A natural biomaterial promotes hybridization chain reaction for ultra-sensitive detection of miRNA-155.

MicroRNA (miRNA) is an important biomarker for early diagnosis of cancers. However, sensitive and convenient methods for miRNA detection remain a challenge. Here, we use a natural biopolymer sporopollenin purified from Ganoderma lucidum spores as a substrate for isothermal amplification (hybridization chain reaction, HCR). Sporopollenin capsules (SP) promotes HCR and forms longer and more abundant double-stranded DNA (dsDNA) than graphene oxide (GO) and carbon nanotubes (CNTs). The nanoporous structure of sporopollenin capsules containing abundant water provides a hydrous environment and enhances the hybridization efficiency of DNA significantly. We construct an ultrasensitive fluorescent biosensor to detect miR-155. The efficient HCR amplification on SP leads to an ultralow detection limit of 1 aM for miR-155 and a wide linear range of 1 aM-10 fM (R = 0.99). Furthermore, our fluorescence biosensor can discriminate miRNA mutants with high selectivity. This biosensor is also highly sensitive in human serum (detection limit 10 aM). It adsorbs less serum protein than GO and CNTs, thus minimizing the interference caused by the non-specific adsorption. Our study would promote medical application of SP-based biosensor in the future.