By John P. Roche
Glioblastoma multiforme (GBM) is an aggressive form of malignant brain cancer. The American Association of Neurological Surgeons estimates that GBM causes 52 percent of primary brain tumors and 17 percent of primary plus metastasized brain tumors. More than 20,000 primary brain tumors are diagnosed in the United States each year, so improved treatment and monitoring of brain cancer is a critical medical need. New research from Vikas Berry and Ankit Mehta and colleagues at the University of Illinois at Chicago discovered a powerful new tool that might be able to help fill this need—sheets of carbon atoms called graphene.
What is Graphene?
Graphene is a one-atom-thick layer of carbon atoms that form a single molecule. Each carbon atom in graphene is bound to three other carbon atoms, creating a honeycomb plane of interlinked hexagonal rings (see the image above). Graphene is familiar to us all—the lead in pencils is made up of graphite, which consists of many layers of graphene stacked together. Scientists knew that graphite was made up of layers of carbon sheets, but they were unable to isolate individual sheets of graphene until Andre Geim and Konstantin Novoselov did so in 2004, initially using pencil graphite and Scotch tape. Geim and Novoselov and colleagues then performed electrical tests on graphene, which were first published in 2005, and an explosion of research on the molecule followed. Andre Geim and Konstantin Novoselov won the Nobel Prize in Physics in 2010 for their discovery.
Graphene offers tremendous promise for a wide range of uses. Its appeal lies in its amazing properties: it is the thinnest material known to science; it is 300-times stronger than steel; and it has high electrical conductivity, making it attractive for electrical components. It also forms a filter-like grid that allows water to pass through but which blocks most other compounds, offering promise for water desalinization and other ultrafiltration applications. And it has promise for biological engineering, including the capacity, as Berry and Mehta discovered, to detect cancer cells.
Graphene as a Sensor
Graphene can be used as a sensor because it is highly sensitive to electrical and chemical conditions. Carbon atoms have four outer-shell electrons, allowing it to form four bonds with other atoms. In graphene, each carbon atom is bound to three other carbon atoms with three of these outer-shell electrons; the fourth electron remains unbound, creating a cloud of electrons above and below the graphene sheet. This electron cloud creates graphene's incredible electrical conducting properties—it also makes it attractive as a sensor.
Berry and colleagues used graphene to compare GBM cancer cells with normal brain cells called astrocytes. The cancer cells and normal cells were from cultured human cell lines, and single layers of graphene were synthesized and then transferred onto silicon dioxide chips. Berry's team adhered the cancer cells and the normal cells to graphene sheets and then measured the resulting changes in the atomic vibration of the atoms in the graphene. This allowed the scientists to compare the characteristics of the cancer cells and the normal cells.
Cancer cells grow rapidly, fueling their growth with a form of energy conversion called anaerobic fermentation. This rapid growth leads to two pronounced changes in cancer cells relative to normal cells: (1) an accumulation of hydrogen ions, making their surface more acidic and (2) an increase in their negative charge caused by an increase in sialic acid. When Berry and colleagues adhered the cancer cells to graphene, the high negative charge on the surface of the cancer cells repelled the electrons in the electron cloud of the graphene sheet, which in turn changed the vibrational energy of the carbon atoms in the graphene relative to normal cells. They measured this change in vibration with an optical measurement system called Raman spectroscopy that uses a laser beam to measure vibrational energies.
Detection of Cancer at the Level of an Individual Cell
The brain cells were about 40–50 micrometers in size, and the spatial resolution of the Raman spectroscopy Berry used was 0.7 micrometers, so Berry and colleagues could easily detect cancer at the spatial level of an individual cell, an astounding achievement.
Additional work will be required to test and further develop this graphene-sensor technique, including testing in a mouse model of cancer, which Berry and colleagues are pursuing. But the promise is considerable because a graphene cancer sensor could improve the sensitivity of treatment evaluation for GBM cancer cells, and could be used for confirmation of remission following treatment.
You can read the complete study by Keenan and colleagues in Nature Communications at: