Bioengineers from the University of California, San Diego, have created an electrical graphene chip that is able to detect mutations in DNA. Researchers say the technology could be used in a wide range of medical applications in the future, including blood testing for early cancer screenings, tracking disease biomarkers and even real-time detection of viral and even microbial sequences.
Professor of bioengineering and team leader, Ratnesh Lal says the team is at the forefront of developing a fast and affordable digital method to detect gene mutations at high resolution. This is on a scale of a single nucleotide change in a nucleic acid sequence. The technology is currently in the proof-of-concept stage and is a first step of many towards a biosensor chip that can be implanted directly into the body to help look for specific DNA mutations and send that information to a mobile device wirelessly.
The team developed a new technique that helps to detect the most common genetic mutation called a single nucleotide polymorphism (or SNP), which is a variation of a single nucleotide base (A, C, G, or T) in the DNA sequence. Most SNPs do not affect health directly, but some are associated with pathological conditions such as cancer or diabetes. SNP detection methods that are currently in use are quite slow and cost a lot of money.
The new chip consists of a DNA probe that is embedded onto a graphene field effect transistor. The DNA probe is an engineered piece of double stranded DNA that is made up of a sequence coding for a specific type of SNP. The chip is made and fabricated to capture DNA or RNA molecules with the single nucleotide mutation. When such pieces of DNA or RNA are bound to the probe, an electrical signal is triggered.
The biosensor chip is made of a double stranded DNA probe that is embedded onto a graphene transistor and can electronically detect DNA SNPs. (Image credit: University of California – San Diego)
Simply put, the chip performs DNA strand displacement. The new complementary strand binds stronger to one of the strands in the double helix and displaces the other strand. In the study, the DNA probe is the double helix which holds two complementary DNA strands that are built to bind weakly to each other. DNA strands that contain the SNP will bind to the normal strand and knock off the weak strand. The chip will generate an electrical signal when a strand binds to the probe that contains SNP.
One of the best features of this chip is that the DNA probe is attached directly to a graphene transistor, allowing the chip to run electronically. This is the first time dynamic DNA nanotechnology has been combined with high resolution electronic sensing. The resulting technology is one that may potentially be used with wireless electronic devices in order to detect SNPs.
Size of a single gene mutation biosensor. (Image credit: University of California – San Diego)
Another great improvement is the use of double stranded DNA probes instead of other SNP detecting methods, which generally use single stranded DNA probes. When double strands are used, only DNA strands that are a perfect match to the normal strand will be able to displace the weak strand. Lal says a single stranded DNA probe just isn’t capable of providing this amount of selectivity, where even a DNA strand with one mismatching nucleotide base can bind to the probe and generate false positives.
These new probes are also able to be much longer than previously used versions. This enables the chip to detect an SNP within longer stretches of DNA. In this particular study, Lal and his team had successful SNP detections with probes that were as long as 47 nucleotides. This is the longest DNA probe that has ever been used in SNP detection. Longer probes ensure that the DNA sequence being detected is unique in the genome, leading to a much higher level of sensitivity and specificity.
Schematic showing DNA strand displacement on the biosensor chip. A perfect match DNA strand shown in green binds to the normal strand shown in red of the DNA probe and displaces the weak strand (black). (Image credit: Lal Research Group at UC San Diego)
The team plans to scale up the technology and add wireless capability to the chip. After that, researchers would like to test the chip in a clinical setting and use it to conduct liquid biopsies. They also would like to use the technology to create a whole new generation of diagnostic methods and personalized treatments in the medical field.