When an electrode (29) such as a grid applied with a negative voltage is installed in front of an objective lens (23), low energy electrons among secondary electrons (25) generated from a sample (24) by an electron beam or the like is reflected by the electrode to come into a detector (22) installed in the sample (24) side, while electrons of higher energy are not detected, since they are not reflected by the electrode. Accordingly, since only the electrons of lower energy of the secondary electrons can be detected by discriminating the secondary electrons by the energy, it is possible to obtain a detection signal, e.g., rich in the information on the surface state of the sample.

Disclosed herein are specimen imaging systems, comprising: a sample stage in a vacuum environment, the sample stage configured to support a specimen; an electron beam generator configured to focus an electron beam on a first predetermined location on the specimen; a nanospray dispenser configured to dispense a nanospray onto a second predetermined location on the specimen; a mass spectrometer; and an extraction conduit configured to extract a plume of charged particles generated as a result of contact between the nanospray and the specimen and deliver the charged particles to the mass spectrometer. The system can create a topological and chemical map of the specimen by analyzing at least a portion of the specimen with a mass spectrometer to determine a chemical composition of the specimen at the second predetermined location and analyzing at least a portion of the specimen with the electron beam to determine a surface topology.

An electron energy loss spectrometer is described having a direct detection sensor, a high speed shutter and a sensor processor wherein the sensor processor combines images from individual sensor read-outs and converts a two dimensional image from said sensor into a one dimensional spectrum and wherein the one dimensional spectrum is output to a computer and operation of the high speed shutter is integrated with timing of imaging the sensor. The shutter is controlled to allow reduction in exposure of images corresponding to the individual sensor readouts. A plurality of images are exposed by imaging less than the full possible exposure and wherein the plurality of images are combined to form a composite image. The plurality of images can be comprised of images created by exposing the sensor for different exposure times.

An electron energy loss spectrometer is described having a direct detection sensor, a high speed shutter and a sensor processor wherein the sensor processor combines images from individual sensor read-outs and converts a two dimensional image from said sensor into a one dimensional spectrum and wherein the one dimensional spectrum is output to a computer and operation of the high speed shutter is integrated with timing of imaging the sensor. The shutter is controlled to allow reduction in exposure of images corresponding to the individual sensor readouts. A plurality of images are exposed by imaging less than the full possible exposure and wherein the plurality of images are combined to form a composite image. The plurality of images can be comprised of images created by exposing the sensor for different exposure times.

Specimen imaging systems and methods including a sample stage in a vacuum environment. The sample stage is configured to support a specimen, an electron beam generator configured to focus an electron beam on a first predetermined location on the specimen, a nanospray dispenser configured to dispense a nanospray onto a second predetermined location on the specimen, a mass spectrometer, and an extraction conduit configured to extract a plume of charged particles generated as a result of contact between the nanospray and the specimen and deliver the charged particles to the mass spectrometer. The systems and methods can create a topological and chemical map of the specimen by analyzing at least a portion of the specimen with a mass spectrometer to determine a chemical composition of the specimen at the second predetermined location and analyzing at least a portion of the specimen with the electron beam to determine a surface topology.

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.

A multi-electron beam system that forms hundreds of beamlets can focus the beamlets, reduce Coulomb interaction effects, and improve resolutions of the beamlets. A Wien filter with electrostatic and magnetic deflection fields can separate the secondary electron beams from the primary electron beams and can correct the astigmatism and source energy dispersion blurs for all the beamlets simultaneously.

The present invention relates to a method of mass spectrometry, an apparatus adapted to perform the method and a mass spectrometer. More particularly, but not exclusively, the present invention relates to a method of mass spectrometry comprising the step of associating parent and fragmentation ions from a sample by measuring the parent and fragmentation ions from two or more different areas of the sample and identifying changes in the number of parent ions between the areas in the sample, and corresponding changes in the number of fragmentation ions between the two areas.

An electron energy loss spectrometer is described having a direct detection sensor, a high speed shutter and a sensor processor wherein the sensor processor combines images from individual sensor read-outs and converts a two dimensional image from said sensor into a one dimensional spectrum and wherein the one dimensional spectrum is output to a computer and operation of the high speed shutter is integrated with timing of imaging the sensor. The shutter is controlled to allow reduction in exposure of images corresponding to the individual sensor readouts. A plurality of images are exposed by imaging less than the full possible exposure and wherein the plurality of images are combined to form a composite image. The plurality of images can be comprised of images created by exposing the sensor for different exposure times.

An imaging system that selectively alternates a first, non-destructive imaging mode and a second, destructive imaging mode to analyze a specimen so as to determine an atomic structure and composition of the specimen is provided. The field ionization mode can be used to acquire first images of ionized atoms of an imaging gas present in a chamber having the specimen disposed therein, and the field evaporation mode can be used to acquire second images of ionized specimen atoms evaporated from a surface of the specimen with the imaging gas remaining in the chamber. The first and second image data can be analyzed in real time, during the specimen analysis, and results can be used to dynamically adjust operating parameters of the imaging system.