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Biosensor chip detects single nucleotide polymorphism wirelessly, with higher sensitivity

Illustration of graphene-based SNP detection chip wirelessly transmitting signal to a smartphone. Credit: Lal et al

A chip that can detect a type of genetic mutation known as a single nucleotide polymorphism (SNP) and send the results in real time to an electronic device, such as a smartphone, has been developed by a team led by the University of California (UC), San Diego.

According to the team, their chip is at least 1,000 times more sensitive at detecting an SNP than current technology and could lead to cheaper, faster and portable biosensors for early detection of genetic markers for diseases such as cancer.

The UC researchers point to several limitations of traditional SNP detection methods: they have relatively poor sensitivity and specificity; they need amplification to get multiple copies for detection; they require the use of bulky instruments; and they cannot work wirelessly.

The new DNA biosensor is a wireless chip that's smaller than a fingernail and can detect an SNP that's present in picomolar concentrations in solution, the UC team says.

"Miniaturised chip-based electrical detection of DNA could enable in-field and on-demand detection of specific DNA sequences and polymorphisms for timely diagnosis or prognosis of pending health crises, including viral and bacterial infection-based epidemics," says Professor Ratnesh Lal of UC.

The chip essentially captures a strand of DNA containing a specific SNP mutation and then produces an electrical signal that is sent wirelessly to a mobile device. It consists of a graphene field effect transistor with a specially engineered piece of double stranded DNA attached to the surface. This piece of DNA is bent near the middle and shaped like a pair of tweezers. One side of these so-called "DNA-tweezers" codes for a specific SNP. Whenever a DNA strand with that SNP approaches, it binds to that side of the DNA-tweezers, opening them up and creating a change in electrical current that is detected by the graphene field effect transistor.

What drives this technology is a molecular process called DNA strand displacement – when a DNA double helix exchanges one of its strands for a new complementary strand. In this case, the DNA-tweezers swap one their strands for one with a particular SNP, the UC team explains.

This is possible due to the particular way the DNA-tweezers are engineered. One of the strands is a ‘normal’ strand that is attached to the graphene transistor and contains the complementary sequence for a specific SNP. The other is a ‘weak’ strand in which some of the nucleotides are replaced with a different molecule to weaken its bonds to the normal strand. A strand containing the SNP is able to bind more strongly to the normal strand and displace the weak strand. According to the researchers, this leaves the DNA-tweezers with a net electric charge that can be easily detected by the graphene transistor.

When the SNP-containing strand binds, the researchers explain, it opens up the DNA-tweezers, changing their geometry so that they become almost parallel to the graphene surface. This brings the net electric charge of the DNA close to the graphene surface, giving a larger signal and making the chip very sensitive.

Next steps include designing array chips to detect up to hundreds of thousands of SNPs in a single test. Future studies will involve testing the chip on blood and other bodily fluid samples taken from animals or humans, the UC team concludes.

Author
Bethan Grylls

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