Laser microdissection system and method

The laser microdissection system achieves precise and reliable specimen collection by aligning collection device wells with specimen contours and using a scanning unit to manage beam movement, addressing adherence issues in existing systems.

JP2026017537APending Publication Date: 2026-02-04LEICA MICROSYSTEMS CMS GMBH
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Patent Information

Application Number
JP2025122458
Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
Priority Date
2024-07-23
Filing Date
2025-07-22
Publication Date
2026-02-04

AI Technical Summary

Technical Problem

Existing laser microdissection systems face challenges in accurately and reliably separating dissectates into collection wells without adherence to well walls, leading to inefficiencies in specimen collection.

Method used

A laser microdissection system that utilizes a well positioning unit to align the center of collection device wells with the anatomical specimen based on contour data, combined with a scanning unit to move the manipulation beam and a controller to manage these operations, ensuring precise specimen collection.

Benefits of technology

Enables high-precision and reliable collection of anatomical specimens into collection wells, minimizing adherence to well walls and improving overall specimen collection accuracy.

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Abstract

To provide a laser microdissection system or the like capable of collecting an anatomical specimen with high accuracy and reliability.SOLUTION: The laser microdissection system 100 comprises a microscope 110 having an objective 114 directed toward a sample space 120, a laser light source 126 for generating a manipulation light beam, a dissection unit 134 for coupling the manipulation light beam into the microscope and for separating a dissection specimen 104 from a sample 102 arranged in the sample space by directing the manipulation light beam onto the sample in accordance with contour data relating to a contour 304 of the sample surrounding the dissection specimen, a well positioning unit 138 for moving a harvesting apparatus 108 arranged below the sample and comprising a well 106 for capturing the dissection specimen relative to an optical axis of the objective, and a controller 140 for controlling the well positioning unit in order to move the harvesting apparatus on the basis of the contour data such that a center of an opening of the well is arranged below the dissection specimen.SELECTED DRAWING: Figure 1
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Description

[Technical Field]

[0001] The present invention relates to a laser microdissection system. The present invention further relates to a method for laser microdissection. [Background technology]

[0002] Laser microdissection systems use laser light focused through a microscope objective to separate small portions, called dissectates, from a sample. The sample can be, for example, a thin tissue section cut to isolate specific cells or other microscopic regions of interest. The separated dissectates are captured by a collection device for further processing. The collection device can include one or more wells for collecting the dissectates. When a dissectate is separated, it is important that it falls into the desired well and does not adhere to the well walls. Summary of the Invention [Problem to be solved by the invention]

[0003] It is an object of the present invention to provide a laser microdissection system and method for laser microdissection that can obtain anatomical specimens with high accuracy and reliability. [Means for solving the problem]

[0004] The above-mentioned object is achieved by the subject matter of the independent claims. Advantageous embodiments are defined in the dependent claims and in the following description.

[0005] The proposed laser microdissection system comprises a microscope having an objective lens directed toward a sample space and a laser light source configured to generate an operation light beam. The laser microdissection system also comprises a dissection unit configured to couple the operation light beam to the microscope and separate an anatomical specimen from a sample disposed in the sample space by directing the operation light beam toward the sample according to contour data relating to a contour of the sample surrounding the anatomical specimen. The laser microdissection system also comprises a well positioning unit configured to move a collection device having at least one well disposed below the sample relative to the optical axis of the objective lens. The well is configured to capture the anatomical specimen. The laser microdissection system further comprises a controller configured to control the well positioning unit to move the collection device based on the contour data so that the center of the opening of the well is positioned below the anatomical specimen.

[0006] The microscope can include an optical detection system configured to generate an image of the sample. The microscope objective can be used to focus the manipulation light beam in the sample space. For example, the manipulation light beam can be focused by the objective onto the sample to cut a dissected specimen from the sample. The manipulation light beam can also be focused onto a plane above or below the sample, defocusing the manipulation light beam relative to the sample. A short pulse of defocused manipulation light can be used to pull the dissected specimen away from the sample using radiation pressure, thereby separating the dissected specimen. A short defocused laser pulse can also be used to eject the dissected specimen into a well, for example, if the dissected specimen is still attached to the sample after cutting. The separated dissected specimen can fall into the well under the influence of gravity.

[0007] The collection device may include more than one well. For example, the collection device may include a multi-well plate including 6, 12, 24, 48, 96, 384, 1536, or 3456 wells. The collection device may also include one or more containers, such as PCR tubes or Petri dishes with or without snap-on lids, each container forming a well.

[0008] To collect the anatomical specimen into the well, the controller controls the well positioning unit before separating the anatomical specimen. The well is positioned based on the contour data so that the center of the well opening is located below the anatomical specimen. That is, for example, when viewed from above through a microscope objective lens aimed at the sample, the anatomical specimen appears to cover the center of the well opening. This arrangement ensures that the separated anatomical specimen falls or is ejected near a region of the well bottom that is close to the center of the well, regardless of where the anatomical specimen is located within the microscope's field of view. This prevents, for example, the anatomical specimen from adhering to the well wall or from being completely removed from the well. This allows the proposed laser microdissection system to collect anatomical specimens with high precision and reliability.

[0009] In one embodiment, the controller is configured to control the dissection unit to cut out the sample along the contour after the well has been positioned. In this embodiment, the anatomical specimen is at least partially separated from the sample by using the manipulation light to cut out the sample along the contour. To this end, the sample can be kept stationary while the manipulation light beam is moved along the contour. It is also possible to move the sample while keeping the manipulation light beam stationary, or to move both the sample and the manipulation light beam. By cutting out the sample, the anatomical specimen can be separated from the sample with high precision.

[0010] In another embodiment, the controller is configured to determine the area of ​​the sample surrounded by the contour based on the contour data, and control the well positioning unit to move the collection device so that the center of the opening of the well is positioned below the area of ​​the sample surrounded by the contour. If the contour is not closed, the controller can first determine a closed contour based on the contour data, for example, by connecting two endpoints of the open contour. In this embodiment, the collection device is positioned so that the center of the opening of the well appears within the area of ​​the sample surrounded by the contour when viewed from above, for example, through a microscope objective aimed at the sample. This ensures that the dissected specimen can be collected with high accuracy.

[0011] In another embodiment, the controller is configured to determine the center of the contour based on the contour data and control the well positioning unit to move the collection device so that the center of the well opening is positioned below the center of the contour. The controller may be configured to determine the center of the contour, for example, by determining the geometric center of a set formed from multiple points defined by the contour. In this embodiment, the collection device is positioned so that, when viewed from above, for example, through a microscope objective lens aimed at the sample, the center of the well opening appears directly above the center of the contour. That is, there is a line parallel to the optical axis of the objective lens connecting the center of the well opening center and the center of the contour. This ensures that the dissected specimen can be collected with high accuracy. The center of the contour can also be determined based on a surrounding rectangle or a surrounding circle, for example, by determining the geometric center of the surrounding rectangle or circle as the center of the contour.

[0012] In another embodiment, the laser microdissection system includes a sample positioning unit configured to move the sample relative to the optical axis of the objective. The sample positioning unit may include a movable microscope stage, such as an xy stage. The sample positioning unit allows the sample to be positioned within the field of view of the objective. Furthermore, the sample positioning unit allows the sample and the collection device to be accurately positioned relative to each other, allowing for the collection of dissected specimens with high precision.

[0013] In another embodiment, the controller is configured to control the sample positioning unit to move the sample based on the contour data. For example, based on the contour data, a region of the sample where the anatomical specimen will be generated can be placed in the field of view of the objective. If the manipulation beam is stationary, the sample positioning unit can be used to move the sample to cut the anatomical specimen in a manner similar to a table saw.

[0014] In another embodiment, the cutting unit comprises a scanning unit configured to move the manipulation beam within the field of view of the objective. In such an embodiment, the scanning unit can be used to move the manipulation beam over the specimen with minimal effort, while the sample remains stationary. This reduces the number of moving parts in the laser microdissection unit and therefore increases the precision with which the dissected specimen can be separated from the sample.

[0015] In another embodiment, the scanning unit includes two prisms rotatably arranged around an optical axis between the laser light source and the objective lens. The optical axis here refers to the optical axis of the objective lens or its extension, for example, via a beam splitter. Each prism deflects the manipulation beam according to its rotation. The beam deflections by each prism are vectorially added. Therefore, by rotating the two prisms, the manipulation beam can be moved within the field of view of the objective lens. In particular, the rotation of the prisms also causes a change in the beam offset at the output of the scanning unit. This beam offset compensates for the lateral deflection of the manipulation beam that would occur in the pupil plane of the objective lens. As a result, the manipulation beam always passes through the pupil of the objective lens, regardless of the deflection angle. In this embodiment, the manipulation beam can be moved over the specimen with minimal effort while the specimen remains stationary.

[0016] In one embodiment, the scanning unit may also include at least one of a scanning mirror device and a spatial light modulator, such as a digital mirror device, each of which may be configured to achieve at least equivalent functionality compared to a scanning unit including two prisms.

[0017] In another embodiment, the laser light source comprises at least one pulsed laser. The pulsed laser generates pulsed laser light capable of forming a manipulation beam. The pulsed laser light comprises a series of laser light pulses interrupted by intervals during which no laser light is emitted. The duration of the intervals during which no laser light is emitted may be adjustable. The at least one pulsed laser may be configured to generate pulsed laser light. Forming the manipulation beam from such pulsed laser light may be used to cut away a sample in a manner that does not damage the remaining sample. Furthermore, the at least one pulsed laser may be controlled to generate short laser pulses. Such short laser pulses may be formed into a manipulation beam that is defocused relative to the sample. Such a manipulation beam may be used to detach a dissected specimen from the sample using radiation pressure exerted on the sample by the manipulation beam.

[0018] In another embodiment, the laser light source comprises at least one UV laser light source configured to generate UV laser light from which the manipulation beam is formed, the short wavelength of UV laser light allowing for precision cutting and minimizing damage to adjacent areas of the anatomical specimen by reducing the potential for thermal diffusion.

[0019] In another embodiment, the laser microdissection system includes an input unit configured to receive user input. The controller may be configured to generate contour data based on the user input. The input unit may be, for example, a keyboard and / or a mouse used in combination with a monitor or other display device configured to display an image of the sample. In this embodiment, the user can use the laser microdissection system itself, rather than an external device, to determine the area of ​​the sample from which the dissection specimen will be generated. This makes the laser microdissection system self-contained. Furthermore, because the contour data is generated by the laser microdissection system itself, no post-processing is required to adapt the contour data to the laser microdissection system, further enhancing the ease of use of the sample manipulation device.

[0020] In another embodiment, the controller is configured to receive the contour data via at least one of a data storage device and a computer network. In this embodiment, the laser microdissection device is configured to receive the contour data from an external source. For example, the contour data may be generated using image analysis software running on external hardware such as a personal computer, a server, or a cloud service. The controller may be configured to adapt the external contour data to the laser microdissection device, for example, by changing the format of the contour data. The ability to use contour data generated by an external source increases the versatility of the laser microdissection device.

[0021] In another embodiment, the controller is configured to generate contour data based on an image captured by the microscope. For example, the controller may be configured to perform semantic segmentation of the image to generate the contour data. For example, a region may be determined to be a specific type of cell to be isolated from the remainder of the sample. The results of the image segmentation may then be used to determine potential anatomical specimens to be separated from the sample. In such an embodiment, the laser microdissection device is configured to generate the contour data itself. This greatly assists the user in determining potential anatomical specimens and facilitates automation of many workflows involving the laser microdissection device. Furthermore, because the contour data is generated by the laser microdissection system itself, there is no need to manually or automatically adapt the contour data to the laser microdissection device, making the laser microdissection device easier to use.

[0022] In another embodiment, the controller is configured to generate the contour data using machine learning. For example, the controller may be configured to perform semantic segmentation using machine learning to determine potential anatomical specimens. Machine learning methods can rapidly extract features even from complex scenes, such as microscopic images of specimens. Thus, the use of machine learning can greatly aid in determining potential anatomical specimens, thereby improving the ease of use of the laser microdissection device.

[0023] The present invention further relates to a method for laser microdissection, the method comprising the steps of: a) providing contour data relating to a contour of a sample surrounding an anatomical specimen to be separated from the sample, b) providing a collection device having at least one well positioned below the sample, c) positioning the collection device based on the contour data such that the center of the opening of the well is positioned below the anatomical specimen, d) separating the anatomical specimen from the sample by directing an operating beam at the sample according to the contour data, and e) capturing the anatomical specimen using the well of the collection device.

[0024] Steps a) to e) may be repeated to separate multiple anatomical specimens from the sample. The method has the same advantages as the laser microdissection system described above. In particular, the method may be supplemented with the features described herein in relation to the laser microdissection system. Furthermore, the laser microdissection system described above may be supplemented with the features described herein in relation to the method.

[0025] In one embodiment, the contour data includes at least two contours of the sample, and the collection device includes at least two wells. Steps c)-e) may be repeated sequentially for each contour of the sample using different wells of the collection device to capture each anatomical specimen. In this embodiment, two or more anatomical specimens are separated from the sample, one for each of the at least two contours. Each anatomical specimen is assigned to one of the wells of the collection device. For each anatomical specimen, the assigned well is positioned below the sample before the respective anatomical specimen is separated from the sample. The separated anatomical specimen is then captured in the assigned well. This embodiment of the method allows multiple anatomical specimens to be collected from a single sample with high accuracy and reliability.

[0026] Specific embodiments will be described below with reference to the drawings. [Brief explanation of the drawings]

[0027] [Figure 1] FIG. 1 is a schematic diagram of a laser microdissection system according to one embodiment. [Figure 2] 1 is a flowchart of a method for laser microdissection according to one embodiment. [Figure 3] 3(a) and 3(b) are schematic diagrams of the field of view of the objective lens, illustrating the steps of the method according to FIG. 2; DETAILED DESCRIPTION OF THE INVENTION

[0028] 1 is a schematic diagram of a laser microdissection system 100 according to one embodiment. The laser microdissection system 100 is configured to isolate and collect small portions of a sample 102, hereafter referred to as a dissection specimen 104, in wells 106 of a collection device 108 positioned below the sample 102. The sample 102 may be a biological sample, such as a tissue section, placed on a membrane on a metal frame, for example. Specific cells or other microscopic regions of interest may be isolated from the sample 102 and collected as the dissection specimen 104.

[0029] 1, the collection device 108 is illustratively shown as a multi-well plate. The wells 106 of the collection device 108 may also be formed by PCR tubes, one or more Petri dishes, or similarly suitable containers, which may be placed in a frame for ease of handling. The collection device 108 and / or the individual wells 106 may be removable, allowing for further processing of the dissected specimen 104.

[0030] The laser microdissection system 100 includes a microscope 110 having an optical detection system 112 for capturing an image of the sample 102. The optical detection system 112 includes an objective lens 114, a tube lens 116, and a detector 118. Additional optical elements, such as lenses, filters, apertures, etc., may be part of the optical detection system 112. The objective lens 114 is directed toward a sample space 120 in which the sample 102 is disposed. The objective lens 114 is further configured to receive detected light from the sample 102. The detected light is directed by the objective lens 114 through the tube lens 116 to the detector 118. The detector 118 is configured to generate an image of the sample 102 from the detected light. In this embodiment, a beam splitter 122 is disposed between the objective lens 114 and the tube lens 116. The beam splitter 122 is configured to direct the detected light through the tube lens 116 to the detector 118. The beam splitter 122 may be, for example, a dichroic beam splitter. An illumination system 124 is also part of the microscope 110 and is configured to illuminate the sample 102. The illumination system 124 is illustratively positioned below the sample 102. The illumination system 124 may also be positioned above the sample 102 and configured for incident light illumination. The microscope 110 may further be configured to illuminate the sample 102 via the objective lens 114.

[0031] The laser microdissection system 100 further includes a laser source 126 configured to generate a manipulation beam. The laser source 126 may be comprised of one or more pulsed lasers for generating pulsed laser light from which the manipulation beam is formed. The manipulation beam is focused into the sample volume 120 by the objective lens 114. The manipulation beam can be used to separate the anatomical specimen 104 from the sample 102, for example, by cutting the anatomical specimen 104 from the sample 102 using a focused beam or by pulling the anatomical specimen 104 away from the sample 102 using a defocused beam. In this embodiment, the manipulation beam is directed to the objective lens 114 via a beam splitter 122 disposed in the beam path between the laser source 126 and the objective lens 114. The beam splitter 122 splits the main beam path originating from the sample 102 into two separate beam paths: one beam path extending toward the detector 118 and another beam path extending toward the laser source 126. Beam splitter 122 thereby allows objective lens 114 to be used for both imaging and separating anatomical specimen 104 .

[0032] To move the manipulation beam within the sample space 120, the laser microdissection system 100 includes a scanning unit 128. The scanning unit 128 is disposed between the laser light source 126 and the objective lens 114. In this embodiment, the scanning unit 128 includes two prisms 130 disposed in the beam path between the laser light source 126 and the beam splitter 122. The two prisms 130 are rotatable about an optical axis O′ of the beam path and configured to deflect the manipulation beam in response to their rotation. Thus, by rotating the two prisms 130, the manipulation beam can be moved relative to the sample 102 within the field of view of the objective lens 114. The scanning unit 128 further includes a drive unit 132 for each of the two prisms 130. The two drive units 132 are configured to rotate the prisms 130 independently of each other. In this embodiment, the beam splitter 122 and the scanning unit 128 form a dissection unit 134 of the laser microdissection system 100, which is configured to couple the manipulation beam into the microscope 110 using the beam splitter 122 and to move the manipulation beam in the sample space 120 using the scanning unit 128.

[0033] The sample 102 is placed in the sample space 120 on a sample positioning unit 136 of the laser microdissection system 100. In FIG. 1 , the sample positioning unit 136 is illustratively formed as a microscope stage with an opening that allows the anatomical specimen 104 to fall into the well 106 of the collection device 108 under the influence of gravity. The sample positioning unit 136 is configured to move the sample 102 relative to the optical axis O of the objective lens 114. In particular, the sample positioning unit 136 is configured to move the sample 102 in a plane perpendicular to the optical axis O of the objective lens 114, i.e., in the x- and y-directions, and may also be configured to move the sample 102 in the direction of the optical axis O, i.e., the z-direction. The sample positioning unit 136 allows the sample 102 to be automatically and accurately positioned within the field of view 300 of the objective lens 114 (see FIG. 3 ). This allows the field of view 300 to include a specific region of the sample 102 from which one or more anatomical specimens 104 will be removed.

[0034] The laser microdissection system 100 also includes a well positioning unit 138. The well positioning unit 138 is configured to move the collection device 108 relative to the main body of the laser microdissection system 100. In particular, the well positioning unit 138 is configured to move the collection device 108 relative to the optical axis O of the objective lens 114, i.e., in the X and Y directions. The well positioning unit 138 can be used to position one of the wells 106 of the collection device 108 below the sample 102 so that a dissected specimen 104 from the sample 102 can be collected in the well 106.

[0035] The laser microdissection system 100 further includes a controller 140, an input unit 142, and an output unit 144. The controller 140 is configured to receive user input via the input unit 142 and display visual information to the user via the output unit 144. The input unit 142 is illustratively shown to include a keyboard. However, the input unit 142 may also include a computer mouse, a stylus for use with a touchscreen, or other suitable input device. The output unit 144 is illustratively shown as a monitor. The input unit 142 and the output unit 144 may also be a single element, such as a touchscreen. The controller 140 further includes an external interface 146 and is configured to receive data via the external interface 146. The external interface 146 may include a connector for a storage device, such as a flash drive, and / or a connection to a computer network, such as a local area network or the Internet.

[0036] Furthermore, the controller 140 is configured to perform at least some steps of a method for laser microdissection. To perform the method, the controller 140 is configured to control at least the well positioning unit 138. The controller 140 may also be configured to control at least one element of the optical detection system 112, the illumination system 124, the laser light source 126, the scanning unit 128, and the sample positioning unit 136. The method is described in more detail below with reference to Figures 2, 3a, and 3b.

[0037] 2 is a flow chart of a method for laser microdissection according to one embodiment. The method is described, by way of example only, as being performed using the laser microdissection system 100 according to FIG.

[0038] The method begins at step S200. In step S202, contour data is prepared. The contour data relates to at least one contour 304 (see FIG. 3 ) related to the sample 102, the contour surrounding the anatomical specimen 104 to be separated from the sample 102. The contour data can be generated based on user input. In one embodiment, a user can use the input unit 142 to draw a contour around a region of the sample 102 on an image of the sample 102. The image of the sample 102 can be displayed to the user via the output unit 144. For example, the contour data can be generated by the controller 140 from the contour drawn by the user on the image of the sample 102. The image of the sample 102 is, for example, an image captured by the microscope 110. The controller 140 can also generate the contour data using an image processing method, such as image segmentation, on the image of the sample 102. The contour data can also be generated by an external source. For example, the contour data can be generated on an external device and transferred to the laser microdissection system 100 via the external interface 146. In step S204, the harvesting device 108 is prepared. In this step, the harvesting device 108 can be placed at an intended location within the laser microdissection system 100 either manually by a user or automatically, for example, by a robotic arm. The harvesting device 108 may also be a fixed component of the laser microdissection system 100, in which case the harvesting device 108 is prepared by the laser microdissection system 100. Steps S202 and S204 may be performed simultaneously or sequentially in any order.

[0039] In optional step S206, the sample 102 is positioned. For example, the sample 102 is positioned within the field of view 300 of the objective lens 114 such that the anatomical specimen 104 separated from the sample 102 is visible within the field of view 300. In one embodiment, the controller 140 controls the sample positioning unit 136 to move the sample 102.

[0040] In step S208, the collection device 108 is positioned below the sample 102 so that the center 302 (see FIG. 3) of the opening of one of the wells 106 is located below the anatomical specimen 104 surrounded by the outline 304. That is, for example, when viewed from above through the objective lens 114 along the optical axis O, the collection device 108 is moved so that the center 302 of the well 106 appears below the anatomical specimen. In one embodiment, the controller 140 controls the well positioning unit 138 to move the collection device 108. The positioning of the well 106 will be described in more detail below with reference to FIGS. 3a and 3b.

[0041] In step S210, the anatomical specimen 104 is separated from the sample 102 by directing an manipulation beam at the sample 102 according to the contour data. In one embodiment, the sample 102 is cut along the contour 304 to separate the anatomical specimen 104. To cut the sample 102, the manipulation beam can be focused on the sample 102 using the objective lens 114. The focused manipulation beam can then be moved along the contour 304 using the scanning unit 128. The anatomical specimen 104 can also be separated from the sample 102 by using radiation pressure exerted by a short pulse of the defocused manipulation beam to pull the anatomical specimen away from the sample 102. In step S212, the separated anatomical specimen 104 is then captured in the well 106 of the collection device 108 that was positioned below the anatomical specimen 104 in step S208.

[0042] Steps S206 through S212 can be repeated for different anatomical specimens 104. Each time, in step S208, a different well 106 is placed under a different anatomical specimen 104, and the current anatomical specimen 104 is first isolated and then harvested in steps S210 and S212, respectively. The method then ends in step S214.

[0043] 3a and 3b are schematic illustrations of the field of view 300 of the objective lens 114 and illustrate step S208 of the method according to FIG.

[0044] 3a is a schematic diagram of the field of view 300 of the objective lens 114 before the collection device 108 is positioned, i.e., at the start of step S208. The opening of the well 106 is centered in the field of view 300, such that the center 302 of the opening is centered in the field of view 300. An outline 304 surrounds the anatomical specimen 104, which is located in the upper left corner of the field of view 300 and therefore in the upper left corner of the opening near the wall of the well 106. If the anatomical specimen 104 is separated in this position, the anatomical specimen 104 may adhere to the wall of the well 106.

[0045] FIG. 3b is a schematic diagram of the field of view 300 of the objective lens 114 after the collection device 108 has been positioned. The movement of the well 106 between FIG. 3a and FIG. 3b is indicated by arrow D. As can be seen in FIG. 3b, the well 106 has been moved upward and to the left. The center 302 of the opening is now located below the anatomical specimen 104. More specifically, in FIG. 3b, the center 302 of the opening is located within the area surrounded by the outline 304. In the field of view 300 of the objective lens 114, the anatomical specimen 104 appears to cover the center 302 of the opening. When the anatomical specimen 104 is separated in this position, it falls into the well 106 near the center 302 of the well 106.

[0046] In all figures, identical or similar elements are designated with the same reference numeral. As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items and may be abbreviated as " / ".

[0047] While 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]

[0048] 100 Laser Microdissection System 102 samples 104 Anatomical Specimens 106 wells 108 Collection device 110 Microscope 112 Optical Detection System 114 Objective Lens 116 Tube Lens 118 detector 120 Sample Space 122 Beam Splitter 124 Lighting System 126 Laser Light Source 128 scanning units 130 Prism 132 Drive Unit 134 Anatomy Unit 136 Sample positioning unit 138 well positioning unit 140 Controller 142 input units 144 output units 146 External Interface 300 field of view 302 center 304 Contour D arrow

Claims

1. a microscope (110) having an objective lens (114) directed toward a sample space (120); a laser light source (126) configured to generate an operating beam; a dissection unit (134) configured to couple the manipulation light beam into the microscope (110) and separate a dissected specimen (104) from a sample (102) placed in the sample space (120) by directing the manipulation light beam towards the sample (102) according to contour data relating to a contour (304) of the sample (102) surrounding the dissected specimen (104); a well positioning unit (138) configured to move a collection device (108) having at least one well (106) arranged below the sample (102) relative to an optical axis (O) of the objective lens (114), the well (106) being configured to capture the anatomical specimen (104); a controller (140) configured to control the well positioning unit (138) to move the sampling device (108) based on the contour data so that the center (302) of the opening of the well (106) is positioned below the anatomical specimen (104); A laser microdissection system (100) comprising:

2. the controller (140) is configured to control the dissection unit (134) to cut out the sample (102) along the contour (304) after the well (106) has been positioned. The laser microdissection system (100) of claim 1.

3. The controller (140) is configured to determine an area of ​​the sample (102) surrounded by the outline (304) based on the outline data, and to control the well positioning unit (138) to move the collection device (108) so that the center (302) of the opening of the well (106) is positioned below the area of ​​the sample (102) surrounded by the outline (304). The laser microdissection system (100) of claim 1 or 2.

4. The controller (140) is configured to determine a center of the contour (304) based on the contour data and to control the well positioning unit (138) to move the collection device (108) so that the center (302) of the opening of the well (106) is positioned below the center of the contour (304). The laser microdissection system (100) of any one of claims 1 to 3.

5. the laser microdissection system (100) comprises a sample positioning unit (136) configured to move the sample (102) relative to the optical axis (O) of the objective lens (114); The laser microdissection system (100) of any one of claims 1 to 4.

6. the controller (140) is configured to control the sample positioning unit (136) to move the sample (102) based on the contour data. The laser microdissection system (100) of claim 5.

7. the cutting unit comprises a scanning unit (128) configured to move the manipulation beam within a field of view (300) of the objective lens (114); The laser microdissection system (100) of any one of claims 1 to 6.

8. The scanning unit (128) comprises two prisms (130) arranged rotatably around an optical axis (O') between the laser light source (126) and the objective lens (114). The laser microdissection system (100) of claim 7.

9. the laser light source (126) comprises at least one pulsed laser; The laser microdissection system (100) of claim 7 or 8.

10. the laser microdissection system (100) comprises an input unit (142) configured to receive user input, and the controller (140) is configured to generate the contour data based on the user input. The laser microdissection system (100) of any one of claims 1 to 9.

11. the controller (140) is configured to receive the contour data via at least one of a data storage device and a computer network; The laser microdissection system (100) of any one of claims 1 to 10.

12. the controller (140) is configured to generate the contour data based on an image captured by the microscope (110); The laser microdissection system (100) of any one of claims 1 to 11.

13. the controller (140) is configured to generate the contour data using machine learning; The laser microdissection system (100) of any one of claims 1 to 12.

14. 1. A method for laser microdissection, said method comprising: a) providing contour data relating to a contour (304) of a sample (102) surrounding a specimen (104) to be separated from said sample (102); b) providing a collection device (108) comprising at least one well (106) positioned below said sample (102); c) positioning the collection device (108) based on the contour data so that the center (302) of the opening of the well (106) is positioned below the anatomical specimen (104); d) separating the anatomical specimen (104) from the sample (102) by directing an operating beam onto the sample (102) according to the contour data; e) capturing the anatomical specimen (104) using the well (106) of the collection device (108); A method comprising:

15. the contour data includes at least two contours (304) of the sample (102), the collection device (108) comprises at least two wells (106), and steps c) through e) are repeated successively for each of the contours (304) of the sample (102) using different wells (106) of the collection device (108) to capture each of the anatomical specimens (104); 15. The method of claim 14.

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