Biosensors are a type of important biodevice that integrate biological recognition elements,such as enzyme,antibody and DNA,and physical or chemical transducers,which have revolutionized clinical diagnosis especially under the context of point-of-care tests.Since the performance ofa biosensor depends largely on the bio-solid interface,design and engineering of the interface play a pivotal role in developing quality biosensors.Along this line,a number of strategies have been developed to improve the homogeneity of the interface or the precision in regulating the interactions between biomolecules and the interface.Especially,intense efforts have been devoted to controlling the surface chemistry,orientation of immobilization,molecular conformation and packing density ofsurface-contined biomolecular probes (proteins and nucleic acids).By finely tuning these surface properties,through either gene manipulation or self-assembly,one may reduce the heterogeneity of self-assembled monolayers,increase the accessibility of target molecules and decrease the binding energy barrier to realize high sensitivity and specificity.In this review,we summarize recent progress in interfacial engineering ofbiosensors with particular focus on the use of protein and DNA nanostructures.These biomacromolecular nanostructures with atomistic precision lead to highly regulated inteffacial assemblies at the nanoscale.We further describe the potential use of the high-performance biosensors for precision diagnostics.