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New tool could easily detect cancer protein marker, viruses

Aug 18, 2023

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Researchers have developed a tiny biochip composed of silicon blocks that hold the potential to conduct rapid genetic screening of thousands of molecules.

According to a Science report, this tool could possibly identify over 160,000 distinct molecules in a single square centimeter of space.

This innovative technology has implications in a wide range of medical areas, including cancer protein marker detection and clinical diagnostics of respiratory infections.

Most genetic test sensors depend on monitoring light absorption or emission from targeted molecules designed to bind to the target gene.

These methods employ polymerase chain reaction to generate numerous copies of the target before attempting to identify it, which increases the cost and duration of the testing.

Moreover, the previous genetic screening sensors were unable to identify a wide variety of target compounds and required optical tagging to detect target sequences.

Stanford University authors wrote in the study: “We introduce a label-free genetic screening platform based on high quality (high-Q) factor silicon nanoantennas functionalized with nucleic acid fragments.”

To develop this tool, the scientists used an optical detecting technology based on metasurfaces made of small silicon boxes. These tiny silicon arrays measure approximately 500 nanometers in height, 600 nanometers in length, and 160 nanometers in width.

Silicon boxes can focus near-infrared light on their top surface thanks to the nanoantennas. “These metasurfaces consist of subwavelength nanoantennas that strongly confine light in the near field while affording precise control over the far-field scattering,” explained the study.

As per Science, this approach allows a basic optical microscope to measure the shift in wavelength of light emanating from each silicon block, which varies depending on the molecules on top of the boxes.

To put the tool to the test, the researchers attached 22 nucleotide-long single-stranded gene snippets to silicon boxes and submerged the array in a buffer solution.

When the complementary DNA strands were introduced to the solution, they immediately joined the tethered ones, shifting the wavelength of light emitted from the surface of each box.

According to the author, this tool can easily identify 4000 copies of target genes per microliter.

The results were published in the journal Nature Communications.

Study abstract:

Genetic analysis methods are foundational to advancing personalized medicine, accelerating disease diagnostics, and monitoring the health of organisms and ecosystems. Current nucleic acid technologies such as polymerase chain reaction (PCR) and next-generation sequencing (NGS) rely on sample amplification and can suffer from inhibition. Here, we introduce a label-free genetic screening platform based on high quality (high-Q) factor silicon nanoantennas functionalized with nucleic acid fragments. Each high-Q nanoantenna exhibits average resonant quality factors of 2,200 in physiological buffer. We quantitatively detect two gene fragments, SARS-CoV-2 envelope (E) and open reading frame 1b (ORF1b), with high-specificity via DNA hybridization. We also demonstrate femtomolar sensitivity in buffer and nanomolar sensitivity in spiked nasopharyngeal eluates within 5 minutes. Nanoantennas are patterned at densities of 160,000 devices per cm2, enabling future work on highly-multiplexed detection. Combined with advances in complex sample processing, our work provides a foundation for rapid, compact, and amplification-free molecular assays.

Study abstract: