May 19, 2014
Hybrid graphene biosensor breaks new record
Researchers at the University of Pennsylvania and SPAWAR Systems in San Diego have developed a new method to fabricate large arrays of graphene field effect transistors that does not sacrifice the inherent electronic properties of the carbon material. The team then functionalized the transistors with mu receptors to make hybrid biosensor devices that can detect naltrexone (an opioid receptor antagonist used to treat alcohol dependence) at levels of 10 pg/mL – a value that is around 100 times lower than that obtained using current clinical diagnostic techniques.
Field effect transistors are ideal for studying the electronic properties of the material from which they are made. However, typical lithography techniques to make graphene FETs invariably leave residues that degrade the overall performance of the finished devices. These residues are the bane of graphene research but a team led by A T Charlie Johnson has now developed a method that patterns the graphene devices during transfer from its growth substrate to a Si/SiO2 wafer, so doing away with the lithography step entirely. “With this process, we can fabricate thousands of uniform graphene FETs that are all of equally high quality,” team member Mitchell Lerner told nanotechweb.org.
The researchers made biosensors from their FETs that were composed of a graphene transistor coupled to engineered mu receptor proteins. Mu opioid receptors are members of a class of membrane proteins called G Protein-Coupled Receptors (GPCRs). These receptors naturally exist on cell membranes and detect external stimuli. “As you can guess, this category of proteins is incredibly important to the pharmaceutical industry,” said Lerner. “Indeed, GPCRs are the target of around 40% of all pharmaceuticals today.”
The team employed a shadow mask to pattern large gold stripes over graphene while it was still on its copper foil growth substrate. While transferring the graphene to its final destination (a silicon wafer equipped with electrodes), the graphene covered by gold remained pinned to the foil and only the uncovered graphene peeled off, explained Lerner. The patterned graphene was then carefully placed onto the pre-fabricated electrodes.
The finished devices have excellent properties. For example, the researchers found that the FET carrier mobility (a measure of how fast electrons and holes move through a material) was as high as 1500 cm2 V–1 s–1 on average for a collection of nearly 200 devices. The Dirac point (which indicates how clean a sample is) was 15 V on average – a value that shows that the FET is significantly cleaner than graphene devices made by other methods. “What is more – the yield for our process was over 99% – from device fabrication all the way through to the target sensing,” said Lerner. “All these properties are unparalleled for graphene FETs made to date.”
To test its devices as biosensors, the researchers covalently bound mu receptor proteins to the graphene surface using so-called diazonium chemistry techniques. They then delivered naltrexone to a collection of sensors at varying concentrations to see how the devices reacted. “We found that the mu receptors bind naltrexone as they would do naturally in the body and that this binding causes a change in the local doping levels of the graphene channel,” said Lerner “The signal was seen to be similar over nearly 200 graphene devices, which means that the result is statistically reliable.
It is very nice if one or two devices look like they can detect a target, but it is a whole other ball game to get 20, 200 or even 2000 devices to behave the same way. A few years ago, making that number of graphene transistors would have taken longer than the lifetime of a graduate student.”
The technology could be used to make other types of biosensors, not just the ones studied here, he added. “Our coupling chemistry technique is very general and could be used to link almost any type of protein to the graphene channel to make highly sensitive and specific detectors. Potential targets include proteins for detecting cancers, pathogens and perhaps even volatile organic compounds in the environment – something that might come in useful for defence applications.”
Another application that the team says that it is particularly excited about is drug discovery. “Modern techniques to design new drugs are expensive and still rather inefficient,” says Lerner, “and we need high-throughput analytical techniques able to monitor biological entities in real time while they are being interrogated with potential therapeutic candidates. Our technology could be just the ticket here.”
The researchers now plan to test their sensors in complex biological media, like serum and whole blood. “If our hybrid graphene FETs work just as well under these conditions, they might prove themselves to be tremendously useful in next-generation analytical devices. Hopefully such devices will see their way into the marketplace in the near future.”
The current work is detailed in Nano Letters DOI: 10.1021/nl5006349.
About the author
Belle Dumé is contributing editor at nanotechweb.org