Systems and method for the preparation and delivery of biological samples for charged particle analysis are disclosed herein. An example system at least includes an ion filter coupled to select a sample ion from an ionized sample supply, the ion filter including a quadrupole filter to select the sample ion from the sample supply, an energy reduction cell coupled to receive the selected sample ion and reduce a kinetic energy of the sample ion, a validation unit coupled to receive the sample ion and determine whether the sample ion is a target sample ion, a substrate coupled to receive the sample, wherein the substrate is electron transparent, an ion transport module coupled to receive the sample ion from the ion filter and transport the sample ion to the substrate, and an imaging system arranged to image, with a low energy charged particle beam, the sample located on the substrate, wherein the substrate is arranged in an analysis location. The imaging system including a charge particle emitter coupled to direct coherent charged particles toward the sample; and a detector arranged to detect interference patterns formed from interaction of the coherent charged particles and the sample.

Apparatuses and methods for comparative holographic imaging to improve structural and molecular information of reconstructions is disclosed herein. An example method at least includes acquiring a plurality of holograms of a sample, wherein each hologram of the plurality of holograms is acquired at a different electron beam energy, and determining atomic and structural information of the sample based at least on a comparison of at least two of the holograms of the plurality of holograms.

Methods for using electron diffraction holography to investigate a sample, according to the present disclosure include the initial steps of emitting a plurality of electrons toward the sample, forming the plurality of electrons into a first electron beam and a second electron beam, and modifying the focal properties of at least one of the two beams such that the two beams have different focal planes. Once the two beams have different focal planes, the methods include focusing the first electron beam such that it has a focal plane at or near the sample, and focusing the second electron beam so that it is incident on the sample, and has a focal plane in the diffraction plane. An interference pattern of the first electron beam and the diffracted second electron beam is then detected in the diffraction plane, and then used to generate a diffraction holograph.

An embodiment of the invention relates to a method for carrying out a time-resolved interferometric measurement comprising the steps of generating at least two coherent waves, overlapping said at least two coherent waves and producing an interference pattern, measuring the interference pattern for a given exposure time, thereby forming measured interference values, and analyzing the measured interference values and extracting amplitude and/or phase information from the measured interference values. In at least one time segment, hereinafter referred to as disturbed time segment, of the expo-sure time, the interference pattern is intentionally disturbed or destroyed such that the corresponding measured interference values describe a disturbed or destroyed interference pattern. In at least one other time segment, hereinafter referred to as undisturbed time segment, of the exposure time, the interference pattern is undisturbed or at least less disturbed compared to the disturbed time segment such that the corresponding measured interference values describe an undisturbed or less disturbed interference pattern. The measured interference values that were measured during the entire given exposure time, are filtered, wherein those interference values that were measured during the at least one disturbed time segment, are reduced, suppressed or discarded. The filtered interference values are analyzed and the amplitude and/or phase information is extracted from the filtered interference values.

The present invention is to generate a spatially phase modulated electron wave. A laser radiating apparatus, a spatial light phase modulator, and a photocathode are provided. The photocathode has a semiconductor film having an NEA film formed on a surface thereof, and a thickness of the semiconductor film is smaller than a value obtained by multiplying a coherent relaxation time of electrons in the semiconductor film by a moving speed of the electrons in the semiconductor film. According to the configuration, a spatial distribution of phase and a spatial distribution of intensity of spatial phase modulated light are transferred to an electron wave, and the electron wave emitted from an NEA film is modulated into the spatial distribution of phase and the spatial distribution of intensity of the light. Since the spatial distribution of phase of the light can be modulated as intended by a spatial phase modulation technique for light, it is possible to generate an electron wave having a spatial distribution of phase modulated as intended.

Systems and method for the preparation and delivery of biological samples for charged particle analysis are disclosed herein. An example system at least includes an ion filter coupled to select a sample ion from an ionized sample supply, the ion filter including a quadrupole filter to select the sample ion from the sample supply, an energy reduction cell coupled to receive the selected sample ion and reduce a kinetic energy of the sample ion, a validation unit coupled to receive the sample ion and determine whether the sample ion is a target sample ion, a substrate coupled to receive the sample, wherein the substrate is electron transparent, an ion transport module coupled to receive the sample ion from the ion filter and transport the sample ion to the substrate, and an imaging system arranged to image, with a low energy charged particle beam, the sample located on the substrate, wherein the substrate is arranged in an analysis location. The imaging system including a charge particle emitter coupled to direct coherent charged particles toward the sample; and a detector arranged to detect interference patterns formed from interaction of the coherent charged particles and the sample.

An object wave made of an electron beam influenced by a sample and reference beam made of an electron beam not influenced by the sample are made to interfere with each other where a magnetic field has been applied to the sample to create a first electron-beam hologram and create a first reconstructed phase image from the first electron-beam hologram. An object wave made of an electron beam influenced by the sample and a reference beam made of an electron beam not influenced by the sample are made to interfere where a magnetic field has not been applied to the sample to create a second electron-beam hologram and create a second reconstructed phase image from the second electron-beam hologram. Magnetic field information indicating the influence of the magnetic field on the sample is acquired on the basis of the difference between the first and second reconstructed phase images.

An observation apparatus and method that avoids drawbacks of a Lorentz method and observes a weak scatterer or a phase object with in-focus, high resolution, and no azimuth dependency, by a Foucault method observation using a hollow-cone illumination that orbits and illuminates an incident electron beam having a predetermined inclination angle, an electron wave is converged at a position (height) of an aperture plate downstream of a sample and a bright field condition in which a direct transmitted electron wave of the sample passes through the aperture plate, a dark field condition in which the transmitted electron wave is shielded and a Schlieren condition in which approximately half of the transmitted wave is shielded as a boundary condition of both of the above conditions are controlled, and a spatial resolution of the observation image is controlled by selecting multiple diameters and shapes of the opening of the aperture plate.

Methods and systems for implementing laser-based phase plate image contrast enhancement are disclosed herein. An example method at least includes forming at least one optical peak in a diffraction plane of an electron microscope, and directing an electron beam through the at least one optical peak at a first location, where the first location determines an amount of phase manipulation the optical peak imparts to an electron of the electron beam.

Methods for using electron diffraction holography to investigate a sample, according to the present disclosure include the initial steps of emitting a plurality of electrons toward the sample, forming the plurality of electrons into a first electron beam and a second electron beam, and modifying the focal properties of at least one of the two beams such that the two beams have different focal planes. Once the two beams have different focal planes, the methods include focusing the first electron beam such that it has a focal plane at or near the sample, and focusing the second electron beam so that it is incident on the sample, and has a focal plane in the diffraction plane. An interference pattern of the first electron beam and the diffracted second electron beam is then detected in the diffraction plane, and then used to generate a diffraction holograph.