Nature takes it by a nose

While traditional electronic sensing methods may have reached their limit, rapid advances in molecular biology and genetics have energised the field of artificial olfaction, says Rebecca Simpson. By borrowing from nature’s templates, AO has achieved breakthroughs in detecting substances to the parts per billion – a thousand-fold increase in sensitivity over traditional sensing methods.

ARTIFICIAL olfaction (AO) – the science of complex gas sensing – mimics the biological sense of smell. It provides an objective and quantitative assessment of odour, and can target non-odorant gases in complex mixtures.

Natural systems are far more sensitive and selective than technological systems, and AO researchers are looking at biological olfaction to see what can be learnt from nature. Emerging AO technology presents opportunities for a range of sectors. It is already being applied in the food sector where it can be used to inspect raw materials, control blending, improve shelf life surveillance, assess freshness and detect tampering. AO is also important for environmental monitoring of odours coming from landfill sites, wastewater treatment plants, piggeries, paper or sugar factories, and breweries.

However it is the healthcare and security sectors in which the technology perhaps has the most untapped potential. AO enhances sensitivity and specificity of security systems in detecting explosives, chemical agents and drugs. It also offers accurate non-invasive techniques to warn of illness and monitor disease by recognising patterns in the unique mixtures of exhaled gas caused by bacteria.

To better exploit the opportunities offered by these sectors, GOSPEL researchers have turned to nature for inspiration. The result has been unprecedented increases in accuracy and sensitivity in detecting substances.

Artificial Olfaction

Olfaction means, literally, to smell. This human sense is vital to our interpretation of the world. Understanding how the nose works, and mimicking biological olfaction, is a major focus for research groups. Detecting non-odorant gases, even when they are present in complex mixtures, will become possible as advances are made in understanding the olfactory process.

A GOSPEL research team has used proteins in mouse urine to develop a powerful new generation of biologically-inspired sensors. A thousand-fold increase in sensor sensitivity has been demonstrated using mouse Major Urinary Proteins (MUPs) coated on a traditional piezoelectric crystal.

“MUPs are giving us very high sensitivity and selectivity – at levels that are unachievable with conventional sensing,” according to Professor Krishna Persaud at Manchester University, a lead researcher in the project.

His work was inspired by animals’ delicate sense of smell and the way mice mark their territory. Mice secrete a phenomenal amount of protein in their urine – up to 40mg/ml. MUPs are part of a protein family with a cage-like structure, which traps odorant molecules and then releases them slowly. This helps mice to mark and defend their territory, and it is this feature that makes MUPs stable and useful as a biosensor.

The same sort of odorant binding protein occurs ubiquitously in the noses of mammals, insects and reptiles, and scientists are trying to understand their precise role in olfaction. It is not clear whether they carry molecules away from or towards olfactory detectors, or both.

The proteins are small and very specific about what they bind to, but can be easily engineered to bind to a number of materials. “The unusual properties of MUPs make them particularly suitable for sensors and sensing,” said Professor Persaud. “Development of these concepts will give us sensors which are much more sensitive than traditional systems.”

The team applied MUPs to piezoelectric materials, which resonate with a precise frequency when an electric potential is applied. Target molecules were shown to bind to the MUP coating, changing the mass of the material and altering its resonant frequency.

This technique is well known in artificial olfaction, though detection limits were typically in the range of parts per million. “The mouse urine is giving us sensitivity to the parts per billion,” said GOSPEL leader Dr Udo Weimar at Germany’s University of Tübingen. “GOSPEL’s multidisciplinary approach, and the blending of traditional AO techniques with genetics, molecular biology and biochemistry, is giving us the basis for a whole new generation of sensor.”
“Earlier attempts to develop artificial olfaction systems tried to compete with nature. We’ve realised the futility of this approach, and now we’re collaborating with nature. Nature has given us the tools to target those molecules of specific interest to us.”

The new sensors have many potential applications; though will first be applied to environmental monitoring. They also work well in water so may be used to detect oestrogen levels in processed sewage.

Security applications may include detection of explosives, and in healthcare MUP-based sensors may become important diagnostic tools.
Another biologically-inspired AO technique involves the use of molecular imprinted polymers (MIPs) – which essentially use a molecule’s shape to detect itself. MIPs also promise more accurate and sensitive detection of explosives, and may lead to improvements in food processing, environmental clean-up and process control.

GOSPEL (General Olfaction and Sensing Projects on a European Level) is a Network of Excellence funded by the European Community under the Sixth Framework Programme. It is coordinated by the University of Tübingen and integrates the expertise of 25 research groups across Europe. It also works with over 100 Associate Members from industry and academia worldwide.

One GOSPEL research project used MIPs to detect TNT, one of the explosives commonly used in terrorist attacks.

The technology works by imprinting the molecule that needs to be detected, such as TNT, in a polymer, like cutting shapes in biscuit dough at a molecular level. The molecules are then removed using a solvent, leaving the shape of the target molecule in the polymer. The next time the target molecule is present, for example at an airport security screening, it matches up with and binds to the imprint.

Previously it was thought the technology would only work for liquids and that water molecules were required to bind and selectively absorb target molecules. There had been indications about the possibility to detect gases, and the GOSPEL joint research project made it possible to advance knowledge in this field.

The project allowed one of the lead GOSPEL research partners, the University of Tübingen, to consolidate its experience with quartz microbalances that resonate to signal that a target molecule is present. The frequency at which the quartz resonates decreases when the target molecule settles in the imprint and the quartz microbalance measures this change in frequency.

The university had experience using quartz microbalances at frequencies of 5-10MHz. The platforms developed in the project make it possible to operate the quartz microbalances at frequencies up to 60MHz. The higher frequencies provide better sensitivity and more accurate results.

Dr Horst Krause, Director of Energetic Materials at the Fraunhofer Institute for Chemical Technology (ICT), another GOSPEL partner, says quartz microbalances enable cheap and reliable sensors. “Low-cost detection devices are an indispensable prerequisite for surveillance of, for example, large areas or goods traffic, which is only possible with sensor networks that are cheap and easy to deploy,” He said.

During the GOSPEL research project, the consortium developed innovative testing platforms that will allow, in combination with a laptop, measurements to be taken in the field.

ICT is now looking at how to improve the response of MIPs, while having several different MIPs on a single surface. Dr Krause believes this will lead to wider applications for the technology. “MIPs can be used for food processing, environmental clean-up and process control – the potential applications are endless,” Dr Krause said.

However it is not just a case of developing a device that can identify particular molecules and then rolling it out. Each application will have different challenges, from the characterisation of the target to its reliable detection under varying environmental conditions.

GOSPEL scientists across Europe, including biologists, chemists, physicists, electronic engineers and data processing specialists are addressing the issues which will enable AO to impact on the next generation of technologies. Nature’s templates can be used to solve many technological problems, and promise to unlock a new generation of sensors with unprecedented sensitivity and accuracy.

Poss pull quote: “Earlier attempts to develop artificial olfaction systems tried to compete with nature. We’ve realised the futility of this approach, and now we’re collaborating with nature.”

By Rebecca Simpson. Rebecca took degrees in mathematics and physics before specialising in sensing and instrumentation. She is the Technical Director at the EU-funded artificial olfaction research network, GOSPEL. The network integrates the expertise of 25 artificial olfaction research groups across Europe.