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Herein we propose a hybridization chain reaction based kinetics competition strategy able to recognize the combination/sequence of input signals. Further, a DNA priority encoder and a keypad lock were constructed. This strategy allowed us to develop a one-pot assay that can automatically and smartly respond to multiple inputs.

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The extremely low abundance of circulating tumor DNA in blood samples has limited the development of liquid biopsy techniques for the early diagnosis of major diseases. In this study, we demonstrate a DRN-based screening technique, SCREEN, which achieves the specific capture and enrichment of low abundance SNV nucleic acid samples without selective amplification. The SCREEN technique achieved a 108-fold increase in the abundance of single-nucleotide variant (SNV) nucleic acids from highly homologous mixtures (from 0.01% to 1.08%) and has been shown to significantly increase the abundance of SNV nucleic acids from 0.1% to 51% further through two rounds of capture. As a highly effective pre-enrichment technique, SCREEN has demonstrated the ability to enhance NGS in detecting an ultralow abundance SNV nucleic acid powerfully and has high compatibility with existing molecular diagnostic methods.