Innovative AI Breath Analyzer Diagnoses Diseases by “Smell” – AI System to Detect 17 Diseases from Exhaled Breath with 86% Accuracy

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Re-Posted from Psychology Today: Author Cami Russo

Imagine being able to know if you have Parkinson’s disease, multiple sclerosis, liver failure, Crohn’s diseases, pulmonary hypertension, chronic kidney disease, or any number of cancers based on a simple, non-invasive test of your breath. Breath analyzers to detect alcohol have been around for well over half a century—why not apply the same concept to detect diseases? A global team of scientists from universities in Israel, France, Latvia, China and the United States have developed an artificial intelligence (AI) system to detect 17 diseases from exhaled breath with 86 percent accuracy.

The research team led by Professor Hassam Haick of the Technion-Israel Institute of Technology collected breath samples from 1404 subjects with either no disease (healthy control) or one of 17 different diseases. The disease conditions include lung cancer, colorectal cancer, head and neck cancer, ovarian cancer, bladder cancer, prostate cancer, kidney cancer, gastric cancer, Crohn’s disease, ulcerative colitis, irritable bowel syndrome, idiopathic Parkinson’s, atypical Parkinson ISM, multiple sclerosis, pulmonary hypertension, pre-eclampsia toxemia, and chronic kidney disease.

The concept is relatively simple—identify breath-prints of diseases, and compare it to human exhalation. What makes it complicated is the execution of the concept. For example, how to identify the breathprint of a disease? Is it unique like a fingerprint? To answer these questions requires a deeper look at the molecular composition of breath.

When we exhale, nitrogen, oxygen, carbon dioxide, argon, and water vapor are released. Human breath also contains volatile organic compounds (VOCs)–organic chemicals that are emitted as gases, and have a high vapor pressure at normal temperature. American biochemist Linus Pauling, one of the founders of modern quantum chemistry and molecular biology, and recipient of the 1954 Nobel Prize in Chemistry, and the 1962 Nobel Peace Prize, studied 250 human breath volatiles using a gas-liquid chromatogram in 1971. Pauling is widely regarded as a pioneer in modern breath analysis. Exhaled breath contains approximately over 3,500 components mostly comprised of VOCs in small quantities according to a 2011 study published in “Annals of Allergy, Asthma & Immunology.”

VOCs are the common factor in the smelling process for both breath analyzers and humans. When we inhale, the nose draws in odor molecules that typically contain volatile (easy to evaporate) chemicals. Once the odor molecules contact the olfactory epithelium tissue that lines the nasal cavity, it binds with the olfactory receptors and sends an electrical impulse to a spherical structure called the glomerulus in the olfactory bulb of the brain.

There are approximately 2,000 glomeruli near the surface of the olfactory bulb. Smell is the brain’s interpretation of the odorant patterns released from the glomerulus. The human nose can detect a trillion smells. In Haick’s researcher team, nanotechnology and machine learning replaces the biological brain in the smelling process.

Haick’s team of scientists developed a system, aptly called “NaNose,” that uses nanotechnology-based sensors trained to detect volatile organic compounds associated with select diseases in the study. NaNose has two layers. One is an inorganic nanolayer with nanotubes and gold nanoparticles for electrical conductivity. The other is an organic sensing layer with carbon that controls the electrical resistance of the inorganic layer based on the incoming VOCs. The electrical resistance changes depending on the VOCs.

Artificial intelligence (AI) is used to analyze the data. Specifically, deep learning is used to identify patterns in the data in order to match incoming signals with the chemical signature of specific diseases. The AI system was then trained on more than 8,000 patients in clinics with promising results—the system detected gastric cancer with 92-94 percent accuracy in a blinded test. The researchers discovered that “each disease has its own unique breathprint.”

Efforts are underway to miniaturize and commercialize the innovative technology developed by Haick’s team in a project called “SniffPhone.”  In November 2018, the European Commission’s Horizon 2020 awarded the SniffPhone the “2018 Innovation Award” for the “Most Innovative Project.”

The market opportunity for medical breath analyzers is expected to grow. By 2024, the breath analyzer market is projected to increase to USD 11.3 billion globally according to figures published in Jun 2018 by Grand View Research—alcohol detection has a majority of the revenue share. Currently breath analyzers are used to detect alcohol, drugs, and to diagnose asthma and gastroenteric conditions. Clinical applications are projected to increase due to the introduction of “introduction of advanced technologies to detect nitric oxide and carbon monoxide in breath,” Grand View Research states. According to the study, the medical application segment is expected to grow due to ability of breath analyzers to detect volatile organic compounds (VOCs) that may help in “early diagnosis of conditions including cardiopulmonary diseases and lung and breast cancer,” and act as “biomarkers to assess disease progressions.”

By applying cross-disciplinary innovative technologies from the fields of artificial intelligence, nanotechnology, and molecular chemistry, diagnosing a wide variety of diseases may be as simple and non-invasive as a breath analysis using a handheld device in the not-so-distant future.



Looking at Nanotechnology in Biotechnology

For some time, the difference between a biotechnology company and a pharmaceutical company was straightforward.

A biotechnology focused on developing drugs with a biological basis. Pharmaceutical companies focused on drugs with a chemical basis.

It was sort of an artificial distinction, and is even more so now because pharmaceutical companies haven’t excluded biologics from their portfolios.

At one time there were even distinctions in the definitions related to small molecules versus large molecules, but those are largely in the dustbin of biopharma vocabulary. It’s one reason why “biopharma” itself is a useful word to bridge the two, and really, biotech and pharma are largely interchangeable.

Nanotechnology Versus Biotechnology

But what about nanotechnology? Is that biotechnology?

The answer to that seems to be … yes and no.

Nanotechnology typically refers to technology that is less than 100 nanometers in size. Although not horribly useful for differentiating things on the microscopic—or smaller—scale, there are 25,400,000 nanometers in an inch. So … small. Really small.

Wouldn’t that refer to many drugs? Yes, probably.

But nanotechnology typicallyrefers to tech made of manmade and inorganic materials in that size range. Again, the key word is “typically.”

There is overlap.  Liji Thomas, writing for Azo Nano, says, “Nanobiotechnology deals with technology which incorporates nanomolecules into biological systems, or which miniaturizes biotechnology solutions to nanometer size to achieve greater reach and efficacy….

Bionanotechnology, on the other hand, deals with new nanostructures that are created for synthetic applications, the difference being that these are based upon biomolecules.”

Clear? Probably not. Here are some examples of biotechnology companies utilizing nanotechnology, along with whatever tools they need to develop their compounds.

PEEL Therapeutics. PEEL Therapeutics is a small biotech company, largely in stealth mode, founded by Joshua Schiffman, an associate professor of Pediatrics at the University of Utah and Avi Schroeder, an assistant professor of chemical engineering at the Technion-Israel Institute of Technology. 

Schiffman was doing work on a tumor suppressor gene, p53, which shows up at very high numbers in elephants. Elephants have significantly lower rates of cancer than humans, who normally have two normal copies of p53. Humans with a disease called Li-Fraumeni Syndrome, have only one, and they have a 100 percent change of getting cancer, or very close to it.

What PEEL is attempting to do is build a synthetic version of p53 and insert them into a novel drug delivery system using nanotechnology. “Peel,” by the way, is the phonetic spelling of the Hebrew word for elephants. eP53 has been successfully encapsulated in nanoparticles, and at least in petri dishes, has demonstrated proof of concept. Elephants are not being experimented upon.

Exicure. Based in Skokie, Illinois, Exicure (formerly known as AuraSense) is a clinical stage biotechnology company that’s working on a new class of immunomodulatory and gene regulating drugs that uses proprietary three-dimensional, spherical nucleic acid architecture.

The SNA technology came out of the laboratory of Chad Mirkin at the Northwestern University International Institute for Nanotechnology.

The company has received financing from the likes of Microsoft’s Bill Gates, Aonfounder Pat Ryan, David Walt, co-founder of Illumina, and Boon Hwee Koh, director of Agilent Technologies. 

The technology platform is complex, but it is essentially various single and double-stranded nucleic acids stuck on the outside of a nanosphere.

They are able to easily penetrate cells, which then trigger immune responses.

SpyBiotech. Headquartered in Oxford, UK, SpyBiotech focuses on the so-called “super glue” that combines two parts of the bacteria that causes strep throat. It was spun out of Oxford University, and was based on research performed by its Department of Biochemistry and the Jenner Institute. When the bacteria that cause step throat are separated, they are attracted to each other and attempt to reattach.

The company is working to use this principle to develop vaccines that, instead of using virus-causing bacteria, will bind onto viral infections.

One of the bacteria that can cause strep throat, impetigo and other infections, Streptococcus pyogenes, is often shortened to Spy, hence the name of the company. When Spy is split into a peptide (SpyTag) and its protein partner (SpyCatcher), they are attracted to each other. The researchers isolated the “glue” that creates the attraction, and believe it can be used to bond vaccines together.

The company has backing from GV,formerly Google Ventures, the venture fund backed by Alphabet/Google.

One of the company’s founders is Mark Howarth, professor of Protein Nanotechnology at the University of Oxford. The fact that he’s working on protein nanotechnology undercuts a traditional definition of nanotechnology as not using biological materials. On his website, Howarth notes that SpyTag and SpyCatcher “is the strongest protein interaction yet measured and is being applied around the world for diverse areas of basic research and biotechnology. We are extending this new class of protein interaction, to create novel possibilities for synthetic biology.”

Ultimately, when researchers are developing drugs, they are using whatever tools are necessary to find effective treatments for diseases. Biotechnology may more accurately be thought of as a set of tools and a philosophical approach to solving biological problems, compared to pharmaceuticals, and nanotechnology is yet another tool.

In the wider world of drug discovery and development, there is also increasing use of artificial intelligence, data science and computational algorithms as well. And who knows what will be used tomorrow.