Chemistry professor Ken Suslick developed an artificial “nose” than can diagnose bacterial infections in only a few hours. Photo: L. Brian Stauffer |
Bacterial infections really stink. And that could be the key
to a fast diagnosis.
Researchers have demonstrated a quick, simple method to
identify infectious bacteria by smell using a low-cost array of printed
pigments as a chemical sensor. Led by Univ. of Illinois
chemistry professor Ken Suslick, the team published its results in the Journal of the American Chemical Society.
Hospitals have used blood cultures as the standard for
identifying blood-borne bacterial infections for more than a century. While
there have been some improvements in automating the process, the overall method
has remained largely constant. Blood samples are incubated in vials for 24 to
48 hours, when a carbon dioxide sensor in the vials will signal the presence of
bacteria. But after a culture is positive, doctors still need to identify which
species and strain of bacteria is in the vial, a process that takes up to
another day.
“The major problem with the clinical blood culturing is
that it takes too long,” said Suslick, the Marvin T. Schmidt professor of
chemistry, who also is a professor of materials science and engineering and a
member of the Beckman Institute for Advanced Science and Technology. “In
72 hours they may have diagnosed the problem, but the patient may already have
died of sepsis.”
A colorimetric sensor array is placed in an Petri dish for culturing bacteria and scanned with an ordinary flatbed photo scanner kept inside a lab incubator. The dots change color as they react with gases the bacteria produce. Photo: K. S. Suslick |
While there has been some interest in using sophisticated
spectroscopy or genetic methods for clinical diagnosis, Suslick’s group focused
on another distinctive characteristic: smell. Many experienced microbiologists
can identify bacteria based on their aroma. Bacteria emit a complex mixture of
chemicals as by-products of their metabolism. Each species of bacteria produces
its own unique blend of gases, and even differing strains of the same species
will have an aromatic “fingerprint.”
An expert in chemical sensing, Suslick previously developed
an artificial “nose” that can detect and identify poisonous gases,
toxins, and explosives in the air.
“Our approach to this problem has been to think of
bacteria as simply micron-sized chemical factories whose exhaust is not
regulated by the EPA,” Suslick said. “Our technology is now
well-proven for detecting and distinguishing among different chemical odorants,
so applying it to bacteria was not much of a stretch.”
The artificial nose is an array of 36 cross-reactive pigment
dots that change color when they sense chemicals in the air. The researchers
spread blood samples on Petri dishes of a standard growth gel, attached an
array to the inside of the lid of each dish, then inverted the dishes onto an
ordinary flatbed scanner. Every 30 minutes, they scanned the arrays and
recorded the color changes in each dot. The pattern of color change over time
is unique to each bacterium.
“The progression of the pattern change is part of the
diagnosis of which bacteria it is,” Suslick said. “It’s like
time-lapse photography. You’re not looking just at a single frame; you’re
looking at the motion of the frames over time.”
The researchers tested their array on ten common infectious bacteria. The color changes of the sensor array show what kind of bacteria is growing and even if they are antibiotic resistant. Image: K. S. Suslick |
In only a few hours, the array not only confirms the
presence of bacteria, but identifies a specific species and strain. It even can
recognize antibiotic resistance—a key factor in treatment decisions.
In the paper, the researchers showed that they could
identify 10 of the most common disease-causing bacteria, including the
hard-to-kill hospital infection methicillin-resistant Staphylococcus aureus (MRSA), with 98.8% accuracy. However, Suslick
believes the array could be used to diagnose a much wider variety of
infections.
“We don’t have an upper limit. We haven’t yet found any
bacteria that we can’t detect and distinguish from other bacteria,” he
said. “We picked out a sampling of human pathogenic bacteria as a starting
point.”
Given their broad sensitivity, the chemical-sensing arrays
also could enable breath diagnosis for a number of conditions. Medical
researchers at other institutions have already performed studies using
Suslick’s arrays to diagnose sinus infections and to screen for lung cancer.
Next, the team is working on integrating the arrays with
vials of liquid growth medium, which is a faster culturing agent and more
common in clinical practice than Petri dishes. They have also improved the
pigments to be more stable, more sensitive, and easier to print. The device
company iSense, which Suslick co-founded, is commercializing the array
technology for clinical use.