Although
the CRISPR/Cas system has pioneered a new generation of
analytical techniques, there remain many challenges in developing
a label-free, accurate, and reliable CRISPR/Cas-based assay for reporting
the levels of low abundance biomolecules in complex biological samples.
Here, we reported a novel CRISPR-derived resonance Rayleigh scattering
(RRS) amplification strategy and logical circuit based on a guanine
nanowire (G-wire) assisted non-cross-linking hybridization chain reaction
(GWancHCR) for label-free detection of lipopolysaccharide (LPS). In
the presence of a target, the protospacer-adjacent motif-inserted
aptamer is rationally designed to specifically combine with LPS rather
than Cas12a, suppressing the trans-cleavage activity of CRISPR/Cas12a
and retaining the reporter probes to trigger non-cross-linking aggregation.
Owing to the automatic hybridization chain reaction (HCR), in the
presence of Mg2+, the released G-quadruplex sequence aggregated
to assemble the G-wire superstructure through non-cross-linking. As
a result, a dramatically amplified RRS intensity is observed, allowing
for reporting LPS levels in a low detection limit of 0.17 pg/mL and
a wide linear range among 1.0–100.0 ng/mL. Moreover, this reaction
event is capable of programming to perform classical Boolean logic
tree analysis, including basic logic computing and complex integrated
logic circuits. This study comprehensively analyzed with respect to
information flow, matter (molecular events), and energy (RRS), revealing
the potential promise in designing of molecular-level “Internet
of Things”, intelligent computing, and sensing systems.