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.

System and methods are described for directly measuring mechanical properties of a sample while concurrently imaging the sample using a scanning beam microscope (e.g., a scanning electron microscope (SEM)). The system includes a clamping mount configured to hold the sample and a load cell positioned proximal to the clamping mount and configured to provide a direct, real-time measurement of force on the sample end. The system further includes a controllable probe configured to apply a force to the sample. In some embodiments, the sample load cell is tiltably couplable to a sample held by the clamping mount and the controllable probe is moveable between a plurality of different mounting positions relative to the load cell.

System and methods are described for directly measuring mechanical properties of a sample while concurrently imaging the sample using a scanning beam microscope (e.g., a scanning electron microscope (SEM)). The system includes a clamping mount configured to hold the sample and a load cell positioned proximal to the clamping mount and configured to provide a direct, real-time measurement of force on the sample end. The system further includes a controllable probe configured to apply a force to the sample. In some embodiments, the sample load cell is tiltably couplable to a sample held by the clamping mount and the controllable probe is moveable between a plurality of different mounting positions relative to the load cell.

A method of automated control of a microscope in cryogenic electron microscopy (cryo-EM), wherein the microscope is configured to collect high-magnification micrographs of particles suspended in vitreous ice. Such particles are found in grid squares, and a square contains holes from which high-magnification micrographs are imaged. The method is carried out during an active data collection session, leveraging a pipeline that comprises a set of models. The pipeline evaluates a set of collection locations to determine whether to continue collection at a current grid/square or instead at a new grid/square. The evaluation is based on a set of one or more quality scores derived from one or more pretrained models and machine learning-based active learning. Based on the determination, control information is provided to automatically control the microscope to move to a next target for data collection.

A detection system includes a first electron source configured to generate a first electron beam and to cause the first electron beam to impinge on a sample, a second electron source configured to generate a second electron beam and to cause the second electron beam to impinge on the sample, a detector, and a control system. The control system is configured to control the first electron source to cause the first electron beam to scan an area of the sample, control a charge state of the sample by varying at least one of a landing energy and a beam current of the second electron beam, control the detector to detect electrons emitted by the sample, receive a detector signal from the detector, and generate a voltage contrast image from the detector signal.

A detection system includes a first electron source configured to generate a first electron beam and to cause the first electron beam to impinge on a sample, a second electron source configured to generate a second electron beam and to cause the second electron beam to impinge on the sample, a detector, and a control system. The control system is configured to control the first electron source to cause the first electron beam to scan an area of the sample, control a charge state of the sample by varying at least one of a landing energy and a beam current of the second electron beam, control the detector to detect electrons emitted by the sample, receive a detector signal from the detector, and generate a voltage contrast image from the detector signal.