Caring for a patient with sepsis is tricky. Clinicians must identify the pathogen that is causing a patient’s infection, monitor the patient’s response to treatments, and race against the clock to prevent organ failure and death. Most of the time, physicians can control the infection itself. What ultimately leads to multi-organ system injury and fatality is the patient’s immune system’s over-exuberant response.
Current testing and bedside diagnostics do not provide clinicians with the precise and timely information needed to rapidly change their therapeutic approach. To address this unmet need, investigators have developed a technology that enables measurement of the activation and function of white blood cells from a small aliquot of blood. The results were published today in Nature Biomedical Engineering.
“Our idea was to develop a point-of-care diagnostic test that, instead of focusing on the white blood cell count, would inform us about white blood cell activation state and function," says corresponding author Bruce Levy of Brigham and Women’s Hospital.
The team’s technological advancements are two-fold. The new approach uses microfluidics—tiny channels that aligns cells by their size—allowing investigators to sort out larger white blood cells from smaller red blood cells and other elements of the blood. This sample-sparing approach requires only microliter quantities of blood instead of milliliters and could reduce the risk of iatrogenic anemia among patients.
Secondly, the team utilized a novel technology for measuring the electrical activity of cells, which changes when white blood cells are activated and can distinguish patients with and without inflammation. This electrical measurement—known as isodielectric separation—gave the team important information about the function and activation state of white blood cells, and was more predictive of the patient's clinical course than were white blood cell counts.
The new findings may have implications beyond sepsis. Having a way to accurately and precisely measure the immune system’s response in microliter aliquots of blood could be useful in monitoring patients receiving immune-modulating therapies, including treatment with immune checkpoint inhibitors for cancer or treatment with immunosuppressive drugs after an organ transplant. A more precise diagnostic test for the immune system’s activity would enable clinicians to adjust their immune modulating therapies to maximize benefit and minimize risk for individual patients.