The unique biological and physical properties of nucleic acids enable the kinetically programmable assembly of DNA nanostructures and the development of highly efficient signal amplification schemes. Enzyme-free isothermal amplification has spurred substantial research efforts for the development of low-cost point-of-care diagnostics. While the conventional single amplification approach usually leads to linear amplification, it is appealing to construct cascaded circuits that allow for detecting low amount of target. Herein, we introduce a new isothermal autonomous nonlinear enzyme-free signal amplification paradigm for highly sensitive detection of various analytes through the isothermal DNAzyme-amplified two-layered cascaded hybridization chain reaction (C-HCR-DNAzyme) circuit, in which the output of upstream hybridization chain reaction (HCR-1) layer acts as input to activate downstream hybridization chain reaction (HCR-2) layer and the concomitant assembly of catalytically active DNAzyme. As a versatile and robust amplification procedure, the C-HCR-DNAzyme strategy enables a clear discrimination of the target from its mutants with high selectivity. By incorporating a sensing module, this easy-to-integrate “plug-and-play” amplification scheme was further extended for highly sensitive detection of microRNA in buffer, as well as human serum. The infinite layer of multilayered C-HCR-DNAzyme and the avalanche-like hierarchical reaction acceleration are anticipated to further strengthen the amplification capacity of its bioanalytical applications.

Signal amplification based on isothermal autonomous nonlinear hybridization chain reactions

256th National Meeting (2018)

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