Using salt to fight difficult-to-treat biofilms
A Yale study shows that salt can help deliver drugs to some bacteria-filled biofilms, and possibly deform the biofilm itself
Biofilms—bacterial communities encased in a sticky, polymer-rich matrix—can be difficult to treat because that matrix slows antibiotics and drug-carrying particles. With help from salt, though, Yale researchers have found a way to steer these particles into some biofilms, and even deform the biofilm itself in certain cases. The study is published in Soft Matter.
“Biofilms can be undesirable in biomedical settings—for instance, on medical implants they can lead to infections,” said Professor Amir Pahlavan, who led the study, which was published as an invited article in the journal’s Emerging Investigator series. “We would like to target and eliminate pathogenic bacteria within these biofilms. However, the polymeric matrix surrounding the bacteria acts as a sticky protective layer that limits our ability to deliver drugs deep into the biofilm and allows bacteria to survive antimicrobial treatments.”
Typically, molecules and drug carriers rely on diffusion through the biofilm matrix—passive spreading rather than active targeting.
“Diffusion of nano- and micron-sized particles can be very slow and inefficient,” Pahlavan said, assistant professor of mechanical engineering and materials science. “That can require a large dose of particles, so that some of them reach the target.”
To address this, the researchers explored diffusiophoresis, the motion of suspended particles (also known as “colloids”) caused by a gradual change, or gradient, in the concentration of a dissolved substance. They loaded biofilm-filled pores with a higher-salt solution, then introduced colloidal particles dispersed in a much lower-salt solution. The resulting gradient drove the particles into the biofilms. Without the salt gradient, particle penetration was much more limited.
“One advantage of this idea is that, if it works, you don’t need a huge dose of nanoparticles anymore,” Pahlavan said.
The team grew E. coli biofilms for different lengths of time in dead-end pores on a microfluidic chip, then tracked fluorescent particles. In less-dense biofilms, the salt gradient carried particles substantially deeper than in control experiments without a gradient. But penetration declined as the biofilm matured and became denser, eventually falling to roughly the control level.
“This strategy works, but it depends on where and when you are using it,” Pahlavan said. “If we allow the bacteria to grow for too long, the biofilm becomes very dense, and we cannot get the particle in.”
First author Zehao Chen, a Ph.D. student who performed the experiments and simulations, uncovered a counterintuitive result: 1,000-nanometer particles penetrated farther than 40-nanometer particles.
“One might expect smaller particles to have an advantage in navigating tight spaces,” Chen said. “Instead, under the conditions we tested, the larger particles responded more strongly to the salt gradient.” This suggests that the best carrier size may depend on the biofilm’s state.
The researchers also propose that the gradient caused the biofilm matrix to deform and expand, with the flow washing some of the material away. Whether that process can reliably remove biofilms remains to be tested.
“We’re trying to figure out the exact physics behind this process,” Chen said.
Pahlavan noted that the study turns biofilm density from an obstacle into a design parameter.
“It identifies the window in which gradient-driven delivery works and the denser regime in which that advantage is largely lost,” he said. “The same physics may also matter in water and industrial systems, where biofilms clog pipes and other confined spaces and where particles may need to be delivered into a crowded matrix.”
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Published Date
Aug 6, 2026
