One of the most common indicators of many diseases and cancer in blood is the presence of a genetic mutation known as a single nucleotide polymorphism (SNP). Unfortunately, to date such tests for SNPs are slow, cumbersome and – above all – expensive. Now a team of researchers from the University of California, San Diego (UCSD) have developed a new graphene-based sensor that promises to deliver test results easily, in real time, and inexpensively. The researchers believe this could be a breakthrough in the early detection and screening for many life-threatening illnesses.
SNP is a variation of a single nucleotide base (comprising the nitrogenous bases Adenine, Cytosine, Guanine, and Thymine) in the DNA sequence found in all the cells of our bodies. Though a great many detected SNPs appear to have no observable impact on our well-being, there are a few that are specifically linked with morbid disorders such as cancer, neurodegenerative disorders, diabetes, heart problems, and other diseases. It is these SNPs that the new UC San Diego device is designed to detect.
Other graphene sensors are able to detect various molecules of gas, or even volatile compounds, but the graphene-based DNA probe transistor developed by the UCSD researchers operates by directly incorporating DNA itself into the graphene sensor. It does so by taking advantage of a process known as a DNA strand displacement, where a DNA double helix has one of its strands swapped out and replaced with a complementary strand.
In this case, the DNA probe contains a double helix with two complementary DNA strands that have been altered so that they do not bind strongly to one another. One strand is also a "normal" strand, with all of its nucleotide bases in place and contains a sequence coding for a specific type of SNP. The "weak" strand has had four of its guanine nucleotides replaced with inosines (crystalline nucleosides) to weaken its attachment to the normal DNA strand. It is this weakened strand that is attached to the graphene transistor.
When applied in detection, any DNA strands that are a flawless match to the complementary sequence on the normal strand and, therefore, contain an SNP, will knock off the weakened strand and attach itself in that strand's place. When this occurs, the attached transistor creates a signal to indicate that such a replacement event has occurred.
Currently in the proof-of-concept phase, the researchers believe that this is the beginning of implantable biosensor chip technologies that could detect specific DNA mutations and communicate the data wirelessly to mobile devices in real-time.
"A highlight of this study is we've shown that we can perform DNA strand displacement on a graphene field effect transistor," says Michael Hwang, a materials science PhD student at UCSD. "This is the first example of combining dynamic DNA nanotechnology with high resolution electronic sensing. The result is a technology that could potentially be used with your wireless electronic devices to detect SNPs."
Advantages claimed by the researchers for their double stranded DNA device include the ability for the probe to be much more selective in its detection than single-strand probes that can often false-trigger on partial matches, and increased DNA strand length capabilities – including a 47 nucleotide version developed by the team, and claimed to be the longest DNA SNP probe so far created – that vastly increase sensitivity.
"A single stranded DNA probe doesn't provide this selectivity – even a DNA strand containing one mismatching nucleotide base can bind to the probe and generate false-positive results," says professor Ratnesh Lal, of the Jacobs School of Engineering at UCSD. "We expected that with a longer probe, we can develop a reliable sequence-specific SNP detection chip. Indeed, we've achieved a high level of sensitivity and specificity with the technology we've developed."
The researchers are looking to eventually scale-up their new technology and add wireless capabilities to the device and, one day, hope to test it in clinical trials to conduct real blood biopsies. They also believe that the device may eventually be incorporated in a range of medical pathology tests, including those for early cancer screening, to scan for disease biomarkers, and perform real-time recognition and capture of viral and microbial sequences.
The research results were recently published in Proceedings of the National Academy of Sciences.
Source: UC San Diego
