Remote communities often lack the kind of medical labs necessary for accurate diagnoses and treatments, but new lab-on-a-chip technology from Pitt may make these devices like these portable.
Pitt researchers have created a model that explains how enzymes can move around cells — either engineered microcapsules or primitive biological cells. This model, which appeared in the journal ScienceAdvances in March, could facilitate portable medical diagnostic tests — and explain how life may have formed on Earth.
This work builds on experimental results from Ayusman Sen, a chemistry professor at Penn State. Sen discovered the enzyme-generated currents in 2014, and the Pitt team figured out how to harness those currents to transport simple cells.
As life evolved on Earth, it was important for individual cells to “sniff” each other out and band together in colonies that could work together for survival, Sen said.
This model provides a means for cells to follow their noses, so to speak. Just as a beagle moves toward the scent of a fox, so can these cells hone in on the enzyme by following the route that produces the greatest convective current, Sen said. When dispersed cells collectively follow the same rule, they ultimately end up clustered together.
“It’s not trivial, and that’s the real beauty of it,” said principal investigator Anna Balazs, chemical and petroleum engineering professor at Pitt. “It’s a multi-stage process.”
To move cells around, researchers need three things: Fluid to flow through the channels, enzymes to create local differences in fluid density and gravity to translate this density differential into convection current like a vortex, said first author Oleg Shklyaev, chemical engineering postdoctoral researcher at Pitt.
The microcapsules in the model are leaky, so chemicals on the inside dribble out and react with enzymes that are anchored to a surface like a stone or a plastic well, Balazs said.
This enzymatic reaction floods the region with chemical product, increasing the local density of the fluid. In the presence of gravity, denser fluids sink and lighter fluids rise, which produces a convection current, Balazs said. The microcapsules flow through the vortex toward the enzyme, collecting there in a clump.
Because the model’s three factors — fluid, enzymes and gravity — are based on realistic conditions on Earth prior to life, the model may explain how early cells came together to form multicellular colonies, which are the basis for complex life forms, Shklyaev said.
Besides uncovering the origins of life, Balazs said the Pitt team hopes to leverage their new model for the development of microfluidic lab-on-a-chip technology, in which laboratory functions involving low volumes of fluids are integrated on a small chip device.
According to Balazs, microfluidic devices only currently exist within a laboratory setting, relying on support machines that are too large to carry.
The goal is to make these microfluidic devices completely self-sustaining and portable so clinicians can take them to the patient’s home or hospital room, Balazs said.
The medical applications for microfluidics are virtually limitless, from identifying specific pathogens, to testing antibiotic resistance, to diagnosing genetic diseases. With a truly portable and self-powered device, physicians could bring these diagnostic tools to even the most remote locations on Earth.
“Channels in these devices are about the size of a human hair, and because of the size, it’s very hard to control the transport of reagents and cells,” Balazs said. “You don’t have little winches that you can go in and tweak things.”
Balazs said the model is so useful because it offers a way to tow reagents — substances used in chemical analysis — or biological samples within microcapsules to a specific spot in the channel.
Now it’s possible to position cells from someone’s body or drugs or chemical reagents exactly where you want them in the device, making it possible to set up a multi-stage reaction like a series of dominoes.
“This system is great because it’s very specific and self-powered so it can sit around forever,” Sen said.
Editor’s note: This story has been updated.