Abstract: Methods and apparatus are disclosed for classifying regions of a substrate prior to performing an analytic procedure involving analyte particles supported on the substrate. Regions of the substrate are sparsely scanned using low-energy electron point projection (LEEPP) imaging. Regions are classified as suitable for the analytic procedure (or not) based on defects visible in the respective images. Given one suitable region, neighboring regions are scanned to increase the yield of suitable regions. Based on a distribution of suitable regions, a deposition pattern is planned, and analyte is deposited according to the plan. Following deposition, suitable regions are scanned again to identify or count visible analyte molecules visible. Based on numbers of analyte molecules found, regions are earmarked for analyte characterization, e.g. by low-energy electron holography and reconstruction. A trained machine learning classifier provides consistent, accurate image classification across a range of defect types.

Abstract: 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.

Abstract: 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.

Abstract: Apparatuses and methods for improved reconstructions of electron-based holograms are disclosed herein. An example method at least includes forming a hologram of a sample and a known object, forming a reconstruction of the known object using a reconstruction algorithm, comparing the reconstruction of the known object to a reference reconstruction of the known object, and adjusting the reconstruction algorithm based on the comparison of the reconstruction of the known object to the reference reconstruction of the known object. The example method may further include forming a reconstruction of the sample using the adjusted reconstruction algorithm.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: Apparatuses and methods for improved reconstructions of electron-based holograms are disclosed herein. An example method at least includes forming a hologram of a sample and a known object, forming a reconstruction of the known object using a reconstruction algorithm, comparing the reconstruction of the known object to a reference reconstruction of the known object, and adjusting the reconstruction algorithm based on the comparison of the reconstruction of the known object to the reference reconstruction of the known object. The example method may further include forming a reconstruction of the sample using the adjusted reconstruction algorithm.

Abstract: 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.

Abstract: 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.

Abstract: An apparatus to permit a viewer of a digital microscopy original image to manipulate the display and/or the microscope to obtain an enhanced view of a region of interest within the original image. In one preferred embodiment a spotlight mode matches the gray shade scale for a spotlight region-of-interest to the pixel intensity variation present in the spotlight region. The gray shade scale used for the spotlight mode may then be generalized to the original image. In a preferred embodiment, spotlight mode provides an easy mechanism for permitting a user to command a re-imaging of a selected spotlight region from a displayed image. Such re-imaging may permit the use of imaging parameter selections that better fit the spotlight region.