Graphene and its influence in the improvement for the detection of diseases
The main focus of this project is to develop silicon and graphene based biosensors, with the emphasis on fabrication of a generic graphene biosensor platform. This platform can be applied for the detection of a range of different disease biomarkers. Prototype biosensors are being developed specifically for the detection of biomarkers relating to the diagnosis of Stroke. There are numerous biomarkers related to, but not unique to Stoke, and thus a multiplex sensor platform is highly desirable. The multiplex biosensor will be developed in order to simultaneously detect a panel of biomarkers significant to Stroke diagnosis.
With a Stroke being a blood clotting disorder and one of the leading causes of disability worldwide, early detection of Stroke biomarkers is a key clinical driver for better patient outcomes. Graphene’s excellent electrical conductivity paired with its high surface area to volume ratio makes it an optimal platform for biosensor development. Therefore graphene based biosensors have the potential to be used for early disease detection where biomarkers are often present at low concentrations. In order to convert these devices into biosensors, the graphene surface must be chemically functionalised. A range of surface chemistries can be employed in order to attach amine groups to the device surface. This amine attachment allows for the further binding of a bioreceptor of choice such as an antibody, DNA probe or aptamer.
The general sensor platform can be adapted to several other biomarker system. Sensors have been demonstrated for the pregnancy hormone, hCG and the oxidative stress biomarker relating to prostate cancer risk, 8-OhDG. The exceptional sensitivity obtained with these sensors, paired with the speed and ease of detection of biomarkers makes graphene based biosensors ideal for point of care diagnostics. This allows for more informed front-line medical care and attention for patients.
Several fabrication processes have been optimised for the production of both silicon and graphene based biosensors, including photolithography, plasma etching, metallisation, metal wet etching and annealing. These optimised parameters have been used to produce both graphene and silicon devices on full 4 inch wafers. Various functionalization methods have been attempted on silicon, HOPG and CVD graphene samples, with fluorescence microscopy indicating the presence of amine groups on the surface. In terms of “transfer-free” graphene devices, both Ni and Cu structures have been etched in order to grow graphene on the metal surface (at Cambridge). An undercut etch process will subsequently be used to fabricate suspended graphene devices. Suspended devices have significantly higher surface area to volume ratio and reduced substrate-related electrical doping effects. Electron beam lithography parameters are being optimised to produce graphene nanowires, increasing the sensitivity of devices. Devices will then be functionalised to develop biosensors.
“Our NRN PhD student has done some fantastic work developing graphene sensor devices which we are now making biosensors with. If successful, these will be world’s first lithographic graphene sensors for detection of stroke biomarkers. This could ultimately help diagnose stroke risk earlier” Prof Owen Guy
Our key collaboration is with NRN partner Cardiff University who have been developing a novel functionalisation process for graphene using pi-stacked cyclic aromatic structures. Cambridge University is involved with the view to investigate transfer-free graphene devices. Industrial collaborations with Biovici (graphene sensors) and SPTS in the area of microfluidic devices have also been imperative to support our research development, recognising the power of knowledge exchange between academia and industry.
The NRN grant has enabled us to purchase all the required photoresist, photomasks, metal targets and substrate wafers to allow for the production of both graphene and silicon biosensors. To be able to produce highly sensitive point of care biosensors with the ability to be adapted to a range of biosensors.
Early concept of the multiplex sensor