High Contrast Probe Cleavage Detection

Dubrovsky, Michael; Blevins, Morgan; Boriskina, Svetlana V.; Inc., Diedrik Vermeulen SiPhox; Cambridge,; MA,; USA,; Technology, Massachusetts Institute of

Photonic biosensors that use optical resonances to amplify biological signals associated with the adsorption of low-index biological markers offer high-sensitivity detection capability, real-time readout, and scalable low-cost fabrication. However, they lack inherent target specificity and can be sensitive to temperature variations and other noise sources. In this letter, we introduce a concept of the High Contrast Probe Cleavage Detection (HCPCD) mechanism, which makes use of the dramatic optical signal amplification caused by cleavage of large numbers of high-contrast nanoparticle labels instead of the adsorption of low-index biological molecules. We illustrate numerically the HCPCD detection mechanism with an example of a silicon ring resonator as an optical transducer with gold and silicon nanoparticles as high-contrast labels. Simulations show that it is possible to detect a single cleavage-event by monitoring spectral shifts of micro-ring resonances. Furthermore, detection specificity and signal amplification can be achieved through the use of collateral nucleic acid cleavage caused by enzymes such as CAS12a and CAS13 after binding to a target DNA/RNA sequence.