Rapid genetic screening with high quality factor metasurfaces

TL;DR

This paper presents a rapid, label-free genetic screening platform using high-Q silicon nanoantennas that enables high-throughput, amplification-free detection of specific gene sequences with high sensitivity and specificity.

Contribution

The authors develop a dense array of high-Q silicon nanoantennas for multiplexed, amplification-free genetic detection, achieving high sensitivity and rapid results in complex samples.

Findings

Detects gene fragments down to femtomolar concentrations

Achieves high specificity in clinical samples within 5 minutes

Supports dense array integration with 160,000 pixels per cm²

Abstract

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. We quantitatively detect complementary target sequences using DNA hybridization 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 two gene fragments, SARS-CoV-2 envelope (E) and open reading frame 1b (ORF1b), down to femtomolar concentrations. We also demonstrate high specificity sensing in clinical nasopharyngeal eluates within 5 minutes of sample introduction. Combined with advances in biomarker isolation from complex samples (e.g., mucus, blood, wastewater), our work provides a foundation for rapid, compact, amplification-free and high throughput multiplexed genetic screening assays spanning medical diagnostics to environmental monitoring.