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New Imaging Method Lets Scientists 'See' Cell Molecules More Clearly

January 21, 2009
Vanderbilt University Medical Center
Scientists have developed a unique new imaging tool. The new technique allows for imaging whole cells in liquid with a scanning transmission electron microscope.

(a) The principle of liquid scanning transmission electron microscopy (liquid STEM). A whole cell in liquid is enclosed between two electron-transparent windows of silicon nitride. Images are obtained by scanning a focused electron beam over the sample and detecting the elastically scattered electrons with an annular dark field detector. (b) Liquid STEM images of COS7 fibroblast cells incubated with 10 nm gold nanoparticles conjugated with epidermal growth factor (EGF-Au). The labels are visible as bright spots and the cellular material is shown as light-grey matter. Sharp-edged gold labels are visible in the cluster at arrow #1, while the labels in the cluster at arrow #2 appear blurred and can not be distinguished as individual labels, indicating that cluster #2 is out of the vertical plane of focus. (c) The flow cell is placed in the vacuum of the microscope using the fluid specimen holder.
Credit: courtesy of the National Academy of Sciences, PNAS

Scientists have always wanted to take a closer look at biological systems and materials. From the magnifying glass to the electron microscope, they have developed ever-increasingly sophisticated imaging devices.

Now, Niels de Jonge, Ph.D., and colleagues at Vanderbilt University and Oak Ridge National Laboratory (ORNL), add a new tool to the biology-watcher's box. In the online early edition of the Proceedings of the National Academy of Sciences, they describe a technique for imaging whole cells in liquid with a scanning transmission electron microscope (STEM).

"Electron microscopy is the most important tool for imaging objects at the nano-scale – the size of molecules and objects in cells," said de Jonge, who is an assistant professor of Molecular Biology & Biophysics at Vanderbilt and a staff scientist at ORNL. But electron microscopy requires a high vacuum, which has prevented imaging of samples in liquid, such as biological cells.

The new technique – liquid STEM – uses a micro-fluidic device with electron transparent windows to enable the imaging of cells in liquid. In the PNAS article, the investigators demonstrate imaging of individual molecules in a cell, with significantly improved resolution (the fineness of detail in the image) and speed compared to existing imaging methods.

"Liquid STEM has the potential to become a versatile tool for imaging cellular processes on the nanometer scale," de Jonge said. "It will potentially be of great relevance for the development of molecular probes and for the understanding of the interaction of viruses with cells."

The technique will also become a resource for energy science, as researchers use it to visualize processes that occur at liquid: solid interfaces, for example in lithium ion batteries, fuel cells, or catalytic reactions.

"Our key innovation with respect to other techniques for imaging in liquid is the combination of a large volume that will accommodate whole cells, a resolution of a few nanometers, and fast imaging of a few seconds per image," de Jonge said.

The research was supported by the Laboratory Directed Research and Development Program of ORNL, the SHaRE User Facility at ORNL, Vanderbilt University Medical Center, and the National Institutes of Health.

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Materials provided by Vanderbilt University Medical Center. Note: Content may be edited for style and length.

Journal Reference:

  1. de Jonge, N., et al. Electron microscopy of whole cells in liquid with nanometer resolution. Proc. Natl. Acad. Sci., 2009; Early Edition, January 21-23

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Vanderbilt University Medical Center. "New Imaging Method Lets Scientists 'See' Cell Molecules More Clearly." ScienceDaily. ScienceDaily, 21 January 2009. <>.
Vanderbilt University Medical Center. (2009, January 21). New Imaging Method Lets Scientists 'See' Cell Molecules More Clearly. ScienceDaily. Retrieved May 26, 2017 from
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