Blood spot

Approaching a million people in the UK are being treated with the oral anticoagulant Warfarin to reduce the risk of stroke and other blood clot related conditions. An easy to use nanotechnology-based disposable sensor is being developed that could ensure their treatment regime is effective or detect incipient clots from just a tiny pinprick sample of blood.

Prof Rhodri Williams, a specialist in rheology and fluid mechanics in

school of engineering, is leading the NHS,

and

-funded project to develop the device, which will use zinc oxide (ZnO) nanowire transducers. His team has been working in the field of blood-clot detection for a number of years and has previously established the Clinical Haemorheology Laboratory in Morriston, just outside Swansea.

'The problem with current methods is that there are no established techniques that will detect clots at such an early stage as ours, and none of them interrogate the microstructure of the clot,' said Williams.

'We're not only interested in the fact the clotting time will vary in response to the underlying disease states or therapeutic intervention, we're interested in the fact that clots that do form are subtly altered in terms of their fractal microstructure. By better understanding this, you might be able to ameliorate the dosages or even change the therapeutic regime to better address the particular characteristics of clots in individuals.'

The device will use a wave propagation technique that the researchers have already developed, which in its present form uses relatively large amounts of blood and requires technical and medical know-how to use.

'Although the amounts are not actually all that large — less than a millilitre of blood is drawn from a vein — we see an opportunity to work with far smaller amounts, down to even the sub-pinprick level,' added Williams. 'But in order to do that we will need a step change in the sensitivity of the transduction techniques that we're using. The ZnO nanowires hold great promise in that they would effect this change in sensitivity, which would then allow us to make virtually disposable devices operating on tiny volumes of blood.'

The sensor detects the arrival of a shear wave — a transverse wave that propagates at relatively low audio frequencies in blood as it undergoes coagulation. The waves are designed to reflect at specially constructed surfaces. Knowing when those waves arrive at the surface and are reflected gives an estimate of the stress that the wave is imparting on the surface and thus the structure and density of the clot.

The ZnO nanowires have a piezoelectric property that can be used to determine certain characteristics of the shear waves as they impinge upon and are reflected from the surfaces.

'The beauty of these nanowires is that because of their size we can put literally millions of them together, and each one added increases the sensitivity of the device by a proportionate amount,' said Williams. 'Because they are very small, you can keep the overall size and volume of the device very small, yet maintain the requisite level of sensitivity that we are seeking.'

The device will initially be used in the team's hospital with the aim of being transitioned to pharmacies and ultimately for home use so testing can be carried out in a less stressful environment for patients.

'Making disposable but very reliable sensors for home use is a grand challenge in that we've not only got to overcome the various technical and clinical aspects of the work, but we've also got to ensure that there will be patient compliance in using these techniques,' added Williams. 'This means you have to build as much intelligence into the device as possible, and we have brought on board an expert in human device interface for medical technology.'

Alongside the development of technology using the ZnO nanowires to detect shear wave propagation in visco-elastic materials such as coagulating blood, a parallel effort at Morriston is building a database of the basic rheological responses on coagulating blood in the patient groups in the study.

By the project end in 2012, the team aims to demonstrate that this nanotechnology-based sensing device is viable and can produce clinically relevant data on real patient blood using embedded intelligence to help manage stroke and determine the effectiveness of anticoagulation therapeutic regimes.

'One of the biggest challenges is working with patients,' said Williams. 'I'm used to working with well-behaved samples of fluid where I can simply modify the properties thermally or chemically. People have very complex responses in terms of their body's coagulation to the underlying pathologies.'