The present invention relates to a device and a method for the stoichiometric analysis of samples.

In order to study the spatial distribution of different proteins in the plasma membrane of a complete cell within a short time frame, a device and a method are proposed for the stoichiometric analysis of samples.

The object is established by means of a device for the stoichiometric analysis of samples, said device comprising a) a sample processing device comprising a sample holder for holding the sample, means for setting the temperature, means for adding and removing fluids (including gases) and at least one fluid reservoir, b) an electron microscope with a detector, and c) a computer-controlled process control system for controlling the means for setting the temperature and the means for adding and removing fluids (including gases), a computer-controlled and automated imaging device that captures images by means of the electron microscope, a unit that stores the captured images and an image analysis unit controlled by the computer.

When injection of electrons into a sample supporting member causes a potential gradient between an insulative thin film and a conductive thin film at a site of electron beam injection, the potential barrier of the surface of the insulative thin film becomes thin, and an electron emission phenomenon is caused by tunnel effects. Secondary electrons caused in the insulative thin film tunnel to the conductive thin film along the potential gradient. The secondary electrons, having tunneled, reach a sample while diffusing in the conductive thin film. In the case where the sample is a sample with a high electron transmittance, such as a biological sample, the secondary electrons also tunnel through the interior of the sample. The secondary electrons are detected to acquire an SEM image in which the inner structure of the sample is reflected.

Provided is a transport device in which a reduction in the size and a reduction in the cost of the entire device are possible. A transport unit which is interposed between a sub-chamber and a first treatment chamber is provided with: a transport bar which transports a sample along a right-left direction in a preliminary sample chamber; a support which supports the transport bar; a case which supports the support so as to be rotatable around a rotation axis intersecting the right-left direction; and a second O-ring which seals an inside of the case. The preliminary sample chamber and a first treatment space can communicate with each other through the inside of the case. The transport bar is made so as to be able to transition between a first state where the transport bar can transport the sample between the preliminary sample chamber and the inside of the case, and a second state where the transport bar can transport the sample between the first treatment space and the inside of the case, by rotation of the support with respect to the case.

Provided is an observation method by an electron microscope, in which a biological sample can be observed as it is alive and a situation that the biological sample is moving can be observed using an electron microscope, and a composition for evaporation suppression under vacuum, a scanning electron microscope, and a transmission electron microscope used in the method. The sample observation method by an electron microscope according to the invention includes applying a composition for evaporation suppression containing at least one kind selected from an amphiphilic compound, oils and fats, and an ionic liquid to the surface of a sample to form a thin film, and covering the sample with the thin film, and displaying an electron microscopic image of the sample, which is covered with the thin film and accommodated in a sample chamber under vacuum, on a display device.

A method for investigating at least one nanoscale biological specimen comprises preparing an embedding liquid containing a plurality of the nanoscale biological specimens with a maximum diameter MD30 nm, preparing a thin film of the embedding liquid having an average thickness AT30 nm on an electrically conductive substrate in an application zone of the substrate that is wettable for the embedding liquid, tempering the thin film on the substrate to a measurement temperature MT, with 100 C.MT1 C. and measuring at least one of the nanoscale biological specimens within the thin film on the substrate in an electron beam instrument at the measurement temperature MT, wherein the at least one nanoscale biological specimen is exposed to an electron beam. The invention provides a method for investigating nanoscale biological specimens at a high spatial resolution in a simple manner.

In order to enable use of novel immunostaining for a pathological diagnosis and research, the invention provides a sample exchange chamber including: a container 2 into which a substrate on which a sample is placed can be introduced; a specific solution inlet 3, which is a staining mechanism that stains the sample; a cleaning liquid inlet 4, which is a cleaning mechanism that cleans the sample; an evacuation port 5, which is an evacuation mechanism that evacuates the container; a drain port 6; and a sterilization mechanism 7 that sterilizes the sample and inside of the container.

The invention relates to a workstation (1), a preparation station (2) and a method for manipulating an electron microscopy grid assembly (3). The workstation (1) comprises a first compartment (101), a first gas inlet (102) for generating an overpressure in the first compartment (101), a first glove (104) and a second glove (105), each being fixed in a respective opening (106, 107) of the workstation (1), wherein the first glove (104) and the second glove (105) are movable in the first compartment (101) to manipulate objects in the first compartment (101), wherein the workstation (1) comprises a port (109) for providing a transfer device (4) for an electron microscopy grid assembly (3) in the first compartment (101). The preparation station (2) comprises a coolant reservoir (201, 202), a first part (210) configured to hold a shuttle (6) for holding an electron microscopy grid assembly (3) in a fixed orientation, wherein the preparation station (2) is configured such that the first part (210) is submergable in the cryogenic coolant when the coolant reservoir (201, 202) contains the cryogenic coolant.