21 July 2020

Exhale the diagnosis

Using specialized nanoparticles, engineers at the Massachusetts Institute of Technology have developed a way to monitor pneumonia and other lung diseases by analyzing the air exhaled by the patient. In a study on mice, the group showed the work of this system for monitoring bacterial pneumonia, as well as alpha-1-antitrypsin deficiency, a genetic lung disease.

The method is based on inhaling a gaseous sensor and then analyzing the exhaled air, which within 10 minutes will report on the condition of the lungs and whether the medications the patient is taking work. Additional safety studies will be required before the technology can be used in humans, but no signs of lung toxicity have been observed in experiments on mice.

Control breathing

For several years, the group has been creating nanoparticles that can be used as synthetic biomarkers – peptides that are not produced naturally by the body, but are released from nanoparticles upon contact with proteases.

The peptides covering the nanoparticles can be configured so that they are cleaved by various proteases that are associated with various diseases. If the peptide is cleaved from the nanoparticles by proteases in the patient's body, it is later excreted in the urine, where it can be detected using a paper test strip - researchers have already developed ways to analyze urine for pneumonia, ovarian cancer, lung cancer and other diseases.

Now they have turned their attention to the development of biomarkers that could be detected in exhaled air, and not in urine. This would make it possible to obtain test results faster, as well as avoid the potential difficulty of obtaining a urine sample from patients with dehydration. Chemically modifying the peptides, they attached hydrofluoramines to them – volatile molecules that break off when interacting with proteases and exhale.

Researchers have developed a method for detecting hydrofluoroamines in air using mass spectrometry. They tested the sensors on a mouse model of two diseases – bacterial pneumonia caused by Pseudomonas aeruginosa and alpha-1-antitrypsin deficiency. In both of these conditions, activated immune cells produce protease (neutrophil elastase), which causes inflammation.

In both disease models, researchers have shown that they can detect neutrophil elastase activity within about 10 minutes. Nanoparticles were injected into mice endotracheal, but it is possible to inject them with inhalers similar to those used to treat asthma.

Smart detection

The researchers also demonstrated that they can use nanodetectors to monitor the effectiveness of drug treatment for pneumonia and alpha-1-antitrypsin deficiency.

The lab is currently working on developing new devices for detecting exhaled markers that could simplify their use, potentially even allowing patients to use them at home. If mass spectrometry is now used as a detector, then the authors plan to create a so-called smart mirror in the analyzers of the next generation, on which it will be necessary to breathe, or a device like a car breathalyzer.

The laboratory is also working on sensors that will be able to detect more than one type of protease simultaneously.

Article by L.W.Chan et al. Engineering synthetic breath biomarkers for respiratory disease is published in the journal Nature Nanotechnology.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru according to MIT News: Exhaled biomarkers can reveal lung disease.

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