Imaging method could improve insight into fertility treatments

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 in the Proceedings of the National Academy of Sciences (PNAS), researchers followed 24,000 rapidly moving cells over wide fields of view and through large sample volumes, recording each cell’s path for up to 20 seconds.

‘We can very precisely track the motion of small things, more than 1,000 of them at the same time, in parallel,’ said research lead and National Science Foundation CAREER awardee Aydogan Ozcan, an electrical engineering and bioengineering professor at the University of California, Los Angeles (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.’

According to a statement, 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, accurately reveals 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 17mm²) and large sample volume (up to 17mm³) over several seconds.

The technique, along with a novel software algorithm that the team developed to process observational data, is said to have 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.

Because only four to five per cent of the cells in a given sample travelled in a helical path at any given time, researchers would not have been able to observe the rare behaviour without the new high-throughput microscopy technique.

The PNAS paper reports observations of 24,000 cells over the duration of the experiments. Such a large number of observations provides 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 micro-organisms.

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 behaviour and allow the real-time testing of novel drug treatments to combat some of the most deadly forms of those microbes.