Medical Innovations: MIT Engineers Create Breathalyzer To Detect Breath Biomarkers To Diagnose Diseases Including COVID-19
Source: Medical Innovations Aug 03, 2020 3 years, 11 months, 3 weeks, 3 days, 5 hours, 25 minutes ago
Medical Innovations: MIT engineers have developed an innovative method to monitor pneumonia or other lung diseases by analyzing the breath exhaled by a patient. The new platform can also be improvised to detect pathogens including SARS-CoV-2 that causes COVID-19.
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MIT engineers have designed nanoparticle sensors that can diagnose lung diseases.
If a disease-associated protein is present in the lungs, the protein cleaves a gaseous
molecule from the nanoparticle, and this gas can be detected in the patient’s breath.
Credit: Cygny Malvar
In a laboratory study of mice, the researchers showed that they could use this system to monitor bacterial pneumonia, as well as a genetic disorder of the lungs called alpha-1 antitrypsin deficiency.
The research findings were published in the journal: Nature Nanotechnology.
https://www.nature.com/articles/s41565-020-0723-4
Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science at MIT told Thailand Medical News, “We envision that this technology would allow you to inhale a sensor and then breathe out a volatile gas in about 10 minutes that reports on the status of your lungs and whether the medicines you are taking are working.”
Howvere more safety testing would be needed before this approach could be used in humans, but in the mouse study, no signs of toxicity in the lungs were observed.
Sangeeta Bhatia, who is also a member of MIT’s Koch Institute for Integrative Cancer Research and the Institute for Medical Engineering and Science, is the senior researcher of the project.
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The study’s first author is MIT senior postdoc Leslie Chan. Other authors are MIT graduate student Melodi Anahtar, MIT Lincoln Laboratory technical staff member Ta-Hsuan Ong, MIT technical assistant Kelsey Hern, and Lincoln Laboratory associate group leader Roderick Kunz.
Bhatia’s lab has been working on nanoparticle sensors that can be used as “synthetic biomarkers” for a few years now. These markers are peptides that are not naturally produced by the body but are released from nanoparticles when they encounter proteins called proteases.
The innovative peptides coating the nanoparticles can be customized so that they are cleaved by different proteases that are linked to a variety of diseases. If a peptide is cleaved from the nanoparticle by proteases in the patien
t’s body, it is later excreted in the urine, where it can be detected with a strip of paper similar to a pregnancy test. Bhatia has developed this type of urine test for pneumonia, ovarian cancer, lung cancer, and other diseases.
She turned her attention recently to developing biomarkers that could be detected in the breath rather than the urine. This would allow test results to be obtained more rapidly, and it also avoids the potential difficulty of having to acquire a urine sample from patients who might be dehydrated, Bhatia says.
The study team realized that by chemically modifying the peptides attached to the synthetic nanoparticles, they could enable the particles to release gases called hydrofluoroamines that could be exhaled in the breath. The researchers attached volatile molecules to the end of the peptides in such a way that when proteases cleave the peptides, they are released into the air as a gas.
Developing and working with Kunz and Ong at Lincoln Laboratory, Bhatia and her team devised a method for detecting the gas from the breath using mass spectrometry.
The team then tested the sensors in mouse models of two diseases: bacterial pneumonia caused by
Pseudomonas aeruginosa, and alpha-1 antitrypsin deficiency. During both of these diseases, activated immune cells produce a protease called neutrophil elastase, which causes inflammation.
In both of these diseases, the researchers showed that they could detect neutrophil elastase activity within about 10 minutes. In these studies, the researchers used nanoparticles that were injected intratracheally, but they are also working on a version that could be inhaled with a device similar to the inhalers used to treat asthma.
The study team also demonstrated that they could use their sensors to monitor the effectiveness of drug treatment for both pneumonia and alpha-1 antitrypsin deficiency. Bhatia’s lab is now working on designing new devices for detecting the exhaled sensors that could make them easier to use, potentially even allowing patients to use them at home.
Bhatia said, “Right now we’re using mass spectrometry as a detector, but in the next generation we’ve been thinking about whether we can make a smart mirror, where you breathe on the mirror, or make something that would work like a car breathalyzer.”
Bhatia’s lab is also working on sensors that could detect more than one type of protease at a time. Such sensors could be designed to reveal the presence of proteases associated with specific pathogens, including the SARS-CoV-2 virus.
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