Sample holder for holding sample support, loading station, knife holder, microtome, and corresponding method

Abstract

To easily dispose a sample for a microscope cut out by a microtome in a sample support.SOLUTION: A sample holder (300) for holding a sample support for supporting a sample for a microscope includes clamp devices (302a, 302b, 302c) that are configured so as to clamp one portion of the sample support between first respective edges of an upper leg piece and a lower leg piece by clamping the sample support between the upper leg piece and the lower leg piece, and are configured so as to mutually separate the first respective edges of the upper leg piece and the lower leg piece by operation of external force and to load the sample support into the sample holder. The clamp devices are configured so as to apply clamping force to the sample support body via the first respective edges of the upper leg piece and the lower leg piece when the clamp devices are not operated by external force, and to clamp the sample support between the upper leg piece and the lower leg piece.SELECTED DRAWING: Figure 3

Description

[Technical field]

[0001] The invention essentially relates to a specimen holder for holding a specimen support for supporting a specimen for a microscope, a loading station for loading a specimen support into a specimen holder, a knife holder for a microtome, a microtome and a corresponding method. [Background technology]

[0002] In the field of neuroscience, but also in other fields, for example in biology and medicine, thin sections of tissues or other samples or microscopic samples can be examined, for example by electron microscopy. Such sections are cut out of a specimen block by a microtome and then placed on a sample support. After being cut out, it is difficult to place such microscopic samples on the sample support. Summary of the Invention [Means for solving the problem]

[0003] In view of the above-mentioned situation, there is a need for an improvement in the positioning of a sample for a microscope on a sample support. According to embodiments of the invention, a sample holder for holding a sample support for supporting a sample for a microscope, a loading station for loading a sample support into the sample holder, a knife holder for a microtome, a microtome and a corresponding method are proposed with the features of the independent claims. Advantageous further refinements form the subject matter of the dependent claims and the following description.

[0004] An embodiment of the invention relates to a sample holder for holding a sample support for supporting a sample or a microscopic sample. Such a microscopic sample may, for example, be envisaged for examination in an electron microscope when placed on the sample support. The sample support may be a so-called slot grid, e.g. a circular thin support with slots in which the sample is placed. The sample holder comprises a clamping device with an upper leg and a lower leg. At least one of the upper leg and the lower leg may be configured as a leaf spring. The clamping device is configured to clamp the sample support between the upper leg and the lower leg such that a part of the sample support (e.g. a part of its edge) is clamped between first ends of the upper leg and the lower leg. Furthermore, the clamping device is configured to be actuated by an external force such that the first ends of the upper leg and the lower leg are moved away from each other and the sample support is loaded into the sample holder. In addition, the clamping device is configured to apply a clamping force to the sample support via a first end of each of the upper and lower legs when the clamping device is not actuated by an external force, such that the sample support is clamped between the upper and lower legs.

[0005] Such a sample holder facilitates handling and holding of the sample support after insertion. In particular, such a sample holder allows easy positioning of the sample support when used with a microtome. Typically, such a microtome comprises a knife holder with a knife and a storage box, which is supplied with a liquid, such as water, onto which a microscopic sample cut out of a specimen or specimen block by the knife can drop or slide. For example, the sample support can be positioned in a desired form by the sample holder, and the microscopic sample after being cut out can be easily placed on the sample support. In contrast to manual handling and holding of such a sample support, the sample holder according to an embodiment of the invention allows a significantly easier positioning of a microscopic sample on the sample support. A more detailed description of a method for placing a microscopic sample on a sample support using such a sample holder is given below.

[0006] In an embodiment of the invention, one of the upper and lower legs comprises a through hole configured to accommodate an actuation rod, and the other of the upper and lower legs is configured to be actuated by an external force such that a first end of each of the upper and lower legs is moved away from each other when an external force is applied to the first other of the upper and lower legs via an actuation rod accommodated in the through hole, thereby making it possible, for example, to easily insert a sample support into a sample holder by a device comprising such an actuation rod.

[0007] According to a further embodiment of the invention, at least one of the upper and lower legs is attached at its second end to the sample holder, which allows for a simple and effective attachment of the legs and in particular makes it easy to move the two legs apart from each other by means of the actuation rod.

[0008] According to a further embodiment of the invention, the sample holder is for or configured to hold a plurality of sample supports, e.g. sample supports of the same or similar type. The sample holder comprises a plurality of clamping devices, each of the plurality of clamping devices being configured to hold individually one of the plurality of sample supports. In this way, a large number of microscopic samples can be placed on the respective sample supports in a simple, fast and highly efficient manner.

[0009] According to a further embodiment of the invention, the clamping devices are arranged in a circle with the first ends of the respective upper and lower legs arranged in a circular fashion, which allows the sample holders to be arranged on respective knife holders of the microtome to individually position each of the holder sample supports at the same desired position.

[0010] According to a further embodiment of the invention, each of the plurality of clamping devices is configured to be actuated individually and independently from the rest of the plurality of clamping devices by an external force to move the first ends of each of the upper and lower legs away from each other and load each sample support into the sample holder, such that individual sample supports can be removed from and inserted into the sample holder without affecting other sample supports inserted and held in the sample holder.

[0011] According to a further embodiment of the invention, the sample holder comprises a base, and a number of clamping devices are rotatably mounted on the base, such that the clamping devices are rotatable about a rotation axis relative to the base. This allows the sample holder to be rotated and thus placed on each knife holder of the microtome such that each holder sample support is individually positioned at the same desired position. In addition, this allows the sample holder to be rotated and thus placed on each loading station such that each holder sample support is individually positioned at the same desired position for loading or placing the sample support in the sample holder.

[0012] According to a further embodiment of the invention, the sample holder comprises a latch mechanism configured to allow each of the clamping devices to be attached in the same position and to allow the clamping devices to be released for rotation, making it easier and more efficient to load the sample supports into the sample holder. Additionally, when used with a knife holder, it facilitates the attachment of each of the sample supports.

[0013] Another embodiment of the invention relates to a loading station for loading a sample support into a sample holder. The loading station comprises a receiving area configured to receive the sample holder, an actuation mechanism, and a loading slider. The loading slider is configured to receive the sample support. When the sample holder is received in the receiving area and the clamping device is positioned in the loading position, the actuation mechanism is configured to apply a force to the sample holder and actuate the clamping device of the sample holder to move first ends of upper and lower legs of the clamping device away from each other when the actuation mechanism is activated. In an embodiment, the actuation mechanism comprises an actuation rod configured to extend through a through hole in one of the upper and lower legs and to apply a force to the other of the upper and lower legs to move the first ends of the upper and lower legs away from each other when the actuation mechanism is activated.

[0014] Further, the loading station is configured such that when the loading slider is slidable toward the sample holder, the sample support is accommodated in the loading slider, and the actuation mechanism is actuated, a portion of the sample support is positioned between the first ends of each of the upper and lower legs.

[0015] Such a loading station allows easy loading of one or more sample supports into a sample holder as described above, in particular facilitating the insertion of the sample supports between the legs of the respective clamping mechanisms.

[0016] Another embodiment of the invention relates to an apparatus comprising a sample holder and a loading station, each as described above.

[0017] Another embodiment of the invention relates to a knife holder for a microtome. The knife holder comprises or is configured to be provided with a knife. Such a knife can be used to cut a sample for microscopy from a specimen or specimen block, typically in the form of thin sections or slices. The knife holder further comprises a storage box for receiving a section cut from the specimen by the microtome. Such a storage box is typically configured to be supplied with or filled with a liquid, such as water. Furthermore, the storage box is configured to receive a sample holder for supporting a sample support, and to be able to mount the sample holder in a position relative to the knife. Such a position may be a predefined position or one of a number of predefined positions. Preferably, such a position may be selected by a user. In an embodiment, the storage box comprises a sliding mechanism, for example with a slider and a rail. The sliding mechanism is configured to receive the sample holder, and the sliding mechanism is configured to be mounted in any position or in one or more predefined positions relative to the knife, so that for example the sample holder can be mounted in a desired position.

[0018] Such a knife holder, when used in conjunction with a sample holder as described above, makes it possible to position the sample support in a desired position next to the knife, making it possible to easily place a sample for microscopy on the sample support.

[0019] According to a further embodiment of the invention, the storage box is configured such that when the sample holder holds the sample support and is stored in the storage box mounted in a position relative to the knife, a liquid such as water is provided so that the liquid covers the sample support when the liquid is provided in the storage box. For example, the storage box may have sufficiently high side walls to achieve a fill level of the liquid such that the sample support is below the fill level or surface. Using such a liquid, the microscopic sample after being cut out of the specimen can drop or slide onto the liquid or its surface. This facilitates the subsequent placement of the microscopic sample on the sample support.

[0020] According to a further embodiment of the invention, the knife holder or its storage box comprises a device for removing liquid from the storage box, such that the filling level of the liquid is continuously reduced. This can be achieved, for example, by the device comprising or being a valve in the storage box, for example in a side wall of the storage box. Such a valve must be positioned below the position of the sample support. The device may also comprise or be such a further opening that is configured to be able to be opened and closed.

[0021] In this way, the filling level or surface can be lowered, in particular with a microscopy sample on it, so that the microscopy sample can be placed on the sample support simply by lowering the surface or lowering the filling level of the liquid.

[0022] In addition to such valves and openings, a pump can be used to efficiently remove the liquid, and in addition, this allows for refilling of the liquid. It should be noted that such a pump can also be used, for example, without the valves or openings. For example, a device can be provided that includes such a knife holder and such a pump.

[0023] Another embodiment of the invention relates to a microtome comprising a knife holder as described above. Such a microtome may for example be an ultramicrotome.

[0024] Another embodiment of the present invention relates to a method for loading a sample support into a sample holder using a loading station. The method includes the following steps: the sample holder is placed in a receiving area of ​​the loading station and a clamping device of the sample holder is positioned in a loading position. The sample support is loaded into a loading slider of the loading station. An actuating mechanism of the loading station is actuated to move first ends of upper and lower legs of the clamping device away from each other. The loading slider is slid towards the sample holder and a portion of the sample support is positioned between the first ends of the upper and lower legs. The actuating mechanism is then released and the sample support is clamped between the upper and lower legs. This is a simple way to accurately position the sample support in the sample holder. In an embodiment, a sample holder and a loading station as described above may be used.

[0025] According to a further embodiment of the invention, a method is for loading a plurality of sample supports into a sample holder, when the sample holder comprises a plurality of clamping devices. The method comprises the following steps for each of the further plurality of sample supports: the sample support is loaded into the loading slider; the sample holder is actuated and a next clamping device of the plurality of clamping devices of the sample holder is positioned in the loading position; the actuating mechanism of the loading station is actuated and a first end of each of the upper and lower legs of each clamping device is moved away from each other; the loading slider is slid towards the sample holder and a part of the sample support is positioned between the first ends of each of the upper and lower legs; the actuating mechanism is then released and the sample support is clamped between the upper and lower legs. For the method, in an embodiment, a sample holder with a plurality of clamping devices as described above may be used.

[0026] Another embodiment of the invention relates to a method for placing a sample cut out of a specimen by a microtome on a sample support loaded in a sample holder. The method comprises the following steps: The sample holder is provided in a storage box of the microtome, such storage box may be constituted by a knife holder of the microtome. The sample holder is mounted in a desired position relative to the knife of the microtome (or in particular the knife holder), the sample support having a desired position relative to the knife. A fluid, such as water, is provided in the storage box, which covers the sample support. Then, the sample is cut out of the specimen by the microtome, which is located on a surface and above the sample support, it being noted that samples for such microscopy usually migrate on such surfaces. Furthermore, at least a part of the liquid is removed from the storage box, and the sample (which is located on the surface) is lowered and placed on the sample support.

[0027] This is a very simple and efficient way of positioning a sample for microscopy on a sample support. No manual manipulation of the sample support or the sample for microscopy is required. In an embodiment, a sample holder and microtome as described above may be used.

[0028] According to a further embodiment of the invention, a method is provided for placing a plurality of samples cut out from a specimen by a microtome on each of a plurality of sample supports loaded in the specimen holder, in particular when the specimen holder comprises a plurality of clamping devices. For each of the further plurality of sample supports, the method comprises the following steps: the sample holder is actuated, such that the next sample support has a desired position relative to the knife; a fluid is supplied into the storage box, the fluid covering the sample supports; the samples are cut out from the specimen by the microtome, such that the samples are located on the surface of the fluid and above each sample support; then at least a portion of the fluid is removed from the storage box and each sample is lowered and placed on each sample support.

[0029] In this way, a plurality of samples can be simply, quickly and efficiently placed on each sample support. In this regard, it should be noted that by operating the sample holder to position the next sample support at a desired position, the sample support on which the sample is placed may be covered with or immersed in a liquid. The inventors recognize that such samples adhere to the sample support even when immersed in a liquid such as water. This makes it possible to use a plurality of clamping devices, particularly such a sample holder having a circular shape (a shape like a carousel) as described above. For this method, in an embodiment, a sample holder having a plurality of clamping devices as described above can be used.

[0030] Further advantages and embodiments of the present invention will become apparent from the present specification and the accompanying drawings.

[0031] It should be noted that the features described above and the features further described below can be used not only in the combinations shown respectively, but also in further combinations or alone without departing from the scope of the present invention.

Brief Description of the Drawings

[0032] [Figure 1a] It is a diagram schematically showing a sample holder according to an embodiment of the present invention. [Figure 1b] It is a diagram schematically showing the sample holder of Fig. 1a in different situations. [Figure 1c] It is a diagram schematically showing the sample holder of Fig. 1a in further different situations. [Figure 2a] It is a diagram schematically showing a knife holder according to an embodiment of the present invention. [Figure 2b] It is a diagram schematically showing the knife holder of Fig. 2b in different situations. [Figure 2c] It is a diagram schematically showing the knife holder of Fig. 2b in further different situations. [Diagram 3] It is a diagram schematically showing a sample holder according to a further embodiment of the present invention. [Figure 4]4A-4D diagrammatically show a knife holder according to a further embodiment of the invention; [Figure 5a] FIG. 2 illustrates a schematic diagram of a loading station according to an embodiment of the present invention; [Figure 5b] 5b shows a schematic diagram of the loading station of FIG. 5a in different situations; [Figure 5c] 5b shows a schematic view of the loading station of FIG. 5a from a different perspective; [Figure 6] FIG. 1 illustrates a schematic diagram of a microtome according to an embodiment of the present invention. [Figure 7] 2 is a flow chart that generally illustrates a method according to an embodiment of the present invention. [Figure 8] 4 is a flow chart that illustrates generally a method according to a further embodiment of the present invention; DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0033] FIG. 1a shows a schematic representation of a sample holder 100 according to an embodiment of the invention. The sample holder 100 is for or is configured to hold a sample support 150 for supporting a sample or a sample for a microscope. The sample support 150 may be of a circular shape with slits, for example the sample support 150 may be a so-called slot grid, as used in electron microscopes. FIG. 1a shows the sample support 150 separately from the sample holder 100. FIG. 1b shows the sample holder 100 of FIG. 1a in a different situation, FIG. 1c shows the sample holder 100 of FIG. 1a and FIG. 1b in a further different situation, the sample support 150 is inserted in the sample holder 100. In the following, FIGS. 1a, 1b and 1c are described together.

[0034] The sample holder 100 comprises a clamping device 102 having an upper leg 104 and a lower leg 106. In an embodiment, at least one of the upper leg 104 and the lower leg 106 is configured as a leaf spring. Alternatively, both legs 104, 106 may be configured as leaf springs. The clamping device 102 is configured to clamp the sample support 150 between the upper leg 104 and the lower leg 106 such that a portion of the sample support 150, such as an outer edge or a portion of an outer edge, is clamped between first ends 108, 110 of the upper leg 104 and the lower leg 106, respectively.

[0035] Furthermore, the clamping device 102, referring to FIG. 1b, is actuated by an external force F1 such that the first ends 108, 110 of the upper leg 104 and the lower leg 106 are moved away from each other to load the sample support into the sample holder 100. In an embodiment, one of the upper and lower legs (the lower leg 106 in FIG. 1b) comprises a through hole 116 configured to accommodate an actuation rod 140. The other of the upper and lower legs (the upper leg 104 in FIG. 1b) is actuated by an external force F1 such that the first ends of the upper and lower legs are moved away from each other when an external force is applied to the other of the upper and lower legs via the actuation rod 140 accommodated in the through hole 116. It should be noted that such an actuation rod 140 is typically part of a device separate from the sample holder 100.

[0036] 1b shows a situation in which the legs 104, 106 are moved apart from each other by an external force F1 applied by an actuation rod 140, which in this embodiment is received in and extends through the through hole 116. In addition, a sample support 150 is exemplarily disposed at the first end 110 of the lower leg 106 by its edge.

[0037] In an embodiment, at least one of the upper and lower legs is attached to the sample holder 100 at each second end 112, 114. The sample holder 100 may include a base to which the upper and / or lower legs are attached. Such a base is not shown in Figures 1a, 1b and 1c, but is shown in Figure 2.

[0038] Furthermore, referring to Fig. 1c, the clamping device 102 is configured to apply a clamping force F2 to the sample support 150 via the first ends 108, 110 of the upper and lower legs, respectively, so that the sample support 150 is clamped between the upper and lower legs 104, 106 when the clamping device is not actuated by an external force. Fig. 1c illustrates a situation in which the sample support 150 is clamped between the first ends 108, 110 of the upper and lower legs 104, 106. The actuation rod 140 has been removed from the through hole 116.

[0039] 2 shows a schematic of a knife holder 260 according to an embodiment of the invention. The knife holder 260 can be used as part of a microtome. The knife holder 260 comprises a knife 264, which is used to cut a sample from a specimen or specimen block 268. The specimen block 268 can be held in or by the microtome, as described below. The knife holder 260 further comprises a storage box 266 for storing sections (i.e. samples) cut from the specimen 268 by the microtome using the knife 254.

[0040] The storage box 266 is configured to accommodate a sample holder for supporting the sample support 150, such as the sample holder 100 of Figs. 1a-1c. The sample holder 100 shown in Fig. 2a comprises a base 220 to which the clamping device 102 is attached. The storage box 266 is configured such that the sample holder 100 can be attached in a position relative to the knife 264. In an embodiment, one or more predefined positions can be provided at which the sample holder 100 can be attached. By way of example, one such position is shown by the line P1. When the left end of the base 220 is positioned on the line P, the sample support 150 is positioned, for example, in a desired position relative to the knife 264.

[0041] In an embodiment, the containment box 266 comprises a sliding mechanism 262 configured to accommodate the sample holder 100. For example, the sliding mechanism 262 comprises a rail and a slider that slides on the rail. The sample holder 100 can be mounted, for example, on the slider. The sliding mechanism 262 is configured to be mounted at any position relative to the knife 264 (e.g., along the rail) or at one or more predefined positions. In this way, the sample holder can be mounted, for example, at position P1 by appropriately mounting the sliding mechanism.

[0042] If the position for mounting the sliding mechanism is arbitrary, the user can appropriately select the desired relative position of the sample holder (with the sample support) with respect to the knife 264. If the positions for mounting the sliding mechanism are predefined, the user is assisted in finding the appropriate position (or one of multiple positions) of the sample holder (with the sample support) with respect to the knife 264.

[0043] In an embodiment, the containment box 266 is configured such that when a liquid, such as water, is provided in the containment box 266 and the sample holder 100 is contained within the containment box 266 and attached in a position P1 relative to the knife 264, holding the sample support 150, the liquid covers the sample support 150. By way of example, a fill level 290 of such liquid is indicated by a dashed line within the containment box 266.

[0044] In a further embodiment, the knife holder 260 is configured such that liquid can be removed from the storage box 266 such that the filling level 290 of the liquid is continuously reduced. For example, the knife holder 260 or the storage box 266 may comprise a valve (not shown here) for such purpose. For example, if the current filling level of the liquid corresponds to the filling level 290, the sample support 150 is completely covered with liquid, i.e. the sample support 150 is below the surface. By opening the valve (manually or automatically), the filling level is reduced and after a sufficient amount of liquid has been removed, the filling level is below the sample support 150, e.g. part of the sample support 150 or the entire sample support 150 is above the filling level and above the surface.

[0045] Fig. 2b shows the knife holder 260 or parts thereof diagrammatically in different views and situations. By way of example, the knife 254 is shown cutting a section or sample 269 from a specimen 268. The sample 269 is moving on a surface 291, which has a height corresponding to a filling level 290. The sample support 150 held by the sample holder 100 is below the surface 291. After the cutting process is finished (after which the sample 269 is cut from the specimen 268), the filling level 290 may be lowered and the sample 269, still moving on the surface 291, is placed on the sample support. This is shown in Fig. 2c.

[0046] Fig. 3 shows a schematic representation of a sample holder 300 according to a further embodiment of the invention. The sample holder 300 is configured to hold a plurality of sample supports and comprises a plurality of clamping devices. By way of example, three clamping devices are indicated with references 302a, 302b, 302c. By way of example, the sample holder 300 comprises 16 clamping devices, indicated with the numbers 1 to 16 in Fig. 3 (not all of these clamping devices are shown in Fig. 3). Each of the plurality of clamping devices is configured to individually hold one of the plurality of sample supports. It is noted that a different number of clamping devices may be provided, e.g. 8, 12, 18, 24, etc.

[0047] Each of the clamping devices such as 302a, 302b, 302c may be similar or equivalent to clamping device 102 shown in Figures 1a-1c. In an embodiment, the clamping devices such as 302a, 302b, 302c are arranged in a circle such that the first ends of each of the upper legs and each of the lower legs are arranged in a circular configuration. This is shown by way of example in Figure 3.

[0048] In an embodiment, each of the plurality of clamping devices, such as 302a, 302b, 302c, is configured to be actuated individually and independently from the rest of the plurality of clamping devices by an external force to move the first ends of each of the upper and lower legs away from each other to load each sample support into the sample holder 300. In an embodiment, the sample holder 300 comprises a base 320, and the plurality of clamping devices are rotatably mounted to the base 320, such that the plurality of clamping devices, such as 302a, 302b, 302c, are rotatable relative to the base 320 about a rotation axis 324.

[0049] In an embodiment, the sample holder 300 includes a latch mechanism configured to allow multiple clamping devices, such as 302a, 302b, 302c, to be attached to each of the clamping devices at the same position and to allow the multiple clamping devices to be released for rotation. For example, such a latch mechanism may include a pin 328 biased (e.g., downward) to the clamping device and a slit or groove 330 for each clamping device. In the example shown in FIG. 3, the clamping device 302a is positioned at a specific position. The multiple clamping devices can be rotated, for example, by a tool inserted into the receiving portion 326. After a clockwise rotation of, for example, 22.5° (the angle may be different for the other number of clamping devices), the clamping device 302b reaches the position previously held by the clamping device 302a. Due to the latching mechanisms 328, 330, a small force is required to initiate the rotation.

[0050] In an embodiment, the sample holder 300 includes a handle 322 that allows the entire sample holder 300 to be easily grasped and inserted, for example, into a knife holder.

[0051] Fig. 4 shows a schematic representation of a knife holder 460 according to a further embodiment of the invention. The knife holder 460 can be used as part of a microtome. The knife holder 460 comprises a knife 464, by means of which a sample is cut from a specimen or specimen block (not shown here, but similar or equivalent to Fig. 2). The knife holder 460 further comprises a storage box 466 for storing sections (i.e. samples) cut by the microtome from the specimen using the knife 464.

[0052] The storage box 466 is configured to accommodate a sample holder for supporting the sample support 150, such as the sample holder 300 of FIG. 3. The storage box 466 is configured to allow the sample holder 300 to be mounted in a position relative to the knife 464. In an embodiment, one or more predefined positions may be provided at which the sample holder 300 can be mounted. By way of example, one such position is shown by the line P2. When the left end of the base 320 is positioned on the line P2, the sample support 150 is positioned in a desired position relative to, for example, the knife 264.

[0053] In an embodiment, the containment box 466 comprises a sliding mechanism 462 configured to accommodate the sample holder 300. For example, the sliding mechanism 462 comprises a rail and a slider that slides on the rail. The sample holder 300 can be mounted on the slider, for example. The sliding mechanism 462 is configured to be mounted at any position relative to the knife 464 (e.g., along the rail) or at one or more predefined positions. In this way, the sample holder can be mounted at position P2, for example, by appropriately mounting the sliding mechanism.

[0054] If the position for mounting the sliding mechanism is arbitrary, the user can appropriately select the desired relative position of the sample holder (with the sample support) with respect to the knife 464. If the position for mounting the sliding mechanism is predefined, the user is assisted in finding the appropriate relative position (or one of multiple positions) of the sample holder (with the sample support) with respect to the knife 464. By operating the sample holder 300, when mounted in the storage box 466, each of the multiple clamping devices, and thus each of the multiple sample supports held by the multiple clamping devices, can be positioned next to the knife 464.

[0055] In an embodiment, the containment box 466 is configured such that when a liquid, such as water, is provided in the containment box 466 and the sample holder 300 is contained within the containment box 466 and mounted in a position P2 relative to the knife 464 to hold the sample support 150, the liquid covers the sample support 150. By way of example, a fill level 490 of such liquid is indicated by a dashed line within the containment box 466.

[0056] In a further embodiment, the knife holder 460 further comprises a device 492 for removing liquid from the receiving box 466, such that a filling level 490 of the liquid is continuously reduced. For example, the device 492 can comprise or be a valve for such purpose. For example, if the current filling level of the liquid corresponds to the filling level 490, the sample support 150 is completely covered with liquid, i.e. the sample support 150 is below the surface. By opening the valve 492 (manually or automatically), the filling level is reduced and, after a sufficient amount of liquid has been removed, the filling level is below the sample support 150, e.g. part of the sample support 150 or the entire sample support 150 is above the filling level and above the surface.

[0057] In an embodiment, pump 494 (and lines or pipes for liquid) may be provided by means capable of pumping liquid 498 from reservoir 496 through valve 492 to containment box 466, for example, until fill level 490 is reached. Pump 494 may also be used to remove liquid from containment box 466 through valve 492, for example, to supply liquid to reservoir 496. Pump 494 may be, for example, an automatic pump.

[0058] It should be noted that the knife holder 460 of Figure 4 may be similar to or the same as the knife holder 260 of Figure 2. The sliding mechanisms 262 and 462 may differ in that the sliding mechanism 262 is specifically adapted for the sample holder 100 and the sliding mechanism 462 is specifically adapted for the sample holder 300. However, the sliding mechanisms 262, 462 may be the same and may be configured such that either the sample holder 100 or the sample holder 300 can be attached to the sliding mechanism 262, 462.

[0059] Figure 5a shows a schematic diagram of a loading station 570 according to an embodiment of the invention. The loading station 570 is envisaged or configured to load a sample support into a sample holder such as sample holder 100; 300. By way of example, sample holder 300 is shown in Figure 5a.

[0060] The loading station 570 includes a receiving area 572 configured to receive the sample holder 300, an actuation mechanism with an actuation knob 578, and a loading slider 574. The loading station 570 can include, for example, a lock bar 576 configured to attach or lock the sample holder 300 when the sample holder 300 is received in the receiving area 572. The loading slider 574 is configured to receive, for example, a sample support in the receiving section 580. The actuation mechanism 578 is configured to apply a force to the sample holder 300 when the sample holder 300 is received in the receiving area 572 and the clamp device 302a is positioned in the loading position P3, so that the actuation mechanism 578 is actuated to apply a force to the sample holder 300 and the clamp device 302a of the sample holder 300 is actuated to move the first ends of the upper and lower legs of the clamp device 302a away from each other.

[0061] Figure 5c illustrates the loading station 570 of Figure 5a in cross section along line AA. In an embodiment, as shown in Figure 5c, the actuation mechanism 582 includes an actuation rod, such as the actuation rod 140 illustrated in Figures 1a-1c, configured to extend through a through hole in one of the upper and lower legs and apply a force to the other of the upper and lower legs to move the first ends of the upper and lower legs away from each other when the actuation mechanism 582 is actuated.

[0062] In an embodiment, the actuation mechanism 582 comprises an actuation knob 578, a lever or connector 584, and an actuation rod 140. These components are coupled together and disposed inside the loading station 570, such that when the actuation knob 578 is pressed downward as seen in direction R1, the actuation rod 140 is pressed upward as seen in direction R2. For example, the actuation mechanism 582 can be configured such that when the actuation knob 578 is pressed downward (and the actuation knob 578 is in a lower position), the actuation mechanism 582 is locked by rotating the actuation knob 578, so that the actuation rod 140 remains in an upper position of the actuation rod 140. This allows the sample support to be inserted. The actuation knob 578 is then released and the actuation rod 140 can return to the lower position of the actuation rod 140, for example by a spring or the like.

[0063] Further, the loading station 570 is configured such that the loading slider 574 is slidable toward the sample holder 300, and when the sample support is accommodated in the loading slider 574 and the actuation mechanism is actuated, a portion of the sample support is positioned between the first ends of each of the upper and lower legs.

[0064] The actuation mechanism may then be released and the sample support 150 may be clamped with the clamping mechanism 302a. This situation is shown in FIG. 5b. The slider 574 may then be removed. The sample holder 300 may then be actuated to position the next clamping device in the loading position. By repeating the above steps, multiple sample supports can be loaded into the sample support 300.

[0065] 6 shows a schematic representation of a microtome 600 according to an embodiment of the invention. The microtome 600 comprises a knife holder, such as, for example, the knife holder 460. The knife holder 460 comprises, for example, the sample holder 300. Furthermore, the microtome 600 may comprise an actuation and / or positioning mechanism 602 and a holding mechanism 604.

[0066] The actuating and / or positioning mechanism 602 may be configured such that the knife holder 460 can be attached to the actuating and / or positioning mechanism 602. The holding mechanism 604 may be configured to hold a specimen or specimen block as shown in FIG. 2. The actuating and / or positioning mechanism 602 may rotate and / or move the knife holder 460, and thus its knife, in different directions to achieve a desired orientation and / or position of the knife relative to the sample. By moving the holding mechanism 604, and thus the specimen held by the holding mechanism 604, up and down, sections may be cut from the specimen. This results in the situation shown in FIG. 2b and FIG. 2c.

[0067] Figure 7 illustrates, in a flow diagram, a schematic of a method according to an embodiment of the invention, which involves loading a sample support into a sample holder, such as sample holder 300 shown in Figure 3, using a loading station, such as loading station 570 shown in Figures 5a-5c.

[0068] In step 700, the sample holder is placed in the receiving area of ​​the loading station and the clamping device of the sample holder is positioned in the loading position. This situation is shown in FIG. 5a. In step 702, the sample support is loaded into the loading slider of the loading station. In step 704, the actuating mechanism of the loading station is actuated to move the first ends of the upper and lower legs of the clamping device away from each other. This situation is shown in FIG. 1b for an individual clamping device. In step 706, the loading slider is slid towards the sample holder and a part of the sample support is positioned between the first ends of the upper and lower legs. In step 708, the actuating mechanism is released and the sample support is clamped between the upper and lower legs. This situation is shown in FIG. 5b. In step 710, the sliding mechanism can be slid away again. If no more sample supports need to be loaded, the sample holder can be removed from the loading station.

[0069] In an embodiment, the method may include further steps for loading further sample supports into the sample holder. For each further sample support, the following steps may be performed: In step 712, the sample support is loaded into the loading slider. In step 714, the sample holder is actuated to position the next clamping device of the clamping devices of the sample holder in the loading position. In the example of FIG. 5a, clamping device 302b takes the position of clamping device 302a. In step 716, the actuating mechanism of the loading station is actuated to move the first ends of the upper and lower legs of each clamping device away from each other. In step 718, the loading slider is slid towards the sample holder and a portion of the sample support is positioned between the first ends of the upper and lower legs. In step 720, the actuating mechanism is released and the sample support is clamped between the upper and lower legs. In step 722, the sliding mechanism may be slid away again. If no further loading of sample supports is required, the sample holder may be removed from the loading station.

[0070] Figure 8 shows, in a flow diagram, a schematic representation of a method according to an embodiment of the invention. The method involves placing a sample, cut from a specimen by a microtome, such as microtome 600 shown in Figure 6, on a sample support loaded in a sample holder, such as sample holder 100 shown in Figures 1a-1c, 2 or in a sample holder, such as sample holder 300 shown in Figure 3. See in particular Figures 2b and 2c.

[0071] In step 800, the sample holder is placed in the storage box of the microtome. In step 802, the sample holder is attached in a desired position relative to the knife of the microtome, and the sample support has a desired position relative to the knife. In step 804, a fluid is provided in the storage box, and the fluid covers the sample support. Such a situation is shown in Fig. 2a and Fig. 4. In step 806, a sample is cut from the specimen by the microtome, and the sample is located on the surface of the fluid and above the sample support. Such a situation is shown in Fig. 2b. In step 808, at least a portion of the fluid is removed from the storage box, and the sample is lowered and placed above the sample support. Such a situation is shown in Fig. 2c. When the sample no longer needs to be placed on the sample support, the sample holder may be removed from the knife holder, and the sample support may then be removed from the sample holder, for example for use in an electron microscope.

[0072] In an embodiment, the method may include a further step for placing a further sample, cut from the specimen by the microtome, on each of the multiple sample supports loaded in the sample holder. For each further sample support, the following steps may be performed: In step 810, the sample holder is actuated so that the next sample support has the desired position relative to the knife. This may include using a tool to rotate the clamping device. In step 812, a fluid is provided in the containment box (e.g., by returning the fluid to the containment box) so that the fluid covers the sample support. The situation as shown in Figures 2a and 4 arises again. Note that in this situation, the rotated away sample support and the sample placed on the sample support are below the surface. However, the liquid does not remove the sample from the sample support, as adhesion forces act only on placing the sample on the sample support as described above.

[0073] In step 814, samples are cut from the specimen by a microtome, and the samples are positioned on the surface and above the respective sample supports. This is again the situation shown in FIG. 2b. In step 816, at least a portion of the fluid is removed from the containment box and the respective samples are lowered and positioned above the respective sample supports. This is again the situation shown in FIG. 2c. When the samples no longer need to be placed on the sample supports, the sample holder may be removed from the knife holder, and the sample supports may then be removed from the sample holder, for example for use in an electron microscope.

[0074] It should be noted that not only single samples are placed on individual sample supports in this manner. If desired, for example, multiple such samples can be cut from a specimen and placed side-by-side on the same sample support. After the desired number of samples have been placed on the sample supports, the sample holder can be actuated to provide the next sample support.

[0075] As used in this specification, the term "and / or" includes any and all combinations of one or more of the associated listed items and may be abbreviated as " / ".

[0076] Although some aspects have been described in the context of an apparatus, it will be apparent that these aspects also represent a description of a corresponding method, where a block or apparatus corresponds to a step or feature of a step, and similarly, aspects described in the context of a step also represent a description of a corresponding block or item or feature of a corresponding apparatus. [Explanation of symbols]

[0077] 100,300 Sample holder 102, 302a, 302b, 302c Clamping device 104 Upper leg piece 106 Lower leg piece 108,110 First end 112,114 Second end 116 Through hole 140 Actuating rod 150 Sample Support 220,320 base 260,460 Knife holder 262,462 Sliding mechanism 264,464 Knives 268 specimens 290,490 Filling level 291 Surface 322 Handle 324 Rotation axis 326 Storage Unit 328 Pin 330 Groove 492 Valve 494 Pump 496 Reservoir 498 Liquid 570 Loading Station 572 Containment Area 574 Slider 576 Rock Bar 578 Operating knob 580 Containment Section 582 Operating Mechanism 584 Lever 600 Microtome 602 Actuating and / or positioning mechanisms 604 Retention mechanism 700~722,800~816 Method steps F1,F2 force P1,P2 position R1,R2 direction

Claims

1. A sample holder (100, 300) for holding a sample support (150) for supporting a sample (269) for use with a microscope, The sample holder (100, 300) is equipped with a clamping device (102, 302a, 302b, 302c) having an upper leg piece (104) and a lower leg piece (106), The clamping device (102, 302a, 302b, 302c) is configured to clamp the sample support (150) between the upper leg piece (104) and the lower leg piece (106), so that a portion of the sample support (150) is clamped between the first ends (108, 110) of the upper leg piece (104) and the lower leg piece (106). The clamping device (102) is configured to be actuated by an external force (F1) so that the first ends (108, 110) of the upper leg piece and the lower leg piece are separated from each other, and the sample support is loaded into the sample holder (100, 300). The clamping device (102, 302a, 302b, 302c) is configured to apply a clamping force (F2) to the sample support (150) via the first ends (108, 110) of the upper leg piece and the lower leg piece, respectively, when the clamping device is not being operated by an external force, so that the sample support is clamped between the upper leg piece (104) and the lower leg piece (106). Sample holder (100, 300).

2. One of the upper leg piece and the lower leg piece (106) is provided with a through hole (116) configured to accommodate an operating rod (140), and the other of the upper leg piece and the lower leg piece (104) is configured to be actuated by the external force so that when the external force is applied to the other of the upper leg piece and the lower leg piece via the operating rod (140) housed in the through hole (116), the first ends of each of the upper leg piece and the lower leg piece are separated from each other. A sample holder (100, 300) according to claim 1.

3. At least one of the upper leg piece (104) and the lower leg piece (106) is configured as a leaf spring. A sample holder (100, 300) according to claim 1 or 2.

4. At least one of the upper leg piece and the lower leg piece is attached to the sample holder at their respective second ends (112, 114). A sample holder (100, 300) according to claim 1.

5. To hold multiple sample supports (150), the sample holder (300) is equipped with multiple clamping devices (302a, 302b, 302c), each of which is configured to individually hold one of the multiple sample supports (150). The sample holder (300) according to claim 1.

6. The plurality of clamping devices (302a, 302b, 302c) are arranged in a circular pattern, and the first ends of each of the upper and lower leg pieces are arranged in a circular shape. The sample holder (300) according to claim 5.

7. Each of the plurality of clamping devices (302a, 302b, 302c) is operated individually and independently of the rest of the plurality of clamping devices by an external force, so that the first ends of the upper leg piece and the lower leg piece are separated from each other, and each sample support (150) is loaded into the sample holder (300). A sample holder (300) according to claim 5 or 6.

8. The sample holder (300) comprises a base (320), and the plurality of clamping devices are rotatably mounted on the base (320), and the plurality of clamping devices (302a, 302b, 302c) are rotatable about a rotation axis (324) relative to the base (320). The sample holder (300) according to claim 5.

9. The sample holder (300) includes latch mechanisms (328, 330) configured to allow each of the plurality of clamping devices (302a, 302b, 302c) to be mounted in the same position, and to allow the plurality of clamping devices to be released for rotation. The sample holder (300) according to claim 8.

10. A loading station (570) for loading a sample support (150) into a sample holder (300), The loading station (570) includes a storage area (572) configured to accommodate the sample holder (300), The loading station (570) comprises an operating mechanism (582) and a loading slider (574), The loading slider (574) is configured to accommodate the sample support (150), The operating mechanism (582) is configured to apply force to the sample holder (300) when it is activated while the sample holder (300) is housed in the housing area (572) and the clamping device is positioned in the loading position (P3), thereby activating the clamping device of the sample holder and causing the first ends of the upper and lower legs of the clamping device to separate from each other. The loading station (570) is configured such that the loading slider (574) is slidable toward the sample holder (300), and when the sample support is housed in the loading slider (574) and the operating mechanism is activated, a portion of the sample support is positioned between the first ends of the upper leg piece and the lower leg piece. Loading station (570).

11. The operating mechanism (582) comprises an operating rod (140) which, when the operating mechanism (582) is operated, extends through a through hole provided in one of the upper leg piece and the lower leg piece, and is configured to apply force to the other of the upper leg piece and the lower leg piece, causing the first ends of each of the upper leg piece and the lower leg piece to be separated from each other. The loading station (570) according to claim 10.

12. The loading station (570) is for loading the sample support (150) into the sample holder (100, 300) described in claim 1. A loading station (570) according to claim 10 or 11.

13. A sample holder (100, 300) according to claim 1, The loading station (570) according to claim 10, A device equipped with the following features.

14. A knife holder for a microtome (260, 460), The knife holder (260, 460) is equipped with or configured to have a knife (264, 464), and further comprises a storage box (266, 466) for storing sections cut from a specimen (268) by the microtome, The aforementioned storage boxes (266, 466) are configured to house sample holders (100, 300) for supporting the sample support (150), The storage boxes (266, 466) are configured such that the sample holder can be attached to the knife (264, 464) at relative positions (P1, P2). Knife holder (260, 460).

15. The storage boxes (266, 466) are configured such that when the sample holder (100) holds the sample support (150) and is housed in the storage box (266) which is mounted at the positions (P1, P2) relative to the knife (264), a liquid is supplied, and when the liquid is supplied into the storage box (266), it covers the sample support (150). The knife holder (260, 460) according to claim 14.

16. The knife holder (260, 460) further comprises a device (492) for removing the liquid from the containment box (266) so that the liquid filling level (290, 490) decreases continuously. The knife holder (260, 460) according to claim 15.

17. The storage box (266, 466) is equipped with a sliding mechanism (262, 462) configured to house the sample holder (100, 300), and the sliding mechanism (262, 462) is configured to be mounted at any position relative to the knife or at one or more predetermined positions. A knife holder (260, 460) according to any one of claims 14 to 16.

18. A knife holder (260, 460) according to claim 14, comprising the sample holder (100, 300) according to claim 1.

19. A microtome (600) comprising a knife holder (260, 460) according to claim 14.

20. A method for loading a sample support (150) into a sample holder (100, 300) according to claim 1 using a loading station (570) according to claim 10.

21. A method for loading a sample support (150) into a sample holder (100, 300) using a loading station (570), wherein the method is: The steps include (700) placing the sample holder in the storage area of ​​the loading station and positioning the clamping device of the sample holder in the loading position, The steps include loading the sample support into the loading slider of the loading station (570) (702), Step (704) of activating the operating mechanism (582) of the loading station (570) to separate the first ends of the upper and lower legs of the clamping device from each other, The steps (706) include sliding the loading slider toward the sample holder to position a part of the sample support between the first ends of the upper leg piece and the lower leg piece, The steps include releasing the operating mechanism and clamping the sample support between the upper leg piece and the lower leg piece (708), A method that includes this.

22. The above method involves loading a plurality of sample supports into the sample holder, with respect to each of the plurality of sample supports: The steps include loading the sample support into the loading slider (712), Step (714) of operating the sample holder to position the next clamping device among the multiple clamping devices of the sample holder at the loading position, Step (716) of activating the operating mechanism of the loading station to separate the first ends of the upper and lower legs of each clamping device from each other, The steps (718) include sliding the loading slider toward the sample holder to position a part of the sample support between the first ends of the upper leg piece and the lower leg piece, The steps (720) include releasing the operating mechanism and clamping the sample support between the upper leg piece and the lower leg piece, The method according to claim 21, including the method described in claim 21.

23. A method for placing a sample cut from a specimen (268) by a microtome onto a sample support (150) loaded into a sample holder (100, 300), wherein the method is: The steps include: (800) installing the sample holder in the microtome housing box, Step (802) involves attaching the sample holder to a desired position relative to the knife of the microtome so that the sample support has a desired position relative to the knife, The steps (804) include supplying fluid to the containment box so that the fluid covers the sample support, The steps (806) include cutting the sample from the specimen using the microtome so that the specimen is positioned on the surface of the fluid and above the sample support, The steps include removing at least a portion of the fluid from the containment box and lowering the sample to place it on the sample support (808), A method that includes this.

24. The method involves placing the multiple samples cut from the specimen by the microtome into each of the multiple sample supports loaded into the sample holder, with respect to each of the further multiple sample supports. Step (810) of activating the sample holder so that the next sample support is in a desired position relative to the knife, The steps (812) include supplying fluid to the containment box so that the fluid covers the sample support, The steps (814) include cutting the sample from the specimen using the microtome so that the sample is positioned on the surface of the fluid and above each of the sample supports, The steps (816) include removing at least a portion of the fluid from the containment box and lowering each of the samples to place them on each of the sample supports, The method according to claim 23, further comprising:

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