A new smell testing device developed by U.K. researchers, which uses breakable capsules filled with scented oils, has the potential to replace the "gold standard" scratch-and-sniff tests and help diagnose both chronic neurological conditions and acute respiratory infections that involve an impaired sense of smell, including COVID-19.

In a paper published Wednesday in the Journal of the Royal Society Interface, a group of engineers and neurologists from Queen Mary University of London detailed their creation of a novel capsule-based smell test, in which the oil-filled capsules are packed individually between two strips of adhesive that can be pinched together to burst the capsule and release the controlled odors. This design is more accessible to people with physical impairments than what is currently used for measuring smell, according to the paper. 

"Absence of sense of smell is associated with isolation, anhedonia and depression," the authors reported in the paper — anhedonia is the loss of one's capacity for pleasure. "The sense of taste is heavily reliant on a functioning olfactory system, and a reduction (hyposmia) or loss (anosmia) of olfaction may be a sign of a head trauma, the result of aging or an acute or chronic medical [disorder]."

The state-of-the-art method for detecting a reduction or loss of smell is the 1984 University of Pennsylvania Smell Identification Test, a 40-item paperboard test that requires the test-taker to scratch a fragrant coating in order to release an odor that they identify using multiple choice. But this design has drawbacks.

Ahmed Said Ismail, now a lecturer at Queen Mary University and co-author of the paper, told The Academic Times that the amount of odor released in such tests is dependent on the extent to which the individual scratches, which could affect the outcome of the test. The proposed capsule-based smell test solves this problem because the amount of odor it releases is controlled by the amount of oil encapsulated, based on theoretical models that the research team developed. According to Ismail, the test is also cheaper than scratch-and-sniff tests, which cost nearly $27 per unit.

Ismail said they took an interest in the topic after hearing that their colleagues at Queen Mary's medical school were looking for a smell testing device that is cheaper and more efficient than the options currently available. "The capsules [are] made by dripping concentric drops using coaxial nozzles, in which the aromatic oil is the inner liquid and a bio-fluid compound called alginate is the outer liquid," Ismail said — a coaxial nozzle is a double nozzle made up of both an inner and an outer nozzle. "The alginate then gets solidified into a shell containing the oil in a process called ionic gelation." 

In the paper, the authors explained that alginate, a polysaccharide extracted from brown algae, can preserve materials for long periods of time, noting that it is commonly used to encapsulate products such as oils, vitamins, dyes and drugs. "To our knowledge, the use of oil-containing alginate capsules has never been previously used to test olfaction," the authors said.

To precisely control the amount of oil encapsulated in their product, Ismail and the research team developed a mathematical model that ensured that the capsules were easy to break. "The most interesting part of the research is the theoretical models we developed to accurately predict and control important characteristics of these capsules, including the amount of oil encapsulated, the size of the capsules and the strength of the capsule's shell," Ismail said. "Controlling the strength of the shell, in particular, is really crucial to provide capsules that are not too stiff to be broken by a fingertip grip."

The researchers tested different makeups of the capsule, and found that smaller capsules formed a thicker shell and required a stronger grip to rupture. A stronger grip was also needed for capsules with a higher alginate concentration, which made the shell stiffer. Capsules with a 2% alginate concentration were found to be ideal for all patient use, while the 4% concentration was too difficult to rupture.  

The prototype smell test contained six spherical capsules filled with a scented oil — mint, orange, clove, coconut, cherry or onion. The capsule is placed between the adhesive strips, and a participant is instructed to crush the capsule with their fingers, peel apart the strips to release the scent and identify the scent. "Based on your ability to recognize the smell, you get a score that can inform you if you are experiencing a loss of smell," Ismail said.

A preliminary screening test was conducted with a group of eight patients with Parkinson's disease. The participants were tested with both the capsule method and the standard scratch-and-sniff method. The two tests measured the same six odors. Additionally, in both tests, onion and clove were the easiest odors to identify.

The participants more often correctly identified the smell using the capsule design compared to the scratch-and-sniff test. And five of the participants reported preferring the capsule smell delivery method because they found it easier to rupture the capsules. This was particularly true for those with tremors caused by Parkinson's disease. 

"Capsules are stable for long time periods at room temperature and, in [our] small proof-of-concept study, the capsules effectively and consistently release odor when ruptured by participants showing a better performance in comparison with the traditional scratch and sniff test," the authors said in the paper. 

Ismail said their new capsule-based smell test can help efficiently diagnose various diseases linked to the loss of smell, such as COVID-19. If an individual tests positive for smell loss with no alternative explanation, they could be quarantined and assumed to have COVID-19 until they are able to take a later antigen test, for example. "This would allow for an early triage system and reduce strain on resources and space requirements," Ismail explained. 

The researchers plan to collaborate with public services and the health care industry, which might be interested in producing their smell kits on a large scale. They are also working to generalize the technique and scale up clinical testing to build a database of patient scores for diseases in which the loss of smell is a key symptom. 

"Although you might think that testing your ability to smell is something easy and you can do it yourself, surprisingly, many do not even notice when they lose their sense of smell," Ismail said. "It may go unnoticed by infected individuals. Therefore, an objective smell test such as our capsule-based test would alleviate this."

The study, "A novel capsule-based smell test fabricated via coaxial dripping," published April 28 in the Journal of the Royal Society Interface, was authored by Ahmed Said Ismail, Gregory R. Goodwin, J. Rafael Castrejon-Pita, Alastair J. Noyce and Helena S. Azevedo, Queen Mary University of London.

Correction: A previously published version of this article incorrectly stated Dr. Ahmed Said Ismail's title. The error has been corrected.