A new detector for scanning transmission electron microscopes may help researchers develop more effective drugs and map how cancer spreads from cell to cell, or enable them to probe the causes of other cell-based diseases.
A new detector for scanning transmission electron microscopes (STEM) is fast and sensitive enough to take stop-frame images of molecules as they react in living cells. Ordinarily, the electrons emitted from STEMs and other electron microscopes are so energetic, they blow apart living cells.
Developed by physicists at Cornell University, the detector can be retrofit onto existing STEM systems. Cornell has licensed the technology to FEI, a manufacturer of high-performance microscopes in Hillsboro, OR.
“Electron microscopes are already widely used, but none of the detectors are as good as ours,” says Cornell professor of applied and engineering physics David Muller. “I’ll get flak from them [other sensor developers] for saying it, but it’s true and they know it.”
Muller developed the electron microscope pixel array detector (EMPAD) with physics professor Sol Gruner and researchers from both of their labs.
Its ability to tease out information and image the interaction of molecules and atoms in living cells has many possible applications. It can help researchers develop more effective drugs and map how cancer spreads from cell to cell, or enable them to probe the causes of other cell-based diseases and conduct craniofacial research.
In its most basic terms, the detector is “a really high-speed, really sensitive camera that outperforms just about everything else,” says Muller. Muller and his team back up his claims in a research paper recently published in Microscopy Microanalysis.
Ordinarily, STEMs scan a narrow beam of electrons back and forth over a sample. As the electrons emerge from the bottom, a detector measures their varying intensity to create an image of the sample.
Conventional detectors have several problems, says Muller. They are slow, and the energetic electrons in their beam blow apart fragile samples and living things.
They also have to discard information from some areas of the image to improve quality in other areas. The concept is similar to adjusting the contrast of a photograph or video, which makes some parts of the image clearer while washing out or blackening other areas.
Muller and Gruner borrowed from the X-ray detector they built for the Cornell High Energy Synchrotron Source (CHESS) to get around these problems.
EMPAD starts with a 128x128-pixel array of highly sensitive micron-sized detectors. They act like the image detector of a camera, but they are much more sensitive. This enables them to image a frame in less than one millisecond, 100 times faster than conventional STEM detectors. Their image contrast (technically, dynamic range) is roughly 1,000 times greater than conventional detectors
EMPAD’s sensitivity delivers another important advantage: it uses less energetic electrons and still slashes exposure times. This reduces the time it takes to image samples from hours to minutes, and allows researchers to work with cells and fragile molecules. Scientists can, for example, take rapid sequential exposures of cellular processes (freeze-frame movies) or view the same specimen from different angles without damaging the sample.
EMPAD’s detector also collects unusual information. In addition to measuring the intensity of electrons that emerge from the sample, it also captures the angle at which they emerge.
“When an electron scatters in a different direction, instead of throwing it away, we gain additional information,” says Muller. “If you have an image of a scattering electron, you can reconstruct almost everything you need to know about the sample.”
For example, Muller and Gruner can map the structure of large cells or calculate a material’s atomic structure, right down to local strains, tilts, rotations, polarity, and even electric and magnetic fields.
Cornell’s Center for Technology Licensing has licensed the device to FEI, which plans to retrofit it onto existing STEMs. Meanwhile, Muller and Gruner are working on improving the detector.
“Everything it does now, we can make it do better,” says Muller. “Basically, we’re not anywhere near fundamental design limits. It’s a matter of time and money.”