Illustration of graphene-based SNP detection chip wirelessly transmitting signal to a smartphone. [Image from the University of California San Diego]
The chip detects the genetic mutation known as a single nucleotide polymorphism (SNP). The researchers suggest that the chip is at least 1,000 times more sensitive at detecting the mutation than technology that is currently available. The development could create cheaper, faster and more portable biosensors for detecting genetic markers for diseases like cancer.
SNP occurs when there is a change in a single nucleotide base (A, C, G or T) in the DNA. It is known as the most common genetic mutation. Most types don’t affect health, but other types have been known to increase the risk of developing pathological conditions like cancer, diabetes, heart disease, neurodegenerative disorders, autoimmune and inflammatory diseases.
Typical SNP detection methods have poor sensitivity and specificity and require amplification to receive multiple copies for detection. They also need bulky instruments and cannot work wirelessly, according to the researchers.
However, the UC San Diego-developed chip is wireless and smaller than a fingernail and can detect genetic mutations that are in picomolar concentrations in solution.
“Miniaturized chip=based electric 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,” Ratnesh Lal, professor of bioengineering, mechanical engineer and materials science at the university, said in a press release.
The chip captures a strand of DNA that has a specific SNP mutation. Then it creates an electrical signal that is sent wirelessly to a mobile device. The chip is made from a graphene field effect transistor with an engineered piece of double stranded DNA that is specifically designed for the chip and attached to the surface. The DNA is bent in the middle so that it is shaped like a pair of tweezers and one side of the DNA is able to code for specific SNP. If a DNA strand with that SNP comes into contact with the engineered DNA strand, the DNA with SNP will attach to the side that codes for the mutation. This opens up the tweezer shape of the DNA and creates a change in the electrical current that the graphene field effect transistor detects.
DNA strand displacement, the molecular process behind the technology, occurs when a DNA double helix exchanges one of its strands for a new complementary strand. In the engineered version of the DNA, the tweezers exchange a normal strand with a particular SNP. The normal strand is attached to a graphene transistor and has a complementary sequence for a specific SNP. The other strand of the DNA is considered the weak strand where some nucleotides are replaced with different molecules to weaken the bond to the normal strand. SNP strands can then bind more strongly to the normal strand to displace the weak one. The DNA tweezers then have a net electric charge that is easily detected by the graphene transistor.
The new chip is a continuation of a first label- and amplification-free electronic SNP detection chip that Lal’s team developed in the past. The new chip they created has added wireless capability and is at least 1,000 times more sensitive than the previous chip.
The researchers plan to design array chips in the future that can detect up to hundreds of thousands of SNPs in a single test. Other studies will involve testing the chip on blood and other bodily fluid samples.
The research was published in the journal Advanced Materials and was supported by grants from the National Institute on Drug Abuse and the National Institute on Aging with departmental development funds from the department of mechanical and aerospace engineering at UC San Diego.
