123RF/ GRISPB
123RF/ GRISPB

Osh Agabi’s solution to one of biotechnology’s thorniest problems looks like an iridescent purple nipple the size of a steering wheel. Other than that, it’s inconspicuous. It doesn’t beep or pulse or hum. Hanging from a wall, it just sits quietly and smells.

Airports, arenas, factories, people — they all stink, and they stink in particular ways. We know this because our noses tell us so. But attempts to re-create our oldest sensory experience with machines and technology have been woefully lacking. Modern everyday devices might be smart enough to recognise our faces and voices, read our pulses and track our motions, but they can’t smell. The best example of a commercial device that can reliably pick up chemical signals in the air hasn’t changed in years. It’s called a smoke detector.

But Koniku, which Agabi founded in 2015, says it’s landed upon a sensory breakthrough. In July the company struck an agreement with the world’s biggest brewer, Anheuser-Busch InBev, to deploy the Konikore, as the purple bubble is called, to measure how a beverage’s aromatic notes are perceived and experienced by the nose, with the aim of enhancing flavour. And in the next few weeks, the Konikore is expected to start showing up in some US airport terminals, thanks to a partnership with Airbus that’s geared towards bomb detection. Koniku has also signed a development deal with electronic sensor manufacturer Thermo Fisher Scientific to create a method for detecting traces of marijuana on people suspected of driving under the influence.

“What the camera did for vision, we’re now doing for smell,” Agabi says. “I believe we are the first company to build a smell camera on the smell sidewalk.” The difference with Koniku’s “camera” is that the purple encasement contains tiny living nerve cells. They’re suspended inside a proprietary solution designed to replicate the mucosa, the layer of membrane high up in our nasal cavities. The cells contain specific transmembrane proteins programmed to recognise odour molecules, precisely as those in our nose would catch a whiff. The reaction triggers a cascade of signalling events, eventually leading to a chip reader that interprets which receptors were triggered. And there you have it: the authentic recognition of an odour.

Koniku is one of at least three start-ups attempting to bring their biotechnological achievements in odour detection out of the laboratory. Together they’re racing for investors, customers and regulatory approval. One of them, Aromyx, in Mountain View, California, has been testing how its own receptor-based platform reacts in the presence of a variety of diseases, including pancreatic cancer, prostate cancer and malaria. And that got started before a viral pandemic forced the world to reconsider what could be wafting around us in the air. Aromyx’s vision is to reduce the size of the instrument that underlies the technology of its lab-based system to the size of a pregnancy test, capable of telling you that you have cancer or Covid-19 (or, better yet, nothing).

In addition to Aromyx and Koniku, there’s Aryballe, a French start-up that’s attracted backing from Samsung Electronics and Hyundai for its handheld sensor, the NeOse Advance. Aryballe’s device contains peptides, or fragments of proteins, that operate in gas rather than liquid like the Konikore.

For Avery Gilbert and other veteran smell scientists, the battle for smell-sensor supremacy is reminiscent of the late 1990s and early 2000s, when advancements in olfactory research brought about a flurry of electronic devices with catchy names — AromaScan, the Cyranose, ScenTrak. None lived up to their hype and became anything close to a universal odour reader. Gilbert says a biological sniffing system has the potential to do much more. “My feeling is it’s got to be way more efficient,” he says. “You’re using what mammalian noses are using. It’s much closer to what we’re smelling and wanting to smell.”

Because smell is so subjective, not to mention that doctors might miss something if they have a bout of hay fever, it’s not generally considered a reliable diagnostic method. But the fragrant properties of a disease can tell us something, with the right sensor. When a virus attacks a healthy cell, it alters the cell’s metabolic activity, producing abnormal byproducts that enter the bloodstream and are eventually excreted via breath, sweat, or urine. These byproducts, which can include acetone, isoprene, and methanol, are classified as volatile organic compounds, or VOCs.

In theory, this should be the earliest possible detection of any possible infection event

Healthy individuals can produce thousands of VOCs in a single breath. A sick individual might exhale the biomarkers of a disease. “In theory, this should be the earliest possible detection of any possible infection event,” Silverman says. “You’re measuring the output of an infected cell. That can happen far before you get any viral replication.”

All that remains will be to successfully scale up its olfactory technology, safely prepackage the receptors, make it easy enough to use in a doctor’s office and convince the US Food and Drug Administration of its harmlessness. Success is far from assured, but Aromyx plans to start trying in the next few months.

“Why has it always been so difficult to solve olfaction?” Agabi asks. “The physics that rely on it are quite hard. Vision, comparatively, is an easy problem. When people see something, you have these photons that interact with sensors that convert that energy. Pretty straightforward, because these are energy particles by definition. Sound is a compression of air — an energetic particle. But smell is a different beast.”

Compared with what we know about vision and hearing, our understanding of the olfactory process, whether the inhalation of a molecule or the perception of an odour, remains in the Dark Ages. Here’s what we do know: about 400 receptor types in our noses capture ambient molecules bobbing about in the air. These molecules trigger a complex chain reaction ultimately transforming into a perception, a signal. The signal pinballs its way around our brains: a coffee, dark roast; Christmas morning; Mom’s kitchen.

Our nasal receptors are capable of discriminating billions, if not trillions, of smells, particularly ones that act as flavour components for food or drink. The newest smell technology tries to mimic this by drawing on an array of disciplines, from neuroscience and organic chemistry to machine learning, data science — and, more recently, epidemiology. For obvious reasons, scent-based disease detection has got a fresh look over the past year. To some, the dream of a device that can blend into the background and monitor someone’s breath or sweat for illness has never been closer to reality. Then again, if smell technology has been consistent about one thing over the years, it’s a failure to deliver on its promises.

Bloomberg Businessweek. More stories like this are available on bloomberg.com.

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