Non-Classical Hybridization Chain Reactions

Hybridization chain reaction (HCR), as an enzyme-free and isothermal molecular signal amplification technique, has been used to construct powerful biosensing platform for multiple kinds of targets. However, biosensors based on conventional HCR (cHCR) suffered slow kinetics and insufficient sensitivity from the low efficiency of free hairpins linear cross hybridization in surrounding solution. To achieve super-fast and ultrasensitive monitoring target molecules, non-classical HCRs (ncHCRs) have been gradually developed by combining cHCR with other signal amplified tools, designing the new probes polymerization modes and changing hairpins spatial distribution. In this review, we categorized ncHCRs into three types, including cascaded linear HCRs, nonlinear HCRs and localized HCRs. Working principles and applications of ncHCR is detailed discussed to show its advantages such as excellent sensitivity, stable signal output, and ideal reaction time in vitro & vivo. Finally, we also give a perspective about the current challenges and future development of ncHCRs.