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CN-115704827-B - System for loading and/or manipulating a sample in a sample transfer apparatus

CN115704827BCN 115704827 BCN115704827 BCN 115704827BCN-115704827-B

Abstract

The present invention relates to a system (100) for loading a sample into a sample transfer apparatus (180) and/or manipulating a sample in a sample transfer apparatus (180) at low temperatures. The system (100) includes a sample transfer apparatus (180) configured to receive a sample through a receiving opening (182) of the sample transfer apparatus (180) and configured to transfer the sample to a processing unit or an analysis unit, and a drying box (110) having an interface opening (112) and configured to be coupled to the sample transfer apparatus (180) such that the interface opening (112) of the drying box (110) is located opposite the receiving opening (182) of the sample transfer apparatus (180).

Inventors

  • Harder Lily Klein

Assignees

  • 徕卡显微系统有限公司

Dates

Publication Date
20260505
Application Date
20220803
Priority Date
20210804

Claims (20)

  1. 1. A system (100) for loading a sample into a sample transfer apparatus (180) at low temperature and/or for manipulating a sample in a sample transfer apparatus (180), comprising The sample transfer apparatus (180), the sample transfer apparatus (180) being configured to receive a sample through a receiving opening (282) of the sample transfer apparatus (180) and to transfer the sample to a processing unit or an analysis unit, and A drying oven (110), the drying oven (110) having an interface opening (112) and being configured to be connected to the sample transfer apparatus (180) such that the interface opening (112) of the drying oven (110) and the receiving opening (282) of the sample transfer apparatus (180) face each other to enable a sample to be transferred from the drying oven (110) into the sample transfer apparatus (180), Wherein the drying box (110) comprises a bracket (174), the bracket (174) being used for supporting the drying box (110) on the ground, and wherein the drying box (110) is configured such that, in operation, the drying box (110) is placed relative to the sample transfer apparatus (180) by the bracket (174) such that the interface opening (112) is located above the receiving opening (282) of the sample transfer apparatus (180) when the sample transfer apparatus (180) is placed on the ground below the drying box (110).
  2. 2. The system (100) according to claim 1, wherein the drying oven (110) comprises an interface opening cover (214) for opening and closing the interface opening (112) of the drying oven (110).
  3. 3. The system (100) according to claim 2, wherein the sample transfer device (180) comprises a receiving opening cover (284) for opening and closing the receiving opening (282) of the sample transfer device (180).
  4. 4. A system (100) according to claim 3, wherein the drying oven (110) comprising the interface opening cover (214) in its closed state is configured to be connected to the sample transfer device (180) comprising the receiving opening cover (284) in its closed state.
  5. 5. The system (100) of claim 4, wherein a distance between the interface opening cover (214) in its closed state and the receiving opening cover (284) in its closed state is in the range of 0 to 10 mm when the drying oven (110) is connected to the sample transfer device (180).
  6. 6. The system (100) of claim 4, wherein a distance between the interface opening cover (214) in its closed state and the receiving opening cover (284) in its closed state is in the range of 0 to 5mm when the drying oven (110) is connected to the sample transfer device (180).
  7. 7. The system (100) according to any one of claims 1 to 6, wherein the drying oven (110) and the sample transfer apparatus (180) are connectable to each other by a mechanical and/or magnetic connection.
  8. 8. The system (100) according to any one of claims 1 to 6, wherein when the drying oven (110) and the sample transfer apparatus (180) are connected to each other, the resulting connection constitutes a closed connection.
  9. 9. The system (100) according to any one of claims 1 to 6, wherein when the drying oven (110) and the sample transfer apparatus (180) are connected to each other, the resulting connection constitutes a sealed connection.
  10. 10. The system (100) according to any one of claims 1 to 6, wherein the drying oven (110) comprises an inlet (220) for introducing an inert gas into the interior of the drying oven (110).
  11. 11. The system (100) according to any one of claims 1 to 6, wherein the drying oven (110) comprises an outlet for exhausting gas out of the interior of the drying oven (110).
  12. 12. The system (100) according to any one of claims 1 to 6, wherein the drying oven (110) comprises a sample supply container opening (230) configured to be connected with a sample supply container (232).
  13. 13. The system (100) of claim 12, wherein the drying oven (110) includes a sample supply container opening cover (234) for opening and closing the sample supply container opening (230) of the drying oven (110).
  14. 14. The system (100) of any of claims 1 to 6, wherein the drying oven (110) comprises an inert gas opening (240) configured to connect with an inert gas storage container (344).
  15. 15. The system (100) according to any one of claims 1 to 6, wherein the sample transfer device (180) comprises an inert gas reservoir at low temperature.
  16. 16. The system (100) according to any one of claims 1 to 6, wherein the drying cabinet (110) comprises a humidity sensor (250) and/or a measuring device (152) for detecting the humidity inside the drying cabinet (110).
  17. 17. The system (100) according to any one of claims 1 to 6, wherein the drying cabinet (110) comprises at least one at least partially closable user opening (160), the user opening (160) providing user access to the interior of the drying cabinet (110).
  18. 18. The system (100) of claim 17, wherein the drying oven (110) includes a foil cover (162) at least partially covering the user opening (160).
  19. 19. The system (100) of claim 17, wherein the user opening (160) of the drying oven (110) includes a glove mount for mounting a glove that extends into an interior of the drying oven (110) when mounted.
  20. 20. The system (100) according to any one of claims 1 to 6, wherein the drying oven (110) comprises an electromechanical coupling mechanism for decoupling the drying oven (110) from the sample transfer device (180) and for coupling the drying oven (110) with the sample transfer device (180).

Description

System for loading and/or manipulating a sample in a sample transfer apparatus Technical Field The present inventive concept relates to a system for loading a sample into a sample transfer apparatus and/or for manipulating a sample in a sample transfer apparatus at a low temperature, the system comprising a sample transfer apparatus configured to receive a sample through a receiving opening of the sample transfer apparatus and configured to transfer the sample to a processing unit or an analysis unit. More specifically, the sample transfer apparatus of the system according to the inventive concept is used in the field of cryogenic microscopy for transferring a sample to be inspected to, for example, a cryogenic electron microscope (cryo-EM) or a cryogenic optical microscope (cryo-LM), or in another example, for loading and/or manipulating a sample or sample carrier or sample holder inside the sample transfer apparatus, and then transferring the sample or sample carrier or sample holder to another processing unit, such as a FIB (focused ion beam) apparatus, for further processing of the sample, or to an analysis unit, such as a cryogenic microscope, for inspecting the sample. Background US 10,144,010 B2 discloses a handling container for cryogenic microscopy, which handling container substantially corresponds to a sample transfer apparatus of the above-mentioned type. Cryogenic microscopy includes, inter alia, cryogenic light microscopy and cryogenic electron microscopy. Low temperature fixation is a common sample preparation method in low temperature electron microscopy. In which the aqueous sample is frozen (cryogenically fixed) very rapidly to a temperature below-150 ℃, i.e. it is cooled very rapidly to avoid ice crystal formation. Cryogenic immobilization has proven to be particularly useful in the study of structural biology. The object to be investigated, for example a cell, enzyme, virus or lipid layer, is thus embedded in a thin vitrified ice layer. The greatest advantage of low temperature fixation is that biological structures can be obtained in their natural state. For example, biological processes can be stopped at any point in time by cryofixation and studied in this vitrified state, for example in a cryoelectron microscope, but also in an optical microscope with corresponding sample cooling, the cryooptical microscope being used mainly for locating relevant areas in the sample, which areas can be recorded and then observed in more detail in the cryoelectron microscope. The frozen sample is usually located on a per se known electron microscope sample carrier, such as a grid or pin holder frame (pin stub mount) for scanning electron microscopy, which has to be transferred (under the above-mentioned low temperature conditions and with water removed) into a corresponding sample carrier holder, which can then be transferred in a suitable holder into the aforementioned microscope. Hitherto, there have been quite temporary solutions in which liquid nitrogen is stored in, for example, a styrofoam container in which the necessary handling steps for transferring the grid into the sample carrier holder are carried out. The low temperature nitrogen formed by the liquid nitrogen ensures the necessary low temperature on the one hand and creates an anhydrous atmosphere in the styrofoam container on the other hand, so that the sample can be prevented from being contaminated with water and thus the sample can be prevented from being contaminated with ice crystals. In order not to impair the quality of the frozen sample, it is very important to transfer the frozen sample in a cooled and contamination-free, in particular water-free, manner between the processing unit used (e.g. a cryogenic fixture, FIB ("focused ion beam") device, a freeze fracturing device or a coating device) and the analysis device (in this case mainly a cryogenic optical microscope and/or a cryogenic electron microscope). For this reason, in everyday laboratory practice, it has so far been common to employ quite temporary solutions or to manufacture the loading and transfer systems exclusively internally. The sample to be examined must first be placed on a sample carrier/grid, and then the sample carrier is usually placed on a sample holder/cartridge. The sample holder/cassette is then transferred into a sample transfer apparatus, also known as a low temperature-CLEM shuttle ("low temperature-optical-electron-microscopy shuttle"). The sample transfer apparatus may be connected to a cryogenic stage, such as a cryogenic microscope, to which the sample is transferred by transferring the sample holder/cartridge to the cryogenic stage. It is noted that other embodiments of the process are possible and other applications are contemplated, for example, where the sample or sample carrier is loaded directly into the sample transfer apparatus without a sample holder/cartridge. In the above case, the frozen sample is processed in a cold environment, e.g