High-throughput Optical Blood Imaging for the Detection of Rare Cells using Ultrasonic Particle Alignment

Millions of blood samples are analysed in the NHS every year. A wide range of parameters are measured, however there are significant limitations with existing technologies, particularly those relating to the detection of rare cells and bacteria in the blood in a way that permits timely medical intervention.

Modern computers have the power to examine images of billions of blood cells, and flag up those of interest. However, taking images of the cells individually (as is done in some existing machines) is not fast enough, being limited to a few thousand cells per second. In this project we will flow a sample of blood through a tiny chamber and use ultrasound to align all the cells into a single sheet; this key step means that it will be possible for a microscope to take an image of thousands of the cells at once. In this way we predict it will be possible to image around 50,000 cells per second. Without this acoustic focussing, the cells would not all be in focus, and many would overlap with each other.

Working with our partners at Southampton hospital, we shall initially test our system by looking for cancer cells in the blood. Recent research has shown that individual cells from a cancer can become detached and enter the blood stream, and it is in this way that cancers spread to different areas of the body (metastasize). These cells are present in very small numbers - in 10 ml of blood even one tumour cell hidden amongst billions of normal cells could indicate a cancer. Later on in the project we will also consider looking at leukaemia cells, parasite infections (such as malaria), and potentially bacterial infections.

There are several challenges facing the project including creating an ultrasonic force field that is both strong and uniformly focussed, the difficulties of capturing images of the moving stream of blood cells without motion blur, and integrating the image processing to deal with the huge amounts of data that will be produced. The different applications we consider vary enormously in the challenge they present, ranging from the tiny and difficult to manipulate bacteria, through to the much more numerous malaria parasites inside red blood cells.

Given the huge potential health benefits of having our systems made widely available, we will work closely with industrial companies that have experience of creating diagnostic machines to bring our technology into widespread use as soon as possible. Into the future we see many further developments, including systems that are able to capture the rare cells as they are detected, and collaborative research projects with clinical scientists to use our devices to enable new insights into the workings of diseases.

Through this project we seek to create a whole blood imaging system that can detect cancers and blood borne diseases at an earlier stage than is currently possible. For example, detecting the very rare circulating tumour cells (CTCs) that are hidden among the vast numbers of other blood cells, or screening for rare parasites. Ultimately this will lead to lowered death rates and extended quality of life for millions of people both in the UK and worldwide.

This project will pump-prime further research collaborations with biologists and clinicians that will have impact on our understandings of cancers and its treatment. We hope to extend the system in the future to include an active separation stage so that the cells can be isolated and studied in detail. This could help elucidate the mechanisms of the spread of metastatic cancers, and also lead to the development of systems that permit individually targeted treatments for patients.

Since the technology is based upon a blood test that can produce results in under an hour, it is readily applicable to large scale deployment in hospitals and other points of care. The technology lends itself to small, relatively low cost devices (exampled by the disposable acoustic concentration devices that Southampton recently developed for Prokyma Ltd.). This means that it is both feasible and commercially attractive to mass produce a system that can be sold worldwide. Thus, with our partner Leica Microsystems we are in a position to enhance the UK's already strong position in the medical diagnostics market.