A Gold Standard Gets a Modern Makeover
Measuring antibiotic resistance in hours
By Liz Sheeley
Antibiotic resistance continues to be a difficult problem to solve. One of the most effective ways to curb the increasing resistance is to test the infectious bacteria’s reaction to several antibiotics before choosing which one to prescribe to a patient. Typically, that process takes several days, but now Professor Kamil Ekinci (ME, MSE) and his group have cut that time down to hours.
Their work, published in Proceedings of the National Academies of Science, uses a microfluidic device to first capture bacteria within a small channel and then detect the bacteria’s growth before and after exposure to antibiotics.
This time-lapse video (left) captures a control experiment, showing the E.coli cells are immobilized and growing in the microchannels with no drug exposure. The right shows the normalized electrical resistance change of the microchannels over time. Each second in the video corresponds to about 3 min in the experiment. Video courtesy of Ekinci
This new rapid antibiotic susceptibility test works in the same way as the tried-and-true method by measuring bacterial growth in antibiotics. But instead of having to see the growth, they can measure growth with electrical currents. This allows them to understand how the bacteria are reacting to a treatment on a microscale.
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 a couple of hours.
The test is simple to implement and operating the device doesn’t require expensive training, while the traditional method does. Building the microfluidic device was the most difficult aspect of this work, Ekinci says, as it needed to have very small constrictions so trap the tiny bacteria inside. They pushed current photolithography techniques to their limits to create such an intricate device.
The technology to measure the tiny differences in electrical signals already exists—it’s how a smart phone operates. Ekinci decided to use the concept of electrical resistance as a way to measure the growth rate (whether it was positive or negative) of the bacteria. By doing this, he only needed to wait for tens of bacteria to grow rather than thousands, which is how many are necessary using the current method.
This time-lapse video (left) shows E. coli growth in the presence of the antibiotic ampicillin in the microchannels. The trapped cells are elongating and swelling, but do not divide, and finally burst. The right shows the electrical resistance change and the resistance fluctuations of the microchannels over time, each second in the video corresponds to about 3 min in the experiment. Video courtesy of Ekinci
The more bacteria present, the greater the resistance to electrical current . Taken over time, multiple resistance measurements can track the growth rate of these bacteria when exposed to different antibiotics. Whichever antibiotic inhibits the growth the most would be the best one to prescribe to the patient suffering from the infection.
Tests like these are necessary because bacteria develop resistance when they are exposed to an antibiotic, but survive treatment. Letting any survive allows the bacteria to adapt to that antibiotic, creating a stronger form of that bacteria, leading to superbugs.
This type of test could be easily implemented into the clinic to be used to test bacteria in urinary tract infections, which are quite common.