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s the medical industry continues its quest for accurate and reliable diagnostic tools, more is becoming understood about the science of the sniff. The olfactory system of mammals is a powerful bio-sensor, its complex network of receptors capable of receiving and distinguishing between a near-unlimited number of odours and other chemical compounds.
There is perhaps no better demonstrator of the power of mammalian olfaction than man’s best friend. Dogs have around double the number of olfactory biosensors when compared to humans, providing a much greater specificity of detection. Past and ongoing studies have been delving into the clinical potential of this canine super-sense, trialling the ability of trained dogs to match or even outperform modern diagnostic technologies when sniffing out the chemical signatures of diseases ranging from cancer and diabetes to malaria and Parkinson’s disease.
In April 2019, cancer screening firm BioScentDX presented a study that found that four trained beagles were able to correctly identify lung cancer samples with 96.7% accuracy, offering the prospect of a non-invasive test and more frequent screening, which is usually limited by the radiation exposure involved.
Rather than using dogs directly, a University of Bristol spinout company called Rosa Biotech is taking a different approach. The company was incorporated in January 2019 to develop and commercialise products based on the academic work of Professor Dek Woolfson at the Bristol BioDesign Institute. Woolfson and his team built a series of barrel-shaped proteins that mimic the mammalian olfactory system, but with a simpler structure that makes them easier to produce and handle.
“It is these barrels that provide the basis for Rosa’s technology,” Woolfson said earlier in 2019. “We make arrays of different barrels, load each barrel with a dye, and then expose the array to something that we want to analyse, for instance a bodily fluid that may show signs of disease. Molecules in the sample dislodge the dyes to different extents across the array. This gives coloured patterns that are analysed using machine learning. By recording patterns for healthy and diseased samples, we hope to build sensors for early-stage diagnosis of disease.”
These manufactured protein barrels underpin every application being pursued by the company, which include both clinical uses and conversations with other industries, including the food and drinks sector.
“We use exactly the same sensor for all of those different applications as we’re developing for diagnostics,” says Rosa Biotech CEO Dr Andy Boyce. “So actually the only thing that’s different is the way in which we analyse that data or perhaps pre-treat some of the samples, but at the point they go on to the sensor, it’s exactly the same sensor each time.”
Ultimately the company’s platform has the potential to achieve a breakthrough in so-called array-based differential sensing; in other words, the ability to run a sample through a sensor array to look for subtle changes in the reaction without knowing exactly what you’re looking for. Work has been done in the past to develop non-organic differential sensor arrays (or ‘electronic noses’) such as metal oxide sensors, but Boyce notes that these have fallen by the wayside due to the instruments’ lack of sensitivity. A biologic array like Rosa’s could make differential sensing work, tackling many of the disadvantages of developing molecule-specific tests.
“The more we come to understand the biology of diseases, the more we realise how little we know about how much variability there is with diseases, especially in chronic diseases, from individual to individual,” Boyce says. “You might develop a test that detects a single molecule or a single protein in a patient, and that might be very indicative but only in a very small number of people – in which case you’re missing the opportunity to make an early diagnosis in a much larger percentage of people.”