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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.
Over the course of the study—reported online Sept. 17, 2012, in the Proceedings of the National Academy of Sciences—researchers
followed an unprecedented 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 and
National Science Foundation CAREER awardee Aydogan Ozcan, an electrical
engineering and bioengineering professor at 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.”
The
latest study is an extension of several years of NSF-supported work by
Ozcan and his colleagues to develop lens-free, holographic microscopy
techniques with applications for field-based detection of blood-borne
diseases and other areas of tele-medicine. Those efforts recently
resulted in a Popular Mechanics Breakthrough Award and a National
Geographic Emerging Explorer Award, among others. Ozcan’s research is
also supported through an NIH Director’s New Innovator Award, Office of
Naval Research Young Investigator Award and an Army Research Office
Young Investigator Award from the Department of Defense.
For
the recent work, Ozcan and his colleagues—Ting-Wei Su, also of UCLA,
and Liang Xue, of both UCLA and Nanjing University of Science and
Technology in China—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% of the time, is in a clockwise (right-handed)
direction.
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Because
only 4 to 5% 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.
“This
latest study is an extension of truly novel and creative work,” says
Leon Esterowitz, the NSF biophotonics program officer who has supported
Ozcan’s efforts. “The holographic technique could accelerate drug
discovery and prove valuable for monitoring pharmaceutical treatments of
dangerous microbial diseases.”
The
PNAS paper reports observations of 24,000 cells over the duration of
the experiments. 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. Many of the dangerous protozoa found in
unsanitary drinking water and rural bodies of water have only been
observed in small samples moving through an area that is roughly two
dimensional. The new lens-free holographic imaging 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.
High-throughput lensfree 3D tracking of human sperms reveals rare statistics of helical trajectories
Source: National Science Foundation
