US20050235542A1

US20050235542A1 - Microtome for producing thin sections

Info

Publication number: US20050235542A1
Application number: US11/103,596
Authority: US
Inventors: Rolf Metzner; Roland Walter
Original assignee: Leica Microsystems Nussloch GmbH
Current assignee: Leica Biosystems Nussloch GmbH
Priority date: 2004-04-21
Filing date: 2005-04-12
Publication date: 2005-10-27
Also published as: DE202004006265U1

Abstract

A microtome for producing thin sections includes a knife holder (32) with a cutting knife (33), a sample holder (34) for samples (42) embedded in a cartridge (40), a feed device (31) for changing the distance between the cutting knife (33) and the cartridge (40), and a drive device for producing a cutting movement between the cutting knife (33) and the cartridge (40). The microtome also includes a reading device (54) for coded information (45) applied to a cartridge (40), and a control device (10) with a computer for coordination of functional sequences. A magazine (60) with code (62) and partitions (61) holds prepared cartridges (40), and a handling device (50) provides for the controllable removal of a cartridge (40) and positioning on the sample holder (34) as well as returning cartridges into the magazine (60). The reading device (54, 53) is assigned to the magazine housing and/or the handling device (50).

Description

The invention relates to a microtome having the features of the preamble of claim 1.
WO 00/62035 A1 discloses such a microtome having an automatic function sequence. The sample, embedded in a cartridge, is provided with an individual identification code and automatically fixed to a sample holder. The information contained in the code is read. The thin sections corresponding to the code are prepared and deposited on an object carrier. After that, the cartridge is removed from the sample holder, if appropriate indexed further and kept in a collecting container. The thin sections on the object carrier are prepared further and evaluated one after another by image analysis. The images recorded are stored. If further thin sections are needed from a specific sample, the corresponding cartridge has to be found from the collecting container and introduced into the system again.
DE 101 54 843 A1 discloses a microtome in which an indexed cartridge is fixed manually in a sample holder. The sample holder with the cartridge is moved relative to the cutting knife of the microtome. During each new cutting movement, the code applied to the cartridge is read by a reading device fitted to the microtome housing and supplied to a printer in order to label an object carrier. The thin section produced in each case is deposited manually on the object carrier printed in parallel therewith. In this way, confusion when assigning thin section and labeled object carrier is minimized.
The coded information applied to the cartridge can relate both to statements about the sample and about the preparation technique and the execution of the section. An apparatus for the corresponding labeling of cartridges or object carriers is disclosed by DE 101 15 065 A1.
The invention was based on the object of rationalizing the operations of sample preparation and indexing, sample storage and thin section creation in a microtome and nevertheless of largely ruling out the risk of confusion when evaluating the samples.
In a microtome of the type mentioned at the beginning, this object is achieved according to the invention by the characterizing features of claim 1. Advantageous refinements emerge from the features of the subclaims.
The desired rationalization is given firstly by the fact that suitable specialized staff is able to concentrate on processing the samples with embedding in the cartridge and indexing, with information relating to the execution of the section. Insertion into the magazine, likewise provided with an unambiguous code, can be carried out as desired, since, by means of the reading device, both specific cartridges can be selected specifically and, as is also the case in cartridges processed step-by-step one after another, the information read out in each case can be used for labeling the object carrier.
Further rationalization is given by the fact that other suitable specialist personnel are able to introduce the filled magazines into the handling device and are then able to concentrate on removing the section and identifying the object carriers. During automatic labeling of the object carriers corresponding to the code of the cartridge just selected, which is carried out at the same time as the production of the section, auxiliary staff are also able to place the thin section respectively produced on the prepared object carriers. Of course, it is also possible to deposit the thin section automatically on the labeled object carrier and also to introduce the magazines automatically into the handling device.
The filled and likewise indexed magazines can be kept in a space-saving manner and permit rapid access to selected cartridges. If the magazines are stored in a refrigerated housing or a refrigerated chamber, temperature-sensitive samples can also be stored securely over a relatively long time period and kept in stock for subsequent examination. In this case, it is advantageous if the magazine is stored in a refrigerated or insulated chamber on the microtome during the production of the thin sections.
An exemplary embodiment of the microtome according to the invention is illustrated schematically in the drawing and will be described in more detail in the following text by using the figures, further advantages being brought out. Here,
FIG. 1 shows an overall view of the microtome with peripheral devices,
FIG. 2 shows a handling device with magazine on the microtome,
FIG. 3 shows an empty cartridge with identification area and
FIG. 4 shows a cartridge with embedded sample and individual cartridge code.
In FIG. 1, an overall view of the microtome is shown schematically by using function blocks. A handling device 50 with magazine 60 is connected by a handling device control line 13 to a control device 10. The latter is connected via a microtome control line 12 to the microtome 30 and via an object carrier printer control line 11 to an object carrier printer 20, and monitors and controls the functional sequences of the microtome 30. The control device 10 can in this case be a separate higher-order computer system, as illustrated in FIG. 1, or also, in a manner not further illustrated, integrated in the object carrier printer 20 or in a housing, not illustrated, including the microtome 30 and the handling device 50. In the case of the disk microtome 30 illustrated in FIG. 1, the cutting movement is produced by a rotating disk 35. The sample 42 embedded in a cartridge 40 and to be microtomed is inserted by a handling device 50 into the sample holder 34 in a depression 36 in the rotatably mounted disk 35. Here, the code stored on the cartridge 40 is read and registered by the control device 10. The functioning of the handling device 50 will be described in more detail later by using FIG. 2. In order to produce thin sections, the sample 42 is moved from an initial position in the area of the handling device 50, guided rotationally past the cutting knife 33 fixed in the knife holder 32 and moved into an end position corresponding to the initial position. During this, the object carrier printer 20 removes an object carrier 25 from the object carrier supply 21 and, by using pre-definitions from the control device 10, creates on the object carrier 25 an identifier which ensures an assignment to the sample 42 just microtomed. The object carrier 25 printed in this way is provided at the object carrier ejector 22, where the thin section is deposited manually or automatically on the object carrier 25. In order to produce a further thin section from the same sample 42, the feed device 31 is moved forward in the direction of the rotatably mounted disk 35 by a value predefined by the control device 10 which corresponds to the required thin section thickness, and the procedure just described is repeated.
Manual operation of the object carrier printer 20 or of the control device 10 is possible via the input device 23 and can be monitored via the display device 24. For instance, an operator is able to input corrections to the cutting speed or the cutting window or to improve the production of the section in this way and to initiate the renewed production of thin sections. The procedures are repeated until either the thin section produced has the required quality or the desired number of thin sections have been produced from the sample 42 just inserted and have been deposited on the correspondingly printed object carriers 25.
FIG. 2 shows a handling device 50 with magazine 60 fitted to a microtome. The magazine 60 is introduced manually or automatically into a refrigerated/insulated housing 55, which can be a constituent part of the handling device 50. During insertion, a magazine code reading device 53 fitted to or in the refrigerated/insulated housing 55 reads a magazine code 62 applied to the magazine 60 and transmits it to the control device 10. The magazine code 62 is evaluated there. In the magazine 60, there is a relatively large number of prepared cartridges, not further illustrated, arranged one after another in partitions 61. The magazine 60 is stored within the refrigerated/insulated housing 55 such that it can be displaced in a magazine guide 63 and is moved to a predetermined initial position by means of control predefinitions from the control device 10 in accordance with the evaluated magazine code 62. From one of the partitions 61, by means of a gripper 51 which is fixed to a displacer 52, a cartridge 40 with embedded sample 42 is then introduced laterally into the sample holder 34 by means of a translational movement. The selected cartridge 40, as it is guided out, is led past a cartridge code reading device 54 with its identification area 43 described in more detail in FIG. 3 and merely indicated in FIG. 2. The handling device 50 transmits the data read by the reading device 54 via the handling device control line 13 to the control device 10, which evaluates said data and, for example, transmits it to the object carrier printer 20 via the object carrier printer control line 11 for the purpose of corresponding printing of the object carrier 25. Additional information relating to the further treatment can be stored individually in the control device 10 in relation to each of the samples stored in the magazine 60. This information can contain the desired number of thin sections, the section thickness, the section plane and the cutting speed, and in this way can be used for the further optimal control of the microtome 30. After the thin sections have been created as described in relation to FIG. 1, the cartridge 40 is returned from the sample holder 34 into the associated partition 61 of the magazine 60. By displacing the magazine 60 in the magazine guide 63, the next cartridge to be microtomed is brought into the gripping position, picked up by the gripper 51 and inserted into the sample holder 34 as described above by the displacer 52 in order to produce a thin section. Each of the steps described here can be implemented by individually controllable drive means. However, it is advantageous, for example, to couple the stepping movement of the magazine 60 with the linear ejection movement of the displacer 52 and gripper 51, which permits efficient, sequential processing of a filled magazine 60. For this purpose, the upper or lower side of the magazine 60 is provided with guide channels 64 arranged at right angles to the direction of the stepping movement. In these guide channels 64, coupled to the linear movement of the displacer 52, there runs, for example, a pin bar, which is not specifically illustrated, is mounted such that it can pivot, the pin of which engages in the guide channels 64 of the magazine 60 and, guided along an inclined control profile, not further illustrated, ensures a stepping movement of the magazine 60 in the direction of the magazine guides 63. Of course, the guide channels 64 themselves can also be arranged obliquely with respect to the direction of the stepping movement. Then, the translational movement of the displacer 52 and gripper 51 can be used directly to produce the stepping movement.
The magazine 60 illustrated in FIG. 2 has partitions 61 aligned obliquely with respect to the magazine guide 63, so that the cartridges and therefore also the embedded samples are aligned with their section plane parallel to the plane of the sample holder 34. The angle of inclination of the partitions 61 in the magazine 60 therefore preferably coincides with the angle at which the cutting movement on the microtome 30 is carried out. In order to configure the identification area 43 of the cartridges 40 in the magazine 60 such that it can be read from the outside, the partitions 61 can be arranged vertically in the magazine 60. It is advantageous in this case that the magazine 60 can then hold more cartridges. However, in this case it is disadvantageous that, as a cartridge 40 is being guided out of the magazine 60 in order to insert the same into the sample holder 34 on the microtome 30, an inclined movement in the direction of the section-producing plane is additionally necessary, if the latter is not designed to be oblique, as illustrated in FIG. 1.
An empty cartridge 41 with an empty identification area 43 is illustrated in FIG. 3. The cartridge 41 has apertures 44, illustrated as square, in its housing for the improved fixing of the embedding material for the samples. Shortly before, during or after the respective sample has been embedded in the empty cartridge 41, an individual cartridge code 45, illustrated in FIG. 4, is applied by the operator in the identification area 43.
FIG. 4 shows a cartridge 40 with sample 42 embedded and an individual cartridge code 45 applied in the identification area 43. The individual cartridge code 45 normally contains only data which permits the sample to be assigned to a patient and to an examination or removable time, because of the restricted space in the identification area 43 of the cartridge 40. However, if code identifiers with a high information storage density are used, all the information data relating to the sample 42 and additional information data relating to the creation of the thin sections can be stored on the cartridge itself. The effort for information processing in the control device 10 can be reduced in this way, since the cartridge 40 itself already contains all the relevant information in its individual cartridge code 45.
Since a large number of parameters influence the quality of the thin sections produced by the microtome 30, it is advantageous to deposit additional information and findings about the condition of the sample 42 embedded in the cartridge 40 in a data base belonging to the control device 10 or in the individual cartridge code 45. For instance, if it is a soft sample, the preferred cutting speed should be chosen differently than in the case of a hard sample. The size of the sample influences the size of the cutting window. Thus, in conjunction with the microtome according to the invention, findings about these parameters can already be assigned during the sample processing to each individual cartridge by experienced personnel and already have an advantageous influence in advance on the quality of the thin sections subsequently produced. For instance, together with the magazine code 62, the position of each cartridge in the magazine 60 and the individual cartridge code 45 associated with one another can be stored in a data base belonging to the control device 10. Given appropriate capacity of the magazine code 62, this information can also be stored directly there.
For the purpose of coding, bar codes known per se, two-dimensional dot(bar)codes, magnetic storage media or (film) microchips which can be programmed and read by radio can be used.
Thus, it is then possible to move deliberately to a specific cartridge in a time-saving manner and without processing each individual cartridge step-by-step one after another and to select said cartridge for further processing.
Since temperature-insensitive samples 42 can even be stored at room temperature but the production of thin sections of samples 42 embedded in paraffin is often problematical at room temperature, the magazine 60 together with the cartridges stored there can also be cooled down in the refrigerated/insulated housing 55 mentioned in the description relating to FIG. 2 before the production of a section. In this case, the control device 10 ensures that the sample 42 is brought to the optimum cutting temperature. Given an appropriate configuration as a refrigerated housing 55, even the freezing temperature of the sample 42 otherwise used only in the case of what are known as cryostat microtomes can also be achieved. Conventional cryostat microtomes have the disadvantage that the entire microtome is located in a refrigerated chamber, which results in an increased power consumption and makes the design, handling and cleaning of the microtomes more difficult. In the case of the microtomes according to the invention, however, there is the advantage that the operating personnel can operate in an accustomed manner, as in the case of a conventional microtome, and it is nevertheless possible to process samples which can otherwise only be microtomed in the frozen state. The ideal cutting temperature can on the one hand be stored in a data base which belongs to the control device 10 such that it can be assigned to the individual cartridges or magazines, or stored in the magazine code 62 itself.

LIST OF DESIGNATIONS

10 Control device
11 Object carrier printer control line
12 Microtome control line
13 Handling device control line
20 Object carrier printer
21 Object carrier supply
22 Object carrier ejection
23 Input device
24 Display device
25 Object carrier
30 Microtome
31 Feed device
32 Knife holder
33 Cutting knife
34 Sample holder
35 Disk
36 Depression
40 Cartridge
41 Empty cartridge
42 Embedded sample
43 Identification area
44 Apertures
45 Individual cartridge code
50 Handling device
51 Gripper
52 Displacer
53 Magazine code reading device
54 Cartridge code reading device
55 Refrigerated/insulated housing
60 Magazine
61 Partitions
62 Magazine code
63 Magazine guide
64 Guide channels

Claims

1. A microtome for producing thin sections, containing

a) a knife holder (32) with cutting knife (33),

b) a sample holder (34) for samples (42) embedded in a cartridge (40),

c) a feed device (31) for changing the distance between cutting knife (33) and cartridge (40),

d) a drive device for producing a cutting movement between cutting knife (33) and cartridge (40),

e) a reading device (54) for coded information (45) applied to the cartridge (40), and

f) a control device (10) with computer for coordination of all the functional sequences, wherein

g) a magazine (60) with code (62) and partitions (61) for holding prepared cartridges (40), and also

h) a handling device (50) for the controllable removal of a cartridge (40) and positioning on the sample holder (34) as well as returning into the magazine (60) are provided, and

i) the reading device (54, 53) is assigned to the magazine housing and/or the handling device (50).

2. The microtome as claimed in claim 1, wherein the magazine (60) is coupled to the microtome (30).

3. The microtome as claimed in claim 1, wherein a bar magazine (60) is provided.

4. The microtome as claimed in claim 1, wherein the magazine (60) and the partitions (61) are aligned in such a way that the cartridges (40) are kept with their section plane parallel to the plane of the sample holder (34) as they are fed to the sample holder (34).

5. The microtome as claimed in claim 4, wherein the handling device (50) contains a displacer (52) for the removal and return of the cartridges (40).

6. The microtome as claimed in claim 1, wherein the magazine (60) is stored in a refrigerated housing (55).

7. The microtome as claimed in claim 6, wherein the magazine (60) is mounted in the refrigerated housing (55) such that it can be displaced under control.

8. The microtome as claimed in claim 1, wherein a disk microtome (30) with sample holder (34) guided rotationally past the cutting knife (33) is provided.

9. The microtome as claimed in claim 1, wherein the thin sections are deposited on an object carrier (25) and the control device (10) is connected to a printer (20) in order to label the object carriers (25).