Graphene’s host of impressive attributes includes several properties that are ideal for sensing. Now researchers have successfully fabricated a generic biosensing platform based on functionalized graphene and used it to detect markers related to cancer risk for the first time. The sensitivity of detection outperforms other assay-based sensors allowing valuable early-stage detection of the disease.
“What you need to detect biomarkers is high surface to volume ratio – graphene as a material has an inherently high surface to volume ratio,” says Owen Guy, associate professor in the College of Engineering at Swansea University in the UK, who led this latest research. “That, and its superb electronic transport properties make it an excellent material for biosensing.”
Guy explains how he was studying silicon carbide (SiC) systems for electronics when someone at a conference pointed out that graphene could be grown on SiC. “In 2006 it was early days for graphene – a lot of people were mainly from a physics background so looking at fundamental properties, growing graphene, improving the quality and characterization,” says Guy. “We were doing lots with the medical school here in Swansea at the time so we thought of attaching antibodies and looking at sensing.”
Guy and his team, a collaboration between researchers at the Centre for Nanohealth, Swansea University, in Wales and the Research Institute of the Petroleum Industry in Iran, showed that they could attach antibodies to functionalized graphene. The antibodies would bind with a range of specific biomarkers, resulting in detectable changes in the current-voltage measurements.
This generic sensing platform demonstrated the first detection of cancer biomarkers in a system of this kind at a sensitivity of 0.1 ng/ml – five times the sensitivity of conventional immunoassay-based devices. The researchers have also used the platform for detecting cardiac and pregnancy biomarkers, detecting pregnancy biomarkers at concentrations as low as a pictogram per millilitre.
Functionalization and further challenges
Guy explains how Zari Tehrani, a senior researcher in the team at Swansea, spent a great deal of time developing and optimizing the functionalization process. While similar chemistry had been demonstrated before, Tehrani developed a process that was much faster, occurring over minutes instead of hours and with no need for harsh chemical conditions.
Another challenge was proving that the desired interactions with target antibodies had taken place. The researchers used quantum-dot-labelled antibodies to “see” that the antibodies had attached to the functionalized graphene.
“The breakthrough I suppose was when we saw the quantum-dot-labelled antibodies on the sensor – then we knew we had what we thought we had,” says Guy, adding, “I think Zari was already quite sure but you have to prove it.”
Few layers better than single layer
Guy and his team used “epitaxially” grown graphene, which can be produced over large areas on silicon carbide substrates and can be processed like a silicon wafer. “At the time people doing chemistry were using solution-based graphene, which results in small flakes that aren’t really suitable for higher-throughput fabrication of devices,” explains Guy.
“There are also many different types of graphene and different layer thicknesses – single layer, bilayer, multilayer graphene,” he adds. “A purist might say only single layer is really graphene but we were less concerned with single layers because few-layer graphene actually works better.”
He explains that the chemical functionalization effectively introduces defects into the graphene that disrupt the conduction. “With few-layer graphene the layer beneath may still conduct so it’s more tolerant,” he says.
Future work will focus on optimization and further studies to understand how the sensor responds to non-specific markers. “We are also looking at scaling up from single devices to wafer devices, transfer to different markers, and then multiplexing to test for different biomarkers at the same time,” says Guy.
The full details are available at 2D Materials 1, 025004.
Article by Anna Demming