UCLA researchers have developed a new way to observe and track large numbers of rapidly moving objects under a microscope, capturing precise motion paths in three dimensions. Researchers followed 24,000 rapidly moving cells over wide fields of view and through large sample volumes, recording each cell's path for as long as 20 seconds.

"We can very precisely track the motion of small things, more than a thousand of them at the same time, in parallel," says research lead Aydogan Ozcan of UCLA. "We were able to achieve sub-micron accuracy over a large volume, allowing us to understand, statistically, how thousands of objects move in different ways."

Ozcan and his colleagues used offset beams of red and blue light to create holographic information that, when processed using sophisticated software, accurately reveal the paths of objects moving under a microscope. The researchers tracked several cohorts of more than 1,500 human male gamete cells over a relatively wide field of view (more than 17 square millimeters) and large sample volume (up to 17 cubic millimeters) over several seconds.

The technique, along with a novel software algorithm that the team developed to process observational data, revealed previously unknown statistical pathways for the cells. The researchers found that human male gamete cells travel in a series of twists and turns along a constantly changing path that occasionally follows a tight helix--a spiral that, 90 percent of the time, is in a clockwise (right-handed) direction.

Because only four to five percent of the cells in a given sample traveled in a helical path at any given time, researchers would not have been able to observe the rare behavior without the new high-throughput microscopy technique. Such a large number of observations provide a statistically significant dataset and a useful methodology for potentially studying a range of subjects, from the impact of pharmaceuticals and other substances on large numbers of cells -- in real time -- to fertility treatments and drug development.

The same approach may also enable scientists to study quick-moving, single-celled microorganisms. The technique could potentially reveal unknown elements of protozoan behavior and allow real-time testing of novel drug treatments to combat some of the most deadly forms of those microbes.

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