The biosensing technology plays an important role in environmental monitoring, safety control and medical diagnosis. Precise control of the interaction between bio-recognition probe and the interface is critical to improve the sensitivity, specificity and selectivity of biosensors. In a typical bioprobe immobilization, the heterogeneity of self-assembled monolayers on the surface increases the binding energy barrier and decreases the recognition efficiency and rate. We found that DNA nanostructures, such as tetrahedral DNA nanostructures (TDNs), could increase the homogeneity of self-assembled monolayers via enthalpy-entropy compensation, which enables precise regulation of interfacial property at the nanoscale. By regulating the intermolecular distance of bioprobes, the hybridization efficiency and hybridization rate of DNA probes can be improved significantly. The detection limit of DNA and microRNA can be pushed down to 10 aM limit. The detection limit of antigen detection can be improved to 100 pM and the detection limit of small molecule (cocaine) can be pushed to 33 nM. By using TDNs, we developed a universal detection platform for nucleic acids, proteins, small molecules and cells with superior detection sensitivity. To further use TDN probes in cells and in vivo, we explored the transport pathways of TDNs into the cell and directed their targeting location to specific organelles. We aim to develop DNA nanostructure-based bioprobes for intracellular and in-vivo imaging.

Contents
1 Introduction
2 Physicochemical perspectives on DNA immobilization: enthalpy-entropy compensation
3 DNA hybridization regime on DNA nanostructured biosensing interface
4 Biosensors with designed DNA nanostructures
4.1 Nucleic acids detection
4.2 Protein detection
4.3 Small molecules detection
4.4 In vivo detection
5 Conclusion and outlook