

Final Activity Report Summary - ASTHMA (Microfluidic Biochips for transendothelial migration of eosinophils for the study of asthma.)

According to the World Health Organization (WHO), '300 million people suffer from asthma and 255 000 people died from asthma in 2005.' Asthma is a condition that affects all countries regardless of their development and is considered to be the most common chronic disease among children. The causes of asthma are complex with genetic and environmental factors playing important roles. Modern understanding of asthma is of a complex series of events leading to inflammation in the lungs characterised by airway narrowing and mucus overproduction leading to airflow limitation. Steroids play an important part in the treatment of asthma as they help to prevent the inflammation in the airways of the lungs. Unfortunately, they can also cause many unpleasant side effects and some patients do not benefit from their use. A type of white blood cell called the eosinophil causes much of asthmatic inflammation. Eosinophils are not normally present in healthy lungs but an asthmatic person's symptoms worsen as more eosinophils enter their lungs. Here, they release many substances damaging to the lining of the airway which also stimulate the release of large quantities of mucus leading to many of the symptoms of asthma such as wheezing, breathlessness and tightness in the chest.

The important role of eosinophils in asthma has resulted in a great deal of research effort to understand the mechanisms that control their entry from the blood vessels into the tissues of the asthmatic lung. One of the main aims of this project between Cellix and the University of Aberdeen was to investigate the multi-step cascade which results in recruitment of free-flowing eosinophils in the bloodstream to adhered cells on the walls of microcapillaries and subsequent transmigration through the microcapillary wall into the tissues of the lungs (i.e. the inflammatory process involving eosinophils).

Eosinophils are difficult cells to work with in the laboratory as normally they are only present in very small numbers in the blood. Thus, large volumes of blood are required to ensure sufficient numbers of eosinophils can be isolated from volunteer donors to conduct meaningful experiments. Part of Cellix's expertise is the ability to deal with microlitre sample volumes (i.e. small volumes of cells or whole blood). Because of this, assays investigating eosinophil recruitment could be conducted with only milliliter blood sample volumes collected from donors. An additional advantage is that the volume of expensive reagents required for each experiment is also greatly reduced.

Together, researchers from the University of Aberdeen and Cellix, worked on the development of a biochip that facilitated the study of how eosinophils move from the blood vessels into the tissues of the lungs in asthma. The research involved prototyping the biochip which resulted in several iterations before a working model was successfully established. Following this, a series of validation experiments or assays were conducted to compare to standard, known results with larger volumes (this was done with a number of cell types including T cells or cell lines). Once the protocol had been optimised, experiments were conducted that investigated the adhesion of eosinophils to microcapillaries in the biochip that mimicked the dimensions of those found in the human body while also investigating the effect of compounds that could inhibit this adhesion, migration and transmigration steps that characterise in the inflammatory process.