An electron diffraction imaging system for imaging the three-dimensional structure of a single target molecule of a sample uses an electron source that emits a beam of electrons toward the sample, and a two-dimensional detector that detects electrons diffracted by the sample and generates an output indicative of their spatial distribution. A sample support is transparent to electrons in a region in which the sample is located, and is rotatable and translatable in at least two perpendicular directions. The electron beam has an operating energy between 5 keV and 30 keV, and beam optics block highly divergent electrons to limit the beam diameter to no more than three times the size of the sample molecule and provide a lateral coherence length of at least 15 nm. An adjustment system adjusts the sample support position in response to the detector output to center the target molecule in the beam.

An electron diffraction imaging system for imaging the three-dimensional structure of a single target molecule of a sample uses an electron source that emits a beam of electrons toward the sample, and a two-dimensional detector that detects electrons diffracted by the sample and generates an output indicative of their spatial distribution. A sample support is transparent to electrons in a region in which the sample is located, and is rotatable and translatable in at least two perpendicular directions. The electron beam has an operating energy between 5 keV and 30 keV, and beam optics block highly divergent electrons to limit the beam diameter to no more than three times the size of the sample molecule and provide a lateral coherence length of at least 15 nm. An adjustment system adjusts the sample support position in response to the detector output to center the target molecule in the beam.

A method for improving the quality/integrity of an EBSD/TKD map, wherein each data point is assigned to a corresponding grid point of a sample grid and represents crystal information based on a Kikuchi pattern detected for the grid point; comprising determining a defective data point of the EBSD/TKD map and a plurality of non-defective neighboring data points, comparing the position of Kikuchi bands of a Kikuchi pattern detected for a grid point corresponding to the defective data point with the positions of bands in at least one simulated Kikuchi pattern corresponding to crystal information of the neighboring data points and assigning the defective data point the crystal information of one of the plurality of neighboring data point based on the comparison.

A method includes simulating diffraction in a transmission geometry of relativistic electron bunches from a crystallographic structure of a crystal thereby simulating diffraction of the relativistic electron bunches into a plurality of Bragg peaks. The method includes selecting a range of angles between a direction of propagation of the relativistic electron bunches and a normal direction of crystal including an angle at which a diffraction portion is maximized. The method includes sequentially accelerating a plurality of physical electron bunches to relativistic energies toward a physical crystal having the crystallographic structure and diffracting the plurality of physical electron bunches off the physical crystal at different angles and measuring the diffraction portion into the respective Bragg peak at the different angles. The method includes selecting a final angle based on the measured diffraction portion into the respective Bragg peak at the different angles and generating a pulse of light.

Molecular structure of a crystal may be solved based on at least two diffraction tilt series acquired from a sample. The two diffraction tilt series include multiple diffraction patterns of at least one crystal of the sample acquired at different electron doses. In some examples, the two diffraction tilt series are acquired at different magnifications.

3D information may be extracted from two 2D images by capturing a first image of a sample at a first orientation. The sample may be titled at a second or different orientation, resulting in a second image of the titled sample to be captured. Third dimension of information may be extracted from the images.

There is provided a scanning transmission electron microscope capable of producing plural types of STEM (scanning transmission electron microscopy) images using a single detector. The electron microscope (100) has an electron source (10) emitting an electron beam, a scanning deflector (13) for scanning the beam over a sample (S), an objective lens (14) for focusing the beam, an imager (22) placed at a back focal plane of the objective lens (14) or at a plane conjugate with the back focal plane, and a scanned image generator (40) for generating scanned images on the basis of images captured by the imager. The scanned image generator (40) operates to form electron diffraction patterns from the electron beam passing through positions on the sample by the scanning of the electron beam, to capture the electron diffraction patterns by the imager so that plural images are produced, to integrate the intensity of each pixel over an integration region that is set based on the size of an image of a transmitted wave in a respective one of the produced images for each of the produced images such that the signal intensity at each position on the sample is found, and to generate the scanned images on the basis of the signal intensities at the positions on the sample.

There is provided a scanning transmission electron microscope capable of producing plural types of STEM (scanning transmission electron microscopy) images using a single detector. The electron microscope (100) has an electron source (10) emitting an electron beam, a scanning deflector (13) for scanning the beam over a sample (S), an objective lens (14) for focusing the beam, an imager (22) placed at a back focal plane of the objective lens (14) or at a plane conjugate with the back focal plane, and a scanned image generator (40) for generating scanned images on the basis of images captured by the imager. The scanned image generator (40) operates to form electron diffraction patterns from the electron beam passing through positions on the sample by the scanning of the electron beam, to capture the electron diffraction patterns by the imager so that plural images are produced, to integrate the intensity of each pixel over an integration region that is set based on the size of an image of a transmitted wave in a respective one of the produced images for each of the produced images such that the signal intensity at each position on the sample is found, and to generate the scanned images on the basis of the signal intensities at the positions on the sample.

A method for correcting distortion in a coherent electron diffraction imaging (CEDI) image induced by a projection lens makes use of a known secondary material that is imaged together with a sample of interest. Reflections generated from the secondary material are located in the image, and these observed reflections are used to approximate a beam center location. Using a known lattice structure of the secondary material, Friedel pairs are located in the image and unit cell vectors are identified. Predicted positions for each of the secondary material reflections are then determined, and the position differences between the observed reflections and the predicted reflections are used to construct a relocation function applicable to the overall image. The relocation function is then used to adjust the position of image components so as to correct for the distortion.

The present disclosure provides methods of collecting electron diffraction patterns from nanocrystals to obtain a three-dimensional structural model of a compound, as well as methods of identifying compounds and methods of determining polymorphic forms. In addition, the present disclosure provides methods of characterizing a first compound from a sample, as well as methods of screening compounds from a sample. The present disclosure also provides systems for characterizing a compound from a sample, which systems include modules for high-performance liquid chromatography, dispensing, and electron microscopy.