Sensor/assay development

Affimers and active binders

Many tests rely on the concept that proteins used to identify disease (biomarkers) are captured by antibodies or antibody mimetics (artificial peptides or proteins designed to act like antibodies). A biosensor is a device that converts the capture of a biomarker into an output that can be read by the user. The binding of an antibody/antibody mimetic to a biomarker is a passive event and in itself does not lead to an easily detectable signal. Instead, binding leads to a local change in the electrical properties of the sensor’s surface, which is measurable. However, while antibody-biomarker binding is generally highly specific (i.e. not prone to interference), changes in electrical properties upon binding of biomarkers can be small, with the consequence that manufacturing procedures are challenging and it is expensive to minimize batch-to-batch variations of the sensors. As there is an ever-increasing demand for better, more reliable, and faster detection of biomarkers, active antibody mimetics will be developed, which still exploit the specificity of antibody mimetics, but expand the way the biomarker can be detected.  The “capture” and “detection” elements can be combined at the molecular level to create an “active” enzyme-switch sensor, which directly translates biomarker binding into a signal. We have developed such a system, utilizing Affimer affinity reagents, a class of non-antibody binding protein. Affimers have been selected against key biomarker targets including C-reactive protein, procalcitonin and C. difficile toxin B. Applicability to rapid diagnostics is confirmed by the rapid (results in minutes), simple, and sensitive quantification of analytes in biological samples, along with consistency with other, well established tests, robust batch-to-batch reproducibility and stability at fridge and room temperatures.

The ultimate aim is to combine the biosensor with sample handling fluidics so that the test will be performed on a miniaturised scale “on-chip” so that a portable diagnostic device can be created.