Photoacoustic method measures blood cell oxygen in real time

Washington University in St. Louis (WUSTL; St. Louis, MO) biomedical researcher Lihong Wang, Ph.D., and colleagues have developed a photoacoustic method to measure oxygen in individual red blood cells in real time. The method could eventually be used to determine how oxygen is delivered to normal and diseased tissues or how various disease therapies impact oxygen delivery throughout the body.

Related: Deep down and label-free: Bioimaging with photoacoustics

Red blood cells deliver oxygen through arteries, capillaries, and veins to the body's cells and tissues. To date, the state-of-the-art device for measuring the amount of oxygen in the blood is through a device that clamps onto the index finger called a pulse oximeter. However, this measures only the oxygen level in the body's arteries, so it doesn't give a full picture of oxygen metabolism.

But Wang's method, called photoacoustic flowoxigraphy, uses light in a novel way that allows researchers to watch red blood cells flowing through tiny capillaries, the smallest of the body's blood vessels at about the width of one red blood cell.

“By firing two laser pulses of different colors at a red blood cell 20 µs apart—nearly simultaneously—we hit the same red blood cell at almost the same location, so we get signals back at both colors,” Wang says. “That allows us to figure out the color of the red blood cell at any given moment. By watching the color change, we can determine how much oxygen is delivered from each red blood cell per unit of time or distance. From there, we can determine the average oxygen delivery per unit length of capillary segment.”

Wang, the Gene K. Beare Distinguished Professor of Biomedical Engineering, and colleagues were able to watch the red blood cells choose which direction to travel when they encountered a “fork” in the capillary, called bifurcation. The cells travel in bunches to where oxygen is most needed in the body at that time, he says.

And although the cells travel very quickly, the speed of the device—200 Hz, or 20 3D frames/s—allows the researchers to see the cells in real time. (In comparison, a film at a movie theater moves at 30 Hz—fast enough that the eye can't see the individual frames.)

Photoacoustic flowoxigraphy enables oximetry at the single-cell level, says Wang, adding that the method has applications for further biological studies as well as in the clinical setting.

"There are many biomedical questions that this technology could answer: How would cancer or diabetes change oxygen metabolism? How would cancer therapy or chemotherapy affect oxygen level?" Wang says. "We'd like to see if we could use this technique to monitor or predict therapeutic efficacy."

Wang and colleagues would like to license the technique to a company that would move it forward to make it available to biologists and physicians for applications.

Their work appears in the Proceedings of the National Academy of Sciences; for more information, please visit http://www.pnas.org/content/early/2013/03/27/1215578110.

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