In 2004, two UK scientists used a piece of Scotch tape to isolate single layers of graphene from a block of graphite, or pencil lead. Ever since, physicists and materials scientists have been trying to take advantage of the nanomaterial’s unique properties to use it in the construction of transistors, capacitors, and solar cells. The UK researchers, Andre Geim and Konstantin Novoselov, won the 2010 Nobel Prize in Physics for their work, which extended well beyond the tape trick of course.
In recent years, graphene has come to the attention of biomedical researchers, who think its malleability makes it ideal for biological applications, ranging from disinfecting hospitals to detecting tumors to delivering drugs to sequencing DNA. The unique properties of graphene are being explored for many different potential uses in medicine.
The idea behind graphene-based DNA sequencing is to create a membrane from the material, immerse it in a conductive fluid, and apply a voltage to one end so DNA can be drawn through miniscule pores in the graphene. The method, called nanopore sequencing, would allow DNA to be analyzed one nucleotide at a time.
“The notion is that since the nucleotides have different dimensions and different electrical properties, they would effect different blockages of the pore,” says Harvard University’s Daniel Branton. “So one could directly read the changes in electrical currents as an indicator of the different nucleotides moving through the pore.”
Researchers initially focused on a membrane derived from bacteria called alpha-hemolysin for nanopore sequencing. But the problem with passing DNA through alpha-hemolysin, Branton says, is that at 5 nanometers wide, its pores are too big to separate half-nanometer DNA nucleotides. With a $3.6 million grant by the National Human Genome Research Institute to develop a graphene-based nanopore sequencer, Branton is one of several researchers now focusing on graphene as a substitute for alpha-hemolysin.
At just one atomic layer, or .34 nanometers, thick, pores created in graphene are about as deep as the space between bases in double-stranded DNA, according Jiwook Shim, a researcher at the University of Illinois at Urbana-Champaign. This makes for high-resolution sequencing, he says.
Examining long strings of DNA one base at a time can enable researchers to more clearly, quickly, and accurately detect repeated, omitted, or mutated nucleotides—all possible contributors to genetic traits or disease. Shim’s group is using graphene nanopores not only to sequence DNA, but also to find methylated sites in a patient’s DNA, which could be indicative of diseases such as cancer. “The conventional method to detect methylation in DNA takes more time and is more expensive,” Shim says. Nanopore technology could be faster and cheaper.
At the Wake Forest School of Medicine, cancer biologist Ravi Singh also aims to use graphene to help patients. His group is developing rolled nanotubes for tumor-imaging. Work by other labs has shown that graphene nanotubes can cross cell walls, Singh says, and by loading their surface with glucose nanoparticles, he aims to turn graphene tubes into missiles targeted at tumors. Tumor cells feed on glucose, so once in the bloodstream, the glucose-coated nanotubes would be absorbed by tumors. A PET or CT scan would find the radiolabels carried by the tubes, enabling imaging of the tumors that have taken them up.
“Instead of having a simple molecule of glucose linked to a single radiolabel, we can have a whole bunch of radiolabels on a single tube,” Singh says. “This increases sensitivity,” and allows for detection of much smaller tumors, and tumors at an earlier stage.
Despite its less-than-a-nanometer thickness, graphene’s surface is large enough that multiple imaging agents could be placed on a tube. A tube also coated with iron oxide or gadolinium would be detected by magnetic resonance imaging. And, Singh adds, engineered correctly the tubes would be secreted to urine and flushed from the body with little toxicity.
The tubes could also be used in near-infrared-radiation therapy, Singh adds. Exposed to near-infrared light, graphene generates a tremendous amount of heat. And near-infrared light can penetrate human flesh to different degrees. A nanotube at a tumor site could be stimulated with an external laser that would pass through normal tissue, heating only the site where the nanotube is located, Singh says. Burning the tumor that way, he says, would eliminate the need for surgery or drugs.
To be sure, drug delivery is yet another possible application for the wonder material. The University of Wisconsin’s Weibo Cai says graphene “is one of the most versatile materials for bio-applications because it is much less toxic than some of the other materials in nanoparticles.” Any number of drug molecules could be attached to its surface. The technology, he says, could bombard disease targets that are “overexpressed on the surface of cells or vasculature.”
Similarly, graphene could carry genes to specific locations in the body. Graphene easily absorbs DNA onto its surface, says Wake Forest’s Singh. And because the nanotubes can cross cell membranes, graphene coated in a specific gene might be targeted to penetrate the cell nucleus and deposit a gene to be replicated. Singh considers it a potential therapeutic technique for multiple diseases.
At Case Western Reserve University, Rigoberto Advincula is looking at graphene’s antimicrobial properties, which could make it useful for mitigating infections in hospitals, or as specialty coatings for stents and medical devices. “We found that graphene is able to mitigate growth of bacterial colonies,” Advincula says, either because of its oxidizing properties, or because the material is like a “knife” or “sharp object” when in contact with bacterial membranes. It could slow down the spread of so-called superbugs, which have developed resistance to antibiotics.
Biomedical graphene research is still in its infancy, however. For now, Singh and others seeking to apply graphene to biomedicine remain focused on engineering its surface to be as compatible and nontoxic to the human body as possible and on targeting it as precisely as possible.
For all its amazing properties, graphene is extremely tricky to work with. Singh says that every addition of a molecule to its surface changes the way a nanotube interacts with the biological environment, how toxic it is, and how stable it is. He predicts it will be at least 15 years before patients benefit from graphene-based diagnostics like those he is developing.
But three decades from pencil lead to a cancer cure wouldn’t be bad.
