High Contrast Probe Cleavage Detection

Abstract

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.