  Photonic biosensors that use optical resonances to amplify signals from
refractive index changes offer high-sensitivity, real-time readout, and
scalable, low-cost fabrication. However, when used with classic affinity assays
they struggle with noise from non-specific binding and are limited by the low
refractive index and small size of target biological molecules. In this letter,
we introduce the High Contrast Cleavage Detection (HCCD) mechanism, which makes
use of dramatic optical signal amplification caused by the cleavage of large
numbers of high-contrast nanoparticle reporters instead of the adsorption of
labeled or unlabeled low-index biological molecules. We evaluate the advantages
of the HCCD detection mechanism over conventional target-capture detection
techniques when using the same label and the same photonic biosensor platform
and illustrate numerically the possibility for attomolar sensitivity for HCCD
using an example of a silicon ring resonator as an optical transducer decorated
with silicon nanoparticles as high-contrast reporters. In the practical
realization of this detection scheme, detection specificity and signal
amplification can be achieved via collateral nucleic acid cleavage caused by
enzymes such as CRISPR Cas12a and Cas13 after binding to a target DNA/RNA
sequence in solution.
