ULTRA-SENSITIVE GRAPHENE NANO-BIOSENSORS

Illnesses like cancer, cardiovascular diseases, Alzheimer's, Parkinson's, and diabetes have negative effects on patients, society and insurance systems. The ever-ageing population has a critical demand for more efficient, affordable healthcare.Nanotechnology is building nanometre sized devices for electronics and medical applications, raising expectations for better diagnostics and 'smart' treatments. Nanosensors could identify disease biomarkers at the earliest possible stage, potentially intercepting more serious illness. Available therapeutic options informed by early detection are greatly enhanced e.g. prostate cancer, the 2nd largest killer of male cancer patients, better than 70% chance of successful treatment if detected early. Biomarkers are often present at very low concentrations. Monitoring of biomarkers like prostate-specific-antigen, glucose or other blood-based markers at clinical concentrations - possible using nano-sensor arrays - could provide genuine benefits to patients. Non-invasive smart-testing using urine or breath samples would have a hugely beneficial impact on chronic patients and for monitoring biomarker levels after treatment. Current diagnosis of disease biomarkers is based on detection of fluorescently labeled probe molecules which interact with specific substrate-bound receptors. This is expensive and time-consuming, with limited sensitivity. Nanoscale electrochemical biosensors can achieve much higher sensitivities, using label-free biomarkers. We will exploit our recent advances in graphene growth and semiconductor surface functionalisation, to develop wafer-based, graphene/Silicon Carbide (SiC) technology for novel biosensor applications. Graphene, a single atomic layer of graphite, has some exceptional electronic properties such as its zero bandgap and very high carrier mobilities at room temperature - similar to carbon nanotubes. Graphene can be grown on SiC substrates using silicon sublimation. The principal advantage of graphene/SiC over conventional graphene - from exfoliation of graphene flakes from graphite substrates - is the capacity for graphene growth on flat, large-area wafers (up to 100mm in diameter), on which devices can subsequently be fabricated using standard semiconductor processing. Nano-channel graphene electronic devices will be fabricated on SiC substrates. We have shown that graphene can be bio-functionalized and will use surface functionalisation chemistry to attach bio-receptors to nano-channel graphene devices. Because of their high surface/volume ratio and quantum confinement properties, the electrical properties of graphene nano-channels have increased signal/noise ratios and are strongly influenced by minor perturbations, enabling biomarker detection at ultra-sensitive (fM) analyte levels. Current transport through the nanosensor should show extreme sensitivity to its local environment.A proof-of-concept nano-channel bio-sensor will be developed using antibody-functionalized graphene, capable of specific and selective interaction with the target prostate cancer biomarker, 8-hydroxydeoxyguanosine (8-OHdG). When the bio-molecule binds to the functionalised surface, it produces an electrical signal, which can be detected. The key to an effective biosensor is that only specific bio-molecules will bind to the receptor and produce a response. Selectivity can be controlled by choosing the correct bio-receptor.The functionalisation chemistry proposed allows for attachment of a variety of antibody, enzyme, or aminoacid bio-receptors. Our graphene/SiC biochip could eventually provide an ultra-sensitive, fast-diagnosis, cost-effective test for numerous disease biomarkers - potentially revolutionizing healthcare by bringing diagnosis and monitoring to the point-of-care. Once trialed, mobile monitoring systems, transmitting a signal to a hand held readout display, could allow translation of healthcare from hospitals to patients in their own homes.

Nano-biosensors will provide early detection and diagnosis of disease, and enable real-time monitoring of patient's conditions with less invasive and more user-friendly technology - benefitting their quality of life. We will lay the foundations for a generic, ultrasensitive, biosensor technology that can be adapted to selectively and specifically detect numerous biomarkers - depending on the bio-receptor attached to the Graphene/Silicon Carbide device. Novel biosensor technology, validated for detection of a prostate cancer marker, could be used to functionalise discrete arrays of nanochannel devices for multiplexed sensing of a variety of biomarkers for real-time monitoring of multiple diseases. The flagship cross-disciplinary project will engage with academics and clinicians from across Swansea's Centre for Nanohealth (CNH) and with other universities to develop nanotechnology-based diagnostics for: diabetes, cancer, cardiovascular diseases, arthritis, and reproductive medicine, ensuring feedback between the sensor development team and clinical end-users. Dissemination of the sensor capabilities and communication with industry, academia, government agencies and the NHS will be essential to the eventual uptake of biosensor technology by the health service. The project will enable Dr. Guy to develop a world-class research group at Swansea and act as a springboard for new international collaborative research, building on links with Rice, Houston, CNM Barcelona, Linkoping, RPI, Catania, Bologna, STFC, and SOLEIL. Joint proposals developing biosensors for specific medical applications and integrating sensors with signal processing, display electronics, sampling, microfluidics and therapeutics. Integrated, miniaturized, hand-held, user-friendly, biosensor detection systems, could be used in a cost-effective hand-held POC device for reliable, real-time data capture for clinical analysis and interpretation. Once trialled clinically, mobile monitoring systems could eventually be used for Patient Self Assessment (PSA). At risk patients or patients undergoing or having undergone medical therapies or treatment could monitor themselves for disease biomarkers via non-invasive using urine or breath tests, significantly improving their quality of life. Biosensors have huge potential for innovation and intellectual property (IP) creation. The UK has several world class pharmaceutical and biotechnology companies that would benefit from the ultrasensitive, label-free detection system proposed. Industry is already geared up to market biochip technology, and Swansea University would work closely with industrial partners to exploit and commercialize the technology and IP developed. There are huge market applications for biosensor diagnostics in diabetes, cardiovascular disease and cancer treatments. The medical device market was 145 billion Euros in 2003, with in-vitro diagnostics representing 18 billion Euros. Nanotechnology will have a big impact on this expanding market in the coming years, offering faster and more accurate analyses of smaller samples and the potential for implantable devices - a paradigm shift in healthcare. Dr. Guy is in discussions with several major companies and small & medium sized enterprises including: pharmaceutical company UCB; Boots Centre for Innovation BCI; 3M; MicroPharm, Applied Nano Detectors (AND), Surface Technology Systems (STS) and SEAS Nanosolutions, regarding the commercial development of nano-biosensor technology. As well as the medical diagnostics and pharmaceutical markets, there are commercial opportunities in sensors for pathogens, hazardous chemical and biological agents and in agriculture. Following development of proof of concept devices, we will hold discussions on formal collaboration and licensing agreements. Dr. Guy has a strong track record of industrial engagement and knowledge transfer will aggressively exploit the technologies resulting from these projects.