Embedding Proteins within Spatially Controlled Hierarchical Nanoarchitectures for Ultrasensitive Immunoassay

Modulating the precise self-assembly of functional biomacromolecules is a critical challenge in biotechnology. Herein, functional biomacromolecule-assembled hierarchical hybrid nanoarchitectures in a spatially controlled fashion are synthesized, achieving the biorecognition behavior and signal amplification in the immunoassay simultaneously. Biomacromolecules with sequential assembly on the scaffold through the biomineralization process show significantly enhanced stability, bioactivity, and utilization efficiency, allowing tuning of their functions by modifying their size and composition. The hierarchically hybrid nanoarchitectures show great potential in construction of ultrasensitive immunoassay platforms, achieving a three order-of-magnitude increase in sensitivity. Notably, the well-designed HRP@Ab₂ nanoarchitectures allow for optical immunoassays with a detection range from picogram mL^-1 to microgram mL^-1 on demand, providing great promise for quantitative analysis of both low-abundance and high-residue targets for biomedical applications.