Laser microdissection system and method

Abstract

A laser microdissection system includes: a microscope having an objective lens aligned with a sample space; and a laser light source configured to generate a steering beam. The laser microdissection system also includes a dissection unit configured to couple the steering beam to the microscope and to separate the segregation from the sample disposed in the sample space by directing the steering beam onto the sample according to profile data relating to a profile on the sample surrounding the segregation. The laser microdissection system further includes a hole location positioning unit configured to move a collection arrangement comprising at least one hole location disposed below the sample relative to an optical axis of the objective lens, where the hole location is configured to capture the educt. The laser microdissection system also includes a controller configured to control the hole location positioning unit to move the collection arrangement based on the profile data such that the center of the opening of the hole location is positioned below the segregation.

Description

Technical Field

[0001] This invention relates to a laser micro-cutting system and a laser micro-cutting method. Background Technology

[0002] Laser microdissection systems use a laser focused through the objective lens of a microscope to separate small portions of a sample, called "dissectates." The sample can be a thin section of tissue, for example, cut to separate specific cells or other microscopic regions of interest. The separated dissectates are then captured by a collection arrangement for further processing. The collection arrangement may have one or more wells for collecting the dissectates. It is crucial that the dissectates fall into the desired wells without adhering to the well walls as they are separated. Summary of the Invention

[0003] The purpose of this invention is to provide a laser micro-cutting system and a laser micro-cutting method, which can achieve high-precision and reliable collection of segregated materials.

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

[0005] The proposed laser micro-cutting system includes: a microscope having an objective lens aligned with a sample space; and a laser source configured to generate a manipulating beam. The laser micro-cutting system also includes a cutting unit configured to couple the manipulating beam into the microscope and to separate the dissociated material from the sample arranged within the sample space by guiding the manipulating beam onto the sample based on contour data relating to the contour surrounding the dissociated material. The laser micro-cutting system also includes a hole positioning unit configured to move a collection arrangement containing at least one hole positioned below the sample relative to the optical axis of the objective lens. The hole is configured to capture the dissociated material. The laser micro-cutting system also includes a controller configured to control the movement of the hole positioning unit to the collection arrangement based on the contour data, such that the center of the hole opening is positioned below the dissociated material.

[0006] Microscopes may include an optical detection system configured to generate images of the sample. The microscope's objectives can be used to focus a manipulator beam within the sample space. For example, an objective can focus the manipulator beam onto the sample to cut away the sequestrant. The manipulator beam can also be focused onto a plane above or below the sample, creating a defocused state relative to the sample. Short-pulse defocused manipulator beams can be used to peel the sequestrant from the sample using radiation pressure, thereby separating it. Short-duration defocused laser pulses can also be used to eject the sequestrant into an aperture, for example, if the sequestrant remains attached to the sample after cutting. The separated sequestrant then falls into the aperture under gravity.

[0007] The collection arrangement may contain multiple wells. For example, the collection arrangement may contain a multi-well plate with 6, 12, 24, 48, 96, 384, 1536, or 3456 wells. The collection arrangement may also contain one or more containers, such as PCR tubes or culture dishes with or without snap-on caps, each container forming a well.

[0008] To collect the segregated material from the well, the controller positions the well before separating the segregated material by controlling the well positioning unit. The well is positioned so that the center of the well opening is located below the segregated material, based on contour data. In other words, when viewed from above (e.g., through the objective lens of a microscope aimed at the sample), the segregated material appears to cover the center of the well opening. This arrangement ensures that the separated segregated material, regardless of its position in the microscope's field of view, falls or is ejected to the area near the center of the well at the bottom. This, for example, prevents the segregated material from adhering to the well wall or remaining uncollected. The proposed laser microdissection system thus achieves highly accurate and reliable segregated material collection.

[0009] In one embodiment, the controller is configured to control the cutting unit to cut the sample along a contour after the hole positioning is completed. In this embodiment, at least a portion of the dissociated material is separated from the sample by cutting the sample along the contour using a manipulating light. For this purpose, the manipulating light beam can be moved along the contour while the sample remains stationary. Alternatively, the sample can be moved while the manipulating light beam remains stationary, or both the sample and the manipulating light beam can be moved simultaneously. Cutting the sample allows for the separation of the dissociated material from the sample with high precision.

[0010] In another embodiment, the controller is configured to determine the sample region surrounded by the contour based on contour data and control the well positioning unit to move the collection arrangement so that the center of the well opening is positioned below the sample region surrounded by the contour. When the contour is not closed, the controller can first determine a closed contour based on the contour data (e.g., by connecting the two endpoints of the open contour). In this embodiment, the collection arrangement is positioned such that when viewed from above, for example, through the objective lens of a microscope aligned with the sample, the center of the well opening appears within the sample region surrounded by the contour. This ensures that the separated material can be reliably collected with high accuracy.

[0011] In another embodiment, the controller is configured to determine the center of the profile based on profile data and control the aperture positioning unit to move the collection arrangement so that the center of the aperture opening is positioned below the center of the profile. The controller may be configured to determine the center of the profile, for example, by determining the geometric center of a set of points defined by the profile. In this embodiment, the collection arrangement is positioned such that, when viewed from above, for example, through the objective lens of a microscope aligned with the sample, the center of the aperture opening appears directly above the center of the profile. In other words, there exists a line parallel to the optical axis of the objective lens that connects the center of the aperture opening and the center of the profile. This ensures that the separated material can be reliably collected with high precision. The center of the profile may also be determined based on the surrounding rectangle or surrounding circle of the profile, for example, by determining the geometric center of the surrounding rectangle or surrounding circle as the center of the profile.

[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 lens. The sample positioning unit may include a movable microscope stage, such as an xy stage. The sample positioning unit enables the sample to be positioned within the objective lens's field of view. Furthermore, the sample positioning unit allows for precise relative positioning of the sample and the collection arrangement, achieving high-precision collection of the separated material.

[0013] In another embodiment, the controller is configured to control the sample positioning unit to move the sample based on contour data. For example, based on the contour data, the sample region to which the segregation is to be generated can be moved into the objective lens field of view. If the manipulation beam remains stationary, the sample positioning unit can be used to move the sample to cut the segregation in a manner similar to a sawing operation.

[0014] In another embodiment, the cutting unit includes a scanning unit configured to move the manipulation beam within the objective lens's field of view. In this embodiment, the sample can be kept stationary, and the scanning unit is used to move the manipulation beam over the sample with minimal effort. This reduces the number of moving parts in the laser microscopy separation unit, thereby improving the accuracy of separating the precipitate from the sample.

[0015] In another embodiment, the scanning unit includes two prisms rotatably arranged between the laser source and the objective lens about an optical axis. Here, the optical axis refers to the optical axis of the objective lens or its extension axis (e.g., achieved via a beam splitter). Each prism deflects the manipulating light according to its rotation. The beam deflections caused by each prism are vector-superimposed. Therefore, by rotating the two prisms, the manipulating beam can be moved within the objective lens's field of view. 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 manipulating beam at the objective lens's pupil plane. Thus, regardless of the deflection angle, the manipulating beam always passes through the objective lens pupil. In this embodiment, the sample can be kept stationary, and the movement of the manipulating beam on the sample can be achieved with minimal effort.

[0016] In one embodiment, the scanning unit may further include at least one of a scanning mirror device and a spatial light modulator (such as a digital mirror device). Both the scanning mirror device and the spatial light modulator may be configured to perform at least the same functions as a scanning unit comprising two prisms.

[0017] In another embodiment, the laser source includes at least one pulsed laser. The pulsed laser generates pulsed laser light, thereby forming a manipulating beam. The pulsed laser consists of a series of laser pulses interrupted by intervals of no laser emission. The duration of the intervals of no laser emission is adjustable. At least one pulsed laser can be configured to generate pulsed laser light. The manipulating beam formed by such pulsed laser light can be used to cut the sample in a manner that does not damage the rest of the sample. Furthermore, at least one pulsed laser can be controlled to generate short laser pulses. Such short laser pulses can form a manipulating beam defocused relative to the sample. Such manipulating beam can use the radiation pressure applied to the sample by the manipulating beam to peel off exfoliants from the sample.

[0018] In another embodiment, the laser source includes at least one ultraviolet laser source. The ultraviolet laser source is configured to generate ultraviolet laser light, thereby forming a manipulated beam. The ultraviolet laser has a shorter wavelength, enabling high-precision cutting and reducing the probability of thermal diffusion, thus minimizing damage to the region adjacent to the segregated material.

[0019] In another embodiment, the laser microdissection system includes an input unit configured to receive user input. A controller can generate contour data based on the user input. The input unit may be a keyboard and / or mouse used in conjunction with a display 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 sample area from which the precipitate is to be generated. This makes the laser microdissection system independently operable. Furthermore, since the contour data is generated by the laser microdissection system itself, no subsequent processing is required to adapt the contour data to the laser microdissection system, making the sample manipulation device easier to use.

[0020] In another embodiment, the controller is configured to receive contour data via at least one of a data storage device and a computer network. In this embodiment, the laser microdissection apparatus is configured to receive 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, server, or cloud service. The controller may be configured to adapt external contour data to the laser microdissection apparatus (e.g., by changing the format of the contour data). The ability to use contour data generated from an external source makes the laser microdissection apparatus more versatile.

[0021] In another embodiment, the controller is configured to generate contour data based on images captured by the microscope. For example, the controller may be configured to perform semantic segmentation of the images to generate contour data. For instance, a region may be identified as a specific type of cell to be separated from the rest of the sample. The results of the image segmentation process can then be used to determine potential exfoliants to be separated from the sample. In such embodiments, the laser microdissection apparatus is configured to generate contour data itself. This greatly assists the user in identifying potential exfoliants, thereby significantly increasing the automation of many workflows involved in the laser microdissection apparatus. Furthermore, since the contour data is generated by the laser microdissection system itself, there is no need (manually or automatically) to adapt the contour data to the laser microdissection system, making the laser microdissection apparatus easier to use.

[0022] In another embodiment, the controller is configured to generate contour data using machine learning. For example, the controller may be configured to perform semantic segmentation using machine learning to identify potential segregators. Machine learning methods are capable of rapidly extracting features from even complex scenes such as sample microscopic images. Therefore, using machine learning can greatly help in identifying potential segregators, thereby improving the ease of use of laser microdissection apparatuses.

[0023] The present invention also relates to a laser micro-cutting method. The method includes the following steps: a) providing contour data related to the contour of a precipitate surrounding a sample to be separated from the sample. b) providing a collection arrangement including at least one aperture disposed below the sample. c) positioning the collection arrangement based on the contour data such that the center of the aperture opening is positioned below the precipitate. d) separating the precipitate from the sample by manipulating a beam of light onto the sample according to the contour data. e) capturing the precipitate using the aperture of the collection arrangement.

[0024] Steps a) to e) can be repeated to separate multiple precipitates from the sample. The method has the same advantages as the laser microdissection system described above. In particular, the method can be supplemented by the relevant features described herein in conjunction with the laser microdissection system. Similarly, the aforementioned laser microdissection system can also be supplemented by the relevant features described herein in conjunction with the method.

[0025] In one embodiment, the profile data includes at least two profiles on the sample, and the collection arrangement includes at least two well positions. For each profile on the sample, steps c) through e) can be repeated sequentially, using different well positions in the collection arrangement to capture the corresponding precipitate. In this embodiment, two or more precipitates can be separated from the sample—each precipitate corresponding to one of the at least two profiles. Each precipitate is assigned one well position in the collection arrangement. For each precipitate, its assigned well position is positioned below the sample before the corresponding precipitate is separated from the sample. The separated precipitate is then captured into the assigned well position. This embodiment of the method enables the collection of multiple precipitates from a single sample with high accuracy and high reliability. Attached Figure Description

[0026] The specific embodiments will be described below with reference to the accompanying drawings, in which: Figure 1 This is a schematic diagram of a laser micro-cutting system according to one embodiment; Figure 2 This is a flowchart of a laser micro-cutting method according to one embodiment; Figure 3 a and 3b are schematic diagrams of the objective lens field of view, showing the results based on... Figure 2 The steps of the method. Detailed Implementation

[0027] Figure 1 This is a schematic diagram of a laser microdissection system 100 according to one embodiment. The laser microdissection system 100 is configured to separate a small portion of a sample 102 (hereinafter referred to as sequestrum 104) and collect it in well positions 106 of a collection arrangement 108 disposed below the sample 102. The sample 102 may be a biological sample, such as a tissue section placed on a metal frame membrane. Specific cells or other microscopic regions of interest can be separated from the sample 102 and collected as sequestrum 104.

[0028] Figure 1 An exemplary embodiment of the collection arrangement 108 is a multi-well plate. The wells 106 of the collection arrangement 108 may also be composed of PCR tubes (arranged in a frame for easy handling), one or more culture dishes, or other similar suitable containers. The collection arrangement 108 and / or individual wells 106 may be removable for subsequent processing of the isolates 104.

[0029] The laser microdissection system 100 includes a microscope 110 having an optical detection system 112 for capturing an image of a sample 102. The optical detection system 112 includes an objective lens 114, a tube lens 116, and a detector 118. Other optical elements such as lenses, filters, and apertures may be part of the optical detection system 112. The objective lens 114 is aligned with a sample space 120 where the sample 102 is disposed. The objective lens 114 is further configured to receive detection light from the sample 102. The detection light is guided by the objective lens 114 to the detector 118 via the tube lens 116. The detector 118 is configured to generate an image of the sample 102 from the detection 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 guide the detection light to the detector 118 via the tube lens 116. For example, the beam splitter 122 may be a dichroic beam splitter. An illumination system 124 is also part of the microscope 110 and is configured to illuminate the sample 102. Illumination system 124 is exemplarily arranged below sample 102. Illumination system 124 may also be arranged above sample 102 and configured for incident light illumination. Microscope 110 may also be configured to illuminate sample 102 via objective lens 114.

[0030] The laser microdissection system 100 also includes a laser source 126 configured to generate a manipulation beam. The laser source 126 may include one or more pulsed lasers for generating pulsed laser light, thereby forming the manipulation beam. The manipulation beam is focused into the sample space 120 by the objective lens 114. Separation of the dissociated material 104 from the sample 102 can be achieved using the manipulation beam, for example, by using a focused beam to cut the dissociated material 104 from the sample 102, or by using a defocused beam to peel the dissociated material 104 from the sample 102. In this embodiment, the manipulation beam is directed to the objective lens 114 via a beam splitter 122 arranged 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 distinct beam paths, one extending to the detector 118 and the other extending to the laser source 126. Thus, the beam splitter 122 allows the objective lens 114 to be used simultaneously for imaging and dissociated material 104 separation.

[0031] To achieve the manipulation of the beam within the sample space 120, the laser microdissection system 100 includes a scanning unit 128. The scanning unit 128 is arranged between the laser source 126 and the objective lens 114. In this embodiment, the scanning unit 128 includes two prisms 130 arranged in the beam path between the laser source 126 and the beam splitter 122. The two prisms 130 are arranged to be rotatable about the optical axis O' of the beam path and configured to deflect the manipulation beam according to their rotation. Therefore, 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 also 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 the cutting unit 134 of the laser micro-cutting system 100. The cutting unit uses the beam splitter 112 to couple the manipulation beam to the microscope 110 and uses the scanning unit 128 to realize the movement of the manipulation beam within the sample space 120.

[0032] Sample 102 is positioned in the sample space 120 of the sample positioning unit 136 of the laser micro-cutting system 100. Figure 1 In this embodiment, the sample positioning unit 136 is exemplarily configured as a microscope stage with an opening, allowing the separated material 104 to fall into the aperture 106 of the collection arrangement 108 under gravity. The sample positioning unit 136 is configured to move the sample 102 relative to the optical axis O of the objective lens 114. Specifically, 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 can also be configured to move the sample 102 along the direction of the optical axis O (i.e., in the z direction). Through the sample positioning unit 136, the sample 102 can be automatically and precisely positioned in the field of view 300 of the objective lens 114 (see [reference]). Figure 3 In this way, a specific area of ​​the sample 102 to be removed, or one or more segregated material 104, is moved into the field of view 300.

[0033] The laser microdissection system 100 also includes a hole positioning unit 138. The hole positioning unit 138 is configured to move the collection arrangement 108 relative to the main body of the laser microdissection system 100. Specifically, the hole positioning unit 138 is configured to move the collection arrangement 108 relative to the optical axis O (i.e., in the x and y directions) of the objective lens 114. Using the hole positioning unit 138, a hole 106 of the collection arrangement 108 can be positioned below the sample 102 such that the segregated material 104 cut from the sample 102 can be collected into the hole 106.

[0034] The laser micro-cutting system 100 also 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 exemplarily a keyboard. The input unit 142 may also include a suitable input device such as a computer mouse or a stylus for use with a touchscreen. The output unit 144 is exemplarily 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 also 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).

[0035] Furthermore, the controller 140 is configured to perform at least some steps of the laser micro-cutting method. For performing the method, the controller 140 is configured to control at least the hole positioning unit 138. The controller 140 may also be configured to control at least one of the following components: the optical detection system 112, the illumination system 124, the laser source 126, the scanning unit 128, and the sample positioning unit 136. Reference will be made below. Figure 2 , Figure 3 a and Figure 3 b. Describe the method in more detail.

[0036] Figure 2 This is a flowchart of a laser micro-cutting method according to one embodiment. The method described herein is only for illustrative purposes. Figure 1 The laser micro-cutting system 100 shown is used as an example for explanation.

[0037] The method begins at step S200. In step S202, contour data is provided. The contour data corresponds to at least one contour 304 on sample 102 (see...). Figure 3The contour 304 surrounds the sequestra 104 to be separated from sample 102. Contour data can be generated based on user input. In one embodiment, the user can use input unit 142 to draw a contour around a region of sample 102 on an image of sample 102. The image of sample 102 can be displayed to the user via output unit 144. For example, contour data can be generated by controller 140 based on the contour drawn by the user on the image of sample 102. For example, the image of sample 102 is an image captured by microscope 110. Controller 140 can also generate contour data on the image of sample 102 using image processing methods such as image segmentation. Contour data can also be generated by an external source. For example, contour data is generated on an external device and transmitted to laser microdissection system 100 via external interface 146. In step 204, a collection arrangement 108 is provided. In this step, collection arrangement 108 can be manually positioned by the user or automatically positioned (e.g., by a robotic arm) to its intended position in laser microdissection system 100. The collection arrangement 108 can also be a fixed part of the laser micro-cutting system 100, in which case the collection arrangement 108 is provided by the laser micro-cutting system 100. Steps S202 and S204 can be performed simultaneously or sequentially in any order.

[0038] 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 precipitate 104 to be separated from the sample 102 is visible in the field of view 300. In one embodiment, the controller 140 controls the sample positioning unit 136 to move the sample 102.

[0039] In step S208, the collection arrangement 108 is positioned below the sample 102, such that the center 302 of the opening of one of the apertures 106 (see...) Figure 3 The aperture 106 is positioned below the segregated material 104, which is surrounded by contour 304. In other words, the collecting arrangement 108 is moved such that, when viewed from above (e.g., along its optical axis O via objective lens 114), the center 302 of the aperture 106 is positioned below the segregated material. In one embodiment, controller 140 controls aperture positioning unit 138 to move collecting arrangement 108. The positioning of aperture 106 will be referenced to... Figure 3 a and Figure 3 b will be explained in detail below.

[0040] In step S210, the dissociated material 104 is separated from the sample 102 by guiding the manipulation beam onto the sample 102 according to the contour data. In one embodiment, the sample 102 is cut along the contour 304 to achieve the separation of the dissociated material 104. To cut the sample 102, the manipulation beam can be focused onto the sample 102 using the objective lens 114. Then, the focused manipulation beam can be moved along the contour 304 using the scanning unit 128. Radiation pressure applied by a short pulse of the defocused manipulation beam can also be used to separate the dissociated material 104 from the sample 102 by peeling it off. In step S212, the separated dissociated material 104 is then captured in the aperture 106 of the collection arrangement 108 arranged below the dissociated material 104 in step S208.

[0041] Steps S206 to S212 can be repeated for different segregated substances 104. Each time, in step S208, different orifice positions 106 are positioned below different segregated substances 104, and in steps S210 and S212, the current segregated substance 104 is first separated and then collected. Then, the method ends in step S214.

[0042] Figure 3 a and Figure 3 b is a schematic diagram of the field of view 300 of objective lens 114, and an explanation. Figure 2 Step S208 of the method.

[0043] Figure 3 a is a schematic diagram of the field of view 300 of the objective lens 114 before the positioning and collection arrangement 108, i.e., at the beginning of step S208. The opening of the aperture 106 is centered in the field of view 300, such that the center 302 of the opening is located at the center of the field of view 300. The contour 304 surrounds the segregated material 104 located at the upper left corner of the field of view 300 and therefore at the upper left corner of the opening near the wall of the aperture 106. If the segregated material 104 separates at this location, it may adhere to the wall of the aperture 106.

[0044] Figure 3 b is a schematic diagram of the field of view 300 of the objective lens 114 after the collection and arrangement 108 is positioned. Arrow D indicates the aperture position 106 from... Figure 3 a to Figure 3 The movement of b. For example... Figure 3 As shown in b, the orifice position 106 has moved upward and to the left. At this point, the center 302 of the opening is located below the segregated material 104. More specifically, in Figure 3 In step b, the center 302 of the opening is located within the area enclosed by the contour 304. In the field of view 300 of the objective lens 114, the dissociated material 104 appears to cover the center 302 of the opening. If the dissociated material 104 separates at this location, it will fall into the aperture 106 and be close to the center 302 of the aperture 106.

[0045] In all the accompanying drawings, elements that are identical or functionally similar are identified by the same reference numerals. The term "and / or" as used herein includes any one or more of the listed related items and may be abbreviated as " / ".

[0046] Although some aspects have been described in the context of the apparatus, it should be understood that these aspects also represent a description of the corresponding method, where a module or device corresponds 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 module, entry, or feature of the corresponding apparatus.

[0047] Figure Labels 100 Laser Microcutting System 102 samples 104 Separated matter 106 holes 108 Collection and Arrangement 110 Microscope 112 Optical Inspection System 114 Objective Lens 116 tube lens 118 detectors 120 Sample Space 122 beam splitter 124 Lighting System 126 Laser source 128 scanning units 130 prism 132 drive units 134 cutting units 136 Sample positioning units 138-hole positioning unit 140 Controller 142 Input Unit 144 Output Units 146 External Interface 300 field of view 302 Center 304 Outline D arrow

Claims

1. A laser micro-cutting system (100), comprising: Microscope (110) having an objective lens (114) for aligning with the sample space (120). A laser source (126) is configured to generate a manipulating beam; The cutting unit (134) is configured to couple a manipulation beam to the microscope (110) and to separate the precipitate (104) from the sample (102) arranged in the sample space (120) by guiding the manipulation beam to the sample (102) according to contour data related to the contour (304) surrounding the precipitate (104) on the sample (102); A well positioning unit (138) configured to move a collection arrangement (108) relative to the optical axis (O) of the objective lens (114), the collection arrangement including at least one well (106) disposed below the sample (102), wherein the well (106) is configured to capture the separated material (104); and The controller (140) is configured to control the hole positioning unit (138) to move the collection arrangement (108) based on the contour data, such that the center (302) of the opening of the hole (106) is positioned below the segregated material (104).

2. The laser micro-cutting system (100) according to claim 1, wherein the controller (140) is configured to control the cutting unit (134) to cut the sample (102) along the contour (304) after the hole (106) is positioned.

3. The laser micro-cutting system (100) according to claim 1 or 2, wherein the controller (140) is configured to determine the sample (102) region surrounded by the contour (304) based on the contour data, and control the hole positioning unit (138) to move the collection arrangement (108) so that the center (302) of the opening of the hole (106) is positioned below the sample (102) region surrounded by the contour (304).

4. The laser micro-cutting system (100) according to any one of the preceding claims, wherein the controller (140) is configured to determine the center of the contour (304) based on the contour data and control the hole positioning unit (138) to move the collecting arrangement (108) so that the center (302) of the opening of the hole (106) is arranged below the center of the contour (304).

5. The laser micro-cutting system (100) according to any one of the preceding claims includes a sample positioning unit (136) configured to move a sample (102) relative to the optical axis (O) of an objective lens (114).

6. The laser micro-cutting system (100) according to claim 5, wherein the controller (140) is configured to control the sample positioning unit (136) to move the sample (102) based on contour data.

7. The laser micro-cutting system (100) according to any one of the preceding claims, wherein the cutting unit includes a scanning unit (128) configured to move and manipulate a beam within the field of view (300) of the objective lens (114).

8. The laser micro-cutting system (100) according to claim 7, wherein the scanning unit (128) includes two prisms (130) rotatably arranged between the laser source (126) and the objective lens (114) about the optical axis (O').

9. The laser micro-cutting system (100) according to claim 7 or 8, wherein the laser source (126) comprises at least one pulsed laser.

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

11. The laser micro-cutting system (100) according to any one of the preceding claims, wherein the controller (140) is configured to receive contour data via at least one of a data storage device and a computer network.

12. The laser micro-cutting system (100) according to any one of the preceding claims, wherein the controller (140) is configured to generate contour data based on images captured by the microscope (110).

13. The laser micro-cutting system (100) according to any one of the preceding claims, wherein the controller (140) is configured to generate contour data using machine learning.

14. A laser micro-cutting method, comprising the following steps: a) Provide profile data relating to the profile (304) of the precipitate (104) surrounding the sample (102) to be separated from the sample (102); b) Provide a collection arrangement (108) including at least one pore (106) disposed below the sample (102); c) Based on the contour data, locate the collection arrangement (108) so that the center (302) of the opening of the hole (106) is located below the segregated material (104); d) Separating the segregated material (104) from the sample (102) by guiding the manipulation beam onto the sample (102) according to the contour data; and e) Use the pores (106) of the collection arrangement (108) to capture the segregated material (104).

15. The method of claim 14, wherein the profile data includes at least two profiles (304) on the sample (102), the collection arrangement (108) includes at least two pores (106), and steps c) to e) are repeated sequentially for each profile (304) on the sample (102) and the corresponding segregated material (104) is captured using the different pores (106) of the collection arrangement (108).

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