Graphene-Based Biosensors Sense DNA Cancer Markers

DNA cancer markers passing through the blood or serum of a patient can potentially be detected through graphene-based biosensors, which could usher in a period of liquid biopsy. Conversely, plenty of DNA is required in present-day designs.

Scientists at the University of Illinois at Urbana-Champaign have conducted a new study that revealed that crumpling graphene in the sensor makes it over 10000 times more susceptible to DNA by producing electrical “hot spots.”

According to the scientists, crumpled graphene could be utilized in vast varieties of bio-sensing applications to achieve a rapid diagnosis. The researchers have published their study results in the Nature Communication journal.

This sensor can detect ultra-low concentrations of molecules that are markers of disease, which is important for early diagnosis. It’s very sensitive, it’s low-cost, it’s easy to use, and it’s using graphene in a new way.

Rashid Bashir, Study Lead and Professor of Bioengineering, University of Illinois at Urbana-Champaign

Bashir is also the dean of the Grainger College of Engineering at the University of Illinois at Urbana-Champaign.

While the concept of searching for the telltale signs of cancer sequences in nucleic acids, like DNA, or its cousin RNA, is not new, this is the first-ever electronic sensor to identify trace amounts of cancer sequences, like those potentially found in the serum of a patient, without extra processing.

When you have cancer, certain sequences are overexpressed. But rather than sequencing someone’s DNA, which takes a lot of time and money, we can detect those specific segments that are cancer biomarkers in DNA and RNA that are secreted from the tumors into the blood.

Michael Hwang, Study First Author and Postdoctoral Researcher, Holonyak Micro & Nanotechnology Lab, University of Illinois at Urbana-Champaign

Graphene is a flat carbon sheet measuring one atom thick. It is a low-cost and well-known material intended for electronic sensors. But nucleic-acid sensors that have been designed so far need a process known as amplification, in which a fragment of RNA or DNA is isolated and copied several times in a test tube. But this process takes a long time and is prone to errors.

Hence, Bashir’s team set out to boost the sensing power of graphene to such an extent that a sample can be tested without having to amplify the DNA on the firsthand.

Several other methods to increase the electronic properties of graphene have utilized meticulously designed nanoscale structures. Instead of fabricating unique structures, the research team at the University of Illinois at Urbana-Champaign merely expanded a thin plastic sheet, then placed the graphene over it, and finally released the tension in the plastic. This caused the graphene to scrunch up and develop into a crumpled surface.

The researchers then tested the ability of the crumpled graphene to detect DNA and a cancer-associated microRNA in a buffer solution as well as in undiluted human serum. The team observed that the performance of this crumpled graphene enhanced by tens of thousands of times when compared to that of the flat graphene.

“This is the highest sensitivity ever reported for electrical detection of a biomolecule. Before, we would need tens of thousands of molecules in a sample to detect it. With this device, we could detect a signal with only a few molecules,” added Hwang. “I expected to see some improvement in sensitivity, but not like this.”

To find out the reason for this increased sensing power, Narayana Aluru, a mechanical science and engineering professor, along with his research team, utilized comprehensive computer simulations to analyze the electrical properties of the crumpled graphene and how DNA physically communicates with the surface of the sensor.

The team discovered that the cavities in the crumpled graphene behaved as electrical hotspots, while serving as a trap to pull and retain the RNA and DNA molecules.

“When you crumple graphene and create these concave regions, the DNA molecule fits into the curves and cavities on the surface, so more of the molecule interacts with the graphene and we can detect it,” stated Mohammad Heiranian, a graduate student and co-first author of the study. “But when you have a flat surface, other ions in the solution like the surface more than the DNA, so the DNA does not interact much with the graphene and we cannot detect it.”

Moreover, when the graphene was crumpled, a strain was generated in the material that altered its electrical properties and induced a bandgap—an energy obstacle that must be overcome by electrons to pass via the material. This bandgap made the crumpled graphene to be more responsive to the electrical charges present on the RNA and DNA molecules.

This bandgap potential shows that crumpled graphene could be used for other applications as well, such as nano circuits, diodes or flexible electronics.

Amir Taqieddin, Study Coauthor and Graduate Student, University of Illinois at Urbana-Champaign

Although DNA was utilized in the initial demonstration of the sensitivity of the crumpled graphene for biological molecules, the latest sensor could be adapted to sense a wide range of target biomarkers. Bashir’s research team is currently testing the crumpled graphene in sensors for both small molecules and proteins.

“Eventually the goal would be to build cartridges for a handheld device that would detect target molecules in a few drops of blood, for example, in the way that blood sugar is monitored. The vision is to have measurements quickly and in a portable format,” concluded Bashir.

The study was financially supported by the National Science Foundation through the Illinois Materials Research Science and Engineering Center. Aluru and Bashir also are both affiliated with the Beckman Institute for Advanced Science and Technology and the Materials Research Lab at the University of Illinois at Urbana-Champaign Illinois.