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Medicine and Health

Medical diagnostics: the next generation

The breakthrough work achieved by the partners in this project puts Europe well ahead of the USA in the very competitive area of medical diagnostics. MEBIOCE is a medical breakthrough that has already attracted great interest.
Diagnostic techniques for identifying pathogens or cancerous cells need to be very sensitive if they are to identify low levels of contamination or the very early stages of illness. This project has developed a system to identify abnormal cells at concentrations down to a hundredth of those that can be detected by conventional tests.
The three-stage process, which involves tiny magnetic beads, new separation membranes and a computerised image recognition system, brings together two SMEs and a series of university research centres. It should result in a commercial product within the next year.

An illness spotted early usually means quicker, more effective and less costly treatment. As a result, it is not surprising that the subject of new diagnostic tests has become one of the hottest topics in medical research. At the moment, though, there is a trade-off between the sensitivity of a test and the precision of its results. The ideal test would yield quantitative information and yet would be extremely sensitive.
MEBIOCE offers just such a combination. Using powerful new techniques to isolate and count mammalian cells and bacteria, it can measure their concentrations at extraordinarily low levels - down to a hundredth of those possible with current tests. Amongst other things this will mean earlier diagnosis of cancer and less risk of bacterial contamination in food. The project partners estimate that the potential market for their technology could be worth about 21 billion ECU.
MEBIOCE has brought together two SMEs, each with complementary experience in detecting specific types of cells at very low concentrations. Several universities have also contributed to designing and testing the new system, which will be on sale soon. The project's results have already caused considerable interest.

The need to do better

MEBIOCE relies on the fact that many diseases and disease-causing organisms can be identified by the cells they leave behind. The bloodstream of someone suffering from a bacterial infection contains cells of the organism itself, whilst in the case of a cancer patient the tell-tale markers are damaged versions of the patient's own cells. Either way, locating these abnormal cells is an important first step towards identifying the illness.
Early in the course of an illness the number of abnormal cells can be very small, so the detection system must be sensitive. An existing technique, DNA analysis using the polymerase chain reaction, is sensitive but time consuming, gives little information about the number of abnormal cells present and doesn't preserve the cell when visual confirmation is essential in medical diagnosis. Another technique, flow cytometry, yields quantitative information but is not very sensitive.
There is a similar compromise in the methods used to detect bacterial contamination of food and water. Traditional cultures are quantitative and allow the cells to be examined further using other techniques, but they take several days to do. Newer indirect methods based on the presence of the chemical ATP are much quicker, but are not quantitative or specific, often lack sensitivity and damage the cells so that they cannot be examined further. There is clearly room for improvement.
The project began in 1994 with two main partners. The French partner BIOCOM, which coordinated the project, contributed its expertise in cell separation and image recognition systems. The Norwegian company Dynal is one of the specialists, using magnetic beads for biological separations.

An attractive approach

The MEBIOCE system uses a three-stage approach, first capturing cells with immuno-magnetic beads and collecting them in a flow separator, then concentrating them using special membrane filters, and finally, using computer-based image-recognition technology to pick out and characterise those that are of interest.
Dynal is an SME founded in 1986 to develop magnetic bead technology, otherwise known as immunomagnetic separation. The company makes its magnetic beads from polymers mixed with tiny grains of iron oxide. These are then covered with a smooth layer of polymer to which proteins and other biological molecules can stick. A further layer, this time of antibodies, increases the system's precision by attracting only particular types of cell.
The beads stand the best chance of coming into contact with very rare cells if they are very tiny and used in large quantities, thus providing the maximum surface area to mix with the sample. The smaller the beads, however, the more difficult they are to separate in the next stage of the process, so a compromise is needed. The best size of beads has proved to be just under three micrometres in diameter.
After mixing the beads with the sample of blood or other material to be tested, the next task is to separate them so that they can be analysed. In theory this is simple - just apply a powerful magnet and the beads will move towards it - but previous methods have been slow and labour-intensive. BIOCOM has developed the first automated magnetic separation system (CELF), based on a long spiral tube through which the sample flows continuously. When a nearby electromagnet is switched on, the beads stick to the walls of the tube. When the magnet is switched off the beads can be flushed out of the tube and on to the next stage of the process.
The cells are then concentrated and the beads removed using advanced filters developed at the Catholic University of Louvain. The filters are made from microporous polymers. As well as separating they can also serve as culture media for mammalian cells, helping to reduce the need for animal experiments.

Improving the image

The final step is image analysis to identify and count the harmful cells. BIOCOM, which employs about 20 people, has been working in this area since 1986 and is an European leader, having installed more than 400 image analysis systems. Each uses a microscope attached to a video camera to view the sample. A computer then analyses the shapes, colours and contrasts in the video image, decides which represent cells of different kinds, and counts them.
The MEBIOCE system, however, is different. Instead of a microscope it uses an approach borrowed from astronomy, where researchers use long photographic exposures to reveal distant stars. BIOCOM's device (ASTERIAS) uses a highly sensitive video camera and long exposures to build up a picture of an entire sample at once. This, says the company, is simpler and quicker than assembling several hundred separate images obtained through the limited field of view of a microscope.
BIOCOM has developed two image analysers using this principle: one for research laboratories and another targeted at rapid analyses in hospitals and industry. Both have the ability to work at different wavelengths, so samples can be examined with both visible light and, for instance, ultra-violet fluorescence. The multiple-wavelength approach is an important aid to characterising cells accurately.

Ahead of the USA

Another project partner, the University of Nantes, and four other French universities - Marseilles, Nice, Compiègne and Lyons - are now testing the system. Full evaluation for medical diagnostics may take a further two or three years, but in the meantime the partners plan to market a system for measuring microbiological contamination. Promising markets are the analysis of food and drinking water, and control of sterility in the pharmaceutical industry.
Once the system has proven itself in the medical field, detecting micrometastases - potential nuclei for new cancers - and making non-invasive genetic antenatal diagnosis are two of its most likely applications. The magnetic beads could even potentially be used to remove harmful cells as well as to detect them; blood given by donors, for example, could be cleansed of undesirable cells before being used for transfusions. The total demand for the new tests is estimated to be 60 million tests a year.
The work has already generated a lot of interest, and the partners believe that they are ahead of the USA in this highly competitive field. Such an innovative project, they say, would not have been possible without both the contacts and the money provided by BRITE-EURAM.


Project Title:  
Ultra high sensitivity integrated detection technology for cellular and bacteriological qualification and control with bioselective polymers

Industrial and Materials Technologies (BRITE-EURAM/CRAFT/SMT)

Contract Reference: BE-7899

Cordis DatabaseFor more information on this project,
go to the CORDIS Database Record