Engineering Modular and Tunable Single Molecule Sensors by Decoupling Sensing from Signal Output

Biosensors play key roles in medical research and diagnostics, but there currently is a lack of sensing platforms that combine easy adaptation to new targets, strategies to tune the response window to relevant analyte concentration ranges and allow for the incorporation of multiple sensing elements to benefit from multivalency. Utilizing a DNA origami nanostructure as a scaffold for arranging the different sensor components, we here propose an approach for the development of modular and tunable single-molecule sensors capable of detecting a variety of biomolecular targets such as nucleic acids, antibodies and restriction enzymes while offering mechanisms to tune the dynamic window, the specificity, and the cooperativity of the sensor.