How low can you go? Measuring proteins in a single blood cell

Measuring proteins in cells is something we excel at at Sanquin. But when cell numbers are small, it becomes challenging. Sanquin researcher Arjan Hoogendijk is working with colleagues on a technique that should make this possible. This development can advance a wide range of research, from understanding blood cells to improving immunotherapies.

De bottleneck

Sanquin has extensive experience with proteomics, the mapping of proteins in cells. This provides valuable information for research into, for example, blood clotting disorders and is widely used within Sanquin. But for many research questions, only very few cells are available, for example from a tumor biopsy or during the development of cultured blood. That is precisely the bottleneck: current methods still require relatively large numbers of cells to perform reliable protein measurements.

“Doctors and researchers want to be able to classify cells as precisely as possible,” says Arjan. “You can look at molecules on the outside of a cell, or at RNA that tells you which proteins a cell is likely to produce. But the most direct information comes from measuring the proteins themselves.”

Blood cells

“Ideally, I want to be able to measure a single cell,” Arjan says. “We’re going to see how low we can go: 1,000, 100, 10… With cultured cells, we’re currently down to about 40.”
To make the step to blood cells, which are much more challenging, Arjan starts with white blood cells. “We already know a lot about them, there are many different types, and you can easily isolate them from blood.” He wants to make the technique as simple as possible, with minimal pipetting. The goal is to perform the entire technique in… a yellow pipette tip.

The applications are broad. Researchers studying the development of blood cells from stem cells can use this technique to better track the exact stages cells go through. That helps with questions about cultured blood, but also with understanding what goes wrong in diseases such as leukemia. Other Sanquin researchers are working on T cells, immune cells that are isolated from tumors and expanded as a form of immunotherapy. To distinguish between different types of T cells in tumor tissue, it is essential to be able to analyze very small numbers of cells.

In addition, the new approach makes experiments more compact. Instead of culture flasks, researchers can switch to small wells, allowing many different conditions to be tested in parallel. That speeds up research.

Arjan is now starting a pilot project with his team, supported by a grant from Sanquin. This is expected to generate sufficient results to apply for follow-up funding and to further implement the technology within Sanquin. If successful, a single cell could soon be enough to deliver a great deal of new knowledge.