CryoSCAPE Enables Accurate Single-Cell Profiling in Diverse Populations

Human blood is a complex and delicate mixture, often used by researchers and clinicians to understand the body's inner workings. One reason for this is that drawing a blood sample is less invasive and less painful than performing an internal organ biopsy.

However, blood can behave quite differently outside the body. For certain emerging research techniques, timing is critical, as changes begin the moment blood is drawn. Within just six to eight hours, some elements of the molecular makeup of blood may change significantly, potentially yielding entirely different experimental results.

This time delay is not a concern if the blood draw occurs near a facility capable of conducting these experiments on-site. However, for clinical trials or research projects recruiting participants from remote locations, or clinics without advanced laboratory facilities, transporting blood samples quickly enough becomes a logistical challenge.

This limitation disproportionately affects underprivileged and socioeconomically disadvantaged communities, as most clinical sample collection is concentrated near major research centers, leaving these populations underrepresented in studies.

To address these challenges, researchers at the Allen Institute for Immunology, a division of the Allen Institute, have developed a novel method called CryoSCAPE. This technique aims to "stop the clock" on blood sample degradation and reduce experimental costs, broadening the applicability of cutting-edge blood draw technologies.

CryoSCAPE uses a simple chemical mixture, pre-packaged in a small tube, to put blood into a form of suspended animation. This preserves the blood’s fragile molecules in their natural state and protects them from damage during freezing.

This scalable immune profiling technology, designed to enhance the reach and affordability of blood-based research, is detailed in a recent study published 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. We wanted to solve this problem by developing a methodology that allows immediate blood stabilization at the bedside.”

 Peter Skene, Director and Study Developer, Allen Institute

The strategy seeks to increase the scope of a class of studies called single-cell technologies, which, one cell at a time, determine the precise molecular makeup of thousands or more of a patient's cells.

A blood stabilization technique like this could help improve the accuracy of experimental results and introduce single-cell methods to research in a variety of human populations as these single-cell methods become more popular in the research community and eventually find their way into clinical use.

This technique allows you to, in a way, keep the sample at the stage it was when the patient first gave blood. It would be a game changer for institutions and clinics that don not have a lot of resources.”

Lisa Forbes Satter, Immunologist and Pediatrician, Baylor College of Medicine

Satter is also associated with Texas Children’s Hospital and collaborates with researchers at the Allen Institute to study rare immune-deficiency disorders.

Single-cell RNA sequencing, the most popular of the new single-cell technologies, reads out the genes that have been turned on or off in a cell by gathering data about the complete set of RNA molecules found in each individual cell.

RNA is especially picky: a team from the Allen Institute discovered that RNA sequencing data from cells examined immediately following a blood draw differs entirely from those obtained just six hours after blood collection.

However, because it keeps the cells alive and in a state that is similar to their natural state in the body, the new method of stabilizing blood may also be helpful for other purposes, according to its creators.

Additionally, by scaling up the single-cell experiments, the Allen Institute team is now able to process hundreds of blood samples simultaneously. According to Skene, the technology could be utilized to expand the scope of immunology research conducted at the Allen Institute and other locations.

The volunteers would not have to travel to a research lab, blood could be collected at local clinics or pop-up locations, lowering the barriers to research study participation. Skene and his colleagues anticipate that more members of underserved communities will be able to participate in clinical trials and research studies as a result of these lowered barriers.

The group also intends to use the strategy to help biopharmaceutical companies, who normally have to send blood samples to a central lab for analysis, expedite and grow their clinical trials.

As a team, we have developed a lot of exciting but complicated new approaches, but we also need to make these approaches accessible. Now we are working to open access to this technology, to get to a point where we can actually have a broader impact.”

Julian Reading, Senior Manager, Flow Cytometry, Allen Institute