You must have noticed the sudden change in pitch of a siren on a police car zooming past. That’s the Doppler effect. Scientists at Purdue University have now used the Doppler effect to look inside living cells in a novel approach to detect pathogens and treat infections.

In this unique method, Doppler is used to quickly track metabolic activity in cells and can be used to detect pathogenic microbes in food, water, and other environments and identify treatments for antibiotic-resistant bacteria.

These findings are published in the article “Doppler imaging detects bacterial infection of living tissue,” in the journal Communications Biology by a team of researchers at Purdue University including David Nolte, PhD, professor of physics and Astronomy, John Turek, PhD, professor of basic medical sciences, Eduardo Ximenes, PhD, research scientist in the department of agricultural and biological engineering, and Michael Ladisch, PhD, professor of agricultural and biological Engineering.

“First we did biodynamic imaging applied to cancer, and now we’re applying it to other kinds of cells,” says Nolte. “This research is unique. No one else is doing anything like it. That’s why it’s so intriguing.”

The team exposed immortalized cell lines to different pathogens such as Salmonella and E. coli, and used the Doppler effect to spy out how the cells reacted in a biodynamic assay. “Living 3D in vitro tissue cultures, grown from immortalized cell lines, act as living sentinels as pathogenic bacteria invade the tissue,” note uncthe authors.

This method can be used to quickly detect if an unknown microbe is pathogenic or not, allowing the time and opportunity for precautionary measures and the identification of effective antibiotics.

“This directly measures whether a cell is pathogenic,” says Ladisch. “If the cells are not pathogenic, the Doppler signal doesn’t change. If they are, the Doppler signal changes quite significantly. Then you can use other methods to identify what the pathogen is. This is a quick way to tell friend from foe.”

This new approach can also help differentiate bacterial strains resistant to antibiotic treatment.

Antibiotic resistance is a devastating problem in hospitals where individuals with already compromised immune systems may be infected resulting in potentially fatal bacterial sepsis, or septicemia. This is different from the viral sepsis that has been discussed in connection with COVID-19, though in future studies the team will investigate the application of the method in detecting viral sepsis.

Doppler apparatus
David Nolte works with the Doppler apparatus to peer inside living cells, giving him insight into intracellular activity, metabolism, and pathogenicity. [Purdue University photo/Rebecca McElhoe]

Treating sepsis is challenging. Giving the patient broad-spectrum antibiotics may sound like a good idea, but it often does not help and could make the situation worse. When bacteria come into contact with antibiotics that do not kill them it makes them resistant to that antibiotic and more difficult to treat in future infections.

Culturing the patient’s tissues and homing in on the correct antibiotic to use can take time the patient does not have, usually eight to ten hours. This new biodynamic assay allows scientists to put the patient’s bacterial samples in an array of tiny petri dishes containing the tissue sentinels and treat each sample with a different antibiotic.

Using Doppler, they can then quickly detect which bacterial samples show drastic metabolic changes indicating they have been beaten back by antibiotics.

“When we treat with antibiotics, the bacteria don’t have to multiply much before they start to affect the tissue sentinels,” says Nolte. “There are still too few bacteria to see or to measure directly, but they start to affect how the tissues behaves, which we can detect with Doppler.”

In less than half the time of a traditional culture and diagnosis, doctors using this approach can tell which antibiotic to administer, bolstering the patient’s chances for recovery.

The researchers have worked closely with the Purdue Research Foundation Office of Technology Commercialization to patent and license their technologies. They plan to further explore whether this method would work for tissue samples exposed to nonliving pathogenic cells or dried spores, and to test for and treat viral sepsis.