UVA researcher wins federal grant to develop tools for studying rare circulating cells

A University of Virginia School of Engineering and Applied Science faculty researcher earned a major new federal grant to develop emerging tools to work with some of the rarest circulating cells in the human body, a step toward better treatments for diseases such as cancer and infection.

The project is led by Nathan Swami, a professor of electrical and computer engineering who also holds an affiliated appointment with the University of Virginia Cancer Center. The four-year, $1.1 million National Institutes of Health grant addresses a longstanding challenge in biology and medicine: researchers using current cell-testing methods to study or develop new treatments often miss rare but highly influential circulating cells that are hidden within larger cell populations. 

Most existing approaches to studying cells focus on identifying broad categories - such as red blood cells, immune cells and others. But within those groups are smaller subpopulations of cells that may drive disease progression, treatment response and even immunity, Swami said. Researchers need better tools to observe not just what those cells are made of chemically, but how they physically behave. 

From hidden cells to better diagnoses

We develop tools that can measure at the cellular and molecular scale, but focus on the physical properties of molecules and cells. There are many functions in our body where physical properties make a huge difference."

Nathan Swami, professor of electrical and computer engineering, University of Virginia School of Engineering and Applied Science

For example, Swami's research centers on cellular plasticity - the ability of cells to change physical properties and adapt to new conditions. In diseases ranging from cancer to infection, small subpopulations of cells can drive outcomes, despite representing only a tiny fraction of the total cell population. 

To study them though, researchers first need better ways to find them. Current biopsy methods work well for examining the chemical composition of cells - the DNA and RNA of cells - but don't isolate live cells to gather information on their physical properties and behavior. Swami's grant is to develop the tools to isolate and study these important circulating cell populations so that researchers can develop better treatments to improve patient health. 

Swami and his team will build microfluidic devices to identify cell types based on physical attributes as well as artificial intelligence-powered computational tools to do the large-scale data analysis needed to interpret data from the devices. 

Swami's system aims to integrate microfabricated devices, neural-network-based analytics and embedded decision-making directly onto microchips - a kind of large-scale data collection that is only now becoming practical, because the computing power needed for real-time data analysis is only now starting to exist, he said.

"We want to integrate these tools with electronics and systems so researchers can measure single-cell physical properties on a microchip, and then make a decision on whether to collect a subpopulation of cells and develop analytical systems with computational functions to work with specific cells of interest," Swami said.

For diagnostic tools, the technology could expand access to so-called liquid biopsy approaches, which use blood or other accessible fluids to monitor disease progression or treatment response rather than relying on more invasive surgical biopsy procedures to collect tissue samples. 

One day, this might mean that instead of a patient's surgical biopsy followed by delayed lab results and an eventual treatment plan, clinicians with this device could use blood to create a liquid biopsy sample to better measure the current function of cells and apply patient treatments more quickly and directly.

In the future, the technology could also help distinguish how immune cells respond to infections or identify circulating tumor cells that signal changes in cancer progression.

Swami's project reflects UVA's broader strengths in interdisciplinary research, bringing together engineering, medicine and analytical science. It is funded by an R01 grant, the NIH's flagship, highly competitive program supporting independent, investigator-initiated biomedical research.

The grant, titled "Inline impedance-activated recognition, tracking and sorting system on single-cell biophysical metrics," is funded through the NIH's National Institute of General Medical Sciences and runs through March 2030.