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
Exhaled
Biomarkers Can Reveal Lung Disease
Specialized
nanoparticles create a “breath signal” that could be used to diagnose pneumonia
and other infectious or genetic diseases.
Using
specialized nanoparticles, MIT engineers have developed a way to monitor
pneumonia or other lung diseases by analyzing the breath exhaled by the
patient.
In a 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.
“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,” says Sangeeta
Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology
and Electrical Engineering and Computer Science at MIT.
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.
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 author of
the paper, which appears today in Nature Nanotechnology. The first author of
the paper 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.
Monitoring
the breath
For
several years, Bhatia’s lab has been working on nanoparticle sensors that can
be used as “synthetic biomarkers.” These markers are peptides that are not
naturally produced by the body but are released from nanoparticles when they
encounter proteins called proteases.
The
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 patient’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.
More
recently, she turned her attention 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.
She and
her 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.
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 researchers
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.
For 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.
Smart
detection
The
researchers 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.
“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
says.
Her 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 perhaps the SARS-CoV-2 virus.