From health monitoring to the detection of diseases, biosensors play a crucial role in our everyday lives. Unfortunately, in many cases, the practical use of biosensors requires costly instruments, time-consuming multi-step procedures and highly trained personnel to implement. Recent years, however, have witnessed tremendous efforts in the development of cheap and miniaturized optical sensing devices that can even be integrated with ubiquitous smartphone sensors and software. These point-of-care sensing approaches could not only facilitate the goal of ‘personalized medicine’ but also bring the diagnostic technology to resource-poor regions of the world where many infectious diseases are so prevalent. This technological boost creates an ever-growing need for new and improved optical biosensors capable of continuous monitoring of analytes in a single-step process with low-cost sensor devices. The development of such biosensors, nonetheless, faces several common challenges. A typical biosensor comprises a molecular recognition unit (e.g. protein or nucleic acid) and a detection unit designed to report this binding event in the form of an optical signal (e.g. as color or fluorescence change). One of the challenges here is to detect rather “inert” analytes that are not able to generate a strong optical signal upon binding to a molecular recognition site. Another challenge is posed by the strength of this molecular recognition interaction, which dictates the useful dynamic range of the biosensor. The ability to extend, narrow and tune this useful dynamic range, could greatly benefit applications where target concentrations span several orders of magnitude (e.g. monitoring progression of viral infections) or where a sharp dose response is essential to achieve high precision (e.g. monitoring of highly toxic substances). The aim of this project was to globally address these challenges by decoupling the molecular recognition and signal transduction units of the biosensor with the help of self-assembled and programmable DNA origami nanostructures. A more specific objective was to demonstrate this fundamental approach by designing a sensitive and tunable biosensor for glucose, whose sensing is of utmost importance for the disease monitoring of diabetic patients. Different biomimicry approaches were proposed to be tested that could lead to strategies to tune the useful dynamic range of the proposed biosensor platform with the aim to achieve sensitivity at a physiologically relevant glucose concentration.
