Modular dna origami platform for the design of tunable glucose biosensor
Biosensors play a crucial role in our everyday lives from health monitoring to disease detection. The rapid advancement of sensing technologies dictates an ever growing need for improved biosensors which are capable to continuously monitor analytes in a single-step process and yield low-cost devices. The performance of many biosensors is, however, limited by the binding strength of their molecular recognition unit which dictates the dynamic range of the sensor and is often tightly connected to the signal transduction unit, i.e. its signal output. In this project, I propose to globally solve this limitation by decoupling the molecular recognition and signal transduction units of the biosensor by exploiting self-assembled and programmable DNA origami nanostructures. This fundamental approach will be demonstrated by the design of a sensitive and tunable biosensor for glucose, whose sensing is of utmost importance for the disease monitoring of diabetic patients. DNA origami will be utilized to precisely position all biosensor elements:  multifluorophore FRET pair, which will serve as a signal transduction and amplification unit as well as glucose/galactose binding proteins and glucose functionalities, which will provide a molecular recognition unit. Different biomimicry strategies to tune the useful dynamic range of the biosensors will be evaluated aiming to achieve sensitivity at a physiologically relevant glucose concentration. Finally, the potential to combine these advanced glucose biosensors with low-cost read-out instruments (such as smartphone cameras) will be assessed. The DNA origami glucose sensor proposed here is of great promise for the development of wearable and low-cost glucose sensing devices for diabetes monitoring, which will grow into a large demand in our society. Moreover, it will allow me to merge DNA nanotechnology, molecular biology, spectroscopy and chemistry research, laying the foundations upon which to build my future career in Europe.