Identifying blood groups by using modular sensors? A joint study by scientists of the Austrian Centre of Industrial Biotechnology (acib) in Graz and the Centre de Recherche sur les Macromolécules Végétales (CERMAV, CNRS) in Grenoble has brought this vision a step closer to reality. The scientists used non-natural amino acids to equip a receptor, with the help of which bacteria attach themselves to human cells, with the affinity for specific blood groups. These receptors could soon form the basis of biosensors capable of determining blood groups. This novel approach was published recently in the renowned scientific journal ACS Chemical Biology.
The identification of blood groups in overview
The surfaces of our red blood cells are coated in blood group antigens. These coatings made from sugar molecules 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 Rh system. These blood group antigens also have a property that is suggested by their name: namely that antibodies can be formed against them. This is especially important for blood transfusions, where it is vital to ensure the donated blood comes from a compatible donor group. If donor and recipient blood are incompatible, serious transfusion reactions or an immune reaction can occur, the blood clots and this can lead to the death of the patient. Precise determination of the blood group is thus of critical importance.
Tests until now inadequate and inflexible
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 such as compatibility testing for blood transfusions can be handled in an inexpensive, fast and unambiguous manner using classic serological tests.
The situation is altogether different for determining individual special characteristics including family relationships, congenital variants in blood group properties or for clinical symptoms with Rhesus incompatibility. In these cases, serological tests are totally 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. It is in this major problem area that molecular-biological methods such as DNA analyses have proved to be very promising. Nevertheless, there still are numerous disadvantages in these genotyping methods: they are not only expensive and time-consuming, but also have only been possible at fixed specific locations until now. This rules these methods out for use in blood donor facilities or mobile blood donation stations.
Biosensor technology identifies even rare antigens
The new biosensor technology developed by acib and French researchers may soon allow analysis of the entire patient erythrocyte antigen range in both a significantly shorter time and location-independent. “To manufacture a biosensor, we need a receptor as the basis, and one which 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", acib key-researcher Birgit Wiltschi explains, and she adds: “These glycoproteins bind to the sugar molecular structure of the blood cells where they absorb and pass on information in much the same way as a news-gathering radio station, and they trigger biochemical reactions with this information.” While these receptors are able to recognize sugar chains, they are not specific enough by nature to work as biosensors and clearly recognize and determine different blood antigens. This is the challenge. In order to "fine tune" the lectins, the researchers replaced some individual amino acids using biotechnological methods. They brought in fluorinated molecules and proteins were produced, which hold the fluorine atoms at precisely pre-determined positions. Wiltschi: “In the course of our work it was seen that the fluorine atoms influence the receptor structure, as a result the affinity of the receptor for the oligo-saccharides (sugar polymers) was increased for blood group A.” With this finding research has been brought an important step closer to clear and unambiguous determining of the rarer blood group antigens.
Diagnostic systems and target-specific therapeutic substances
This novel research approach from synthetic glycobiology is opening up new possibilities for the production of receptors for modular detection systems. Programmable biosensors of this kind have enormous potential not only in medical diagnosis, but also for environmental analysis, and they can make comprehensive blood tests in significantly shorter time a reality within the near future.
About the project
The SynBiocarb Project is being carried out in the scope of the EU-Horizon2020 Programme, with a funding volume of € 4 million over a period of 48 months. The project brings together 14 partners from research and industry, including acib GmbH, Graz University of Technology and the University of Natural Resources and Life Sciences, Vienna. The partners are carrying out joint work on synthetic glycobiology approaches for diagnostic applications and target-specific therapeutic substances.
The Austrian Centre of Industrial Biotechnology (acib) is an international Research Centre for Industrial Biotechnology with locations in Vienna, Graz, Innsbruck, Tulln, Vienna (A), Hamburg, Heidelberg, Bielefeld (D), Pavia (I) and Barcelona (E), Canterbury (AUS), New Zealand (NZL) and Taiwan. Using the concepts of nature, acib-scientists replace traditional industrial methods with new, more economic and ecological technologies.
Actually, acib is an international network of 150+ international universities and industry partners, including BASF, DSM, Sandoz, Boehringer Ingelheim RCV, Jungbunzlauer or VTU Technology. Owners are the Universities of Innsbruck and Graz, Graz University of Technology, the University of Natural Resources and Life Sciences, Vienna and Joanneum Research.
At acib 250+ scientific employees with up to 30+ years of experience in industrial biotechnology work in more than 170 research projects. The competence center acib is sponsored within COMET (Austrian Competence Centres for Excellent Technologies) by the BMVIT, BMWFW and the provinces of Styria, Tyrol, Lower Austria and Vienna. The COMET program is handled by the FFG