Researchers at the University of Cambridge in the UK recently published a groundbreaking study in *Nature Nanotechnology*, revealing a new method to detect antibodies using quartz nanopores and DNA-based barcodes. The innovative approach leverages the unique properties of dumbbell-shaped DNA structures, offering a highly accurate and scalable detection system.
In this research, Nicholas Bell and Ulrich Keyser utilized DNA origami techniques to design a structure that carries a digital barcode made up of multiple dumbbell-shaped DNA hairpins. By threading these structures through a nanopore, they were able to read a three-digit barcode with an impressive 94% accuracy. This system was further enhanced by incorporating antigens into the DNA strands, allowing the detection of up to four different antibodies simultaneously.
The team engineered a double-stranded DNA molecule where one strand contained the dumbbell-shaped hairpin structures. These hairpins acted as molecular markers, enabling precise signal detection when passing through the nanopore. To optimize the system, the researchers experimented with varying numbers of hairpins per DNA strand. They found that 11 hairpins per strand provided the best balance between data capacity and signal strength.
Building on this, they developed a three-digit binary system that generated eight unique barcodes. These barcodes were then embedded into DNA carriers that presented specific antigens. The study showed that the presence of antibodies did not significantly interfere with the DNA’s movement through the nanopore, making it possible to accurately detect their presence based on the barcode reading.
To validate the technology, the researchers tested it with biotin, BrdU, and puromycin, successfully detecting antibodies at concentrations as low as 10 nanomolar. They believe this method could revolutionize both scientific research and clinical diagnostics, offering a fast, sensitive, and multiplexed detection platform.
This development follows recent advances in nanopore technology for protein detection. Earlier studies, such as those from the University of Pennsylvania, have explored ways to modify nanopores to accommodate larger proteins, enabling the distinction between monomeric and dimeric forms of certain molecules. The Cambridge team's work now expands the potential of nanopores beyond DNA to include complex biomolecules like antibodies, opening new possibilities for real-time, high-throughput analysis.
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