Real answers in real time

Have this spin-out company from Southampton found the holy grail of biological threat detection? Dr Richard Williams thinks not – but they have come very close

A NEW biochemical detection technology being developed by University of Southampton spin-out company Stratophase is promising to provide an effective and practical method detection of biological threats. The technology, which uses an optical silicon chip to detect toxins, viruses and bacteria in real time, and offers substantial improvements in reliability, functionality and cost over existing biochemical detection technologies, has applications in public and military security applications, healthcare diagnostics and process control.

Surface plasmon resonance (SPR) is the excitation of surface plasmons by light.  The basic technique has been used in biosensing and lab-on-a-chip measurement measurements for some time.

What is different about the Stratophase innovation (dubbed ‘Spectrosens’) is the application of SPR techniques to detect multiple targets simultaneously, creating the possibility for the development of a range of highly cost-effective instrumentation that could scan for multiple targets simultaneously.

The team evolved from a research group at the Optoelectronics Research Centre at Southampton University, who between them had many years of expertise in writing optical circuits for telecoms applications. They realised that these robust silicon chips had the potential to be extremely sensitive, miniature biological detectors. Three years down the line and Stratophase has developed the product to the point where a multi-sensor technology demonstration unit is available in a portable, suitcase-based format.  Funding has come in the main from US-based venture capital, supplemented by early product sales and two technology call awards from the UK government.

Stratophase has developed its Spectrosens product to the point where a multi-sensor technology demonstration unit is available in a portable, suitcase-based format

The technology is based upon continuously directing a laser beam at the surface of a silicon chip containing a series of engineered nano-scale mirrors, known as a Bragg Grating. The wavelength, or colour, of light reflected back to the detector remains the same until a binding event takes place on the sensor surface. Antibodies against a wide range of target organisms - including viruses, bacterial cells, spores and protein toxins - can be bound to the surface of the sensor, allowing continuous real-time monitoring for multiple targets. The vision for Stratophase has been of an inexpensive multi-agent biological ‘smoke detector’, which continuously scans the atmosphere for a specifically-targeted range of threat agents. The sensor is currently being optimised to allow it to provide sensitive detection across the full range of target particle sizes. 

A particular feature of Spectrosens is its ability to interrogate the sensor constantly with multiple wavelengths of light. This provides real-time information on the size of the attached biological agent and thus its specific identity. This gives the potential to reduce the incidence of false positive detection events: a significant factor for use in real-world applications where a constantly changing natural background of biological material is to be expected.

The platform becomes a robust and sensitive biological detector when the chip is pre-coated with antibodies to specific target molecules spanning bacteria, viruses and toxins. It can detect changes caused by the presence of biological and chemical substances on the surface of the chip with a precision better than one part in one million, in near real-time.

It also eliminates some of the drawbacks of using existing biochemical detection technologies as ‘detect and warn’ devices, such as traditional SPR and other techniques based on the use of antibodies. In particular, simultaneous interrogation of the sensor at a range of wavelengths provides a multi-dimensional view of binding events on the chip surface, thus differentiating between the intended target antigen and other molecules and therefore reducing false alarms.

The potential of the technology has been recognised by governments and the company is in commercial discussions with more than 20 blue chip companies around the world.

The University of Applied Sciences at Aschaffenburg in Germany has recognised the potential of Stratophase technology for widespread commercial applications, and its advantages over other technologies to provide cost-effective and practical detection of critical biochemical contaminants in the drug discovery, pharmaceutical manufacturing, process control and food industries. It has bought a sensing unit for a three-year government-funded research project that will research into how the technology could be implemented to produce a practical sensor system for industrial biotechnology applications. In particular, its design will enable a network of sensors to be built across a manufacturing platform for continuous multi-point testing.

The University project, which began earlier this year, will investigate combining the technology with microfluidic structures to create a robust and cost-effective biochemical sensor for commercial use. It will probe the capabilities of the sensor, treating the surface to explore its sensitivity to additional biological reactions, and evaluating its reaction to extended ranges of wavelengths of light.

Professor Dr Ralf Hellmann, Head of the Laboratory for Opto-Electronics and Sensors at the University of Applied Sciences at Aschaffenburg, believes there is considerable potential for Stratophase’s technology in commercial applications.
He sees the fact that is it a purely optical process as a key advantage of the technology. This eliminates the usual complication with other technologies of preparing the liquid specimen with fluorescent tags.

In addition, it has distinct advantages for commercial sensing over technologies such as SPR. For example, the silicon surface of the sensor gives access to a far broader range of binding reactions compared to the gold surface used in SPR. Moreover, its use of fibre optics enables a network of sensors to be built across a production platform with a central point for the analysis of sample readings. With the combination of its high sensitivity, optical transducer and size (less than 1cm2), the new sensor has significant potential in applications beyond biotechnology.

The holy grail of biological detection in homeland security applications is a small, inexpensive device requiring almost no user intervention, which continuously scans a wide area for every known biothreat agent - and every unknown biothreat agent too - in real time, while instantly communicating any useful information to everyone who needs to know.

While this may be some way off, useful work is progressing, based on a range of detection technologies, but none has to date none has offered a viable, useful solution for practical detection instrumentation able to meet today’s very real threat. Spectrosens can detect a far wider range of pathogens and detects these in real time, while also reducing the very real problem of false alarms. It a significant leap forward for the development of instrumentation for use in counter-terrorism and military applications.

Having already established the technology’s functionality for homeland security, Stratophase is now moving into new areas which will exploit its capabilities even further, like the research project in Aschaffenburg. This project will take the core principles of the sensors and examine their use for new applications. It enables us to test the technology for specific applications and feed the results back into further development.

There is considerable activity worldwide to find practical and reliable solutions for detection of biochemical threats, most notably in homeland security. No country is more active in this than the US, where the market for biochemical detection is currently worth approximately $725m and is forecast to grow to more than $2.4bn by 2012[1] The National Strategy for Homeland Security states that ‘affordable, accurate, compact and dependable sensors, however, are not available’. It makes specific reference to the need to develop ‘sensitive and highly selective systems that detect the release of biological or chemical agents’. [2] In the UK, the Home Office has launched a research programme to identify how science and technology can strengthen UK capabilities to combat terrorism. [3]

References
1 US Homeland Security Biological Detection Technology & Market Forecast 2007-2012 © HSRC 2006 Catalogue # 200606-12
 
2 The National Strategy for Homeland Security, Office of Homeland Security July 2002 www.whitehouse.gov/homeland/book/sect5.pdf
 
3 The Home Office Chemical, Biological, Radiological & Nuclear science and technology programme: http://security.homeoffice.gov.uk/science-technology/using-cbrn-science-technology/?version=1


By Dr Richard Williams. David was appointed CEO of Stratophase in 2003 when the company was spun out of the University of Southampton, and he has been instrumental in several funding rounds.