A microfluidic device that mimics physiological conditions in blood cells could aid the study of sickle cell anaemia.

Sickle cell anaemia is a genetic blood disorder, characterised by red blood cells that take on an abnormal, rigid, sickle shape. The disease affects millions, particularly in sub-saharan Africa and southern Asia, and can lead to painful crises, tissue damage and early death. The sickle shape is caused by a conformational change in mutant hemoglobin that occurs after oxygen is released in the tissues provoking haemoglobin polymerization. The cell deformation occurs in less than a second after deoxygenation making it difficult to study using existing techniques.

Now, two teams led by Antigoni Alexandrou (Laboratory for Optics and Biosciences, Ecole Polytechnique, CNRS, INSERM) and by Charles Baroud (Laboratory for Hydrodynamics, Ecole Polytechnique, CNRS) in Palaiseau, France, have developed a microfluidic tool to study the effects of deoxygenation on haemoglobin polymerisation. They show that using a platform of water droplets in oil on a chip, the amount of oxygen in the cells contained in the droplet can be controlled by varying the oxygen within flowing microdroplets as the carrier oil can act as a sink or source of oxygen. Polarised light microscopy is used to detect polymerised haemoglobin fibres, which allows distinction between sickle cells and normal cells.

Red blood cells are encapsulated in microfluidic drops, while the carrier oil provides transport but also acts as an oxygen sink

'This approach allows many independent experiments to be performed in series, while providing a way for the cells' mechanical and biochemical environment to be precisely controlled,' says Baroud. Since a small number of cells can be enclosed in one droplet, this approach can serve as a general system to isolate and measure the behaviour of single cells, following changes in the environment or addition of biochemical reagents, he adds.

'This work is a good example of new information that may be obtained by combining clever optical techniques with confined geometries namely, picoliter droplets in oil,' says Aaron Wheeler, an expert in lab-on-a-chip devices for bioanalysis from the University of Toronto, Canada. 'I imagine that this tool could be useful for biologists who are studying sickle cell anaemia and trying to determine how to prevent it,' he adds.

Alexandrou's and Baroud's teams are hopeful that their device will help shed new light on the mechanisms involved in the disease and will provide a way to explore the effects of potential drugs on sickle cells. The major challenge will then be to build on this new technology to develop innovative treatments, they say.

Philippa Ross 

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