Cutting out contamination

Ensuring water is safe to drink is a key concern for water companies, but existing technology is lacking. Dr Helen Bridle explains how she became involved in improving monitoring systems to stem the spread of waterborne infections
research. Its been invaluable to the success of my career and was instrumental in securing a permanent position at Heriot-Watt University and joining the Institute of Biological Chemistry, Biophysics and Bioengineering, which is a newly formed highly interdisciplinary research institute with lots of potential for interesting collaborations. Im also really glad to have the freedom to follow my own interests in developing my research and am enjoying building up my research group. Are you involved in any other research that you would like to highlight? I am involved in a number of different projects from a large EU collaborative project (worth 9 million) to the smaller scale Crucible projects. The EU project focuses on the use of molecular methods to deliver on the challenge of determining species and viability of waterborne pathogens. An alternative approach that I am working on is the use of Raman spectroscopy, and together with Dr Robert Thomson, we are developing new instrumentation to rapidly collect Raman signatures from Cryptosporidium. In the area of medical applications, I am working on a Medical Research Council (MRC)-funded project using microfluidics to separate bacteria from blood. The aim is to detect biomarkers of antibiotic resistance. I also have several smaller projects including developing simulations of particle flow in microfluidics to inform design of such systems, a rapid method for norovirus detection and the application of nanoparticles in water treatment. In your opinion, what are the benefits of interdisciplinary and industrial collaborations? The benefits are the exposure to interesting new problems and potential solutions as well as the opportunity to work with and learn from people with very different backgrounds. Were lucky in Scotland to have the Crucible scheme where 30 young scientists of all different disciplines are brought together for training and to generate new interdisciplinary projects. It is also an excellent opportunity to explore new areas and Ive been involved in many interesting projects resulting from the Crucible, eg. whether we can

Dr Helen Bridle

Could you begin by outlining your primary research interests? Why have you chosen to pursue these fields of study? My research is focused in two main areas: the monitoring of waterborne pathogens, and the use of microfluidics for biological applications. Evidently, these overlap in the use of miniaturised systems for the detection of viruses, bacteria and protozoa in water, but I am also involved in projects using microfluidics in medical applications, such as separating bacteria from blood for biomarker analysis. My interest in biosensors and microfluidic systems stems from a course I studied at Chalmers University during my Masters it was fascinating to learn about these systems and their potential uses in biology. The choice to focus on waterborne pathogens for my fellowship was promoted by discussions with a professor at the University of Edinburgh I became really interested in this area as it is so challenging, but also so relevant to peoples quality of life. I like to feel my research will have an impact and help people. How valuable has your Royal Academy of Engineering/Engineering and Physical Sciences Research Council (RAEng/EPSRC) Fellowship proved? Having an RAEng/EPSRC Fellowship is a fantastic opportunity for me to focus on and develop my

use gaming to promote behaviour change on environmental issues such as reducing energy, food and water usage/waste. Working with industry is an excellent way of ensuring that research is relevant to potential end-users, particularly when developing new technologies. I have a project with Scottish Water and we are discussing the challenges they and all other water companies face in pathogen detection. This has been really useful in directing areas of my research. How do you think science communication can be improved within the media? Scientists need to be realistic about the way the media works and also ensure communication is very clear, providing relevant and easy to understand information. We need to make sure we promote ourselves and our work, especially when we have very important and interesting findings, so that good quality science reaches the general public.

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Dr Helen Bridle

It just takes one...

With developed and developing countries alike suffering outbreaks of disease from waterborne pathogens, advances in the methods of detection are sorely needed. Recent efforts from scientists at the Heriot-Watt University to improve the monitoring of such pathogens could provide the key
Cryptosporidiosis and giardiasis are common illnesses in areas with poor water sanitation but, with a resistance to traditional chlorination treatments, they potentially pose a health risk anywhere in the world. Recently, there have been outbreaks of Cryptosporidium in Sweden, Australia and the US, and it is thought at least 60,000 people are infected each year in the UK from this pathogen alone. Just one microorganism can initiate the illness and detecting its presence in large bodies of water is extremely difficult. For relatively healthy individuals the acute, self-limiting gastroenteritis that Cryptosporidium causes can be nothing more than a short-lived, intensely unpleasant experience, but for those with compromised immune systems it can be fatal. In countries where HIV and AIDS thrive, it is a very serious concern. When Australia last experienced an outbreak in Sydney it cost US $45 million just to implement emergency health measures. With methods of detection currently a laborious process and only a few of the 20 plus species of Cryptosporidia proving infectious, what is needed are integrated systems capable of both sample processing and detection which are sensitive enough to deliver detailed information on the species and viability of a pathogen. As a Royal Academy of Engineering/Engineering and Pysical Sciences Research Council (RAEng/ EPSRC) fellow at Heriot-Watt University in Edinburgh, Dr Helen Bridle is investigating the efficiency of sample processing methods and the use of miniaturised systems for surveying the quality of drinking water. A major challenge in assessing the risk of infectious microorganisms in water has traditionally been the processing of water samples, an integral part of monitoring strategies as pathogens may be present in very low volumes. Identifying one pathogen in 100 ml has been compared to the equivalent of looking for one coffee bean in 40,000 Olympic

Results of the polymer microarray work, indicating some polymers with a high degree of oocyst binding and others which are non-binding.

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Intelligence
swimming pools, states Bridle. Currently, the sizes of samples that are typically processed for Cryptosporidium detection are 1,000 l. open the tough oocyst wall is challenging, this is a very attractive approach. However, present methods of acquiring the Raman spectra are too slow. Together with Dr Robert Thomson, Bridle is developing an instrument for rapid Raman scanning of pathogens. The use of biosensors is another area which Bridle has investigated. In order to develop the most efficient Cryptosporidium biosensors, her team has examined various immobilisation chemistries in order to determine which was the most conducive to oocyst binding. This protocol was then applied to cantilever sensors with Dr Will Shu. While this process is unfortunately unable to offer any information regarding species and viability, it could potentially be used as a fast method for detecting oocysts. Branching into previously uncharted territory, Bridles work does not stop at methods of detection. Ideally, the research she is conducting at Heriot-Watt University will help lead from monitoring pathogens to eradicating them. With no previous studies to build upon, Bridle is taking a first look at the impacts of nanoparticles on Cryptosporidium to determine their suitability as a technique for disinfecting water supplies. As well as breaking new ground in the study of waterborne protozoan pathogens, the Crucible-funded projects interdisciplinary nature is bringing engineering, microbiology and toxicology together to take the field of nanotoxicology in exciting new directions.

Biosensors for real-time monitoring of waterborne pathogens and viability determination OBJECTIVES
To develop tools which enable faster monitoring of water quality to improve public health  To develop improved methods of monitoring for waterborne pathogens  To develop miniaturised systems for biological applications

Picking up pathogens
With Professor Mark Bradley of the University of Edinburgh, Bridle has been investigating how filtration methods of monitoring water can be improved upon with regards to detecting both Cryptosporidium and another protozoan parasite pathogen, Giardia lamblia. Bridle and her colleagues screened 652 polymers in order to determine their adhesion characteristics in the first large-scale study of polymer binding to these protozoan pathogens. Identifying polymers that have oocyst adhesive traits and those that prevent binding would improve sample processing since they can be easily applied as a coating over the existing passive polymeric materials used in filters. Having also examined the interactions between these polymers and Cryptosporidium, Bridle and Bradley have designed a membrane filter that has indicated an improved recovery rate of pathogens available for later downstream detection. Existing recovery rates are low due to pathogens remaining stuck on the filters, Bridle states. The results of this small-scale study have earned Bridle a commercialisation award from Heriot-Watt University and industry collaboration to further develop this effective water monitoring technique.

KEY COLLABORATORS
See website for full list of collaborators.

FUNDING
Royal Academy of Engineering/EPSRC Fellowship (2009) BBSRC Industrial Case Studentship with Scottish Water (2009) BBSRC Summer Research Placement (2010) Royal Society Research Grant (2011) Internal EPSRC Unspent Budget Award (2011) Aquavalens, EU project (2011) Initiating Knowledge Transfer Fund (2012) Heriot-Watt Crucible Funding (2012) Scottish Crucible Funding (2012) MRC Confidence in Concept (2013) STFC Environmental CLASP (2013)

CONTACT
Dr Helen Bridle Research Fellow EM316 Heriot-Watt University Edinburgh Scotland, EH14 4AS UK T +44 131 451 3355 E h.l.bridle@hw.ac.uk http://drhelenbridle.weebly.com/ Dr Helen Bridle undertook a BSc in Natural Sciences at Durham University, allowing her to study Chemistry, Maths, Philosophy and Sports Science. She moved to Gothenburg, Sweden, where her MSc at Chalmers University focused on Advanced Materials with a thesis project entitled Future Display Technologies. She remained at Chalmers during her PhD an interdisciplinary project developing a miniaturised fluidic device for studying biological signalling. Bridles current role at Heriot-Watt University is aimed at improving drinking water quality.

Detection and Interogation

Once water samples have been concentrated, the next stage is pathogen detection, preferably including determination of pathogen species and viability, to give a reliable indication of the public health risk. The detection method water utility companies currently employ for Cryptosporidium is EPA1623, the Environmental Protection Agencys technique of sample processing, followed by microscopy. This method is time-consuming, labour intensive and gives no information on the species and viability. Working on two different approaches, Bridle is exploring both molecular methods and Raman spectroscopy for the identification of pathogen species and viability. The work on molecular methods is in collaboration with the Moredun Research Institute and the aim is to create a microfluidic system to process concentrated water samples. We plan to first image any oocysts present, then undertake excystation to determine viability and finally use molecular techniques to identify the species, says Bridle. The whole detection protocol will take place on-chip in an automated manner, saving time and resources. An alternative approach is that of Raman spectroscopy, which takes a chemical fingerprint of the pathogen, with the potential for species and viability identification without the need to extract molecular material. Since breaking

Working with industry

Bridles expertise in the broad spectrum of water monitoring strategies has particular significance for the 9 million Aquavalens project; a Europe-wide programme dedicated to the delivery of safe drinking water, and water used in food preparation. HeriotWatt University is leading the technology component of the Aquavalens project and Im really excited about being part of it, Bridle explains. In order to meet the EUs Seventh Framework Programme (FP7) call for microbially safe water for human consumption, the team at Heriot-Watt University, along with academic and industrial partners from across Europe, is developing a portfolio of monitoring technologies. There is unlikely to be any onesize-fits-all solution to either sample processing or detection meaning. The evaluation of systems will consider their suitability to a range of unique settings such as different water types and different water treatment/monitoring systems. Although many proposed innovations in detection methods have yet to be validated for commercial use, the water industrys involvement in the Aquavalens project means newly developed technologies will be tested sooner. Validation from testing in real systems outside the lab could significantly improve the chances of Europe and the developing world witnessing a fall in potentially fatal cases of gastroenteritis.

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