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3D movies of living cells

MIT researchers have designed a new kind of microscope which creates 3D images of living cells. This microscope uses a method similar to the X-ray CT scans doctors use to see inside the body. One researcher said that their "technique allows you to study cells in their native state with no preparation at all." And he adds that "for the first time the functional activities of living cells can be studied in their native state." I have to admit that their results are spectacular.
Written by Roland Piquepaille, Inactive on

MIT researchers have designed a new kind of microscope which creates 3D images of living cells. This microscope uses a method similar to the X-ray CT scans doctors use to see inside the body. One researcher said that their "technique allows you to study cells in their native state with no preparation at all." And he adds that "for the first time the functional activities of living cells can be studied in their native state." I have to admit that their results are spectacular.

Images of a cervical cancer cell

For example, you can see above images of a cervical cancer cell taken using this new imaging technique. "Figures a and b show 3D images of the cell. The green structures represent the nucleolus. The nucleus, not visible in these images, surrounds the nucleolus. The red areas are unidentified cell organelles. Figures c through h show the 2D images from which the 3D images were generated. In these images, each color represents a different range of refractive index." (Credit: Michael Feld laboratory, MIT) Here are two links to larger versions of these images, one at MIT and the other one at Nature Methods. Here is also a link to a short video (15 seconds) showing a 3D rendering of a live cervical cancer cell. Credit: Michael Feld Laboratory, MIT)

This microscope has been developed at the MIT Spectroscopy Laboratory which is led by Michael Feld, a professor of physics. Other researchers involved at MIT are Kamran Badizadegan, an assistant professor of pathology at Harvard Medical School who also works at the Spectroscopy Laboratory, and Wonshik Choi, a postdoctoral associate.

So how does this work? The researchers used the same principle behind the concept of 3D CT (computed tomography) images of the human body, "which allow doctors to diagnose and treat medical conditions. CT images are generated by combining a series of two-dimensional X-ray images taken as the X-ray source rotates around the object."

But how did they take these series of images? "The researchers made their measurements using a technique known as interferometry, in which a light wave passing through a cell is compared with a reference wave that doesn't pass through it. A 2D image containing information about refractive index is thus obtained. To create a 3D image, the researchers combined 100 two-dimensional images taken from different angles. The resulting images are essentially 3D maps of the refractive index of the cell's organelles. The entire process took about 10 seconds, but the researchers recently reduced this time to 0.1 seconds."

In "Cells, Live and in 3-D", Technology Review provides additional details. Feld says "other methods for creating three-dimensional images of cells only allow researchers to look at 'controlled artifacts.' To be viewed using a conventional microscope cells have to be treated with fixing agents and stains, and are dead; what's visible in these images is 'not really what a cell looks like,' he says. 'Our technique allows you to study cells in their native state with no preparation at all.' It can, for example, capture chromosomes spooling during cell division or a cervical cancer cell shriveling up when treated with acetic acid."

For more information about this imaging technique, the research work has been published as an advance online article in Nature Methods under the name "Tomographic phase microscopy" (August 12, 2007). Here is the abstract. "We report a technique for quantitative three-dimensional (3D) mapping of refractive index in live cells and tissues using a phase-shifting laser interferometric microscope with variable illumination angle. We demonstrate tomographic imaging of cells and multicellular organisms, and time-dependent changes in cell structure. Our results will permit quantitative characterization of specimen-induced aberrations in high-resolution microscopy and have multiple applications in tissue light scattering."

Now, what's next? Let's return to the MIT news release for the conclusion. "The current resolution of the new technique is about 500 nanometers, or billionths of a meter, but the team is working on improving the resolution. 'We are confident that we can attain 150 nanometers, and perhaps higher resolution is possible,' Feld said. 'We expect this new technique to serve as a complement to electron microscopy, which has a resolution of approximately 10 nanometers.'"

Sources: MIT News Office, via EurekAlert!, August 12, 2007; Katherine Bourzac, Technology Review, August 13, 2007; and various websites

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