Flexible Raman biosensing platform for low-cost health diagnostics

Highly specific, sensitive sensors interfaced with portable, easy-to use, low-cost instruments are needed for rapid point-of-care infection diagnostics, and will lead to better targeted therapy, shorter time to treatment and reduced morbidity. In this project, we propose to realise a generic, flexible, compact sensing platform with high sensitivity and selectivity. The system will comprise a low-cost instrument employing cheap, disposable generic sensor chips that can be readily committed to specific analytes, from small molecules to proteins and DNA, by using conventional surface modification techniques. Paper-based fluidics will be used to deliver analytes straightforwardly from a drop to the sensor surface or, where required, fluidic microsystems may be easily integrated. The sensing system will be demonstrated with clinical samples from patients who have been exposed to controlled infection to whooping cough and for the analysis of priority pathogens such as ebola and plague. This proposal builds upon our recent work on waveguide-enhanced Raman spectroscopy (WERS) to realise a sensor chip which shows surface enhancements comparable to those of surface enhanced Raman spectroscopy (SERS) with improved application flexibility and manufacturability, and upon joint work between Dstl and Chemistry on surface enhanced Raman approaches to bioanalyte detection. The proposed biosensing platform will have widespread application at the point of care for patients, in the detection of infection and the diagnosis of disease, and for broader applications such as environmental monitoring and security, and will be flexibly configurable for specific settings and analytical challenges. The desktop instrument, employing plug-in disposable sensor chips with simple operation will be appropriate for use in the GP's surgery, the ward, or in remote communities.

The creation of an innovative generic biochemical sensing system for application to healthcare diagnosis will provide significant benefits by allowing rapid in-situ decision making and optimised care for infectious diseases. The cheap, disposable sensing platform will be flexibly configurable for multiple assay types, including immunoassays and DNA-based approaches, allowing greater impact for low investment. This capability will be demonstrated for whooping cough and ebolavirus, for example, the first addressing a public health problem which is re-emerging due to reducing efficacy of vaccines and the second representing pathogens that pose the highest risk to national security and public health worldwide. The ability to diagnose these infections locally, rapidly and cheaply has clear societal benefits, but this sensing platform will be applicable to a much wider range of infectious diseases and in several other fields of application. The users and beneficiaries of this research would include primary care healthcare organisations such as hospitals and general practice clinics, government agencies such as Dstl protecting overseas MoD bases and responding to security threats, government departments such as the Home Office monitoring at airports and ports and for illicit drug detection (for example in roadside testing for "drug driving"), and environmental monitoring authorities for water pollution.

Economic benefits will accrue through new opportunities in a worldwide market for manufacturing industry in sensing, instrumentation and photonic devices to commercialise a high-yield platform technology which is cheap to manufacture. Our approach does not suffer from the "niche" market problems faced by many chemical sensing systems, as the analytes to be measured may be post-selected by reconfiguring the chip surface chemistry, without changing the chip itself or the instrument. A multi-use platform like this would have great disruptive potential to overcome current limitations of mobile health and environmental monitoring systems, in particular in low-resource environments where sophisticated laboratory tools are not available. The long term economic and societal impact of this platform is potentially significant worldwide, particularly in remote areas where healthcare needs are most immediate and challenging to address.