Dissection-based microscopy can give scientists genetic information. Weinstein and his colleagues at the Massachusetts Institute of Technology wanted to create a way to do it all in one shot—to take a snapshot of a cell's position and spell out the specific genetic sequences driving it.
That combo is important for scientists studying genetically diverse sets of cells. The immune system is a perfect example, Weinstein says. Immune cell genes can vary down to a single letter of DNA. Each variation can trigger a dramatic shift in the type of antibodies a cell produces. Where that cell is located within a tissue can alter antibody production, too.
Capturing such a complete picture of a cell doesn't require an expensive microscope or a lot of fancy equipment, Regev says. All you need to get started is a specimen and a pipette. First, scientists take cells grown in the lab and fix them into position in a reaction chamber. Then, they add an assortment of DNA bar codes. These stick to RNA molecules, giving each a unique tag. Next, the team uses a chemical reaction to make more and more copies of each tagged molecule—a growing pile that expands out from each molecule's original location.
Eventually, the tagged molecules collide with other tagged molecules, forcing them to link together in pairs. Molecules located close to one another will be more likely to collide, generating more DNA pairs. Molecules further apart will generate fewer pairs. A DNA-sequencing machine spells out the letters of every molecule within the sample, which takes up to 30 hours. An algorithm the team created then decodes the data—which, in the paper, represents roughly 50 million DNA letters of genetic sequences from each original specimen—and converts the raw data to images.
The two methods are complementary, he adds. Light microscopy can see molecules well even when they're sparse within a sample, and DNA microscopy excels when molecules are dense—even piled up on top of one another. He thinks DNA microscopy could one day let scientists speed the development of immunotherapy treatments that help patients' immune systems fight cancer. The method could potentially identify the immune cells best suited to target a particular cancer cell, he says.
Every cell has a unique makeup of DNA letters, or genotype, Zhang says. The possibilities with this category of microscopy are wide open, Regev adds. More from Biology and Medical.
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Using DNA microscopy bottom , scientists can accurately reconstruct an image of cells captured with a fluorescence microscope top.
This Microscope Can See Down to Individual Atoms
A visualization of the data for cell populations in a sample, provided by DNA microscopy. Credit: Weinstein et al.
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Explore further. More information: Joshua A. Published online June 20, DOI: Because of its great depth of focus, a scanning electron microscope is the EM analog of a stereo light microscope.
It provides detailed images of the surfaces of cells and whole organisms that are not possible by TEM. It can also be used for particle counting and size determination, and for process control. It is termed a scanning electron microscope because the image is formed by scanning a focused electron beam onto the surface of the specimen in a raster pattern.
The interaction of the primary electron beam with the atoms near the surface causes the emission of particles at each point in the raster e. These can be collected with a variety of detectors, and their relative number translated to brightness at each equivalent point on a cathode ray tube. Because the size of the raster at the specimen is much smaller than the viewing screen of the CRT, the final picture is a magnified image of the specimen. Appropriately equipped SEMs with secondary, backscatter and X-ray detectors can be used to study the topography and atomic composition of specimens, and also, for example, the surface distribution of immuno-labels.
What is Electron Microscopy? Additional Resources directory index contacts.