When Slower Means Faster

in ME Spotlight-Research, MSE Spotlight Faculty, MSE Spotlight Research, NEWS, Spotlight Research

New method could speed antibiotic tests

By Liz Sheeley

As bacteria grow increasingly resistant to antibiotics, scientists are on the hunt for a fast way test how the bacteria infecting a patient will respond to a particular antibiotic. Professor Kamil Ekinci (ME, MSE), Assistant Professor Chuanhua Duan (ME, MSE) and postdoctoral fellow Vural Kara, along with collaborators from the BU School of Medicine, have developed a new rapid antibiotic susceptibility test that works by measuring the movements of bacteria.

Their work, published in Lab on a Chip, uses a microfluidic device to first capture bacteria within a small channel and then detect the bacteria’s movements before and after exposure to antibiotics. The current gold-standard method for antibiotic susceptibility requires scientists to take a sample of the infection, culture the bacteria so they grow and then test several antibiotics on them. That process takes two to three days. With this new method, results can be seen within an hour.

“Our method is completely different in that it’s not based upon growth, it’s based upon the motion of bacteria,” says Ekinci. “We observed that when you give the bacteria antibiotics they immediately show this decreased movement, and we can connect that to bacterial viability and show antibiotic susceptibility within minutes or tens of minutes because they slow down almost immediately.”

Antibiotic susceptibility testing of two different strains of E. coli - one that is susceptible to the antibiotic and one that is resistant. The left shows how the fluctuations in voltage (which signal movement) of the susceptible strain decrease after exposure to the antibiotic. The resistant bacteria maintain their fluctuations and movement after exposure because they survived the antibiotic treatment. Figure provided by Vural Kara
Antibiotic susceptibility testing of two different strains of bacteria – one that is susceptible to the antibiotic and one that is resistant. The movements of susceptible strain on the left (red), displayed as fluctuations in voltage, decrease after exposure to the antibiotic. The resistant bacteria (right) keep moving after exposure because they survived the antibiotic treatment. Figure provided by Vural Kara

Ekinci, who specializes in nanoscale movements, began investigating bacterial movements back in 2014. The first study used a microcantilever, a device that can measure molecular-scale movements, but also requires other complicated and expensive equipment to act as a biosensor. To translate their work into a more practical application, Ekinci had Kara work with microfluidics, and common electrical testing equipment to generate the electric current and measure the resulting voltage. These tools are less expensive and don’t require extensive training to use, making this method accessible with the potential to be used as a point-of-care diagnostic device.

Kara was tasked with developing a microfluidic chip with a channel small enough to capture the bacteria, but wide enough to allow them to move. Using scientific literature as a resource, Kara developed the chip and determined the voltage to run through the chip to measure bacteria’s movements. The electrical signal needed to be strong enough so they could detect fluctuations in the voltage, but not strong enough to kill the bacteria. These and other variables, like how often they were going to collect a reading, needed to be determined to form the platform.

Then the researchers could show how the measured electrical signal fluctuations corresponded to bacterial movements and after the bacteria were exposed to antibiotics, the fluctuations decreased meaning the bacteria were dying.

Most other rapid antibiotic susceptibility tests use cell culture, meaning bacteria are grown in antibiotics to see if they are affected by the antibiotics—but this technique circumvents that. Cell culture can take longer and sometimes require expensive equipment, which the user needs to be trained on.

“Doctors aren’t as willing to prescribe broad-spectrum antibiotics with the current drug resistance problem and it’s not safe to prescribe them to immunocompromised people like children and pregnant women—you have to target the infection with the correct antibiotic and you have to do it quickly,” says Kara. “But unfortunately the current commercial technologies are not very practical because it can take two days or more to complete.”

Their work was funded by two internal grants: a 2016 Dean’s Catalyst Award and a 2016 Ignition Award. The Dean’s Catalyst Award gives projects seed funding for two years to explore new areas of interest that could spark long-term research endeavors, while the Ignition Award is geared towards funding projects with clear commercial and medical potential. Ekinci and Kara are co-founders of Fluctuate Diagnostic Corporation, a company that is working to commercialize this technology.