How a Human Smell Receptor Works Is Finally Revealed

 Previously mentioned, more data ...  A space we did much in given our products ... 

How a Human Smell Receptor Works Is Finally Revealed

After decades of frustration, researchers have determined how an airborne scent molecule links to shapeshifting olfactory receptors in the nose.

FOR THE FIRST time, researchers have determined how a human olfactory receptor captures an airborne scent molecule, the pivotal chemical event that triggers our sense of smell.

Whether it evokes roses or vanilla, cigarettes or gasoline, every scent starts with free-floating odor molecules that latch onto receptors in the nose. Multitudes of such unions produce our perception of the smells we love, loathe, or tolerate. Researchers therefore want to know in granular detail how smell sensors detect and respond to odor molecules. Yet human smell receptors have resisted attempts to visualize how they work in detail—until now.

Original story reprinted with permission from Quanta Magazine, an editorially independent publication of the Simons Foundation whose mission is to enhance public understanding of science by covering research develop­ments and trends in mathe­matics and the physical and life sciences.

In a recent paper published in Nature    https://doi.org/10.1038/s41586-023-05798-y , a team of researchers delineated the elusive three-dimensional structure of one of these receptors in the act of holding its quarry, a compound that contributes to the aroma of Swiss cheese and body odor.  ... ' 

How a Human Smell Receptor Works Is Finally Revealed

A space we worked for Coffee smells and tastes

How a Human Smell Receptor Works Is Finally Revealed

After decades of frustration, researchers have determined how an airborne scent molecule links to a human smell receptor.

Wynne Parry,  Contributing Writer, May 1, 2023  in Quantamagazine.

For the first time, researchers have determined how a human olfactory receptor captures an airborne scent molecule, the pivotal chemical event that triggers our sense of smell.

Whether it evokes roses or vanilla, cigarettes or gasoline, every scent starts with free-floating odor molecules that latch onto receptors in the nose. Multitudes of such unions produce the perception of the smells we love, loathe or tolerate. Researchers therefore want to know in granular detail how smell sensors detect and respond to odor molecules. Yet human smell receptors have resisted attempts to visualize how they work in detail — until now.

In a recent paper published in Nature, a team of researchers delineated the elusive three-dimensional structure of one of these receptors in the act of holding its quarry, a compound that contributes to the aroma of Swiss cheese and body odor.

“People have been puzzled about the actual structure of olfactory receptors for decades,” said Michael Schmuker, who uses chemical informatics to study olfaction at the University of Hertfordshire in England. Schmuker was not involved in the study, which he describes as “a real breakthrough.”

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He and others who study our sense of smell say that the reported structure represents a step toward better understanding how the nose and brain jointly wring from airborne chemicals the sensations that warn of rotten food, evoke childhood memories, help us find mates and serve other crucial functions.

The complexity of the chemistry that the nose detects has made olfaction particularly difficult to explain. Researchers think that human noses possess about 400 types of olfactory receptors, which are tasked with detecting a vastly larger number of odoriferous “volatiles,” molecules that vaporize readily, from the three-atom, rotten-egg-smelling hydrogen sulfide to the much larger, musky-scented muscone. (One recent estimate put the number of possible odor-bearing compounds at 40 billion or more.)

“In my mind, one of the most amazing things about olfaction is our ability to detect and discriminate such a wide array of volatiles,” said Hiroaki Matsunami, an olfaction researcher at Duke University and an author of the new study.

Caught in the Act

Perched on the surface of neurons in the nose, olfactory receptors change shape when they snag odor molecules. This reconfiguration prompts the neurons to send signals to the odor-processing parts of the brain. Researchers have long sought to see in detail how the interaction between receptor and odor molecule plays out. .... ' 

Odors In Virtual Worlds

 Again, a space we experimented in, especially with regards to coffee.  Here more VR related.

Scientists have come up with a new way to introduce odors into virtual reality via small, wireless interfaces. 

Creating smells in virtual reality is a vexing problem that has prevented consumer VR devices from offering a full sensory experience in most settings. “People can touch in VR,” says Xinge Yu, a professor at the department of biomedical engineering at the City University of Hong Kong and the lead author of the new paper, published today in Nature Communications. “And of course, you can see and hear in VR. But how about smell and taste?”

Previous efforts to create odors in VR have involved multiple wires, messy liquids, and bulky contraptions that don’t lend themselves to home use. 

To tackle the problem, Yu and his co-author, Yuhang Li of Beihang University in Beijing (both of whom have backgrounds designing flexible electronics), developed two wearable interfaces. One can adhere to the skin between the nose and mouth like a bandage; the other straps on beneath a headset like a face mask.

Both types of interfaces use miniaturized odor generators, a grid of tiny containers filled with perfumed paraffin wax. When a heat source beneath the wax is activated, the wax heats up, essentially becoming a scented candle capable of reproducing multiple odors within 1.44 seconds, according to Yu and Li. When the experience is over, a copper coil kicks a magnet to tamp down on the wax and cool down, ending the scent.

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The higher the heat, the stronger the odor and the more easily identifiable the smell, Yu says. That means that interfaces can get very hot—up to 60° C (140° F), which is dangerous for human skin. But Yu says the interface is safe because of an “open” design that lets hot air escape, along with a piece of silicone that forms a barrier between the skin and the actual device.

In a test with 11 volunteers, the interface that goes between nose and mouth was judged safe so long as it was at least 1.5 millimeters from the nose, with a temperature at the skin’s surface of 32.2° C, or 90° F—less than human body temperature. Yu realizes, though, that a scalding hot interface attached to your face might not feel safe enough to use, and he said he and Li were testing ways to make the interface run at lower temperatures or cool down more efficiently.

Yu and Li are not alone in trying to create seamless olfactory experiences in VR. At this year's CES, OVR Technology announced that it would release a headset containing a cartridge with eight “primary” aromas designed to mix and match. 

“This is quite an exciting development,” says Jas Brooks, a PhD candidate at the University of Chicago’s Human-Computer Integration Lab who has studied chemical interfaces and smell. “It’s tackling a core problem with smell in VR: How do we miniaturize this, make it not messy, and not use liquid?”

Artists have long attempted to bring scents into entertainment. In 1960, “Smell-O-Vision” made its first and only appearance with the film Scent of Mystery, which released odors during key plot points via air conditioning. But the effort bombed: during screenings, scents were either delayed or too faint to notice. 

These new interfaces are a notable development that could change how we experience VR. Olfaction is a powerful sense and a prerequisite for our mouths to detect flavor. The possibilities range from the obvious—sniffing a virtual flower field or inhaling VR food—to some less obvious applications. For example, perfumeries could test fragrances virtually.

Medically, scent-equipped VR could be helpful for people who have anosmia, or an inability to smell, according to Yu. Scents can also be therapeutic for patients with memory issues and might even help with mood. Yu told me he noticed he felt happier when he used the green tea scent in his tests. He realized that the smell was nostalgic: “When I was little, I’d have some chocolate with a green tea flavor,” he recalled. “I still remember peeling off the wrapper, and how I loved the smell.”   ... ' 

Robot with Smell Sensor

 Most interesting, comparing the sensors 'rivaling those of dogs'.

TAU Robot Can 'Smell' Odors Using Biological Sensor  By The Jerusalem Post (Israel), January 20, 2023

The robot with the biological sensor. 

Researchers at Tel Aviv University have developed a biological odor sensor whose sensitivity rivals that of dogs.

Scientists at Israel's Tel Aviv University (TAU) have created a biological sensor to help robots detect and interpret odors., TAU's Yossi Yovel said the researchers mated the sensor to an electronic system and had it smell different odors while measuring electrical activity induced by each scent.

Said Yovel, "The system allowed us to detect each odor at the level of [an] insect's primary sensory organ. Then, in the second step, we used machine learning to create a 'library' of smells. "The algorithm can identify smells with 10,000 times greater sensitivity than a standard electronic device.

From The Jerusalem Post (Israel)    

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Smelling, Touching Take Center Stage in Metaverse

More than vision?  

Smelling, Touching Take Center Stage in Metaverse

Associated Press  Haleluya Hadero; Rio Yamat, January 8, 2023

Metaverse technologies unveiled at the 2023 Consumer Electronics Show (CES 2023) included sensory products that can replicate sensations and even odors in virtual reality (VR). VR developer OVR Technology demonstrated a headset containing a cartridge with eight smells that can be combined into different scents, for release later this year. The company is marketing the product as a kind of digital spa combined with Instagram, with the goal of helping consumers relax. Aurora Townsend at VR game developer FireFlare said her team aims to enhance the company's upcoming Planet Theta VR dating application with touch and other sensations. Metaverse expert Matthew Ball doubts such products will see wider use in coming years, outside of fields with large budgets and specific needs like bomb disposal units using haptics, and medical workers.  ... ' 

Digitizing, Measuring Smell

 Was long time interest of ours for product use.

Digitizing Smell: Using Molecular Maps to Understand Odor   Google Blog

Tuesday, September 6, 2022

Posted by Richard C. Gerkin, Google Research, and Alexander B. Wiltschko, Google

Did you ever try to measure a smell? …Until you can measure their likenesses and differences you can have no science of odor. If you are ambitious to found a new science, measure a smell.

— Alexander Graham Bell, 1914.

How can we measure a smell? Smells are produced by molecules that waft through the air, enter our noses, and bind to sensory receptors. Potentially billions of molecules can produce a smell, so figuring out which ones produce which smells is difficult to catalog or predict. Sensory maps can help us solve this problem. Color vision has the most familiar examples of these maps, from the color wheel we each learn in primary school to more sophisticated variants used to perform color correction in video production. While these maps have existed for centuries, useful maps for smell have been missing, because smell is a harder problem to crack: molecules vary in many more ways than photons do; data collection requires physical proximity between the smeller and smell (we don’t have good smell “cameras” and smell “monitors”); and the human eye only has three sensory receptors for color while the human nose has > 300 for odor. As a result, previous efforts to produce odor maps have failed to gain traction.

In 2019, we developed a graph neural network (GNN) model that began to explore thousands of examples of distinct molecules paired with the smell labels that they evoke, e.g., “beefy”, “floral”, or “minty”, to learn the relationship between a molecule’s structure and the probability that such a molecule would have each smell label. The embedding space of this model contains a representation of each molecule as a fixed-length vector describing that molecule in terms of its odor, much as the RGB value of a visual stimulus describes its color. ... '

Smell as Useful Sense

We spent much time examining the power of smell in retail.    Worth a close look. 

Virtual Reality Stinks Because It Does Not Smell

By Wired, August 2, 2022

Illustration shows person wearing virtual reality goggles and uses smoke to imply an odor.

Playing with smell can render a strange world more human, draw us into exploring new environments, and imprint that experience with emotional force and stakes.

Smell is virtual reality's (VR) blind spot. Most VR technologists do not even notice the lack of smells or worry about its consequences, despite the fact that convincing smell technology is becoming available.

Smell is arguably our realest sense—the sense that most grounds us in reality. If virtual reality wants to deliver on its potential, it needs to wake up and smell its nauseating scentlessness.  .... 

Full article in Wired   

Olfactory Displays

We experimented with the control of Olfaction in Retail.  Like the analytical analysis described. 

Scientists Artificially Recreate Smells Using Olfactory Display

Tokyo Tech News (Japan), April 1, 2022

Researchers at Japan's Tokyo Institute of Technology have developed technology that can artificially replicate diverse scents by combining multiple odor components. The researchers defined 185 essential oils using mass spectrometry, then extracted 20 corresponding basis vectors via multidimensional data analysis. They produced various smells by mixing odor components corresponding to these basis vectors, and were able to emulate a variety of scents by adjusting the composition of odor elements. The team also used an olfactory display to generate scents instantly in the gaseous phase from 20 odor components. In a sensory test, people using the display were presented with seven typical essential oils derived from the 185 essential oils; the test subjects reported no significant difference between the original and reproduced smells. ... '

Interacting with Computers Through Smell

In our innovation spaces we also looked at 'communication', and sales via smell and taste.  Since at the time we were makers of some very large coffee blends.    We worked with simulations of blends and how people interacted with them via taste and aroma.  We even tested the ability to 'smell' with computers to test blends and model consumer reaction.  And their reaction in virtual reality settings.

Interacting With Computers Through Smell  By Sandrine Ceurstemont, Commissioned by CACM Staff, October 7, 2021

We typically interact with computers and virtual environments using vision, hearing, and touch, but there is growing interest in also incorporating smell, to replicate more closely how we interact with the real world.

Odors could help people feel more present in virtual reality settings, for example, while smell could also play a role in how we make rapid decisions or recall memories when using computers.

"The question is how can we harness the power of smell in this increasingly digital world," says Marianna Obrist, professor of multisensory interfaces at University College London in the U.K.

There are still challenges to overcome before smell can be widely used as a mode of human-computer interaction, though. A better understanding of how it could impact different aspects of behavior in virtual environments, for example, is needed.

"What we are trying to do is to understand the temporal and spatial diffusion of scent in order to really understand the effect on the user," says Obrist.

In recent work, Obrist and her colleagues investigated whether smell could help direct a person's attention in a virtual reality environment. They conducted experiments in which participants were presented with an abundance of visual stimuli, and had to pick out those that looked like mint leaves. Either sounds, smells, or both were incorporated into the virtual scene, and were emitted from different positions  in the virtual environment, in order to learn whether they could help guide a person towards the mint leaf icons.

Participants were assessed based on the number of mint leaves they spotted and where they were located. The position of each person's head was tracked as they completed the task, to determine the direction they were looking and whether that matched up with the location from which a scent or sound was being emitted.

Obrist and her team found participants typically directed their attention to the source of a sound or smell. Furthermore, they seemed to explore the left side more thoroughly when a sensation was delivered from the left, compared to when it originated from the right side. The researchers think that could be because all the participants were from cultures that read from left to right. "That might have some effect which would need to be accounted for in the future," says Obrist.

They also found differences in how effectively people focused their attention when sound or smell were used on their own, compared to when both modalities were combined. "The integration of sound and smell definitely produced the best results," says Obrist. ... ' 

Directional Smells, Virtual Odors, Stereo Smell

In our innovation enters we tried to enhance smell,  but not usually directionally.  It was expected that the people would determine changes in smell by their own motion.   Might be useful for example in detecting gas leaks in disaster relief operations.  Really a quite interesting change in how aroma sense might be redefined.   But is that useful? 

Digital Nose Stimulation Enables Smelling in Stereo

IEEE Spectrum, Evan Ackerman, May 13, 2021  via ACM

Researchers at the University of Chicago (UChicago) have developed a wireless, nose-worn device that can enable directional smell using tiny electrical impulses. The battery-powered hardware has magnets to keep itself attached to the inside of the nose; it can detect inhalation, and employs electrodes to stimulate the septum and trigger the trigeminal nerve. The model, which connects with external sensors, works well enough that completely untrained people can use it to localize electrically-triggered virtual odors. UChicago's Jas Brooks said, "The sensation our device produces can feel like a 'tickling' or 'sting,' not far from that of wasabi or the smell of white vinegar, except it is clearly directional." The stimulator could be used as an assistive device for people suffering loss of olfactory function.  .. "

Robots Sniffing COVID

 Interesting robot sensor approach to COVID detection.

Startup bets on new coronavirus testing alternative: COVID-sniffing robots

By: Bloomberg - 02 Oct, 2020

Startup bets on new coronavirus testing alternative: COVID-sniffing robots

A biotechnology startup called Koniku is trying to develop robots that could sniff out Covid-19 infections faster than conventional testing.

The technology fuses neurons with a silicon chip to create a “smell cyborg" capable of detecting scents ranging from explosives to pathogens.

Koniku’s first clinical trial began three weeks ago and will examine samples from patients tested for Covid-19 to compare how well the smell-bot detects the virus compared with traditional methods. Small internal trials have already demonstrated that it can accurately detect the presence of influenza A.

“Our goal is to have a device that merges synthetic biology with silicon and maps all of the smells of human life on a global scale," said Oshiorenoya Agabi, the San Rafael, California-based company’s chief executive officer and co-founder. “We should have a device in every home in America to screen for disease."  .... '

Drones Tracking Smells

 We did lots of work examining smells, and sought means to detect and track them. Here an update in the space. Could have used tested for forestry and agriculture  application.    See many posts on digital smell her over a number of years.

Smellicopter Drone Uses Live Moth Antenna to Track Scents

Robots are no match for the sensors insects are born with, but that doesn’t matter if we can just steal them   By Evan Ackerman  in IEEE Spectrum Robotics ...

Can AI Sniff the Roses, Predict the Smell?

Spent some time in examining artificial olfaction for the coffee business. Here we are looking at predicting what something smells or tastes like.   The general approach of predictive machine learning is well described below.  The broad idea of 'digital scent' has been broadly mentioned in this blog.

Using AI to Smell the Roses
UC Riverside News
Iqbal Pittalwala

Researchers at the University of California, Riverside (UCR) used machine learning to understand what a chemical smells like to humans. UCR's Anandasankar Ray and Joel Kowalewski developed a technique for a computer to learn chemical features that activate known human odorant receptors (ORs), then screened about 500,000 compounds for binding ligand molecules for 34 ORs. The team then concentrated on whether their OR activity-estimating algorithm could predict diverse perceptual qualities of odorants, and learned that such activity accurately predicted 146 distinct chemical percepts. Only a few ORs were required for prediction. Said Ray, "The machine learning algorithm can eventually predict how a new chemical will smell, even though we may initially not know if it smells like a lemon or a rose."  ... " 

VR System to Turn Smells into Temperatures

Here is quite an interesting play,  hacking your nose to get a temperature experience?  Skiing VR  experiences?  Thinking about the reality of this.    Temperature sensations .... how about others?

VR System Hacks Your Nose to Turn Smells Into Temperatures
IEEE Spectrum
Evan Ackerman
June 26, 2020

University of Chicago (UChicago) researchers have developed a power-efficient technique for generating different temperature sensations in virtual reality (VR) by essentially hacking the user's nose. The system disperses atomized chemicals to access the trigeminal nerve in the nose in order to replicate hot and cold sensations through odors. The device can produce discrete levels of hot and cold, and vary their intensity by tuning the frequency of the chemical dispersal. UChicago's Jas Brooks said, "Ultimately, any kind of new modalities for VR/AR (augmented reality) will only succeed if they are feasible in a mobile/untethered context. If we want to have thermal experiences that are portable, the device needs to be power-efficient."

Detecting Odors

I often mention research in this area because we spent considerable time looking at the idea of an 'artificial nose' to effectively  test quality in products, especially coffee, but in other areas as well.    Here more in the area.  Note the use of 'Neuromorphic', or brain-inspired chips to address the problem.

Intel Trains Neuromorphic Chip to Detect Odors
in VentureBeat
By Kyle Wiggers

Intel and Cornell University researchers have trained Intel's Loihi neuromorphic processor to identify 10 materials from their odors, demonstrating how neuromorphic computing could be applied to detect precursor smells and potentially find explosives and narcotics, diagnose diseases, and notice signs of smoke and carbon monoxide. The chip was trained by configuring the circuit schematic of biological olfaction, using a dataset compiling the activity of 72 chemical sensors in response to various scents. The researchers said the method kept Loihi's memory of the scents intact, and the chip has "superior" recognition accuracy compared with conventional techniques. Said Intel's Nabil Imam, "This work is a prime example of contemporary research at the crossroads of neuroscience and artificial intelligence and demonstrates Loihi's potential to provide important sensing capabilities that could benefit various industries." ... '

Cyber Agriculture

My own strong interest and background in botany makes me consider this closely, consider the implications.  In particular have been experimenting with basil flavors for years.   While the smells of basils can be considerable, they often do not perform as distinctly in dishes.   Can we program in robust flavors?  Following.

MIT’s ‘cyber-agriculture’ optimizes basil flavors   By Devin Coldewey @techcrunch

The days when you could simply grow a basil plant from a seed by placing it on your windowsill and watering it regularly are gone — there’s no point now that machine learning-optimized hydroponic “cyber-agriculture” has produced a superior plant with more robust flavors. The future of pesto is here.

This research didn’t come out of a desire to improve sauces, however. It’s a study from MIT’s Media Lab and the University of Texas at Austin aimed at understanding how to both improve and automate farming.

In the study, published today in PLOS ONE, the question being asked was whether a growing environment could find and execute a growing strategy that resulted in a given goal — in this case, basil with stronger flavors.

Such a task is one with numerous variables to modify — soil type, plant characteristics, watering frequency and volume, lighting and so on — and a measurable outcome: concentration of flavor-producing molecules. That means it’s a natural fit for a machine learning model, which from that variety of inputs can make a prediction as to which will produce the best output.

“We’re really interested in building networked tools that can take a plant’s experience, its phenotype, the set of stresses it encounters, and its genetics, and digitize that to allow us to understand the plant-environment interaction,” explained MIT’s Caleb Harper in a news release. The better you understand those interactions, the better you can design the plant’s lifecycle, perhaps increasing yield, improving flavor or reducing waste.  .... " 

Smelling Moth Brains are Smarter

Its not news that biological neural networks are very different from those used in artificial neural  networks (ANN)  we still don't know how the former work.    The odor/aroma aspects were of interest when we looked at mechanisms of detecting and delivering smells and taste in coffee.

Why even a Moth’s Brain is Still Smarter than an AI   in Technology Review.
A neural network that simulates the way moths recognize odors also shows how they learn so much faster than machines.

One of the curious features of the deep neural networks behind machine learning is that they are surprisingly different from the neural networks in biological systems. While there are similarities, some critical machine-learning mechanisms have no analogue in the natural world, where learning seems to occur in a different way. .... " 

Computers Sensing Odors

Another area we examined for possible classification of coffee blends, fragrances and for in store understanding of smell 'scapes' in retail spaces.   Investigation has been going on in this space for some time, but with incomplete precision.

It was thought that neural patterns might lead to results.  Some possible results:

In CACM:  " ...  Harvard University researchers have developed a machine-learning algorithm to train a computer to recognize the neural patterns associated with various scents, and to identify whether specific odors are present in a mix of smells.

The algorithm works like other pattern-recognition systems, only the patterns are the neural activation patterns of mice reacting to particular odors.

"Essentially, one odor causes a particular neural activation pattern, and another odor causes a different pattern," says Harvard professor Venkatesh Murthy.  ... " 

More on Generating Smells

This is a topic that we covered in the innovation center, and this blog has covered for about the same time.  Have seen dozens of examples claiming generated digital scent.  We looked and tested how it could be integrated into retail.  By package, shelf, zone and even specific to interaction.  Most recently seeing the ability to integrate the idea into the smart home.  Here in Technology Review, some new developments and a good description of the difficulties involved.  Below, lots more coverage of the idea.

Seeking Delivered Aroma on Demand

One of our longtime interests.  Can you deliver tailored aroma digitally?  On demand and mobile?   There have been a half dozen attempts, none very successful.  Here is another example, delivering popcorn scent to your smartphone with a dongle.  Not what we were attempting to do, simplisitic, looks mainly to be an attention ploy, but another example.  Read more written here about related work.  " ... Hey, My iPhone Smells Like Popcorn! ...  Pop Secret's limited-edition gizmo is an olefactory breakthrough ... " 

And also about scent, Nissan invents the scent of the future.