Near-infrared (NIR)-responsive bioassays based on upconversion
nanoparticle (UCNP) incorporating high-performance semiconductors
have been developed by researchers, but most lack satisfactory ultrasensitivity
for exceedingly trace amounts of target. Herein, for the first time,
the CRISPR/Cas13a system is combined with cascade DNA circuits, fluorescent
resonance energy transfer (FRET) effect, and luminescence-confined
UCNPs-bonded CuInS2/ZnO p–n heterostructures-functionalized paper-working electrode
to construct dual-signal-on paper-supported NIR-irradiated photoelectrochemical
(PEC) (NIR-PEC) and upconversion luminescence (UCL) bioassay for high-sensitive
quantification of miRNA-106a (miR-106a). By constructing an ideal
FAM-labeled aminating molecular beacon (FAM-H2) model, a relatively
good FRET ratio between the UCNP and FAM (≈85.3%) can be achieved.
In the existence of miR-106a, the hairpin-structure FAM-H2 was unwound,
bringing about the distance increase of UCNP and FAM and the restraint
of FRET. Accordingly, both the NIR-PEC signal and the UCL intensity
gradually recovered distinctly. Unlike conventional single-mode PEC
sensors, with NIR excitation, the designed dual-mode sensing system
could implement minimized misdiagnose assay and quantitative miR-106a
determination with low detection limits, that is, 76.54 and 51.36
aM for NIR-PEC and UCL detection, respectively. This work not only
broadens the horizon of application of the CRISPR/Cas13a strategy
toward biosensing but also constructs a new structure of the UCNP-semiconductor
in the exploration of efficient NIR-responsive tools and inspires
the construction of a no-misdiagnosed and novel biosensor for dual-mode
liquid biopsy.