Pulses of antibiotics hit microfluidics
Pulses of antibiotics hit microfluidics lead image
Bacteria’s response to antibiotics is often measured under steady-state conditions, where the drugs are introduced, left to react, and monitored over time. However, studying transient doses might be equally important. Taking antibiotics incorrectly, like skipping a dose or accidentally double-dosing, can contradict the steady-state assumption. Exposing bacteria to antibiotics in waves can also give rise to persistence, where a subset of the bacteria appears to survive the first hit of the drug.
Transient doses are more difficult to monitor, because they require keeping bacteria in one place while changing their environment. Rackus et al. designed a microfluidic chip that uses isolation valves and temperature-sensitive hydrogels to anchor the bacteria in place.
“We introduced liquid agarose, which had the bacteria mixed in, into the chip. We closed these donut-shaped valves to isolate little plugs of the hydrogel,” said author Darius Rackus. “Then we wash out the rest of the hydrogel from the chip, bring the temperature down, and are left with a little pancake of bacteria gel.”
From there, the team opened the valve to expose the bacteria to ampicillin, which permeated into the porous gel for a specific amount of time before being flushed out. This allowed them to explore different antibiotic concentrations and timings.
“Normally, if you’re above a threshold concentration, ampicillin’s effectiveness is just time dependent. The longer you expose it, the more the effect it has,” said Rackus. “When we were looking at the short hits of this antibiotic, we found both a time and concentration dependency.”
The researchers plan to use the chip to explore other doses and exposure profiles and investigate delivering other stimulants to bacteria.
Source: “Parallel study of transient dosing of antibiotics in a microfluidic device,” by Darius G. Rackus, Petra Jusková, Fumiaki Yokoyama, and Petra S. Dittrich, Biomicrofluidics (2022). The article can be accessed at https://doi.org/10.1063/5.0091704 .
