A new microfluidic tool, which can quickly and accurately isolate neutrophils (the most abundant type of white blood cell) from a small blood sample in order to understand the immune system's reaction to traumatic injury, has been developed by a team of scientists led by Massachusetts General Hospital.

Before recent studies, scientists thought neutrophils' role in the body's defense against injury was to release antimicrobial proteins and ingest pathogens, which are fairly small parts to play. But now, research has found that their roles are much more complex. In fact, neutrophils are vital to chronic and acute inflammation, the immune system's response to injury. 

Researchers are now looking to study patterns of protein synthesis and gene expression in neutrophils in order to obtain more information about the immune response to injury. But isolating the cells is usually challenging and takes more than two hours. Neutrophils are sensitive and easily activated, and handling them the wrong way can cause them to change molecular patterns that the researchers are trying to study. This process also requires large blood samples, and even in a large sample, there are very small amounts of messenger RNA. But the new microfluidic device makes this entire process easier and faster.

"Neutrophils are currently garnering a lot of interest from researchers and clinicians, but collecting and processing them has been a real challenge," said Kenneth Kotz, PhD, of the MGH Center for Engineering in Medicine and lead author of the study. "This tool will allow a new range of studies and diagnostics based on cell-specific genomic and proteomic signatures." 

Kotz and his team discovered a system that collects neutrophil-rich samples in less than five minutes, and from microliter-sized blood sample. Also, the cells are not disturbed by this system. Kotz accomplished this by redesigning the antibody-based coating and geometry of the cell-capture module in the device. 

"Until now, it's been logistically impossible to study neutrophils to the extent we have in this paper," said Kotz. "This technology - which is much faster and gentler than current approaches to isolating cells - can be scaled and modified to capture just about any cell type, and we're working to apply it to other cell-based assays."

Laboratory tests showed that the device collected samples successfully, showing gene patterns and protein activity relative to the activation status of the cell. But lab tests are not enough; this device needs to be applied in real-world environments, and that's exactly what Lyle Moldawer, PhD, of the University of Florida College of Medicine and coauthor of the study, did when he tested the device at six different sites. Samples from 26 patients with traumatic injuries were analyzed and showed complex interactions that triggered shifts of gene expression patterns. 

"This technology has been widely implemented in our 'Glue Grant Program,' with a major impact," said Ronald Tompkins, MD, ScD - chief of the MGH Burns Service and study coauthor. "The ability to capture specific cells in a routine clinical environment rapidly and accurately offers a possible change in the paradigm of normal clinical diagnostics."

The study was published in the August issue of Nature Medicine.