By combining biosensor microscopy that provides high contrast for detecting individual biomolecules with novel biochemistry methods that can effectively turn each target molecule into many digitally-counted sensing events, it is possible to achieve attomolar-scale limits of detection for cancer-specific nucleic acid target molecules (miRNA and ctDNA) while simultaneously obtaining thousands-to-one selectivity against single base variants. The presentation will describe the use of photonic metamaterials and associated detection instruments to amplify optical absorption and fluorescence emission. The biodetection technology platforms are used to perform assays using nucleic acid strand displacement reactions and CRISPR/Cas chemistry to sense target biomarkers from complex media. The “amplify-then-digitize” approach represents a new and powerful paradigm for molecular diagnostics, compared to the “digitize-then amplify” approach utilized in methods such as droplet digital PCR (ddPCR). Overall, we seek simple, rapid, room temperature, single-step assay methods that can be operate with small, inexpensive, and robust detection systems for applications in point of care diagnostics, laboratory-based diagnostics, and life science research applications.

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Brian T. Cunningham, "Ultrasensitive and ultra selective liquid biopsy: nanophotonics-driven digital resolution biomolecule sensing combined with target molecule recycling," Proc. SPIE 12373, Optical Biopsy XXI: Toward Real-Time Spectroscopic Imaging and Diagnosis, 1237304 (Presented at SPIE BiOS: January 31, 2023; Published: 6 March 2023); https://doi.org/10.1117/12.2659440.