Low Cost Nanowire Diagnostic Platform

Laboratory tests are a vital and growing part of the accurate diagnosis of a patient's condition, with around 1 billion tests performed in the UK each year. With the expansion of interest in evidence-based medicine, laboratory tests are increasingly used to tailor individual treatment plans according to need, to monitor disease progression, to stratify risk, and for population screening programs. To enable the routine application of predictive, preventative and personalized healthcare, these biochemical tests need to be performed at a large scale, at low cost, and preferably also at point-of-need locations rather than exclusively in clinical laboratories. The realization of this socio-economically highly desirable situation necessitates the development of new, more cost-effective, technologies for the quantification of molecules that are biomarkers for the diagnosis and management of specific diseases. The project aim is to develop a point-of-care (PoC) nanowire diagnostic system to measure inflammatory biomarkers found in a small droplet of blood, and builds on results from EPSRC Nanotechnology for Healthcare project EP/6061696/1. The project will develop a low-cost nanowire platform technology with integrated sample processing. Nanowire fabrication will use a novel top down process and temperatures low enough for large scale manufacture on inexpensive glass or polymer substrates. Our target application is the diagnosis and management of respiratory diseases, including COPD (chronic obstructive pulmonary disease) and asthma, that are often exacerbated by viral infections. Using a translational approach, we will focus on the detection of a number of clinically relevant protein biomarkers of viral infection and treatment. Viral infections trigger an immune response characterized by expression of the antiviral interferons and their down stream response genes (e.g. interferon-inducible protein 10 and beta2-microglobulin) or activation markers such as neopterin. These can be used as early biomarkers of infection, or to evaluate or predict the clinical response to antiviral therapy with interferon-alpha or beta, which are often measured in conjunction with detection of neutralizing antibodies. Tumor necrosis factor alpha (TNFa) and the acute phase protein, C-reactive protein (CRP), are also used as biomarkers of inflammation linked to infective exacerbations. The nanowire arrays will be used to quantify levels of CRP, TNFa, neopterin, IP-10 and beta2-microglobulin (nanowire functionalization with specific antibodies) and levels of antibodies to interferon-beta (functionalization with interferon-beta itself). The project will also explore the potential of DNA aptamers as synthetic antibodies, a more costeffective and nanowire-compatible approach than classical protein antibodies. Many diseases do not have a single biomarker that correlates with disease state, hence the need to use a panel of biomarkers for more accurate diagnosis and management of disease. The project will have unique access to clinical samples -serum and induced sputum- obtained from patients admitted to the Acute Medical Unit at Southampton General Hospital suffering from acute asthma exacerbations, 60-80% of which are triggered by a respiratory virus, and following their recovery. We will also have access to serum samples from asthmatic volunteers undergoing Phase I clinical trials using inhaled interferon-beta which is being developed for treatment of virusinduced asthma exacerbations. Results will be directly compared against data obtained using traditional methods (ELISA) and to clinical outcomes (e.g. respiratory virus detection, exacerbation severity, response to treatment).