THE bacteria they are extraordinarily good swimmers, a trait that can be harmful to human health. One of the most common bacterial infections in healthcare settings results from bacteria entering the body through the catheter, a thin tube inserted into the urinary tract. Although catheters are designed to draw fluids from the patient, bacteria are able to push themselves upstream and into the body through the tubes using a unique swimming motion, causing $300 million in urinary infections each year.
An interdisciplinary project at Caltech has designed a new type of catheter tube that prevents the upstream mobility of bacteria, without the need for antibiotics or other chemical antimicrobial methods. With the new design, optimized by new artificial intelligence (AI) technology, the number of bacteria capable of swimming against the current in laboratory experiments has been reduced by 100 times.
The article, “AI-aided geometric design of anti-infection catheters“, was published in the journal Science Advances.
Catheter designed by AI: here are the advantages
In catheter tubes, the fluid exhibits a so-called Poiseuille flow, an effect in which the movement of the fluid is fastest in the center but slow near the wall, similar to the flow in a river current, where the speed of the water varies from fast in the center slow down near the banks.
Bacteria, as self-propelled organisms, exhibit a unique “two steps forward along the wall and one step back in the middle” motion that produces their forward progress in tubular structures. Researchers at the Brady lab had previously modeled this phenomenon.
“One day I shared this intriguing phenomenon with Chiara Daraio, framing it simply as an 'interesting thing,' and her response moved the conversation toward a practical application,” says Tingtao Edmond Zhou, a postdoctoral scholar in chemical engineering and co -first author of the study. “Chiara's research often plays with all kinds of interesting geometries and she suggested approaching this problem with simple geometries.”
Following this tip, the team designed a catheter with triangular protrusions, like shark fins, along the inside of the tube walls. The simulations produced promising results: These geometric structures effectively redirected the movement of the bacteria, pushing them toward the center of the tube where the faster flow pushed them back downstream. The fin-like curvature of the triangles also generated vortices that further disrupted bacterial progress.
Zhou and his collaborators aimed to verify the design experimentally, but needed additional expertise in biology. For this, Zhou turned to Olivia Xuan Wan, a postdoctoral scholar in the Sternberg lab.
“I study nematode navigation, and this project resonated deeply with my specialized interest in movement trajectories,” says Wan, who is also one of the first authors of the new paper.
For years, the Sternberg laboratory has conducted research on the navigation mechanisms of the nematode Caenorhabditis elegans, a soil organism about the size of a grain of rice that is commonly studied in research laboratories and thus had many tools to observe and analyze the movements of microscopic organisms .
The team quickly moved from theoretical modeling to practical experimentation, using 3D-printed catheter tubes and high-speed cameras to monitor bacterial progress. The catheter with triangular inclusions resulted in a reduction in upstream bacterial movement by two orders of magnitude (a 100-fold decrease).
The team then continued the simulations to determine the triangular shape of the obstacle that was most effective at preventing the bacteria from swimming against the current. They then fabricated microfluidic channels analogous to common catheter tubes with triangular designs optimized to observe the movement of E. coli bacteria under various flow conditions. The observed trajectories of E. coli within these microfluidic environments aligned almost perfectly with simulated predictions.
The collaboration grew as the researchers aimed to continue improving the geometric design of the catheter. Artificial intelligence experts from Anandkumar's lab provided the project with cutting-edge artificial intelligence methods called neural operators.
This technology was able to speed up catheter design optimization calculations so that they took not days but minutes. The resulting model proposed changes to the geometric design, further optimizing the triangular shapes to prevent even more bacteria from swimming upstream. The final design improved the effectiveness of the initial triangular shapes by an additional 5% in simulations.
“Our journey from theory to simulation, to experiment and, finally, to real-time monitoring within these microfluidic landscapes is a compelling demonstration of how theoretical concepts can be brought to life, offering tangible solutions to the world's challenges real,” says Zhou.
New findings on how bacteria can maintain a persistent and fast countercurrent swimming motion over distances comparable to those of many human organs could help prevent life-threatening infections, according to a team of international researchers.
Upstream bacterial migrations often occur where fluids flow in one direction, such as in the human urinary tract and in intravenous and urinary catheter tubing. To what extent and how quickly bacteria can swim against the current has long been poorly understood.
This is mainly due to uncertainty about how the bacteria maintain persistent upstream movement despite also demonstrating run-and-fall dynamics: they move forward, tumble randomly, then move again in another direction.
In a paper published in Science Advances, researchers demonstrated how far bacteria in the catheter can travel despite what appears to be erratic movement. The team designed an experiment with E. coli bacteria swimming against the flow of fluid in microfluidic channels, which they then filmed. They examined the extent to which confinement was important in the macroscopic transport of bacteria.
“Our measurements suggest that bacteria swimming upstream can overcome distances comparable to the size of human organs, tens of millimeters within a few tens of minutes under highly confined conditions,” sai
d Nuris Figueroa-Morales, a postdoctoral bioengineering researcher at the Penn State and lead author of the study. the publication.
“In the human urinary tract, for example, ureters are muscular-walled tubes that undergo successive waves of active muscle contraction to move fluid from the kidney to the bladder. When fully contracted, they collapse into a very narrow slit-shaped cross section, possibly conducive to bacterial migration upstream even through the catheter.”
Flow confinement is an essential ingredient for upstream contamination. Bacteria advance along upstream pathways but are interrupted by downstream transport when transported by fast flows near the center of the channel.
The wider the channel, the more bacteria are transported back before resuming their movement upstream near the walls. In a narrow channel, like a catheter, bacteria move much faster and more consistently upstream, an effect the researchers called “supercontamination.” Their findings could explain why some infections quickly become life-threatening medical emergencies.
“It's a physical mechanism. Like a weather vane on a windy day, the geometry of the bacteria makes them point upstream,” Figueroa-Morales said. “The very narrow channels make this upstream migration more drastic. In the experiments, we made the channels so narrow that most of the bacteria swam close to the walls and swam for a long time against the current. The edges of the microchannel and the flow simply help drive the bacteria directly upstream, causing rapid contamination.”
The study findings have implications for the prevention of medical emergencies due to blood infections and other contamination. For example, to avoid bacterial contamination of intravenous and urinary catheter tubes, hospital procedures require periodic replacement of these devices.
This procedure is painful and carries a high risk of further complications. According to Figueroa-Morales, the findings could help design new flow geometries or surface treatments of catheter tubes to limit bacterial migration upstream.
“Our research could also be relevant to new emerging technologies that seek to improve targeted drug delivery, the use of bacteria for environmental cleanup, and understanding the spread of biocontaminants in soil,” Figueroa-Morales said.
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