Catalytic hairpin assembly as cascade nucleic acid circuits for fluorescent biosensor: Design, evolution and application

Catalytic hairpin assembly (CHA) with advantages of high efficiency, flexible design, and mild reaction condition is considered a promising molecular amplifier. Modified working principle of CHAs has been coupled with multiples signal generation and signal transductions to develop the diversified fluorescent biosensors. Emerging signal amplification techniques were introduced into CHA to meet the requirement of rapid, sensitive, accurate, and specific point-of-care testing (POCT) in vitro. Moreover, others advanced techniques were integrated with CHA to improve the delivery efficiency, enhance the ability, and accelerate reaction speed for in vivo analysis. Thus, the CHA-based fluorescent biosensor has been applied on varying targets, including nucleic acids, metal ions, small molecules, proteins, enzymes, exosomes, and cells. Herein, the review systematically summarized the design principle, evolution, and application of the biosensors, and then discussed the challenges in depth. The aim was to highlight the importance of developing advanced CHA-based biosensors and promoting their practical application.