Graphene biosensor for detection of disease biomarkers


Title: Graphene biosensor for detection of disease biomarkers

 

Start date: July 2011
Client:

UWS Ventures and Swansea University

Investigator Dr David Nugent

david.nugent@elucidare.co.uk

 


Introduction

Illnesses like cancer, cardiovascular diseases, Alzheimer’s, Parkinson’s, and diabetes have negative effects on patients, society and insurance systems. With an ever-ageing population, there is a critical demand for more efficient, affordable healthcare.

Nanotechnology solutions are increasingly being targeted at healthcare applications. Diagnostic devices fabricated using carbon nanotubes and silicon nanowires have been reported to be able to detect fM concentrations of target analytes [1]. Nanoscale-biosensors could 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.

At Swansea, nano channel sensors are being developed to detect disease biomarkers at the earliest possible stage, potentially enabling intervention before the disease develops into a more serious illness. Available therapeutic options informed by early detection are greatly enhanced e.g. prostate cancer, the second largest killer of male cancer patients, has a 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.


Technology

Researchers led by Dr Owen Guy have developed both graphene and silicon nanowire (SiNW) electrochemical devices as nano-channel biosensors. Extensive development of novel and generic chemical and bio-functionaliztion technology has enabled the attachment of antibody “bio-receptors” to epitaxial graphene and SiNWs surfaces. The attached bio-receptors are capable of specific and selective interaction with disease biomarkers. When a target biomarker molecule interacts with the “bio-receptor” functionalized surface, the charge density at that surface is affected. This change can be detected as an electrical signal from the biosensor, enabling highly sensitive (nM) detection of biomarker analytes.

Why use nano-channels?

Nanowires and nano-channels have extremely high surface to volume ratios – making them extremely sensitive to interactions with their surfaces. In combination with excellent electronic conduction properties, this makes nano-channel sensors ideal for the detection of biomarkers at very low concentrations. SiNWs have been developed, but graphene nanochannel sensors show even greater sensitivity.

Graphene is the “new wonder material” with exceptional properties such as extreme carrier mobilities, thermal conductivity, mechanical strength and chemical stability – similar to carbon nanotubes (CNTs), [3]. However, whereas CNTs are generally incompatible with device manufacturing technology, epitaxial graphene can be grown on 100 mm diameter wafer substrates, making it well suited for the fabrication of nano-scale electronics and sensors – using standard semiconductor processing techniques [4-6].

Prototype nano-channel biosensors have been developed using antibody-functionalized graphene and SiNWs, capable of specific and selective interaction with the oxidative stress biomarker, 8-hydroxydeoxyguanosine (8-OHdG). This target biomarker has been linked to several cancers and in particular prostate cancer risk. As 8-OHdG is found in urine, the detection of elevated levels of 8-OHdG in urine represents a non invasive method for early detection and / or monitoring of prostate cancer risk.


Applications

In addition to the sensor device and functionalisation technology, the Swansea team has developed an integrated, hand-held, point of care system.

This system, based on a “credit-card biochip” and hand-held “card reader” is simple to use and completely portable. Each single use card simply slots into the card reader where a reference measurement is taken. The card reader then instructs the patient to drop a sample of urine onto the biochip and a another measurement is subsequently taken. The card reader displays whether or not the biomarker is present in the urine sample and at what concentration. The card reader is then able to give a simple instruction to the patient e.g. "Biomarker detected – please consult your physician".

The POC system can be developed further to send or receive data to / from a trained physician.

The POC biochip system 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.

 


Reference

[1] Sun, X., Liu, Z., Welsher, K., Robinson, J. T., Goodwin, A., Zaric, S., & Dai, H. (2008) Nano-graphene oxide for cellular imaging and drug delivery. Nano research 1, 203--212.

[2] Guy, O. J., Castaing, A., Tehrani, Z., & Doak, S. H. (2010) Fabrication of ultrasensitive graphene nanobiosensors. Proc. IEEE Sensors 2010, 907 -912.

[3] Berger, C., Song, Z., Li, X., Wu, X., Brown, N., Naud, C., Mayou, D., Li, T., Hass, J., Marchenkov, A. N., Conrad, E. H., First, P. N., & de Heer, W. A. (2006) Electronic confinement and coherence in patterned epitaxial graphene. Science 312, 1191--1196.

[4] Pumera, M., Ambrosi, A., Bonanni, A., Chng, E. L. K., & Poh, H. L. (2010) Graphene for electrochemical sensing and biosensing. Trac-Trends In Analytical Chemistry 29, 954--965.

[5] Castaing, A., Guy, O. J., Lodzinski, M., & Wilks, S. (2009) Investigation of Graphene Growth on 4H-SiC. Mater. Sci. Forum 615, 223--226.

[6] Guy, O. J., Lodzinski, M., Teng, K. S., Maffeis, T. G. G., Tan, M., Blackwood, I., Dunstan, P. R., Al-Hartomy, O., Wilks, S. P., Wilby, T., Rimmer, N., Lewis, D., & Hopkins, J. (2008) Investigation of the 4H-SiC surface. Applied Surface Science 254, 8098--8105.