Rapid genetic screening with high quality factor metasurfaces

Hu, Jack; Safir, Fareeha; Abendroth, John M.; Dixon, Jefferson; Pinsky, Benjamin A.; Jeffrey, Stefanie S.; Lawrence, Mark; Dionne, Jennifer A.

Genetic analysis methods are foundational to advancing personalized and preventative medicine, accelerating disease diagnostics, and monitoring the health of organisms and ecosystems. Current nucleic acid technologies such as polymerase chain reaction (PCR), next-generation sequencing (NGS), and DNA microarrays rely on fluorescence and absorbance, necessitating sample amplification or replication and leading to increased processing time and cost. Here, we introduce a label-free genetic screening platform based on high quality (high-Q) factor silicon nanoantennas functionalized with monolayers of nucleic acid fragments. Each nanoantenna exhibits substantial electromagnetic field enhancements with sufficiently localized fields to ensure isolation from neighboring resonators, enabling dense biosensor integration. Quantitative detection of complementary target sequences via hybridization occurs simultaneously for arrays of sensing elements patterned at densities of 160,000 pixels per cm$^2$. In physiological buffer, our nanoantennas exhibit average resonant quality factors of 2,200, allowing detection of purified SARS-CoV-2 envelope (E) and open reading frame 1b (ORF1b) gene fragments with high sensitivity and specificity (up to 94$\%$ and 96$\%$) within 5 minutes of nucleic acid introduction. Combined with advances in nucleic acid extraction from complex samples (eg, mucus, blood, or wastewater), our work provides a foundation for rapid, compact, and high throughput multiplexed genetic screening assays spanning medical diagnostics to environmental monitoring.