Sniffing out trouble intelligently

A few germs or even a whiff of vapour from the exhaled breath of passengers arriving at an Airport could soon be enough to detect persons suffering from noxious diseases. A massive research effort is underway round the world to find the best methods to automate the rapid detection of diseases in both humans and animals. It is even possible that such techniques might be used to detect somebody stressed enough to be planning something violent, but the most immediate applications are in medical diagnostics, where they are already in service on an experimental and research basis, and in fermentation process control. Diseases are much greater threats to human civilisation and animal husbandry than terrorism. The influenza pandemic of 1918/1919 killed between 20 and 40 million people, more than the World War that preceded it. The Black Death of 1347 wiped out one third of the population of Europe, and may not have been something antibiotics could cure if it reappeared today. Animal husbandry likewise has been plagued by epidemics in recent years, whether foot and mouth disease or 'bird flu'. Increased risk arises because of human and animal movement. Since the human race has no intention of returning to horse drawn and sail powered methods of transportation, means needs to be found to be able to quickly screen sick people or animals on arrival or departure so they can be safely quarantined. Sniffing the breath as a means of identifying and diagnosing disease has been used by doctors since ancient times. According to Michael Phillips of the New York Medical College and Menssana Research, patients with diabetic ketoacidosis smell like rotting apples. Chronic renal failure makes the breath smell like stale urine due to increased levels of dimethylamine and trimethylamine in the blood, advanced liver failure causes a musty stench and a patient with a lung abscess may smell like a sewer. British researchers, are developing a system to detect organic substances in the breath which is sensitive to one part per billion, responds in a few seconds, and has the capability to detect the onset of sickness, long before there is any other indication. Transportable Selected Ion Flow Tube Mass Spectrometry, or TSIFT-MS was originally invented at the University of Keele by Professor David Smith and Professor Patrik Spanel, of the J Heyrovsky Institute of Physical Chemistry in the Czech Republic. It came out of research into interactions between molecules in the tenuous clouds of gas between the stars. The main apparatus consists of a long tube through which helium gas is pumped. Ions are introduced at the tube inlet and neutral molecules, with which they might be reacting, are injected further down. It was soon realised that the same method could be used to detect trace amounts of organic molecules on the breath of sick patients, leading to a medical breathalyser currently in use at the North Staffordshire Hospital to study topics which include the effects of renal failure and dialysis treatment. It is now being further researched and developed for more general practical use in the hands of Claire Turner, a researcher in the Sensing Group at the Silsoe Research Institute in Bedfordshire. The technique first passes air and water through a microwave discharge. This generates ions such as H3O+, NO+ and O2-. The first mass spectrometer selects one of these types of ion, which are then allowed to interact with the breath sample. The ions subsequently react with trace organic compounds in the mixture to yield ionised compounds that can be identified by the second mass spectrometer. Acetic acid, for example, with a molecular weight of 60, can take up a single proton, to go to 61, or with an additional water molecule to go to 79, or with two additional water molecules to go to 97. If an attempt was made to ionise acetic acid directly, it would be broken up, and the resulting ions would give no indication as to what they had come from. When Eureka visited Silsoe, the machine was being used to monitor the exhaust from a small fermenter in order to improve its control. Claire Turner explained that the technique could be used to detect traces of ethanol, isoprene, formaldehyde, acetaldehyde, ammonia, acetone and nitric oxide. Ethanol is produced by animals as a normal metabolic product. Isoprene is produced by plants and animals, for example, under oxidative stress. Formaldehyde, and acetaldehyde are found in the breath of patients suffering from different types of cancer. Ammonia is found in patients with uraemia. Nitric oxide is produced in the breath of patients suffering from certain lung diseases. As the machine has evolved, the equipment has progressed downwards from weighing around two tonnes to bench scale. Very much smaller, however, are various developments aimed at detecting particular DNA strands, such as might be produced by noxious disease organisms, or single virus particles. Dr Rachel McKendry from University College, London, revealed to a gathering in Cambridge attended by Eureka that she was working with arrays of eight gold-coated cantilevers that could be coated with complementary DNA molecules that would bind with DNA molecules of interest. When the right DNA molecules come along, they bind to the complementary DNA molecules. Detection comes from the resulting change in stress or mass of the cantilever arm. The active surface can be regenerated so the devices can be re-used. At the meeting, she said the devices could detect five picomoles (10 -12 gramme molecules/litre) of DNA in solution. The research programme is being conducted in collaboration with Christoph Gerber of the National Center of Competence for Nanoscience at the University of Basel and the IBM Research Rueschlikon in Switzerland. Gerber says that the cantilever arrays can now detect femtomoles (10 -15 ) of DNA molecules of interest at an overall DNA concentration in solution of 75 nanomoles. At the same Cambridge meeting that Dr McKendry talked about her own work, she happened to mention that IBM Research had developed a 'Millipede' array which is a chip device with 1024 cantilevers in an area 3mm x 3mm. The device has been developed to store information in polymer sheets by pecking little holes in them, but also offers great potential for DNA detection. Each cantilever arm is sensitive enough to be able to respond to the presence of a single attached virus molecule. Menssana Research Silsoe Research Institute Claire Turner at Silsoe Dr Rachel McKendry at UCL Eureka says Modern transportation may pose a great threat to human and animal health on a global scale but modern technology, a good part of which is British, offers a solution, as well as offering greatly improved sensing systems for process control, especially that based on fermentation Pointers * Transportable Selected Ion Flow Tube Mass Spectrometry can volatile organic molecules down to 1 part per billion in human or animal breath or other gas streams * Micro and nanoscale cantilever devices are able to detect particular DNA molecules down to femtomole levels (10 -15 gramme molecules per litre). Response times are in minutes