If a patient or research study volunteer is having a blood draw at or near a research facility that can perform this type of experiment on site, time delay doesn’t come into play. But for research studies or clinical trials that hope to enroll patients and volunteers in rural areas or draw blood at clinics without an attached high-tech laboratory, rushing the blood samples to the processing site becomes a problem. Most clinical sample collection occurs near major research hubs, limiting understanding of underserved and socio-economically deprived communities.

Now, scientists at the Allen Institute for Immunology plan to tackle the time issue and lower experiment costs to broaden the reach and utility of these cutting-edge technologies for blood draws. The researchers have developed a novel technique, CryoSCAPE, that uses a simple chemical mixture, pre-packaged in a small tube, to put blood into a type of “suspended animation” protecting it from damage during freezing and preserving these delicate molecules in their natural state.

The researchers describe the new approach in an article “CryoSCAPE: Scalable immune profiling using cryopreserved whole blood for multi-omic single cell and functional assays” in the Journal of Translational Medicine.

“Virtually all clinical trials run by biopharmaceutical companies will collect blood at one site, but then they have to ship the blood overnight to a centralized processing site,” said Peter Skene, PhD, director of high resolution translational immunology at the Institute. “We wanted to solve this problem by developing a methodology that allows immediate blood stabilization at the bedside.”

The approach aims to broaden the reach of single-cell technologies, which capture the exact molecular composition of thousands or more of a patient’s individual cells, one cell at a time. As these single-cell methods increase in use in the research world and make their way to clinical use, a blood stabilization technique like this could help increase the accuracy of experimental results and bring single-cell methods to research in diverse human populations, according to the scientists.

Alex Heubeck, researcher at the Allen Institute for Immunology and lead author of the study, works with blood samples in the lab. [Allen Institute]
“This technique allows you to, in a way, keep the sample at the stage it was when the patient first gave blood,” said , Lisa Forbes Satter, MD, an immunologist and pediatrician at Baylor College of Medicine and Texas Children’s Hospital who collaborates with researchers at the Allen Institute to study rare immune-deficiency disorders. “It would be a game changer for institutions and clinics that don’t have a lot of resources.”

The most common of the emerging single-cell technologies, single-cell RNA sequencing, reads out the genes switched on or off in a cell by capturing information about each individual cell’s full suite of RNA molecules. RNA is particularly finicky: The Allen Institute team found that just six hours after blood collection, RNA sequencing data are completely different from those in cells analyzed right after a blood draw.

But the new way of stabilizing blood could be useful for other applications too, its creators say, because it keeps the cells alive and close to their natural state in the body.

The Allen Institute team’s approach also scales up the single-cell experiments to the point that they can now process hundreds of blood samples at once. The technology could be used to broaden the reach of immunology studies at the Allen Institute and elsewhere, Skene said. The method would lower the barriers to participating in research studies because blood could be drawn at neighborhood clinics or pop-up sites, eliminating the need for volunteers to travel to a research laboratory. 

Skene and his colleagues hope these lowered barriers could lead to increased enrollment of members of underserved communities in research studies and clinical trials. The team also plans to use the approach to help streamline and expand clinical trials conducted by biopharmaceutical companies, those that typically need to ship blood samples to a centralized lab for analysis.

“As a team, we’ve developed a lot of exciting but complicated new approaches, but we also need to make these approaches accessible,” noted Julian Reading, senior manager of flow cytometry at the Allen Institute for Immunology. “Now we’re working to open access to this technology, to get to a point where we can actually have broader impact.”

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