The rapid evolution of biosensor technologies has positioned signal amplification strategies as a critical research frontier, driving advancements in detection performance and expanding potential applications. Among various amplification techniques, hybridization chain reaction (HCR) has emerged as a particularly promising enzyme-free, isothermal nucleic acid amplification approach. The HCR mechanism operates through single-stranded DNA initiators that catalyze the alternating hybridization of two metastable hairpin probes, ultimately generating extended double-helix polymers via either linear or branched amplification pathways. Unlike conventional amplification methods, HCR offers superior amplification efficiency while demonstrating remarkable compatibility with nanomaterials and complementary signal enhancement strategies. Although HCR has gained widespread adoption in biosensing applications, existing systems still face notable technical limitations that require. This comprehensive review not only systematically examines these challenges but also provides valuable insights into future development pathways to propel the field forward.
Keywords: Biosensors; DNA technology; Hybridization chain reaction; Signal amplification technique.
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