Biosensors for blood grouping

3D image of red blood cells

Biosensors may soon facilitate the analysis of a patient’s entire red blood cell antigen repertoire. In the form of diagnostic test strips, they could make the analysis swift and location-independent. This could have enormous potential not only in medical diagnosis, but also for environmental analysis if extended to other analytes.

The surfaces of our red blood cells are coated in blood group antigens. These coatings are made from sugar molecules that differ from each other and define a total of 35 blood group systems. The best known of these are the blood groups A, B, AB and 0 and also the Rhesus system. The blood group antigens have an important property that is suggested by their name: Antibodies can be formed against them. This is particularly important for blood transfusions, where it is vital that the blood groups of the blood donor and the recipient are compatible. If donor and recipient blood are incompatible, serious transfusion reactions or an immune response can occur. Blood clotting due to incompatible blood groups can be fatal for the patient. The precise determination of the blood group is thus of critical importance.

Until now, tests for the AB0 group system, Rhesus factor and antibody screening tests including cross-matching blood group determination have been necessary. Routine analyses can be handled in an inexpensive, fast and safe manner using classic serological tests. However, the analysis is much more complicated when individual blood group characteristics are determined: These include family relationships, congenital variants in blood group properties or clinical symptoms with Rhesus incompatibility. In these cases, serological tests are inadequate. An examination for the rarer antibodies, for example, can be like the proverbial search for a needle in a haystack since more than 100 million potential variants are involved. Molecular-biological methods such as DNA analyses have proved to be very promising in this regard. Nevertheless until now, these genotyping methods have a number of disadvantages. They are expensive and time-consuming, and they are offered only by specialized labs.

Biosensor technology identifies even rare antigens

Biosensors may soon combine the benefits of serological tests and DNA analyses and facilitate the analysis of a patient’s entire red blood cell antigen repertoire independently of a specialized lab and in significantly shorter time. The biosensor is based on a receptor that is capable of recognizing the different surface structures of the blood group antigens. Receptors of this kind are found naturally in the form of lectins. These proteins bind to the sugar molecules of the blood group antigens and they ‘read’ the structure of the sugar. This information is passed on to trigger biochemical reactions, much in the same way as a news-gathering radio station. While these receptors are able to recognize sugar chains, they are often not specific enough by nature to work as biosensors and to specifically recognize and identify different blood antigens. In order to “fine tune” the lectins, scientists at the Austrian Centre of Industrial Biotechnology (acib) and the Centre de Recherche sur les Macromolécules Végétales (CERMAV, CNRS) in Grenoble replaced particular amino acids by fluorinated analogues using biotechnological methods. In this way, fluorine atoms were introduced at precisely pre-determined positions, which modulated the affinity of the receptor for the oligo-saccharides (sugar polymers), e.g. for blood group A.

Such programmable biosensors have enormous potential not only in medical diagnosis, but also for environmental analysis. With these biosensors swift, low-cost tests for a number of analytes with sugar moieties could become a reality in the future.

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