GLOWING EMBRYOS: Using a fluorescent microscopy technique that allows viewing times lasting nearly two and a half days, scientists can now track each cell in a growing embryo. Image: Image Courtesy of Philipp Keller
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Using a revolutionary new microscope, scientists can now peer into embryos and watch, in one of the world's smallest 3-D movies, as brains, eyes and other organs form. A team at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, watched zebra fish and fruit fly embryos develop under the scope for as long as 58 hours, charting the location of every cell as it danced around the embryo. This experiment would have been impossible a mere two years ago before a recent spate of innovations advanced microscopy years into the future.
When it comes to watching the inner workings of cells, fluorescence microscopy is second to none. In this technique, scientists attach fluorescent tags to cellular proteins and, by shining a laser on the cells, cause them to light up.
But placing cells under a standard fluorescent microscope essentially sentences them to death. Damaged by the scope's powerful laser, many perish before a few hours pass, so watching any extended process is difficult. In addition, cells under stress often behave differently than normal cells do, a huge stumbling block for scientists trying to draw connections between their experiments and the natural world.
The team at EMBL, headed by Ernst Stelzer, is part of a growing effort to study cells, tissues and even small multicellular organisms in conditions that more closely mimic nature, enabling longer viewing times and less adulterated results. Their technique—known as light sheet microscopy—has produced fascinating breakthroughs, allowing them to see live samples longer and clearer than ever before.
The researchers began by turning microscopy on its side—literally. In traditional fluorescence microscopy the whole sample is usually lit by the laser from above. A cameralike detector focuses on successive planes through the sample, snapping pictures from top to bottom that can be stacked into a 3-D picture. But throughout this process the full force of the laser blasts even cells whose light is not in focus for the detector. What the EMBL team realized was that if they swung the laser 90 degrees, so it shined through the sample from the side instead of from above, they could illuminate just the single slice on which the camera was focusing. None of the other cells were hit.
Suddenly, scientists could make movies that lasted for days. The cells under their microscopes, hit with only one five-thousandth of the energy used in traditional fluorescence microscopy, kept on dividing. The EMBL team took a record 24-hour-long movie of a developing zebra fish embryo. When one of the members presented the data at a conference, he was received like a rock star.
But this was only the beginning—the new setup enabled Stelzer's team to use a much faster camera, recording about 60 million pixels per second. And the benefits multiplied: Because the camera was so sensitive, it could absorb more light in each picture, providing even more data.