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Making Diagnostics Quick and Mobile

Biametrics is a spin-off from the University of Tübingen that focuses on the commercialisation of innovative developments in the field of label-free bioanalyses. The company's platform detects interactions between biomolecules using reflectometric interference spectroscopy (RIfS) and can be integrated into small mobile analytical devices.

The chip used in the biosensor system was developed in the BMBF-funded MoDekt project, a cooperative project between the University of Stuttgart (IPE and ITO), IMS Chips Stuttgart, the IPTC at the University of Tübingen and the University Hospital of Tübingen. (© Biametrics)

Quick, robust and inexpensive at the same time as having very low detection limits - this sounds too good to be true. Biametrics' label-free analysis platform offers all these advantages, making it interesting for use in clinical diagnostics and pharmaceutical drug development, as well as safety testing for pathogens, for example at airports. Label-free analyses have the overall advantage that they do not alter the natural activity of the objects under investigation, in this case any kind of biomolecule, as a result of the labelling of the molecules with specific markers.

The basis of Biametrics' technology had already been developed back in the 1990s by a group of researchers led by Prof. Dr. Günter Gauglitz at the University of Tübingen. That is where the two company founders and Biametrics managing directors met: Dr. Günther Proll and Florian Pröll were both investigating optical biosensor systems using reflectometric interference spectroscopy, RIfS for short. Pröll explains the principle of RIfS: "In materials with different optical characteristics, light is partially reflected and partially passes through the boundaries of two different materials. The reflected rays superimpose on each other, i.e. they interfere with each other in relation to their wavelength. This leads to changes in the reflected light pattern." The two Biametrics' managing directors use soap bubbles to explain the processes: here, interferences result in the fact that some colour components are no longer visible and the colour changes, thereby causing the soap bubble to shine brightly.

Light reflection for qualitative and quantitative analyses
Optical biosensors involve carrier materials such as glass or plastics that allow light to pass through. To enable two materials to interact, the scientists coat glass or plastics surfaces in order to attach molecules with which the reaction partner, which is either dissolved in the sample solutions or bound to the surface of cells, can subsequently interact. The optical properties of the layer will change upon the interaction of the dissolved molecules with the molecule bound on the glass/plastics surface. These changes can be measured with RIfS. “We started off using the methods developed in Gauglitz's department, expanded them further and added proprietary developments. Since 2007, we own a patent portfolio that protects our developments,” said Proll.

A lot of work was needed to develop the company's proprietary surface chemistry. “The key question for us was how could we firmly attach a molecule on the glass carrier in a way that enabled it to remain functional, i.e. to recognise its interaction partner and interact with it,” said Pröll. “The second challenge was to coat the surfaces in a way that would prevent us from measuring unspecific artefacts,” said Proll. The procedure has since achieved a high degree of maturity and is able to detect molecule concentrations as small as one picogramme per square millimetre surface area.

Cooperation secures market access
Biametrics works with bigger companies to sell its innovative sensor technology. These sales partners are focused on specific markets, including diagnostics for example. Proll explains Biametrics' business model: “Basically, we sell a system solution, we sell licences for our technology and we accompany the development of devices. This means that we work closely with manufacturers who are seeking to adapt their products to the specific requirements of our technology. In addition to this, we also develop new applications.”

Biametrics sees the greatest application potential of its technology in the fields of human and veterinary medicine. Using in vitro diagnostics as an example, Pröll explains the advantages of the system: We coat a surface with an antibody and expose the carrier to a blood or serum sample. When potential partners are present in the blood or serum, they will bind to the antibodies on the carrier. This interaction can be measured both qualitatively and quantitatively. In order to do this, we need a second antibody and do not need any washing steps that would lead to false-negative results due to the low affinity of the binding partners.” The direct method means that the interaction can be measured rapidly while also saving on reagent costs. Automation, and hence increase in throughput, can quickly generate high reagent costs.

Biametrics makes diagnostics quick and mobile
Since RIfS enables the time-resolved analysis of samples, the method also provides information about the kinetics of the interactions between the biomolecules: “We can determine the dissociation and association constants of the antibodies and use these data to determine their affinity. This is particularly important in the diagnosis of immune diseases where the affinity of the antibodies correlates strongly with the disease,” said Proll. These data are also important for the development of therapeutic antibodies and more generally for the development of biopharmaceutical drugs. Proll uses complex therapeutic proteins and peptides to explain: “The kinetics tells us how quickly, how often and how strongly these substances bind to the target. This defines the half-life of drugs,” said Proll.

The speed of Biametrics' technology might also contribute to the technology's breakthrough in non-clinical applications. As pathogens such as influenza viruses for example are able to spread around the world in a very short time, “homeland security” has become an excellent market for bioanalytical applications. “For example, a quick assay to test airport passengers for the presence of virus particles would be extremely interesting. At the moment, we are focusing on further developing our proprietary technology to enable such tests to be carried out in less than five minutes,” said Pröll.

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