First 3D images of living cell a 'dream'

By Mike Nagle

- Last updated on GMT

Related tags Microscope

A US scientist says he has fulfilled his dream by creating the
first 3D images of a living cell, finally allowing researchers to
study them in their natural state.

Professor Michael Feld is the director of the George R. Harrison Spectroscopy Laboratory at the Massachusetts Institute of Technology (MIT), US, and along with his lab, has developed a technique to produce the most detailed images yet of what happens inside a cell, without the need for fluorescent markers or other contrast agents.

"Accomplishing this has been my dream, and a goal of our laboratory, for several years," he said.

"For the first time the functional activities of living cells can be studied in their native state."

The new technology is based around the same concept used to create 3D computed tomography (CT) images of the human body, which allow doctors to diagnose and treat medical conditions.

CT images are generated by combining a series of 2D X-ray images taken as the X-ray source rotates around the object.

"You can reconstruct a 3D representation of an object from multiple images taken from multiple directions," said Wonshik Choi, lead author of the research paper.

To generate each individual image, the researchers decided to measure the refractive index of the cell (a measure of how much the speed of light is reduced as it travels through a material).

They did this using interferometry techniques - where light waves passing through the cell are compared to a reference wave.

By taking 100 such 2D images, the scientists then generate a 3D map of how the refractive index changes in different parts of a cell.

The entire process originally took 10 seconds but Prof. Feld and his team have reduced this to 0.1 seconds.

Classical techniques can only provide the average refractive index of a cell and also require the sample to be submersed in liquids of varying refractive index.

This is then examined using a technique such as phase contrast microscopy.

There are more sensitive techniques than this available to scientists, such as microscopy-based methods that quantitatively measure optical phase shifts, but 3D variations still cannot be examined.

Other 3D imaging techniques also require the sample to be prepared, whether through fixing with chemicals, freezing, staining with dyes, or otherwise.

"One key advantage of the new technique is that it can be used to study live cells without any preparation," said Kamran Badizadegan, another scientist involved in the research, and an assistant professor at Harvard Medical School, US.

"When you fix the cells, you can't look at their movements, and when you add external contrast agents you can never be sure that you haven't somehow interfered with normal cellular function," said Badizadegan.

The team at MIT used their new technique to examine physiological changes within the cell, for example time-dependant changes in cell structure.

So far, the technique - described in the 12 August online edition of Nature Methods - has been used to examine several cell types, including HeLa cervical cancer cells, human embryonic kidney cells (HEK 293), and B35 neuroblastoma cells.

They have also used the technique to generate 3D images of the nematode worm, Caenorhabditis elegans , a popular research tool in drug discovery.

Although clearly the technology has now been successfully implemented, there is still work to be done before it can be routinely used by scientists, including drug developers.

The team are currently in the process of combining the system with fluorescence microscopy and other techniques to enable them to examine cell organelles more fully.

The current resolution of the new technique is about 500 nanometers, but the team is working to improve this.

"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."

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