Methods for collecting electron diffraction patterns
AssigneeThe Regents of the University of California
InventorsTamir Gonen, Michael Martynowycz, Johan Hattne
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Abstract
Methods of collecting diffraction patterns from a microcrystal having an ordered array of a molecule are disclosed, which include using an exposure rate of at most 0.02 electrons per square angstrom per second on the microcrystal and using a direct electron detector to record electron diffraction patterns. Also disclosed are methods of determining a structural model for a molecule, identifying a material present in a trace amount within a sample, identifying a polymorph, and identifying the stereochemistry of a molecule.
Claims22
A method of collecting diffraction patterns from a microcrystal having an ordered array of a molecule, the method comprising:
- subjecting the microcrystal having a first orientation or orientation group to a parallel electron beam for an exposure time less than 4 seconds in a transmission electron microscope (TEM) using an exposure rate of at most 0.02 electrons per square angstrom per second on the microcrystal;
- recording at least one electron diffraction pattern (EDP) from the microcrystal having the first orientation or orientation group using a direct electron detector (DED);
- and
- repeating said subjecting and said recording for additional orientations or orientation groups of the microcrystal to obtain an EDP set comprising said at least one EDP and additional EDPs.
A method of determining a structural model for a molecule, comprising:
- subjecting a microcrystal having a first orientation or orientation group to a parallel electron beam for an exposure time less than 4 seconds in a transmission electron microscope (TEM) using an exposure rate of at most 0.02 electrons per square angstrom per second on the microcrystal, wherein the microcrystal comprises an ordered array of the molecule;
- recording at least one electron diffraction pattern (EDP) from the microcrystal having the first orientation or orientation group using a direct electron detector (DED);
- repeating said subjecting and said recording for additional orientations or orientation groups of the microcrystal to obtain an EDP set comprising said at least one EDP and additional EDPs;
- and
- determining a structural model for the molecule by processing the EDP set.
A method of identifying a material present in a trace amount within a sample, the method comprising:
- applying the sample to an electron microscopy (EM) grid;
- subjecting the EM grid, at a plurality of orientations, to a parallel electron beam in a transmission electron microscope (TEM);
- recording electron diffraction patterns (EDPs) from the EM grid at the plurality of orientations;
- and
- identifying a material present in a trace amount within the sample by processing the EDPs, wherein the material comprises a molecule;
- wherein the material comprises a polymorphic form of a microcrystal of the molecule and the microcrystal comprises unit cells with an average volume of at least 10,000 cubic angstroms and at most 1,000,000 cubic angstroms.
A method of identifying the stereochemistry of a molecule, the method comprising:
- obtaining a sample having a molecule with at least one known chiral center and at least one unknown chiral center;
- applying the sample to an electron microscopy (EM) grid;
- subjecting the EM grid, at a plurality of orientations, to a parallel electron beam in a transmission electron microscope (TEM);
- recording electron diffraction patterns (EDPs) from the EM grid at the plurality of orientations;
- and
- identifying the stereochemistry of the molecule based on the at least one known chiral center by processing the EDPs.
Dependencies are inferred from the claim text.