High-energy X-ray technique offers 3D images of intact biological cells

Novel microscope concept can reduce radiation dose a thousand-fold.

Human blood cells under the scanning electron microscope. Credit: National Cancer Institute
Human blood cells under the scanning electron microscope. Credit: National Cancer Institute

Imaging the structures of biological cells on the nanometer scale usually requires X-rays, as their short wavelengths allow to resolve the fine details. However, X-rays also deposit energy that quickly damages biological samples.

Now, DESY scientists have developed a novel X-ray technique that promises three-dimensional images of delicate objects like biological cells using a thousand times less damaging radiation than conventional methods. It also offers imaging of whole cells at high resolution in their native environment, without freezing, cutting or staining them.

X-ray images can be shaped by an assortment means. The recognizable radiographs of teeth or broken bones depend on ingestion — the thick bone leaves a dim shadow in the picture where X-ray photons are consumed. An X-ray microscope developed for imaging cells, for the most part, relies on flexible disseminating of the X-beams in the example to accomplish pictures of significantly higher determination. This is like how pictures are shaped in an optical magnifying instrument.

Villanueva-Perez said, “Although elastic X-ray scattering transfers no energy, in all X-ray microscopes built to date, such scattering processes happen much less frequently than actual absorption. In reality, scattering cannot occur without a fraction of the photon’s energy being deposited in the sample, producing radiation damage.”

Objects turn out to be substantially less engrossing the more enthusiastic the X-beam photons. In any case, such high energies were not viewed as valuable for high-determination microscopy since the flexible diffusing likewise diminishes and another type of scrambling ends up overwhelming. In this inelastic procedure, otherwise called Compton diffusing, the X-beam loses some of its vitality to the protest as it ricochets off an iota and in the process changes wavelength. This, as a rule, produces undesirable featureless foundation or haze in the picture, breaking down the nature of both the picture and the example.

Chapman said, “No one really thought of trying biological microscopy at such high energies. Bright enough X-ray sources didn’t exist, there was no way to focus the beam, and there were no detectors.”

The X-ray source PETRA IV, currently under design, will deliver beams of much higher X-ray brightness at the required high energies than possible today. This still leaves the detector.

Villanueva-Perez said, “The ideal detector should surround the sample, to collect all scattered photons in all directions. This can be built using today’s technology. Once realized, these ingredients will enable scientists to scan whole cells and organelles at a few nanometres resolution in all three dimensions, in their natural state – fulfilling a widespread wish of biologists. Until then, the scientists plan to test their novel concept with biological samples at today’s best X-ray sources like PETRA III with conventional detectors.”

DESY scientists Pablo Villanueva-Perez, Saša Bajt and Henry Chapman from the Center for Free-Electron Laser Science (CFEL) present their concept in the journal Optica.

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