Simplifying and Expediting Inflammatory Biomarker Research with Ella

"Ella is the closest I’ve seen to my goal of one day having a Star Trek-like tricorder. I can take just 25 μL of serum, add it to a cartridge, and in 90 minutes have immune profiling data."

- E. Scott Halstead, M.D., Ph.D., Associate Professor, Department of Pediatrics, Penn State University College of Medicine

E. Scott Halstead, M.D., Ph.D.

The Global Forum on Childhood Pneumonia estimates that 11 million pediatric lives will be lost by the year 2030 if more global action is not devoted to accelerating research efforts against this disease. Among the actions required, is a commitment to research partnerships and breakthrough innovations to both advance our understanding of the immune response during infection and identify earlier time points for therapeutic intervention. Read on to learn how a team of clinician-scientists at Penn State Health are working to address this challenge using Simple Plex assays on Ella.

A systems approach to immune profiling in human pneumonia research

Dr. E. Scott Halstead is an Associate Professor in the Department of Pediatrics at Pennsylvania State University College of Medicine. Dr. Halstead’s research focus has evolved over time, from the examination of systemic inflammatory responses, and now to a focus on pneumonia, both viral and secondary bacterial pneumonia. Together with his collaborator, Daniel J. McKeone, M.D., a Pediatric Hematologist/Oncologist at Penn State Health, he is now driving the systemic immune profiling research forward.

When it comes to identifying translational inflammatory biomarkers, Dr. Halstead explains, “we’re really kind of starting de novo. The number of biomarkers out there is quite small in general, and especially so for lung immune markers.” The team is at the infancy stages of human immune profiling studies but has extensively studied multiple mouse models of acute lung injury to uncover potentially translational biomarkers of pediatric viral pneumonia. “We’re interested in building human immune profiling panels one day and have taken more of a systems approach in our research to doing so, versus a single cytokine or inflammatory protein focus as seen in much of the literature,” says Dr. Halstead.

Follow the breadcrumbs

“I’m a big fan of chemokines as analytes over cytokines,” says Dr. Halstead. His thought process, of course, stems from data collected by the group from various mouse models. But it’s also important to note the fundamentally different roles chemokines and cytokines play in the immune system, “Cytokines exert actions and outcomes, whereas chemokines are more like breadcrumbs the immune system puts down, so immune cells know where to go,” Dr. Halstead explains. He goes on to rationalize, “I thought maybe breadcrumbs are the way to go for immune profiling, maybe there’s more of a stronger signal that’ll last longer – and that’s been holding true for our work.” Several such chemokines the team is excited about from their mouse studies of lung-related infections are CCL17, CXCL9 and CXCL10.

Ella maximizes the use of rare precious samples

“Ella is so much easier and so much less user-dependent than ELISA, and the ability to pick up even very low picograms of analyte per milliliter just blows other platforms out of the water,” says Dr. Halstead. Several years ago, Dr. Halstead was looking for a multiplex assay that had very good sensitivity and reproducibility. In addition to surpassing those criteria, “Ella came with the added bonus of one-button results in 90 minutes,” he adds. His collaborator, Dr. McKeone, also touched on the importance of precious sample types when deciding on an immunoassay approach. “When you work with pediatric samples for IRB approved clinical research, every microliter, every drop of specimen is valuable. Ella needs a very small sample volume, and I can run four analytes at the same time with minimal opportunity for error,” he attests. The team regularly uses the 16 x 4 cartridge format to answer their research questions.

A future-proof solution for profiling immune responses

When asked what they anticipate Ella will enable in the future of their research, the broad applications of real-time immune monitoring results really came to light! “I could see the Ella platform being very useful in monitoring cytokine release syndrome outside of acute respiratory conditions such as during CAR T-cell therapy, and even for better characterizing engraftment syndrome or graft-versus-host disease in a transplant setting with the ability to intervene earlier and quicker, given the fast time to result,” Dr. McKeone envisions.

From a pneumonia perspective, Dr. Halstead forecasts the use of Ella to develop immune-mediated strategies for earlier intervention of severe disease. “I’d like to see whether there’s a lethal signature of chemokines and cytokines that lets me know when an individual is going to handle an infection horrendously and that I’m going to need to maximize therapy,” he adds. When asked if there’s anything else he’d like to add, Dr. Halstead advised, “If you can do something more simply, you’ll have less chance of error. I think this is true in every aspect of my life, including clinical research and medicine.” And we agree, Ella makes getting results far less error-prone than other approaches, greatly simplifying life along the way!

Download this story