New blood screening method sheds light on cell membranes and disease

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A novel way of imaging red blood cells could provide insights into how these oxygen-carrying cells navigate the body’s maze of blood vessels.

The payoff may promise better screening for blood cell related diseases such as malaria and sickle-cell.

Researchers published their findings this month in the Proceedings of the National Academy of Sciences.

A new microscopy technique reveals the most detailed mechanics of red blood cells. Such measurements could lead to cheaper and more accurate screenings for malaria and sickle-cell. Courtesy Gabriel PopescuA new microscopy technique reveals the most detailed mechanics of red blood cells. Such measurements could lead to cheaper and more accurate screenings for malaria and sickle-cell. Courtesy Gabriel PopescuLed by University of Illinois electrical and computer engineering professor Gabriel Popescu, a group of scientists from across the country worked together to create a new microscope technique that is far more accurate in measuring the cell’s outer layer, called a membrane.

“The idea is to combine typical light microscopy with another light beam that you use as a reference point,” said Popescu, in an interview from the Urbana-Champaign campus. “It is very, very sensitive to minute displacements in the membrane, down to the nanoscale.”

Red blood cells are flexible, doughnut-shaped cells that can squeeze through capillaries half their diameter. Such formability enables them to navigate the body efficiently, but has also made their basic form and structure difficult to study.

When a red blood cell’s membrane becomes deformed, it is often due to diseases such as malaria or genetic mutations. Popescu’s team was not only able to see nanoscale changes in these membranes, but also measure them.

“Because the technology is now high throughput (we can analyze approximately a thousand cells per second), the potential for use in clinical testing is great,” said Catherine Best-Popescu, a member of the research team at the University of Illinois.

Diffraction phase microscopy uses two light beams to lock in an image compared to one beam in standard microscopy. The second beam is used as a reference point to create more accurate measurements. Courtesy Gabriel PopescuDiffraction phase microscopy uses two light beams to lock in an image compared to one beam in standard microscopy. The second beam is used as a reference point to create more accurate measurements. Courtesy Gabriel PopescuRather than just replacing all the blood cell analyzers out there, Best-Popescu said the researchers plan to identify key patient populations that would benefit from our instrument and technology, she said. “For example, we may be able to detect/screen for individuals at an increased risk of alcoholism related disorders.”

Collaborators from University of California, Los Angeles, determined that the model used previously to understand these changes didn’t take into account the curvature of the membrane. So they created a new model based on the new data collected from Popescu’s new technique.

“Our findings are really a combination of a new optical method and new theoretical model,” Popescu said. The new technique—which the team calls diffraction phase microscopy—does not damage cells while measuring changes in them, an ideal quality when testing new drugs. According to Popescu, it’s very important for tests to be done on the same cell over a longer period of time.

Popescu said the method is also less expensive and produces larger sets of data than current diagnostic equipment.

“We’ve measured thousands of cells very quickly,” Popescu said. “Our method, in some cases, could be a more accurate alternative to today’s testing methods.”

The National Institutes of Health and the National Science Foundation funded the research, which also included collaborators at the Massachusetts Institute of Technology, the University of Colorado, Harvard Medical School and Harvard University.

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