WO2025093672A1 - Method for operating a microtome, and microtome - Google Patents

Abstract

A first aspect of this disclosure relates to a method for operating a microtome (100, 200) for a cutting process, the microtome (100, 200) having a knife (112) with a cutting edge (114) and having a sample (122) on a sample holder (120); said method comprising the following steps: - determining a light gap (300) which is defined in some sections by the cutting edge (114) and the sample (122), and - orienting the knife (112) and/or the sample (122) such that the light gap (300) has a predefined structure.

Description

Method for operating a microtome and microtome

Technical field

This disclosure relates to a microtome and a method of operating the microtome.

Background

A microtome is a specialized tool that can be used in laboratories to cut extremely thin slices of samples.

To examine material, such as biological material, it is common practice to cut a thin slice from a sample of the material to be examined. The thickness of the thin slice can range from a few nanometers to a few micrometers. The thin slice can then be examined under a microscope. Microtomes typically consist of a knife with a cutting edge and a sample holder in which a sample of the material can be held for the cutting process.

For the cutting process, it is common practice to position the sample precisely relative to the knife. During this adjustment process, care should be taken to ensure that neither the knife nor the sample is damaged. Accordingly, accidental contact between the knife and the sample should be prevented.

During the adjustment process between the knife and the sample, it is common practice to observe the approach between the sample and the knife through a stereomicroscope. However, this observation does not always lead to a reliable estimation of the distance between the sample and the cutting edge of the knife. Therefore, technical adjustment aids such as a movable sample holder can be used. Help it is possible to set a gap between the knife and the sample.

This precision may also be required for adjusting the knife pivot and sample pivot. An angle error can lead to undesirable results during the sectioning process. Manual adjustment, i.e., by hand, can require considerable practice on the part of the operator and be extremely time-consuming.

Improvements for these situations are therefore desirable.

General description

An object of this disclosure relates to improving the performance of thin sections on a sample.

This object is achieved by the embodiments disclosed herein, which are particularly defined by the subject matter of the independent claims. The dependent claims relate to further embodiments. Various aspects and embodiments of these aspects are also disclosed in the summary and description below, which provide additional features and advantages.

A first aspect of this disclosure relates to a method for operating a microtome for a cutting operation, the microtome having a knife with a cutting edge and a sample on a sample holder; comprising the following steps:

- Determining a light gap which is defined in sections by the cutting edge and the sample, and

- Aligning the knife and/or the sample so that the light slit has a predetermined structure. A microtome can be a rotary microtome, suitable for cutting thinner tissue sections. A microtome can also be a cryomicrotome, suitable for cutting frozen samples. This can be useful in preparing samples for biological and/or medical research. A microtome can also be an ultramicrotome, suitable for cutting ultra-thin sections, for example, for electron microscopy. A microtome can also be a laser microtome, which allows samples to be cut non-contact using a laser.

Operating a microtome can refer to the application and handling of a microtome. Operating a microtome can include preparing the sample, adjusting the section thickness, cutting the sample, and/or collecting the sections. The cutting process of the microtome can refer to a cutting or dividing process, i.e., the process of precisely and controlledly cutting thin sections or slices from a sample.

The knife may be a specialized cutting tool used in a microtome to create precise, thin sections of samples. The knife may be interchangeable. The knife cutting edge may refer to the sharpest area or sharp edge of a knife used to cut the sample or material. The cutting edge can have various shapes. For example, the cutting edge can have a straight edge, a serrated edge, a hollow ground, a V-ground, or a convex ground. The knife can be made of glass or diamond, for example.

The sample can refer to the material or substance that is mounted on the microtome and cut into precisely thin sections by the microtome's cutting action. Samples can include biological tissue, plant parts, or other materials. The sample holder can be a device or component that serves to hold and stabilize the sample on the microtome during the sectioning process. The sample holder can precisely fix the sample in a position. The sample holder can potentially ensure that the sections are precise, consistent, and reproducible.

The light gap can refer to a space or opening between the cutting edge of the knife and the sample. In other words, light can pass through a space formed, for example, between the cutting edge and the sample. The light gap can possibly have a contour. The contour of the light gap can refer to the external shape or outline of the space through which light can pass. The contour of the light gap can be divided into different sections. At least one section of the contour can be formed by the cutting edge and/or the sample. In other words, one section of the contour can be formed by the cutting edge and another section of the contour by the sample or a sample surface. In particular, a light gap can also be defined based on a reflection of a structure in the sample, e.g., a reflection of part of the cutting edge. For example, a user can be positioned such that they can capture a reflection of the cutting edge, whereby the cutting edge is reflected on a sample surface. In other words, the light gap can be defined in sections by the cutting edge and a mirror image of the cutting edge in the sample surface or front surface of the sample. The method can therefore comprise determining a light gap that is defined in sections by the position of the cutting edge relative to the sample.

Determining a light gap can refer to the process of identifying, measuring, or characterizing the light gap. This can involve measuring the size, width, length, and/or other dimensions of the light gap. This can be done, for example, using special measuring instruments, optical techniques and/or the naked eye of a user.

Alignment of the knife and/or sample can refer to the process of adjusting, setting, or positioning the knife and/or sample. During alignment, a specific angle and/or distance between the knife and sample can be set. Alignment can be performed by controlling motors that move the knife and/or sample holder. Alignment of the knife and/or sample holder can also be performed manually by a user.

The structure can refer to the arrangement, shape, geometric features or other characteristic quantities, e.g. polygon, contour, color (wavelength), etc. For example, the structure can comprise certain patterns, geometries or arrangements that were deliberately introduced or designed and serve as a target value. The predetermined structure can mean that the arrangement, pattern or shape was deliberately determined in advance. The predetermined structure can be based on specific goals or requirements of the cutting process. For example, the goal of the adjustment process can be to achieve or at least approximate the light gap to the predetermined structure. The light gap can be changed by aligning the knife and/or the sample until the predetermined structure is achieved.

A potential advantage of the method may be precise alignment using a light slit and precise cutting into thin slices of the sample. Another advantage may be the avoidance of damage to the knife. The method may allow the knife to make a straight cut. To this end, the method can be used to position a cutting surface of the knife substantially parallel to a sample surface (also referred to as the front surface of the sample or "block face") of the sample or a portion of the sample to be cut. An embodiment of the first aspect of the present disclosure relates to a method of operating a microtome for a cutting operation, comprising the step of:

- Illuminate the space between the cutting edge and the sample with a light source.

The illumination source can be a light source, a lamp, or a laser. A light beam path can emanate from the light source. The light beam path can be used, at least in part, to determine the light gap. A light source below the knife can illuminate the space between the knife and the sample.

One advantage of illumination is the precise formation and/or determination of the light gap. This advantageously allows for a clear contour of the light gap. Using ambient light alone, capturing a structure according to which the knife and/or sample are aligned may be more difficult.

An embodiment of the first aspect of the present disclosure relates to a method for operating a microtome for a cutting process, wherein the determination of the light gap is carried out by a sensor, in particular a camera.

Using a sensor, for example, it is possible to quickly and automatically determine or detect the light gap. This allows for a dynamic adjustment process. The sensor can be a camera that detects the light gap and converts it into an electrical signal. A sensor can also be another light sensor. The sensor can detect the actual positions of the light gap. The actual positions of the light gap can be compared with the target positions, for example, of the specified structure. The light gap can then be adjusted, for example, by aligning the knife and/or the sample, so that the actual positions are closer to the target positions. In other words, the specified structure can be adjusted.

An embodiment of the first aspect of the present disclosure relates to a method of operating a microtome for a cutting operation, wherein the structure comprises a shape having two parallel sides, a first side defined by the cutting edge and a second side defined by the sample.

For example, an upper edge of the sample surface (i.e., the "block face") can be arranged parallel to the cutting edge. This would result in a first side of the contour of the light gap being defined by the cutting edge, and a second side of the contour of the light gap being defined by the sample. The sample can be polyhedral, with one surface forming the sample surface. Consequently, the cutting edge can be parallel to a surface of the sample.

The second side can also be defined by a mirror image or reflection of the cutting edge in the sample surface. A reflection of another structure, e.g., a marking in the cutting knife or knife holder, can also be used for alignment.

One advantage of this approach is that the result of the cutting process can be optimally adjusted. The result could, for example, be a slice of the sample with two parallel sides and a predefined distance along at least one section. An embodiment of the first aspect of the present disclosure relates to a method of operating a microtome for a cutting operation, wherein the structure comprises a shape having a predetermined distance defined by the side of the structure of the cutting edge and the side of the structure of the sample.

This distance can also include a distance to a mirrored feature.

By measuring the distance at different points, a parallel or otherwise specified alignment of the knife and sample relative to each other can also be achieved.

An embodiment of the first aspect of the present disclosure relates to a method of operating a microtome for a cutting operation, wherein the sample and/or the knife is moved along or parallel to a first linear axis during alignment.

One advantage of moving along or parallel to a first linear axis can be dynamic pre-adaptation to the cutting or cutting process. For example, a distance between the knife and the sample can be monitored and the sample/knife adjusted so that a specified distance remains constant or changes within specified limits during the linear movement.

An embodiment of the first aspect of the present disclosure relates to a method for operating a microtome for a cutting operation, wherein the alignment is along a first axis of rotation. In particular, a sample can be moved relative to the knife along a linear axis, while maintaining a specified distance. To maintain the distance, alignment can be performed around a first rotational axis. The rotational axis can be, for example, the x-axis, the x-axis, the y-axis, and/or the z-axis in Fig. 1.

An advantage of alignment along a first rotational axis can be a dynamic alignment of the sample to the knife, enabling a smooth cut.

An embodiment of the first aspect of the present disclosure relates to a method of operating a microtome for a cutting operation, wherein the alignment is along a second axis of rotation.

By aligning around two axes of rotation, especially during a linear movement, a given distance can be effectively adjusted.

An embodiment of the first aspect of the present disclosure relates to a method for operating a microtome for a cutting operation, wherein the alignment of the knife is performed by motorized or manual movement of the knife about a first linear axis.

Adjusting the knife, especially when the sample is stationary, can provide several benefits, including greater precision and control of section thickness and quality, greater sample stability to reduce artifacts, and better section consistency. By keeping the sample stationary and the blade moving, the risk of damaging delicate samples is reduced, leading to reliable and accurate results for subsequent analysis. can.

An embodiment of the first aspect of the present disclosure relates to a method for operating a microtome for a cutting operation, wherein the alignment of the sample is carried out by motorized or manual movement of the sample about a second and a third axis which are arranged at right angles to the first linear axis and/or to each other.

Aligning the sample in this way can have the advantage of achieving particularly precise cutting results.

An embodiment of the first aspect of the present disclosure relates to a method of operating a microtome for a cutting operation, wherein the structure comprises a substantially rectangular, triangular or trapezoidal shape.

One advantage of this approach may be that it provides a simple method for determining the shape of the resulting section. For example, the knife and/or the sample can be aligned such that the light gap has the specified structure, possibly a substantially rectangular shape. This can ensure, for example, that the resulting section is a thin and uniformly thick slice.

An embodiment of the first aspect of the present disclosure relates to a method of operating a microtome for a cutting operation, wherein the camera is arranged relative to the sample on the other side of the illumination means such that it is neither arranged on an axis between the illumination means or the sample nor parallel thereto. An advantage of this arrangement may be that the rotation of the knife and/or the sample holder around an axis can be observed.

Advantageously, a mirroring or reflection of at least one component of the knife can be formed.

For example, such an arrangement can reflect the cutting edge on the sample surface.

A further advantage may be that changes in the light gap can be perceived, which are observable by the camera (or a light sensor) by moving the sample or the knife along the axis between the illuminator and the sample (or a parallel axis, e.g. the z'-axis from Fig. 2).

An embodiment of the first aspect of the present disclosure relates to a method for operating a microtome for a cutting process, wherein the illumination means and/or the camera are moved to determine the light gap.

For example, the illuminator can be moved closer to the microtome. One advantage of this movement may be that the illuminator can be placed in a favorable position for observing the light slit.

It is also possible to move the sensor or camera to determine the light gap. The sensor and the lighting device can be moved in such a way that the light and reflections of the light can be captured by the sensor during movement. Moving the camera should also reveal changes in the structure of the light gap that would otherwise be invisible. One advantage of moving the sensor can therefore be a positive effect on measuring the light gap. be.

An embodiment of the first aspect of the present disclosure relates to a method for operating a microtome for a cutting process, wherein the cutting edge of the knife is specified as being straight to determine the light gap.

One advantage may be that the light gap can be determined particularly easily due to the straight cutting edge. A straight cutting edge can mean that saw patterns, gaps, or similar features can be considered negligible for orientation along the cutting edge. This allows for a simple comparison between the light gap (including the straight cutting edge) and the specified structure.

A second aspect of the present disclosure relates to a microtome adapted to:

- to carry out a method according to the first aspect of the present disclosure; and/or

- to exchange information with a device that carries out a method according to the first aspect of the present disclosure.

An advantage of such a microtome may be that the microtome only requires an interface to move the sample holder and the knife, as well as the appropriate software to control or otherwise enable operation according to the first aspect.

Using the microtome, several cutting bands can also be created next to each other by moving the knife sideways. In summary, the methods and devices described here enable automatic sample and knife alignment in (ultra)microtomes using motorized axes and video analysis software. One advantage of the methods and application described here is the software support for the user. All degrees of freedom required for this process can be motorized. Using a camera, a knife edge or cutting edge, a light gap, and a sample top edge can be automatically detected and evaluated using video analysis methods. By automatically actuating the motors, all axes can be aligned so that the microtome is ready to section the sample at the end of the (alignment) process. Automation can also give less experienced users access to (ultra)microtomes. Incorrect settings can also be significantly reduced. The costly risk of blade damage can be reduced, allowing the user to use the time for other tasks. Video analysis allows a greater distance to be used between the sample and knife during adjustment, which reduces the likelihood of damage to the sample and knife.

Short description of the characters

Further advantages and features will become apparent from the following embodiments, some of which refer to the figures. The figures do not always show the embodiments to scale. The dimensions of the various features may be enlarged or reduced accordingly, particularly for the sake of clarity of the description. For this purpose, the figures are at least partially schematic.

Fig. 1 shows a microtome according to an embodiment in a perspective view.

Fig. 2 shows a microtome according to an embodiment of the present disclosure. Fig. 3 shows a microtome according to an embodiment of the present disclosure.

Fig. 4 shows a microtome according to an embodiment of the present disclosure.

Fig. 5 shows a microtome according to an embodiment of the present disclosure.

Fig. 6 shows a microtome according to an embodiment of the present disclosure.

In the following description, reference is made to the accompanying figures, which form part of the disclosure and illustrate certain aspects and embodiments by which the present disclosure may be understood. Like reference numerals refer to like or at least functionally or structurally similar features.

In general, a disclosure of a described method also applies to a corresponding device for carrying out the method or a corresponding system comprising one or more devices, and vice versa. If, for example, a specific method step is described, a corresponding device may include a feature for carrying out the described method step, even if this feature is not explicitly described or illustrated in the figure. In contrast, if, for example, a specific device is described on the basis of functional units, a corresponding method may include one or more steps for carrying out the described functionality, even if these steps are not explicitly described or illustrated in the figures. Similarly, a system may include corresponding device features or features for carrying out a specific method step. The features of the various The exemplary aspects and embodiments described above or below may be combined unless expressly stated otherwise.

Description

Fig. 1 schematically shows a microtome 100 according to one embodiment in a perspective view. The microtome 100 is preferably an ultramicrotome or comprises an ultramicrotome. The microtome 100 includes a knife holder 110 and a sample holder 120. Typically, a typical microtome includes additional components such as a housing and the like, which are not shown in Fig. 1 for illustrative purposes.

The knife holder 110 holds a knife 112. The knife 112 has a cutting edge 114 at the top right of the knife 112. Additionally, a receiving box 116 can be arranged, for example, on or at the knife 112. The sample holder 120 is designed to receive a sample 122. Such a sample 122 can, for example, have the form of a block that can be inserted into the sample holder 120 such that a sample surface 124 of the sample 122 faces the knife 112.

One method of operating such a microtome 100 generally involves moving the sample 122 along a cutting direction c relative to the cutting edge 114 when the sample 122 is properly aligned with the cutting edge 114. The cutting edge 114 is configured to cut a section (or slice) from the sample 122.

A section cut from the sample 122 can, for example, be collected in the receiving box 116. To enable such movement, the knife holder 110 and the sample holder 120 are configured to be movable relative to each other in the cutting direction c. In principle, either the knife holder 110 or the sample holder 120 or both can be configured to be movable along the cutting direction c. In one embodiment, (only) the Sample holder 120 is configured to be movable in the cutting direction c (in both directions, up and down). Furthermore, the knife holder 110 and the sample holder 120 can be configured to be movable relative to each other in the feed direction b to bring the cutting edge 114 into contact with the sample 122 and, in particular, to advance the sample 122 after a section or slice has been cut from the sample 122.

In one embodiment, the knife holder 110 and thus the knife 112 are designed to be movable in the feed direction b, i.e., toward (and away from) the sample 122 or the sample holder 120. In principle, however, the sample holder 120 can also be designed to be movable toward the knife 112 in (or against) the feed direction b.

As already mentioned, the knife 112 or the cutting edge 114 and the sample 122 or the sample holder 120 must be aligned before cutting in order to produce correct and precise sections of the sample.

This may require that the knife holder 110 or the sample holder 120 be mounted for rotation about at least one axis. Five axes are shown in Fig. 1 for illustrative purposes: a z' axis, an x' axis, a y' axis, a z' axis, and an x' axis. Rotation of the knife holder 110 and/or the sample holder 120 about one or more of these axes enables the alignment of the cutting edge 114 with the sample surface 124 of the sample 122.

As can be seen from Fig. 1, the sample holder 120 can generally be configured to be rotatable, for example, about each of three different axes x, y and z.

The sample holder 120 or the sample 122 can also be rotated about the x-axis. The x-axis and the x-axis can be arranged parallel to each other. The x-axis and the x-axis can be widely spaced from each other in the y-direction (e.g., 10 to 50 cm). Similarly, the knife holder 110 could be configured to be rotatable about any of three different axes, of which, for example, only the z' axis is shown (similarly, the x' and y' axes could be used).

It should be noted that the axes shown are aligned according to a Cartesian coordinate system, as is typical for such microtomes; however, this is for illustrative purposes only, and other ways of defining such axes are also possible. The rotation of the knife holder 110 and the sample holder 120 about three different axes each allows for a variety of degrees of freedom for the orientation of the cutting edge 114 and the sample surface 124. Nevertheless, a total of three different axes for both the knife holder 110 and the sample holder 120 may be sufficient to ensure alignment in a sufficient number of ways.

In one embodiment, the knife holder 110 is rotatably mounted about the axis z', wherein the axis z' runs parallel to the cutting direction c. The sample holder 120 is rotatably mounted about the axis x and the axis y. The axis y runs parallel to the feed direction b. As can be seen from Fig. 1, an equivalent to the rotatable mounting of the knife holder 110 about the axis z' would be the rotatable mounting of the sample holder 120 about the axis z. In both alternatives, the cutting edge 114 can be rotated in the same or equivalent manner relative to the sample 122 or its sample surface 124. Similarly, the knife holder 110 could be rotatable about a further axis x' and/or y' (not shown in Fig. 1), which would correspond to the rotatability of the sample holder about the axes x and/or y. Which component of the knife holder 110 and the sample holder 120 should be rotatable about which axes can be selected depending on the preferred type of implementation in the specific microtome.

Furthermore, it should be noted that basically only one or two axes around which either the knife holder 110 or the sample holder 112 can be rotated, may be sufficient to align the cutting edge 114 and the sample surface 124. It should be noted that the knife holder 110 and/or the sample holder 120 may be provided with actuators for motorized movement to facilitate the required rotation about the respective axis.

Fig. 2 shows a microtome 200 according to a further embodiment. The microtome 200 essentially corresponds to the microtome 100 from Fig. 1. In contrast to Fig. 1, the microtome 200 is shown in a sectional view and rotated (the positions of the knife holder and sample holder are reversed). The axes and directions shown in Fig. 1 correspond to the axes shown in Fig. 2. It should be noted that some components of the microtome 100 from Fig. 1 are not shown in Fig. 2, some are shown (with identical reference numerals), and some additional components are shown.

In particular, the microtome 200 comprises, in addition to the knife holder 110 with the knife 112 and the sample holder 120 with the sample 122, an illumination means 230, a sensor 240, and a control means 250. In one embodiment, the illumination means 230 comprises an LED or other light source 232 and a diffusion element or a filter 234 to ensure uniform illumination with the aid of the light source 232. In one embodiment, the sensor 240 can consist of a camera.

The illumination means 230 is arranged such that the space 235 between the cutting edge 114 and the sample 122 is illuminated. In other words, a light beam 238 emitted by the illumination means 230 (or the light source 232) is directed onto the area in which the sample surface 124 of the sample 122 and the cutting edge 114 are arranged. The light passing through the space 235 between the sample surface 124 of the sample 122 and the cutting edge 114 reaches the sensor 240. In this way, a light gap 300 is created, which is or can be detected by the sensor 240. Depending on the current orientation or arrangement of the knife 112 and the sample 122, the light of the light beam 238 can be reflected on a side surface 218 of the knife 112 and/or at the sample surface 124 of the sample 122.

In one embodiment, the microtome 200 comprises a first actuator 260.1, a second actuator 260.2, a third actuator 260.3, and a fourth actuator 260.4. It should be noted that when using only one or two axes about which the knife holder 110 and/or the sample holder 120 are rotatably mounted, one or two actuators would be sufficient.

The first actuator 260.1 is configured to cause the knife holder 110 to rotate about the z' axis. The second actuator 260.2 is configured to cause the sample holder 120 to rotate about the x' axis; such a rotation corresponds to an inclination of the sample holder 120 and thus of the sample 122. The third actuator 260.3 is configured to cause the sample holder 120 to rotate about the y' axis. The fourth actuator 260.4 is configured to cause the sample holder 120 to rotate about the x' axis.

Each of the first, second, third, and fourth actuators 260.1, 260.2, 260.3, 260.4 may be motorized. The control means 250 may be electrically and/or communicatively coupled to each of the first, second, third, and/or fourth actuators 260.1, 260.2, 260.3, 260.4 to actuate them and thus effect the rotation about the respective axis.

In one embodiment, one, two, three, and/or all four of the first, second, third, and fourth actuators 260.1, 260.2, 260.3, 260.4 may also be non-motorized, but configured to be manually actuated or operated, for example, like a handwheel, to effect the mentioned rotation. One or more of the first, second, third, and fourth actuators 260.1, 260.2, 260.3, 260.4 may also be motorized, but configured for manual operation, for example, such that a user must actuate a control element such as a switch to activate the actuator. In one embodiment, the microtome 200 includes a handwheel or actuating wheel 262. The handwheel 262 is configured (in particular by means of a mechanism not shown here) to trigger a cutting movement such that the sample holder 120 moves up and down in the cutting direction c to cut sections from the sample. The handwheel 262 can also be configured to cause a feed movement (e.g., of the knife holder 110) in the feed direction b. Both movements, cutting movement and feed movement, can be coupled such that efficient sectioning of multiple slices is possible. The handwheel 262 can be motorized and/or designed for manual operation. If the handwheel 262 is motorized, an automated cutting movement is possible, so that the handwheel can only be used for additional and/or corrective movements.

Furthermore, lateral movement in the direction of the x-axis may be possible to move the sample after cutting a section or slice to cut another slice adjacent to the first. The handwheel 262 may also be configured to allow such lateral movement. Such lateral movement could also be realized in other ways, for example, by an additional (motorized) handwheel.

The (cutting) movement performed by the handwheel 262 can also be performed by the fourth actuator 260.4.

Fig. 3 shows a microtome 200 with a light slit 300 in a plan view.

The light gap 300 is formed between the cutting edge 114 of the knife 112 and the sample 122. Light can pass through the light gap 300 (i.e., a space located between the cutting edge 114 and the sample 122) and be detected by a user. The light gap 300 has a contour 310. A first section 311 of the contour 310 is formed by the cutting edge 114. A second section 312 of the contour 310 is formed by the sample 122 or the sample surface 124.

Before the cutting process, the sample 122 can be precisely positioned relative to the knife 112 in an adjustment process. A computer-implemented method can be used for this purpose. The computer-implemented method can include, in one step, determining the light gap 300, wherein the light gap 300 is captured by a camera.

The light gap 300 can be defined in sections by the cutting edge 114 and the sample 122. In a further step, the method can include aligning the knife 112 and/or the sample 122 so that the light gap 300 has a predetermined structure. The predetermined structure can comprise an angular, in particular rectangular, shape.

Fig. 4 to Fig. 6 each show a possible step of aligning the knife 112 and/or the sample 122, e.g., the microtome 200 shown in Fig. 2. The steps shown in Fig. 4 to Fig. 6 may be successive steps.

Fig. 4 shows a top view of the microtome 200 during rotation D _z of the knife 112 about a z' axis. The sample 122 remains fixed in one position.

During the rotation D _z of the knife 112, the orientation of the cutting edge 114 changes to a rotated cutting edge 114'. The light gap 300 also changes accordingly. The knife 112 can be rotated such that the rotated cutting edge 114' runs substantially parallel to the sample surface 124 of the sample 122. This step allows the light gap 300 to assume a predetermined structure. The predetermined structure comprises a shape having two parallel sides. A first side is defined by the cutting edge 114 and a second side by the sample 122.

Fig. 5 shows a microtome 200 moving the sample 122 in a side view.

The sample 122 can be rotated about the rotation axis x" and/or the (first) rotation axis x. The rotation axis x is also referred to as the sample tilt axis. The rotation axis x" has a distance Ay of approximately 20 cm from the rotation axis x.

The sample 122 undergoes a rotation D _xn about a rotation axis x", while the knife 112 with the cutting edge 114 remains fixed in one position.

Due to the large distance Ay relative to the dimensions of the microtome 200, the rotation D _xn can, for example, result in a nearly translational movement of the sample 122 in the z-direction. In other words, the sample 122 is moved quasi along or quasi parallel to a first linear axis z' during alignment.

The sample surface 124 is moved to an upper position 124° and/or to a lower position 124 ^° .

The sample 122 is moved in the z-direction in small steps over the entire height of the sample 122 and just beyond. At each step, the light gap 300 can be detected and analyzed with the sensor 240.

The light gap 300 or a distance between the cutting edge 114 and the sample surface 124 can be visually detected (e.g., by means of a pixel graphic). Furthermore, angular deviations of the contour of the light gap can be determined. For example, an angular deviation between a section of the contour formed by the cutting edge 114 and a section of the contour formed by the sample surface 124. For example, 30 measurements can be recorded at different heights of the sample 122. A correction can then be calculated and adjusted based on the analysis of the measurements.

For example, a first correction may include a rotation around the x-axis (or sample tilt axis) using the third actuator 260.3. After the first correction, the light gap 300 should remain the same size when the cutting area is traversed by operating the handwheel or automatically.

Furthermore, a second correction may comprise a rotation about the z' axis by means of the first actuator 260.1. This rotation may be similar to the rotation D _z of the blade 112 shown in Fig. 4. The second correction may be performed with greater precision based on the available measurement data than the rotation D _zl shown in Fig. 4.

The first and second corrections can result in the light gap remaining parallel while the cutting area is traversed.

The cutting movement can be carried out either manually with the handwheel 262 or by software-based control of the fourth actuator 260.4.

In summary, the cutting movement of the 200 microtome can be achieved by rotating the x-axis. This movement can also be motorized. The x-axis can be parallel to the x-axis of rotation or the sample tilt axis. This enables large cutting movements (over 10 mm).

Fig. 6 schematically shows a microtome 200 (e.g. according to the embodiment shown in Fig. 2) during rotation D _y of the sample 122 about a y-axis in a further side view. The sample 122 undergoes a rotation D _y around a rotation axis y, while the knife 112 remains fixed in one position.

During the rotation D _y of the sample 122, the orientation of an upper edge 624.1 of the sample surface 124 changes accordingly to a rotated upper edge 624.1 ' of the sample surface 124. The sample 122 can be rotated such that the rotated upper edge 624.1 ' is arranged substantially parallel to the cutting edge 114 of the knife 112.

After completing the steps described in Fig. 4 to Fig. 6, the adjustment process is complete. The cutting process can then begin.

During each of the steps, the distance from knife 112 to sample 122 can be continuously monitored to avoid contact between knife 112 and sample 122. Correction can be performed using precise motors. Furthermore, a continuous automated evaluation of the light gap 300 can be performed using video analysis.

All displacements, movements, and rotations depicted in the figures are abstract and are presented at an enlarged scale for clarity. Please note that they may be smaller in reality.

The aspects described herein may be implemented by and/or comprise computers. A computer may be a PC, a system-on-chip, a DSP, or an FPGA, to name a few examples. Computer components, software modules, functions, data storage, and data structures may be directly or indirectly interconnected to enable the data flow required for their operation. It is also noted that a module or processor includes, but is not limited to, a unit of code that performs a software operation, and e.g., it can be implemented as a code unit of a subroutine or as a code unit of a software function, or as an object (as in an object-oriented paradigm), or as an applet, or in a computer scripting language, or as another type of computer code. The software components and/or functionality may be located on a single computer or distributed across multiple computers, depending on the situation.

Some embodiments relate to a microscope comprising a system as described in connection with one or more of Figs. 1 to 6. Alternatively, a microscope may be part of or connected to a system as described in connection with one or more of Figs. 1 to 6. Figs. 1 and 2 each show a schematic representation of a microtome 100 or 200, respectively, configured to perform a method described herein. The microtome 100 or 200 may comprise a computer system. The microtome 100 or 200 is configured to capture images and is connected to the computer system. The computer system is configured to perform at least part of a method described herein. The computer system may be configured to execute a machine learning algorithm. The computer system and the other components of the microtome 100 or 200 may be separate units, but may also be integrated into a common housing. The computer system may be part of a central processing system of the microtome 100 or 200 and/or the computer system may be part of a subcomponent of the microtome 100 or 200, such as a sensor, an actuator, a camera or an illumination unit, etc. of the microtome 100 or 200.

The computer system may be a local computer device (e.g., a personal computer, laptop, tablet computer, or mobile phone) with one or more processors and one or more storage devices, or a distributed computer system (e.g., a cloud computer system with one or more processors and one or more multiple storage devices distributed at different locations, e.g., at a local client and/or one or more remote server farms and/or data centers). The computer system may include any circuit or combination of circuits. In one embodiment, the computer system may include one or more processors, which may be of any type. As used herein, the term "processor" may refer to any type of computing circuit, such as a microprocessor, a microcontroller, a complex instruction set computing (CISC) microprocessor, a reduced instruction set computing (RISC) microprocessor, a very long instruction word (VLIW) microprocessor, a graphics processor, a digital signal processor (DSP), a multi-core processor, a field-programmable gate array (FPGA), e.g., a microscope or microscope component (e.g., camera) or another type of microscope, e.g., camera), or any other type of processor or processing circuit. Other types of circuitry that may be included in the computer system may be a custom circuit, an application-specific integrated circuit (ASIC), or the like, such as one or more circuits (e.g., a communications circuit) for use in wireless devices such as mobile phones, tablet computers, laptop computers, two-way radios, and similar electronic systems. The computer system may include one or more storage devices, which may include one or more storage elements suitable for the particular application, such as main memory in the form of random access memory (RAM), one or more hard disk drives, and/or one or more drives that handle removable media such as compact disks (CDs), flash memory cards, digital video disks (DVDs), and the like. The computer system may also include a display device, one or more speakers, and a keyboard and/or a controller, which may include a mouse, a trackball, a touchscreen, a voice recognition device, or other device that enables a system user to input information to and from the computer system. received.

Some or all of the method steps may be performed by (or using) a hardware device, such as a processor, a microprocessor, a programmable computer, or an electronic circuit. In some embodiments, one or more of the key method steps may be performed by such a device.

Depending on specific implementation requirements, embodiments of the invention may be implemented in hardware or software. The implementation may be performed using a non-transitory storage medium such as a digital storage medium, for example, a floppy disk, a DVD, a Blu-ray disc, a CD, a ROM, a PROM, an EPROM, an EEPROM, or a FLASH memory, on which electronically readable control signals are stored that interact (or can interact) with a programmable computer system to perform the respective method. Therefore, the digital storage medium may be computer-readable.

Some embodiments of the invention comprise a data carrier with electronically readable control signals capable of cooperating with a programmable computer system to perform one of the methods described herein.

In general, embodiments of the present invention can be implemented as a computer program product with program code, wherein the program code serves to perform one of the methods when the computer program product is run on a computer. The program code can, for example, be stored on a machine-readable medium.

Other embodiments include the computer program for performing one of the methods described herein, which is based on a stored on a machine-readable medium.

In other words, one embodiment of the present invention is therefore a computer program having program code for carrying out one of the methods described herein when the computer program is running on a computer.

A further embodiment of the present invention is therefore a storage medium (or a data carrier or a computer-readable medium) on which the computer program for performing one of the methods described herein is stored when executed by a processor. The data carrier, digital storage medium, or recorded medium is typically tangible and/or non-transferable. A further embodiment of the present invention is a device as described herein, comprising a processor and the storage medium.

A further embodiment of the invention is therefore a data stream or a sequence of signals representing the computer program for carrying out one of the methods described herein. The data stream or signal sequence can, for example, be configured such that it can be transmitted via a data communication connection, e.g., via the Internet.

Another embodiment comprises a processing means, e.g., a computer or a programmable logic device, configured or adapted to perform any of the methods described herein.

A further embodiment comprises a computer on which the computer program for carrying out one of the methods described herein is installed. A further embodiment of the invention comprises a device or system configured to transmit a computer program for performing one of the methods described herein to a recipient (e.g., electronically or optically). The recipient may, for example, be a computer, a mobile device, a storage device, or the like. The device or system may, for example, comprise a file server for transmitting the computer program to the recipient.

In some embodiments, a programmable logic device (e.g., a field-programmable gate array) may be used to perform some or all of the functions of the methods described herein. In some embodiments, a field-programmable gate array may cooperate with a microprocessor to perform any of the methods described herein. In general, the methods are preferably performed by any hardware device.

The term "and/or" as used here includes all combinations of one or more of the listed aspects and can be abbreviated to "/".

Although some aspects have been described in the context of a device, it is clear that these aspects also represent a description of the corresponding method, with a block or device corresponding to a method step or a feature of a method step. Similarly, aspects described in the context of a method step also represent a description of a corresponding block, element, or feature of a corresponding device. List of reference symbols

100, 200 microtome

110 knife holders

112 knives

114 Cutting edge

116 Recording box

120 sample holders

122 Sample

124 Sample surface

218 Side surface of the knife

230 lighting devices

232 light source

234 Diffusion element or filter

235 Room

238 light beam

240 sensors

250 control devices

260.1 first actuator

260.2 second actuator

260.3 third actor

260.4 fourth actuator

262 Handwheel

300 light slit

310 Contour

311 first section of the contour

312 second section of the contour x, y, z, x', y', z', x" axis b feed direction c cutting direction

Claims

Claims 1. A computer-implemented method for operating a microtome (100, 200) for a cutting operation, the microtome (100, 200) having a knife (112) with a cutting edge (114) and a sample (122) on a sample holder (120); comprising the following steps: - determining a light gap (300) which is defined in sections by the cutting edge (114) and the sample (122), and - Aligning the knife (112) and/or the sample (122) so that the light gap (300) has a predetermined structure. 2. The method according to the preceding claim, comprising the step: - Illuminating the space (235) between the cutting edge (114) and the sample (122) with a lighting means (230). 3. The method according to one of the preceding claims, wherein the determination of the light gap (300) is carried out by a sensor (240), in particular a camera. 4. The method of any preceding claim, wherein the structure comprises a shape having two parallel sides, a first side defined by the cutting edge (114) and a second side defined by the sample (122). 5. The method of any preceding claim, wherein the structure comprises a shape having a predetermined distance defined by the side of the structure of the cutting edge (114) and the side of the structure of the sample (122). 6. The method according to the preceding claim, wherein the sample (122) and/or the knife (112) is moved along or parallel to a first linear axis (z) during alignment. 7. The method according to one of the two preceding claims, wherein the alignment takes place along a first axis of rotation (x). 8. The method according to one of the three preceding claims, wherein the alignment is carried out along a second axis of rotation (y). 9. The method according to any one of the preceding claims, wherein the alignment of the knife (112) is carried out by motorized or manual movement of the knife (112) about a first linear axis (z). 10. The method according to any one of the preceding claims, wherein the alignment of the sample (122) is carried out by motorized or manual movement of the sample (122) about a second and a third axis which are arranged at right angles to the first linear axis (z) and/or to each other. 11. The method according to any one of the preceding claims, wherein the structure comprises a substantially rectangular, triangular or trapezoidal shape. 12. The method according to the preceding claims 2 - 11, wherein the camera is arranged relative to the sample (122) on the other side of the illumination means (230) such that it is neither arranged on an axis between the illumination means (230) or the sample (122) nor parallel thereto. 13. The method according to one of the preceding claims 3 - 12, wherein the illumination means (230) and/or the camera (240) is moved to determine the light gap (300). 14. The method according to one of the preceding claims, wherein the cutting edge (114) of the knife (112) is specified as being straight for determining the light gap (300). 15. Microtome (100, 200), trained to: - to carry out a method according to one of the preceding claims; and/or - to exchange information with a device that carries out a method according to one of the preceding claims.