US 12,566,116 B2 · Method and apparatus of preparing a sample of one or more molecule(s) for imaging with a cryo-electron microscope

Abstract

The present invention relates to a method of preparing a sample of one or more molecule(s) for imaging with a cryo-electron microscope. The method comprises providing a carrier substrate, cryogenically cooling the carrier substrate to form a cryogenically-cooled carrier substrate, generating gas phase ions of the one or more molecule(s) by electrospray ionisation, decelerating the gas phase ions, receiving the gas phase ions on the cryogenically-cooled carrier substrate to form a sample for imaging with a cryo-electron microscope and shielding the cryogenically-cooled carrier substrate after the step of receiving the ions on the cryogenically-cooled carrier substrate. The step of decelerating the ions reduces the energy of each of the ions to be less than 20 eV per charge when received at the cryogenically-cooled carrier substrate. The present invention also relates to an apparatus for preparing a sample of one or more molecule(s) for a cryo-electron microscope.

Claims20

Dependent claims

A method of preparing a sample of one or more molecules for imaging with a cryoelectron microscope, the method comprising:

providing a carrier substrate;
cryogenically cooling the carrier substrate to form a cryogenically-cooled carrier substrate;
generating gas phase ions of the one or more molecules by electrospray ionisation;
decelerating the gas phase ions;
and
receiving the gas phase ions on the cryogenically-cooled carrier substrate to form a sample for imaging with a cryo-electron microscope;
wherein the step of decelerating the ions reduces an energy of each of the ions to be less than 20 eV per charge when received at the cryogenically-cooled carrier substrate,
wherein the step of generating gas phase ions comprises generating one or more charged gas-phase molecules,
wherein, before the step of generating ions, the method comprises a step of receiving a solution comprising the one or more molecules dissolved in a solvent,
wherein the step of generating gas phase ions comprises generating one or more charged gas-phase molecules comprising a solvation shell.

7 more elements

An apparatus for preparing a sample of one or more molecules for a cryo-electron microscope, the apparatus comprising:

an electrospray ionisation source configured to generate one or more gas-phase molecules comprising a solvation shell from a solution comprising the one or more molecules dissolved in a solvent;
one or more ion optic devices configured to guide gas phase ions of the one or more molecules from the electrospray ionisation source towards a deposition chamber;
a voltage supply configured to apply a potential to a carrier substrate within the deposition chamber to receive the gas phase ions generated by the electrospray ionisation source;
a cryogenic cooling system configured to cryogenically cool a carrier substrate;
and
a controller configured to control the voltage supply to apply a potential to a cryogenically-cooled carrier substrate such that the gas phase ions generated by the electrospray ionisation source are decelerated to an energy of less than 20 eV per charge when received at a cryogenically-cooled carrier substrate.

3 more elements

Dependencies are inferred from the claim text.

Method and apparatus of preparing a sample of one or more molecule(s) for imaging with a cryo-electron microscope

Life of this patent

Method and apparatus of preparing a sample of one or more molecule(s) for imaging with a cryo-electron microscope

Life of this patent

Abstract

Claims20