Tom Shelley reports on a remarkable technology that mimics what sensing and antibody systems do in nature
A family of sensors has been developed that uses polymer films with moulded apertures that allow particular molecules to fit into them. Initially developed to detect water contaminants such as herbicides and algal toxins, they can also be made for larger molecules, such as proteins. This is effected by embossing, as opposed to moulding, and – combined with optical, piezoelectric and electrochemical detection – offers a method of identifying a wide range of chemical molecules.
So far three companies have been set up to exploit the Cranfield technology, with potential applications ranging from explosive and drug detection through medicine, to the detection of chemical and biological warfare agents.
Speaking recently at the Institute of Nanotechnology seminar on ‘Products and Processes for Environmental Benefit’ at the Royal Society in London, Professor Anthony Turner, of Cranfield Health at Cranfield University, stated: “Pollution is thought to be behind the dramatic declines in the numbers of European fish, birds, animals and insects. Forty-two per cent of native mammals, 15 per cent of birds, 45 per cent of butterflies and 45 per cent of reptiles are under threat of extinction.” Nor do humans escape the detrimental effects of water pollution, he pointed out, with research linking chemicals with “reproductive disorders, respiratory and bladder cancers, leukaemia, mesothelioma, skin and eye disorders and respiratory diseases”. Cranfield led the Senspol – Sensors for Monitoring Water Pollution from Contaminated Land, Landfills and Sediment – European Thematic Network. And the technique Turner has been working on for many years has been to develop biosensors whereby something in solution combines with a bioreceptor, in such as way as to induce change that can be detected by electronics. However, the biology is relatively fragile. So, for the past 10 years, he has, along with Professor Sergey Piletsky, been researching synthetic alternatives and particularly MIPs – Molecularly Imprinted Polymers.
These work by forming cross-linked polymer round some of the molecules of interest, so that these act as a template. The template molecules are then removed and computer screening of functional monomers is used to identify those that will best bind with the molecule of interest, which they are then used to prepare the polymer. The polymers work in much the same way as a biosensor – which always involves having something binding to something, often a protein binding to an antibody – but can be considered as biomimetic biosensors that are much more robust than the real thing.
Ultimately, it should be possible to establish a printing process that would take the polymer substrate with cavities, mould another polymer sheet against it to form a positive, and then mould a final sheet of polymer against the positive to produce the sensing film containing the cavities. If the cavities were shallow, it might even be possible to form them by using tolls to emboss a continuous web. There are a number of ways in which the binding of the molecules of interest with the cavities in the polymer may be detected. Neurotoxic amino acid (mussels amnesic shellfish poison) can be detected by photo-grafting MIP on to a coated gold chip and detecting binding using an optical technique – surface plasmon resonance. The detection limit is 5mg per litre. Cranfield is far from the only institution researching these materials and surface plasmon resonance seems to be a favourite technique, but Cranfield has also developed other techniques, such as mounting the sensing polymer on a quartz crystal and detecting the frequency change when the chemical species of interest binds to it. In this way, it is possible to detect the drinking water safety guideline of 1 microgramme per litre of microcystin-LR, a toxin produced by algal blooms. It is also possible to detect binding by the blocking of conduction paths through holes in the polymer and by electrochemical means.
So far, Cranfield has produced MIPs for detecting algal toxins (domoic acid and microcystin); explosives (PETN, DRDX, Tetryl, TNT); herbicides and pesticides (Atrazine, Desmetryn, DDT and Lindane); fungal toxins (aflatoxin B1, ochatoxin A, fumonisin B1, patulin, nivalenol and deoxynivalenol), the detection of metabolites (creatine and creatinine), and various pharmaceuticals and drugs of abuse. It is also possible to use the same method to detect smaller molecules, such as chlorophenols, carbon dioxide, ammonia, water and anaesthetic gases. Since bond length in such substances are of the order of 100 picometres in length, this brings sizes down to less than a nanometre and represents the first polymer engineering application, to our knowledge, that is on the picometre, rather than the nanometre, scale.
And since the interactions take place on the nano scale, the team has developed a proprietary technology to produce nano-sized sensors. The idea is based on making the MIPs as nano-sized particles. Particles sizes are only 30 to 100 kilo Daltons (a Dalton is the weight of a hydrogen atom). Cross-linked oligomers are formed in solution and particles are nucleated by coagulation. Turner states that living polymerisation is used to stop growth at a small size. “The particles are so small that it should be possible to use them to replace antibodies in a variety of analytical or even therapeutic applications,” he points out. “Their small size will help them rival state-of-the-art microarray sensors, where up to 6,500 million assays can be performed on a single 1.3 square centimetre chip.”
Three companies are, it seems, involved with Cranfield at present: GSK, Sphere Medical (set up by Scientific Generics and Siemens for detecting near patient chemicals) and an Irish company to detect drugs of abuse. Meanwhile, MIP sensors are just at the point of being commercialised.
Pointers
* By forming plastic membranes or particles in such a way as to accommodate molecules of specific shapes, it is possible to detect harmful molecules with extreme specificity
* Sensors reproduce the action of biology-based biosensors, without the need for any delicate biology
* The technology is close to commercialisation