Selecting mechanism for cell sorting device and cell sorting device
By designing the clamping unit and selecting the moving components in the cell sorting device, the problem of loosening and falling off during movement is solved, and more efficient and accurate cell sorting is achieved.
Patent Information
- Application Number
- CN202411926503.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-25
- Publication Date
- 2025-03-21
AI Technical Summary
In existing cell sorting devices, the aspiration and placement parts are prone to loosening during movement and fall off, affecting the efficiency of cell sorting.
A selection mechanism for a cell sorting device is designed, including a clamping unit, a receptacle and a selection moving assembly. The clamping unit clamps the suction and draining member, the receiving member accommodates the clamping unit, and the selected moving assembly is moved by driving the receiving member to accurately move the suction and draining member to a preset position.
Through the clamping of the clamping unit and the driving of the selected moving components, the loosening and falling of the suction and draining parts are effectively avoided, and the sorting efficiency and accuracy of the cell sorting device are improved.
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Figure CN119662375A_ABST
Abstract
Description
Technical Field
[0001] The present application relates to the field of cell sorting, and in particular to a selection mechanism for a cell sorting device and a cell sorting device. Background Art
[0002] With the development of biomedical field, cell sorting technology has emerged. It separates and processes a specific cell subpopulation from a mixed cell sample according to the characteristics of the cells, so as to realize the functional analysis of specific cells, especially the sorting and extraction of single cells.
[0003] In the related art, when cells are sorted and extracted by micromanipulation, the cell sorting is achieved by moving the suction and release member. However, when the suction and release member moves directly, there is a problem of falling and being damaged, which affects the efficiency of cell sorting. Summary of the invention
[0004] Based on this, it is necessary to provide a selection mechanism and a cell sorting device for a cell sorting device to address the above problems, so as to ensure the long-term normal use of the suction and release parts and improve the cell sorting efficiency.
[0005] The first aspect of the present application provides a selection mechanism for a cell sorting device, which includes: a clamping unit for clamping a suction and release member; a receiving member for receiving the clamping unit; and a selection moving component, which is connected to the receiving member and can drive the receiving member to move so that the suction and release member moves to a preset position.
[0006] The suction and placement piece is clamped and fixed by a clamping unit, the clamping unit is accommodated by a receiving piece, and the receiving piece is driven to move by a selection moving component, so that the suction and placement piece moves to a preset position, thereby helping to prevent the suction and placement piece from falling off due to looseness, and the selection moving component can improve the accuracy of the suction and placement piece during movement, thereby improving the sorting efficiency and sorting accuracy of the cell sorting device.
[0007] In one embodiment, the picking and moving assembly includes a first picking and moving unit, a second picking and moving unit, and a third picking and moving unit. The first picking and moving unit is connected to the second picking and moving unit, the second picking and moving unit is connected to the third picking and moving unit, and the third picking and moving unit is connected to the container. The first picking and moving unit can drive the second picking and moving unit and the third picking and moving unit to move along a third direction, the second picking and moving unit can drive the third picking and moving unit to move along a first direction, and the third picking and moving unit can drive the container to move along a second direction. The first direction, the second direction, and the third direction are perpendicular to each other. The first picking and moving unit, the second picking and moving unit, and the third picking and moving unit respectively drive the suction and release member to move along the third direction, the first direction, and the second direction, so that the suction and release member can always move to a preset position.
[0008] In one embodiment, the first selection moving unit includes a selection driving member, a selection transmission member and a selection moving member, the selection driving member can drive the selection transmission member to rotate, the selection transmission member can drive the selection moving member to move, and the selection moving member is connected to the second selection moving unit and can drive the second selection moving unit to move along a third direction. The setting of the first selection moving unit enables the suction and release member to move along the third direction, thereby improving the efficiency of cell sorting.
[0009] In one embodiment, the second selection moving unit includes a first operating member, a first selection fixing member and a first selection sliding member, the first selection sliding member is slidably connected to the first selection fixing member and the first selection sliding member is connected to the third selection moving unit, the first operating member is connected to the first selection sliding member and can drive the first selection sliding member to move along the first direction relative to the first selection fixing member. The second selection moving unit is provided so that the suction and release member can move along the first direction, thereby improving the efficiency of cell sorting.
[0010] In one embodiment, the third selection moving unit includes a second operating member, a second selection fixing member and a second selection sliding member, the second selection fixing member is connected to the first selection sliding member, the second selection sliding member is slidably connected to the second selection fixing member and the second selection sliding member is connected to the receiving member, the second operating member is connected to the second selection sliding member and can drive the second selection sliding member to move along the second direction relative to the second selection fixing member. The third selection moving unit is provided so that the suction and release member can move along the second direction, thereby improving the efficiency of cell sorting.
[0011] In one embodiment, one of the first selection fixing member and the first selection sliding member is provided with a first selection sliding block, and the other is provided with a first selection sliding rail extending along the first direction, and the first selection sliding block is slidably connected to the first selection sliding rail; one of the second selection fixing member and the second selection sliding member is provided with a second selection sliding block, and the other is provided with a second selection sliding rail extending along the second direction, and the second selection sliding block is slidably connected to the second selection sliding rail. The cooperation of the selection sliding rail and the selection sliding block facilitates the movement of the suction and placement member in the first direction and the second direction.
[0012] In one embodiment, the first operating member and the second operating member are both micrometer structures, which are helpful to improve the movement accuracy of the suction and placement member.
[0013] In one embodiment, the clamping unit comprises a clamping body, and the clamping body is detachably connected to the receiving member. The detachable connection of the clamping body to the receiving member facilitates installation and replacement of the clamping unit.
[0014] In one embodiment, the clamping body is threadedly connected to the receiving member. The threaded connection of the clamping body to the receiving member is helpful for the installation stability and reliability of the clamping unit and is helpful for the subsequent replacement or removal of the clamping unit.
[0015] The second aspect of the present application provides a cell sorting device, which includes the above-mentioned selection mechanism. The cell sorting device can automatically move the suction and release member, improve the cell sorting efficiency, and realize high-throughput cell sorting. BRIEF DESCRIPTION OF THE DRAWINGS
[0016] Figure 1 Schematic diagram of a cell sorting device in some embodiments of the present application.
[0017] Figure 2 This is an axonometric view of the cell sorting device in some embodiments of the present application after removing the housing component.
[0018] Figure 3 for Figure 2 A front view of the cell sorting apparatus with the mechanism removed to show the mechanism.
[0019] Figure 4 for Figure 3 An enlarged view of the selection mechanism in .
[0020] Figure 5 for Figure 4 Axonometric view of the selection mechanism in .
[0021] Figure 6 for Figure 4 Right view of the selection mechanism in.
[0022] Figure 7 for Figure 2 Schematic diagram of the suction and release parts in .
[0023] Figure 8 This is an axonometric view of a mounting assembly and an illumination assembly of a cell sorting device in some embodiments of the present application.
[0024] Fig. 9 This is a front full cross-sectional view of a mounting assembly and an illumination assembly of a cell sorting device in some embodiments of the present application.
[0025] Fig.10 A top cross-sectional view of a mounting assembly and a lighting assembly in some embodiments of the present application.
[0026] Fig.11 This is an axonometric view of the clamping unit of the suction and placement component in some embodiments of the present application.
[0027] Fig.12 This is a cross-sectional view of a clamping unit of a suction and placement component in some embodiments of the present application.
[0028] Fig.13 for Fig.11 Axonometric view of the first clamping drive element of the clamping unit in.
[0029] Fig.14 for Fig.11 Axonometric view of the clamping body of the clamping unit in FIG.
[0030] Fig.15 for Fig.11 A cross-sectional view of the clamping body of the clamping unit in FIG.
[0031] Fig.16 for Fig.11 Axonometric view of the second clamping drive element of the clamping unit in.
[0032] Fig.17 for Figure 8 A top view of a receiving piece for receiving a clamping unit.
[0033] Fig.18 for Figure 8 A sectional view of a receiving piece for receiving a clamping unit.
[0034] Fig.19 It is an axonometric view of the loading mechanism in some embodiments of the present application.
[0035] Fig. 20 for Fig.19 Front view of the loading mechanism in.
[0036] Fig.21 for Fig.19 Axonometric view of the mounting assembly in the mounting mechanism.
[0037] Fig. 22 for Fig.19 A front view of the first carrier in the carrier mechanism.
[0038] Fig.23 for Fig.19 An axonometric view of the second carrier and the first carrier moving unit in the carrier mechanism.
[0039] Fig.24 for Fig.19 Axonometric view of the third carrier and the second carrier moving unit in the carrier mechanism.
[0040] Fig.25 This is an axonometric view of a storage unit of a cell sorting device in some embodiments of the present application.
[0041] Fig.26 for Fig.25 Axonometric view of the reaction tube in the storage unit.
[0042] Fig. 27 This is an axonometric diagram of an imaging mechanism of a cell sorting device in some embodiments of the present application.
[0043] Fig.28 Schematic diagram of imaging of the imaging mechanism of the cell sorting device in some embodiments of the present application.
[0044] Fig.29 This is a schematic diagram of the control mechanism of the cell sorting device in some embodiments of the present application.
[0045] Fig.30 Schematic diagram of a biological culture chip in some embodiments of the present application.
[0046] Fig.31 This is a schematic diagram of a receiving chamber of a biological culture chip in some embodiments of the present application.
[0047] Fig.32 This is a schematic diagram of a containing cavity of a biological culture chip in some embodiments of the present application, wherein the opening diameter of the containing cavity is smaller than the bottom diameter of the containing cavity.
[0048] Fig.33 Schematic diagram of a chip fixing component of a cell sorting device in some embodiments of the present application.
[0049] Fig.34 Schematic diagram of a pressure-applying member in some embodiments of the present application.
[0050] Fig.35 It is a cross-sectional view of the clamping unit in some embodiments of the present application, wherein the spacer, the second clamping drive component and the clamping body are integrally formed.
[0051] Fig.36 It is a top cross-sectional view of a mounting assembly in some embodiments of the present application, wherein the fixing unit includes a fixing member.
[0052] Fig.37 This is a schematic diagram of the operation of the projection mapping of the suction and placement component and the projection marking of the projection identification part of the suction and placement component in some embodiments of the present application.
[0053] Fig.38 Schematic diagram of the clamping unit and the suction and release member in some other embodiments of the present application.
[0054] Fig.39 for Fig.38 A cross-sectional view of the clamping unit and the suction and release part.
[0055] Fig.40 for Fig.38 Cross-sectional view of the clamping unit in FIG.
[0056] Fig.41 It is a partial schematic diagram of the clamping mechanism in other embodiments of the present application.
[0057] Fig.42 It is a schematic diagram of the avoidance mechanism of the suction and release member in some embodiments of the present application, wherein the imaging lighting unit is in the turned-on state.
[0058] Fig.43 It is a schematic diagram of the avoidance mechanism of the suction and release member in some embodiments of the present application, wherein the imaging lighting unit is in a closed state.
[0059] Fig.44 This is a schematic diagram of a receiving component in some embodiments of the present application.
[0060] Fig.45 for Fig.44 Exploded view of the containment component in . DETAILED DESCRIPTION
[0061] In order to make the above-mentioned purposes, features and advantages of the present application more obvious and easy to understand, the specific implementation methods of the present application are described in detail below in conjunction with the accompanying drawings. In the following description, many specific details are set forth to facilitate a full understanding of the present application. However, the present application can be implemented in many other ways different from those described herein, and those skilled in the art can make similar improvements without violating the connotation of the present application, so the present application is not limited by the specific embodiments disclosed below.
[0062] In the description of the present application, it should be understood that if the terms "center", "longitudinal", "lateral", "length", "width", "thickness", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside", "clockwise", "counterclockwise", "axial", "radial", "circumferential", etc. appear, the orientation or position relationship indicated by these terms is based on the orientation or position relationship shown in the accompanying drawings, which is only for the convenience of describing the present application and simplifying the description, and does not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation on the present application.
[0063] In addition, if the terms "first" or "second" appear, these terms are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Therefore, a feature defined as "first" or "second" may explicitly or implicitly include at least one of the features. In the description of this application, if the term "plurality" appears, the meaning of "plurality" is at least two, such as two, three, etc., unless otherwise clearly and specifically defined.
[0064] In this application, unless otherwise clearly specified and limited, if the terms "installed", "connected", "connected", "fixed" and the like appear, these terms should be understood in a broad sense. For example, it can be a fixed connection, a detachable connection, or an integrated connection; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium, it can be the internal connection of two elements or the interaction relationship between two elements, unless otherwise clearly defined. For ordinary technicians in this field, the specific meanings of the above terms in this application can be understood according to the specific circumstances.
[0065] In the present application, unless otherwise clearly specified and limited, if there is a description that a first feature is "above" or "below" a second feature, etc., or similar descriptions appear, it may mean that the first and second features are in direct contact, or that the first and second features are in indirect contact through an intermediate medium. Moreover, the first feature being "above", "above" and "above" the second feature may mean that the first feature is directly above or obliquely above the second feature, or simply means that the first feature is higher in level than the second feature. The first feature being "below", "below" and "below" the second feature may mean that the first feature is directly below or obliquely below the second feature, or simply means that the first feature is lower in level than the second feature.
[0066] It should be noted that if an element is referred to as being "fixed to" or "disposed on" another element, it may be directly on the other element or there may be a central element. If an element is considered to be "connected to" another element, it may be directly connected to the other element or there may be a central element at the same time. If any, the terms "vertical", "horizontal", "upper", "lower", "left", "right" and similar expressions used in this application are for illustrative purposes only and do not represent the only implementation method.
[0067] Cell sorting is a technique that separates cells that meet preset requirements from cells to be sorted based on their characteristics. When it is necessary to perform functional analysis on cells that meet preset requirements, such as analyzing cell culture supernatant to detect cell molecules, and detecting cell functions by cell co-culture, etc., it is necessary to obtain high-purity cells that meet preset requirements.
[0068] The cell sorting device is used to automatically select cells that meet preset conditions from the cells to be sorted, and to separate and purify the cells. It has the advantages of multi-species, high throughput, multiple sorting, short sorting cycle, and high sorting accuracy. Furthermore, compared with traditional manual sorting, sorting cells through a cell sorting device can reduce the interference of human factors, ensure the consistency of cells during the cell sorting process, accurately obtain single cells with complete morphology and high activity, improve sorting efficiency, and achieve high-throughput sorting of single cells.
[0069] The cell sorting device in some embodiments of the present application is described in detail below.
[0070] See also Figures 1 to 3 , which shows a schematic diagram of a cell sorting device 100 in some embodiments of the present invention. For the convenience of comparison and description, the definition Figure 3 The direction perpendicular to the paper surface is a first direction S1, the left-right direction is a second direction S2, and the up-down direction is a third direction S3. The first direction S1, the second direction S2 and the third direction S3 are perpendicular to each other.
[0071] See also Figure 1 and Figure 2 The main body 10 is the main frame of the cell sorting device 100, which is used to support and accommodate the main components of the cell sorting device 100. The main body 10 includes a housing component 11 and a support component 12. The housing component 11 forms a receiving space for the cell sorting device 100, and the support component 12 supports the mechanism disposed in the receiving space. Figure 2 and Figure 3 In some embodiments, the cell sorting device 100 includes a main body 10, a selection mechanism 20, a loading mechanism 30, an imaging mechanism 40, a display mechanism 50, and a control mechanism 60. The main body 10 is used to support and accommodate other mechanisms in the cell sorting device 100, forming a storage space for the selection mechanism 20, the loading mechanism 30, the imaging mechanism 40, and the control mechanism 60. The loading mechanism 30 is used to load the object to be sorted, and the object to be sorted contains cells to be sorted; the imaging mechanism 40 is used to image the cells to be sorted and obtain image information of the cells to be sorted; the display mechanism 50 is used to display the image information of the cells to be sorted obtained by the imaging mechanism 40, and the image information of the cells to be sorted is processed to select cells that meet the preset requirements in the object to be sorted; the selection mechanism 20 is used to absorb and recover the cells that meet the preset requirements in the object to be sorted, so as to achieve the absorption and recovery of the cells that meet the preset requirements and complete the cell sorting.
[0072] The shell assembly 11 is mainly used to form a storage space for the internal mechanism of the cell sorting device 100, prevent external light, foreign matter, etc. from entering the storage space, provide a sterile environment for the cell sorting process, prevent cell contamination, and ensure cell activity and normal cell growth.
[0073] The housing assembly 11 is a hollow structure as a whole, and is used to accommodate the selection mechanism 20, the loading mechanism 30, the imaging mechanism 40 and the control mechanism 60. Generally, the housing assembly 11 is made of a hard material, such as a metal plate, glass, hard plastic, etc. The specific material and light transmittance of the housing assembly 11 are set according to the location of the housing and the required function. For example, the housing that plays an overall protective role can be made of a metal plate, and the housing that prevents light from entering can be made of a light-shielding material.
[0074] In some embodiments, see Figure 1 The housing assembly 11 includes a first housing 111 and a second housing 112. The first housing 111 can move along the second direction S2 relative to the second housing 112. By moving the first housing 111, the object to be sorted can be placed on the loading mechanism 30 and the object to be sorted can be taken out of the cell sorting device 100.
[0075] The first housing 111 is formed of a light-transmitting material, and when in use, the operation of the cell sorting device 100 is observed through the first housing 111. In order to avoid interference of external light on the image information of the cells to be sorted obtained by the cell sorting device 100, and to observe the internal operation state of the cell sorting device 100, the first housing 111 is made of glass or plastic material with low light transmittance, such as an acrylic plate.
[0076] The second shell 112 is mainly used to protect the internal components of the cell sorting device 100, and is made of an opaque metal plate as a whole. In some embodiments, the second shell 112 in contact with the first shell 111 is made of plastic material. On the one hand, it avoids damage to the first shell 111 by the second shell 112 when the first shell 111 is opened, and on the other hand, it avoids collision damage to the to-be-sorted parts and the user when taking them out. Furthermore, the second shell 112 is also provided with heat dissipation holes for heat dissipation of the cell sorting device 100. The heat dissipation holes dissipate the heat generated during the operation of the cell sorting device 100 to avoid the heat affecting the activity of the cells to be sorted, which is beneficial to the long-term use of the cell sorting device 100 and realizes high-throughput sorting of cells.
[0077] See again Figure 2 and Figure 3 The support assembly 12 is used to support the main components of the cell sorting device 100, and includes a base 121 and a support seat 122. The base 121 is used to carry the main components of the cell sorting device 100. The support seat 122 is connected to the base 121 along the third direction S3, and is used to connect and support the main components of the cell sorting device 100.
[0078] The base 121 includes a bottom plate 1211 and a support leg 1212, and the support leg 1212 is connected to the bottom plate 1211 along the third direction S3. The relative position of the support leg 1212 relative to the floor 1211 in the third direction S3 is adjusted to adjust the levelness of the entire cell sorting device 100, so that the cell sorting device 100 can be applied to different desktops, different platforms, etc. In addition, the support leg 1212 also has the functions of shockproof and anti-slip.
[0079] The support seat 122 includes a support plate 1221 and a rib plate 1222. The support plate 1221 is connected to the bottom plate 1211 along the third direction S3. In order to obtain as large an accommodation space as possible, the support plate 1221 is arranged on one side of the bottom plate 1211 in the first direction S1. The arrangement of the support plate 1221 provides connection and support for the main components of the cell sorting device 100 in the third direction S3.
[0080] The ribs 1222 are used to provide auxiliary support for the support plate 1221, and are in the shape of a right triangle, wherein one right angle extends along the third direction S3 and is connected to the support plate 1221 along the first direction S1, and the other right angle extends along the first direction S1 and is connected to the bottom plate 1211 along the third direction S3. In some embodiments, the support seat 122 includes a preset number of ribs 1222. In one embodiment, two ribs 1222 are relatively arranged on both sides of the bottom plate 1211 in the second direction S2. The arrangement of the ribs 1222 makes the overall frame of the cell sorting device 100 more stable.
[0081] In order to facilitate the assembly and replacement of the support plate 1221, the bottom plate 1211 and the rib plate 1222, the support plate 1221, the bottom plate 1211 and the rib plate 1222 are all detachably connected, such as by fasteners. Generally, detachable connections include but are not limited to threaded connections, screw connections, snap-on connections, clamp connections, flange connections, pin connections and socket connections. It should be noted that the connection method between the support plate 1221, the bottom plate 1211 and the rib plate 1222 is not limited, such as the rib plate 1222 can be fixedly connected to the bottom plate 1211 and the support plate 1221 by welding.
[0082] See also Figures 4 to 6 , shows the selection mechanism in some embodiments of the present application. The selection mechanism 20 includes a suction and release member 21, a mounting assembly 22, a selection movement assembly 23, a selection lighting unit 24, a cleaning assembly 25 and a recovery assembly 26. The selection mechanism 20 is used to select cells that meet preset requirements from the objects to be sorted. The automated setting of the selection mechanism 20 realizes automatic absorption of cells, improves the efficiency of cell sorting, avoids damage to cells by manual operation, is conducive to high-throughput cell sorting, and further can realize single cell sorting.
[0083] Combination Figure 7, shows the suction and release parts in some embodiments of the present application. The suction and release part 21 is used to absorb and release cells that meet preset requirements. The suction and release part 21 is provided with a hollow pipe 211 to enable cells to enter the suction and release part 21, and the sucked cells can be stored in the suction and release part 21. The size of at least part of the suction and release part 21 is gradually reduced along the radial direction of the suction and release part 21 to form a suction and release port 212 at one end of the suction and release part 21, and the size of the suction and release port 212 matches the size of the cells to be sucked. When sucking, the cells enter the hollow pipe 211 through the suction and release port 212, and when releasing, the cells leave the suction and release port 212 through the hollow pipe 211. The design of the suction and release port 212 facilitates accurate and effective absorption of cells, thereby improving the sorting efficiency of the cell sorting device 100. The material and size of the suction and release part 21 can be selected according to the size of the cells to be sorted, such as the suction and release part 21 uses a 1 mm glass capillary.
[0084] See also Figures 8 to 10 , shows the mounting assembly and lighting assembly of the cell sorting device in some embodiments of the present application. The mounting assembly 22 is used for mounting and fixing the suction and release member 21 to prevent the suction and release member 21 from falling off during use. Accordingly, the mounting assembly 22 can also be used for replacing the suction and release member 21. The mounting assembly 22 includes a clamping unit 221, a fixing unit 222 and a receiving member 223.
[0085] See also Fig.11 and Fig.12 , shows a clamping unit of the suction and release member in some embodiments of the present application. The clamping unit 221 is used to clamp and release the suction and release member 21, and is connected to the suction and release member 21 along the third direction S3. Figure 7 One end of the suction and release member 21 is used for suction and release of cells to be sorted, and is formed with a suction and release port 212. The other end of the suction and release member 21 is clamped or released by a clamping unit 221. Through the clamping of the clamping unit 221, the suction and release member 21 can be stably used, and through the release of the clamping unit 221, the suction and release member 21 can be replaced. The setting of the clamping unit 221 realizes the fixing or release of the suction and release member 21 without damaging the suction and release member 21.
[0086] Furthermore, the clamping unit 221 includes at least one clamping member that moves between a clamping position and a release position, and the clamping member is used to clamp the other end of the suction and release member. In the clamping position, the clamping member clamps the other end of the suction and release member 21 to achieve the installation and fixation of the suction and release member 21; in the release position, the clamping member releases the other end of the suction and release member 21 to complete the recovery of the suction and release member 21.
[0087] In certain embodiments, the clamping unit 221 comprises a clamping body 2211 and a first clamping driver 2212. The first clamping driver 2212 is used to drive the clamping member to move between the clamping position and the release position. The clamping body 2211 is used to support the first clamping driver 2212. The first clamping driver 2212 is also provided with an opening for passing through the suction and release member 21, and the opening diameter of at least part of the first clamping driver 2212 is slightly larger than the outer diameter of the suction and release member 21, so that the suction and release member 21 passes through the first clamping driver 2212.
[0088] In some embodiments, the clamping body 2211 and the first clamping drive member 2212 are detachably connected to facilitate the installation and replacement of the suction and release member 21. Specifically, the clamping body 2211 and the first clamping drive member 2212 can be threadedly connected, the clamping body 2211 is provided with an internal thread, and the first clamping drive member 2212 is provided with an external thread, and the connection between the first clamping drive member 2212 and the clamping body 2211 is achieved by connecting the internal thread and the external thread. The threaded connection is convenient and reliable, and is convenient for the installation and removal of the first clamping drive member 2212.
[0089] In other embodiments, there may be an interference fit between the clamping body 2211 and the first clamping drive member 2212. The interference fit improves the stability of the assembly of the clamping body 2211 and the first clamping drive member 2212, and facilitates the clamping member to fix the suction and release member 21. The outer diameter of at least part of the first clamping drive member 2212 is not less than the inner diameter of the clamping body 2211, so as to achieve the interference fit between the first clamping drive member 2212 and the clamping body 2211.
[0090] In some embodiments, at least part of the first clamping driver 2212 can be elastically deformed. When the first clamping driver 2212 is connected to the clamping body 2211, the first clamping driver 2212 moves from the release position to the clamping position, and the outer wall of the first clamping driver 2212 contacts and squeezes the inner wall of the clamping body 2211, and the first clamping driver 2212 is elastically deformed, so that the inner wall of the first clamping driver 2212 contacts and squeezes the outer wall of the suction and release member 21, thereby clamping and fixing the suction and release member 21 in the clamping unit 221. In this embodiment, the first clamping driver 2212 is configured as a clamping member.
[0091] In other embodiments, at least part of the inner wall size of the first clamping driver 2212 can be changed, such as the inner wall of the first clamping driver 2212 is set as a cam surface. When the first clamping driver 2212 is connected to the clamping body 2211, the first clamping driver 2212 moves from the release position to the clamping position, and the inner wall size of the first clamping driver 2212 changes, so that the inner wall of the first clamping driver 2212 contacts and squeezes the outer wall of the suction and release member 21, thereby fixing the suction and release member 21 in the clamping unit 221. In this embodiment, the first clamping driver 2212 is configured as a clamping member.
[0092] In some embodiments, the clamping unit 221 includes a first clamping drive member 2212, a second clamping drive member 2213 and a clamping body 2211. The second clamping drive member 2213 is used for the insertion of the suction and release member 21, and at least part of the inner diameter of the second clamping drive member 2213 is slightly larger than the outer diameter of the suction and release member 21, so as to accommodate the suction and release member 21. The second clamping drive member 2213 is arranged between the first clamping drive member 2212 and the clamping body 2211 along the third direction S3. The arrangement of the first clamping drive member 2212 and the second clamping drive member 2213 allows at least two parts of the suction and release member 21 to be accommodated, thereby improving the installation stability of the suction and release member 21.
[0093] In some embodiments, the second clamping drive member 2213 is fixedly connected to the clamping body 2211, such as the second clamping drive member 2213 is welded to the clamping body 2211 or the second clamping drive member 2213 and the clamping body 2211 are integrally formed. In other embodiments, the second clamping drive member 2213 and the clamping body 2211 can be combined in a gap combination, an interference combination, an elastic combination, and a surface combination. The second clamping drive member 2213 and the clamping body 2211 can also be threadedly connected. It can be understood that as long as the second clamping drive member 2213 can be accommodated and placed, the connection method of the second clamping drive member 2213 and the clamping body 2211 is not limited.
[0094] In some embodiments, one end of the second clamping driver 2213 in the third direction S3 is accommodated in the first clamping driver 2212, and at least a portion of the inner diameter of the first clamping driver 2212 is slightly larger than the outer diameter of the second clamping driver 2213. The other end of the second clamping driver 2213 in the third direction S3 is accommodated in the clamping body 2211, and at least a portion of the inner diameter of the clamping body 2211 is slightly larger than the outer diameter of the second clamping driver 2213. At least two portions of the second clamping driver 2213 are accommodated and fixed, which is beneficial to the stability of the installation of the second clamping driver 2213.
[0095] In some embodiments, at least part of the second clamping drive member 2213 can be elastically deformed. When the second clamping drive member 2213 is connected to the first clamping drive member 2212, the outer wall of the second clamping drive member 2213 contacts and squeezes the inner wall of the first clamping drive member 2212, so that the second clamping drive member 2213 is elastically deformed, and the inner wall of the second clamping drive member 2213 contacts and squeezes the outer wall of the suction and release member 21, so that the suction and release member 21 is fixed in the second clamping drive member 2213. In this embodiment, the second clamping drive member is configured as a clamping member.
[0096] In some embodiments, at least part of the inner wall size of the second clamping drive member 2213 can be changed, such as the inner wall of the second clamping drive member 2213 is set as a cam surface. When the second clamping drive member 2213 is connected to the first clamping drive member 2212, the inner wall size of the second clamping drive member 2213 changes, so that the inner wall of the second clamping drive member 2213 is in contact with the outer wall of the suction and release member 21 to achieve the fixation of the suction and release member 21 in the clamping unit 221. In this embodiment, the second clamping drive member 2213 is configured as a clamping member.
[0097] In some embodiments, the clamping unit 221 includes a first clamping driver 2212, a clamping body 2211 and a first elastic member 2214. The first elastic member 2214 is configured between the first clamping driver 2212 and the clamping body 2211 in the third direction S3. The inner diameter of the first elastic member 2214 in the natural state is slightly larger than the outer diameter of the suction and release member 21. In this embodiment, the first elastic member 2214 is configured as a clamping member. The elastic deformation of the first elastic member 2214 in radial direction is changed by adjusting the displacement between the first clamping driver 2212 and the clamping body 2211, so as to realize that the first elastic member 2214 clamps or releases the suction and release member 21. Specifically, the first clamping driver 2212 is provided with an external thread, and the clamping body 2211 is provided with an internal thread, and the elastic deformation of the first elastic member 2214 in radial direction is changed by adjusting the tightening or loosening of the external thread and the internal thread, so as to realize that the first elastic member 2214 clamps or releases the suction and release member 21.
[0098] In some embodiments, the clamping unit 221 includes a first clamping driver 2212, a clamping body 2211, a second clamping driver 2213 and a first elastic member 2214. The first elastic member 2214 is disposed between the first clamping driver 2212 and the second clamping driver 2213 along the third direction S3. When the clamping unit 221 is installed, the elastic deformation of the first elastic member 2214 in radial direction is changed by adjusting the displacement between the first clamping driver 2212 and the second clamping driver 2213. The first elastic member 2214 is configured as a first clamping member. Specifically, the first clamping driver 2212 and the second clamping driver 2213 co-extrudes the first elastic member 2214 on the opposite end faces in the third direction S3, so that the first elastic member 2214 is deformed in radial direction, and the clamping and fixing of the suction and release member 21 is realized.
[0099] In this embodiment, the clamping body 2211 or the second clamping drive 2213 is configured as a first hollow structure for accommodating the suction and release member 21, and the first clamping drive 2212 is configured as a second hollow structure for accommodating the suction and release member 21. The combined action of the first hollow structure, the second hollow structure and the first clamping member 2214 supports and clamps the suction and release member 21.
[0100] Furthermore, the clamping unit 221 also includes a spacer 2215 disposed between the second clamping driving member 2213 and the first elastic member 2214 in the third direction S3, and the spacer 2215 is used for the insertion of the suction and release member 21, that is, the inner diameter of the spacer 2215 is slightly larger than the outer diameter of the suction and release member 21. The spacer 2215 is provided so that at least three parts of the suction and release member 21 can be accommodated, so that the second clamping driving member 2213 can be adapted to the installation of different suction and release members 21.
[0101] In some embodiments, see Fig.35 The spacer 2215, the second clamping driving member 2213 and the clamping body 2211 are integrally formed. By adjusting the displacement between the first clamping driving member 2212 and the clamping body, the displacement between the spacer 2215 and the first elastic member 2214 is changed, and the elastic deformation of the first elastic member 2214 in the radial direction is changed, so that the first clamping member 2214 can clamp or release the suction and release member 21.
[0102] Further, the clamping unit 221 is provided with a first elastic member 2214 and a second elastic member 2216 at intervals along the third direction S3. The first elastic member 2214 and the second elastic member 2214 are arranged at both ends of the spacer 2215 along the third direction S3. Specifically, the first elastic member 2214 is arranged to be located between the first clamping driver 2212 and the spacer 2215, and the second elastic member 2216 is arranged to be located between the second clamping driver 2213 and the spacer 2215. The elastic deformation of the first elastic member 2214 in the radial direction is changed by adjusting the displacement between the first clamping driver 2212 and the spacer 2215, and the elastic deformation of the second elastic member 2216 in the radial direction is changed by adjusting the displacement between the second clamping driver 2213 and the spacer 2215, so as to achieve the first elastic member 2214 and the second elastic member 2216 clamping or releasing the suction and release member 21. In this embodiment, the first elastic member 2214 is configured as a first clamping member, and the second elastic member 2216 is configured as a second clamping member. The first elastic member 2214 and the second elastic member 2216 are provided so that at least two parts of the suction and release member 21 are clamped, thereby ensuring the installation stability of the suction and release member 21.
[0103] Specifically, the first clamping drive member 2212 is provided with an external thread, and the clamping body 2211 is provided with an internal thread. The elastic deformation of the first clamping member 2214 and the second clamping member 2216 in the radial direction is changed by adjusting the tightening or loosening of the external thread and the internal thread, so as to realize the clamping or release of the suction and release member by the first clamping member 2214 and the second clamping member 2216.
[0104] The second clamping drive member 2213 is configured to accommodate the first hollow structure of the suction and release member 21, the first clamping drive member 2212 is configured to accommodate the second hollow structure of the suction and release member 21, and the spacer 2215 is configured to accommodate the third hollow structure of the suction and release member 21. The first hollow structure, the second hollow structure, the third hollow structure, the first clamping member 2214 and the second clamping member 2216 work together to support and clamp the suction and release member 21.
[0105] For specific embodiments, see Fig.13, shows the first clamping drive member of the clamping unit in some embodiments of the present application. The first clamping drive member 2212 includes a first clamping drive portion 2212a, an operating portion 2212b and a second clamping drive portion 2212c. The first clamping drive portion 2212a is provided with a through hole for accommodating at least part of the second clamping drive member 2213, the first elastic member 2214, the spacer 2215 and the second elastic member 2216. The first clamping drive portion 2212a is provided with an external thread, and the first clamping drive member 2212 is connected to the internal thread of the clamping body 2211 through the external thread of the first clamping drive portion 2212a. The inner diameter of the first clamping drive portion 2212a is slightly larger than the outer diameter of at least part of the second clamping drive member 2213, and the outer diameter of at least part of the first clamping drive portion 2212a is slightly larger than the inner diameter of at least part of the clamping body 2211. The second clamping driving portion 2212 c is used to accommodate the suction and placement member 21 , and the inner diameter of the second clamping driving portion 2212 c is slightly larger than the outer diameter of the suction and placement member 21 .
[0106] The operating portion 2212b is radially convexly arranged on the first clamping drive portion 2212a and the second clamping drive portion 2212c, and is configured between the first clamping drive portion 2212a and the second clamping drive portion 2212c. The inner diameter of the operating portion 2212b is slightly larger than the outer diameter of the suction and release member 21. The operating portion 2212b is used to cooperate with external equipment, and the connection between the first clamping drive member 2212 and the clamping body 2211 is realized by the operating portion 2212b. Specifically, the outer peripheral surface of the operating portion 2212b includes an arc portion and a plane portion that are relatively arranged, and the plane portion is used to cooperate with external equipment such as a wrench, so as to realize that the external thread of the first clamping drive member 2212 is connected to the internal thread of the clamping body 2211, and the clamping of the suction and release member 21 is realized.
[0107] In some embodiments, see Fig.14 and Fig.15, shows the clamping body of the clamping unit in some embodiments of the present application. The clamping body 2211 includes a first clamping body part 2211a and a second clamping body part 2211b connected to the first clamping body part 2211a. The first clamping body part 2211a is provided to realize the connection between the hollow pipe 211 of the suction and release member 21 and the recovery component 26, so as to realize the cleaning of the suction and release member 21 and the absorption and release of cells that meet the preset requirements. The first clamping body part 2211a is provided with a first accommodating chamber 2211c, which is used to accommodate at least part of the second clamping driving member 2213 on the one hand, to realize the communication between the first accommodating chamber 2211c and the hollow pipe 211 of the suction and release member 21, and on the other hand, to connect with at least part of the selection lighting unit 24, so as to realize the lighting of the hollow pipe 211 of the suction and release member 21. Specifically, the first accommodating chamber 2211c includes a joint part, which is stepped and is used to connect with the selection lighting unit 24 to realize the lighting of the suction and release member 21. The central axis of the combination portion coincides with the central axis of the suction and release member 21 to ensure the lighting effect of the selection lighting unit 24 on the suction and release member 21. It can be understood that as long as the connection with the selection lighting unit 24 can be achieved, the shape of the combination portion can be adjusted as needed and is not limited to a step shape. Further, the first clamping body portion 2211a is provided with a connecting hole in the radial direction, the connecting hole is connected to the first accommodating cavity 2211c, and the connecting hole is used for connection with the recovery component 26.
[0108] The second clamping body 2211b is provided with a second accommodating cavity 2211d in communication with the first accommodating cavity 2211c, for connecting the first clamping drive 2212 and accommodating the second clamping drive 2213. The first clamping drive 2212 is configured to at least partially extend into the second accommodating cavity 2211d, so that at least part of the first clamping drive 2212 can be accommodated and connected to the clamping body 2211. The first clamping drive 2212 is configured to at least partially extend and protrude from the second accommodating cavity 2211d to form an operating portion 2212b that is convenient for operating the first clamping drive 2212 to move. The surface of at least part of the second clamping body 2211b gradually changes along the third direction S3 to form a tapered surface. This arrangement facilitates the fixing and adjustment of the clamping unit 221. The inner diameter of at least part of the second clamping body 2211b is slightly larger than the outer diameter of the first clamping drive part 2212a. Specifically, the second clamping body 2211b is provided with an internal thread, and the second clamping drive part 2212a is provided with an external thread, and the internal thread is connected to the external thread.
[0109] In some embodiments, see Fig.16, shows the second clamping drive member of the clamping unit in some embodiments of the present application. The second clamping drive member 2213 is a hollow structure, which is used for the suction and release member 21 to pass through, so as to achieve the installation and accommodation of the suction and release member 21. The second clamping drive member 2213 includes a fourth clamping drive portion 2213a, a second flange portion 2213b and a fifth clamping drive portion 2213c. The inner diameters of the fourth clamping drive portion 2213a, the second flange portion 2213b and the fifth clamping drive portion 2213c are slightly larger than the outer diameter of the suction and release member 21, so as to achieve the penetration and accommodation of the suction and release member 21. Combined with Fig.12 and Fig.15 At least part of the fourth clamping driving part 2213a is accommodated in the first clamping main body part 2211a along the third direction S3 to realize the combination of the second clamping driving member 2213 and the clamping main body 2211. The outer diameter of the fourth clamping driving part 2213a is slightly smaller than the inner diameter of at least part of the first clamping main body part 2211a. Fig.12 and Fig.13 At least part of the fifth clamping driving part 2213c is accommodated in the first clamping driving part 2212a to realize the combination of the second clamping driving member 2213 and the first clamping driving member 2212. The outer diameter of the fifth clamping driving part 2213c is slightly smaller than the inner diameter of the first clamping driving part 2212a.
[0110] The second flange portion 2213b is protruded from the fourth clamping driving portion 2213a and the fifth clamping driving portion 2213c in the third direction S3, and is disposed between the fourth clamping driving portion 2213a and the fifth clamping driving portion 2213c. Fig.12 and Fig.15 , the clamping unit 221 also includes a seal 2217 for fixing the second clamping drive member 2213. The seal 2217 is configured between the second flange portion 2213b and the first clamping body portion 2211a in the third direction S3, and the shape and size of the inner diameter of the seal 2217 match the shape and size of the outer diameter of the fourth clamping drive portion 2213a. In this embodiment, the seal 2217 is accommodated in the second accommodating chamber 2211d and supported by the second flange portion 2213b. When the clamping unit 221 is installed, the seal 2217 blocks the communication between the first accommodating chamber 2211c and the second accommodating chamber 2211d, so that the suction and release member 21 directly passes through the suction and release member 21 for the cells to be sorted after passing through the first accommodating chamber 2211c, without passing through the second accommodating chamber 2211d, so as to avoid the second accommodating chamber 2211d affecting the suction and release member 21 for the cells to be sorted. In other embodiments, the sealing member 2217 may also be accommodated in the first accommodating cavity 2211c to prevent the first accommodating cavity 2211c from communicating with the second accommodating cavity 2211d.
[0111] The first elastic member 2214, the second elastic member 2216 and the sealing member 2217 are all annular elastic elements, such as O-rings. It should be noted that the shapes, sizes, quantities and types of the first elastic member 2214, the second elastic member 2216 and the sealing member 2217 are not limited.
[0112] Furthermore, in order to facilitate the installation and replacement of the suction and release member 21 and avoid damage to the suction and release member 21 during installation, the central axes of the first clamping drive member 2212, the first elastic member 2214, the spacer 2215, the second elastic member 2216 and the second clamping drive member 2213 in the third direction S3 all coincide with the central axis of the suction and release member 21 in the third direction S3.
[0113] When the clamping unit 221 is installed, the first elastic member 2214, the spacer 2215, the second elastic member 2216 and the second clamping drive member 2213 are placed into the first clamping drive member 2212 in sequence along the third direction S3, and one end of the second clamping drive member 2213 away from the second elastic member 2216 is accommodated in the first accommodating cavity 2211c of the first clamping main body 2211a along the third direction S3, and the other end abutting the second elastic member 2216 is accommodated in the accommodating cavity of the first clamping drive member 2212 along the third direction S3.
[0114] When the suction and release member 21 is installed, the suction and release member 21 passes through the through holes formed by the first clamping drive member 2212, the first clamping member 2214, the spacer 2215, the second clamping member 2216 and the second clamping drive member 2213 in sequence along the third direction S3 until the end face of the suction and release member 21 is flush with the end face of the second clamping drive member 2213 accommodated in the clamping body 2211. Then, the first clamping drive member 2212 is tightened to cause the first clamping member 2214 and the second clamping member 2216 to undergo radial elastic deformation to fix the suction and release member 21, and to cause the sealing member 2217 to undergo radial deformation to fix the second clamping drive member 2213 and block the first accommodating cavity 2211c and the second accommodating cavity 2211d. When the suction and release member 21 is recovered or replaced, the first clamping driving member 2212 is released to restore the first clamping member 2214 and the second clamping member 2216 to their original state, and then the suction and release member 21 is taken out in the direction opposite to the installation direction.
[0115] In some embodiments, reference Fig.11, the first clamping driver 2212 is provided with a clamping mark 2212d, and the clamping mark 2212d is arranged on the surface of the first clamping driver 2212, and the clamping mark 2212d is used to rotate the first clamping driver 2212 to a preset position to clamp the suction and release member 21, and the preset position is the clamping position. Since the suction and release member adopts the design of a glass capillary, the clamping mark 2212d is arranged to effectively avoid the damage of the glass capillary caused by over-tightening the first clamping driver 2212. In other embodiments, the clamping mark 2212d corresponds to the clamping body 2211 or a mark located on other parts, and when the two are aligned, it is the clamping position.
[0116] See again Figures 8 to 10 In some embodiments, the fixing unit 222 is arranged along the radial direction of the clamping unit 221, and is used to fix and adjust the clamping unit 221. The fixing unit 222 includes a first fixing member 2221 and a second fixing member 2222. The first fixing member 2221 and the second fixing member 2222 are spaced apart along the circumference of the clamping unit 221 and extend along the radial direction of the clamping unit 221. The arrangement of the first fixing member 2221 and the second fixing member 2222 realizes the fixing of at least two parts of the clamping unit 221.
[0117] Combination Fig.12 and Fig.15 The first fixing member 2221 and the second fixing member 2222 are arranged at intervals along the circumferential direction of the second clamping body portion 2211b of the clamping body 2211. Specifically, when the clamping unit 221 is fixed, one end of the first fixing member 2221 in the radial direction of the second clamping body portion 2211b abuts against the conical surface of the fifth clamping driving portion 2213c, and one end of the second fixing member 2222 in the radial direction of the fifth clamping driving portion 2213c also abuts against the conical surface of the fifth clamping driving portion 2213c.
[0118] Further, the first fixing member 2221 and the second fixing member 2222 are fine-tuning members, both of which are set to micrometer structures, which are used for fixing the clamping unit 221 and fine-tuning the clamping unit 221 so that the suction and release member 21 can be in a preset position. Usually, the micrometer structure includes a screw, a fixed sleeve, a differential cylinder and a knob. When fixing, tighten the first fixing member 2221 and the second fixing member 2222 to achieve the fixing of the clamping unit 221. When fine-tuning, rotate the knob and differential cylinder of the first fixing member 2221 and the knob and differential cylinder of the second fixing member 2222 until the suction and release member 21 is in a preset position.
[0119] In some embodiments, the fixing unit 222 further includes a third fixing member 2223. The third fixing member 2223 is arranged along the circumference of the clamping unit 221 and extends along the radial direction of the clamping unit 221. The arrangement of the third fixing member 2223 realizes the support and fixation of the clamping unit 221 of at least three parts.
[0120] In some embodiments, the fixing unit further includes an elastic biasing element 2224 for biasing the third fixing member 2223, one end of the elastic biasing element 2224 is connected to the third fixing member 2223, and the third fixing member 2223 and the elastic biasing element 2224 can be selected from a combination of a spring seat and a spring. The third fixing member 2223 abuts against the clamping unit 221, so that the biasing force of the elastic biasing element 2224 is overcome to move the first fixing member 2221 or the second fixing member 2222, thereby achieving position adjustment of the clamping unit 221. When fixed, the third fixing member 2223 and the elastic biasing element 2224 can provide elastic support for the clamping unit 221 to ensure the installation stability of the clamping unit 221. Further, the third fixing member 2223 is arranged along the first direction S1, and the first fixing member 2221 and the second fixing member 2222 are symmetrically arranged on both sides of the third fixing member 2223 in the first direction S1. It can be understood that as long as the suction and release member 21 can be fixed, the number and type of the fixing units 222 can be set according to actual needs and are not limited here.
[0121] See also Figure 17 to Figure 18 , Fig.17 and Fig.18 Schematic diagram of the container in some embodiments of the present application is shown. Figures 8 to 10 The receiving member 223 is a hollow structure for receiving at least part of the clamping unit 221. The two end surfaces of the receiving member 223 in the third direction S3 are respectively provided with a first opening 2231 and a second opening 2232. The clamping unit 221 passes through the first opening 2231 and the second opening 2232 in sequence along the third direction S3 to place the clamping unit 221. The clamping unit 221 passes through the second opening 2232 and the first opening 2231 in sequence to take out the clamping unit 221. The size of the first opening 2231 is larger than that of the clamping unit 221. The position of the clamping unit 221 relative to the first opening 2231 can be adjusted by moving the first fixing member 2221, and the position of the clamping unit 221 relative to the first opening 2231 can also be adjusted by moving the second fixing member 2222.
[0122] Combination Fig.15 The size of the first opening 2231 is smaller than the outer diameter of the first clamping body 2211a and larger than the outer diameter of the second clamping body 2211b, that is, at least part of the clamping body 2211 protrudes from the first opening 2231 in the third direction S3. Fig.13The diameter of the second opening 2232 is smaller than the outer diameter of the operating portion 2212b and larger than the outer diameter of the second clamping driving portion 2212c, so as to realize the penetration of the suction and release member 21 and the first clamping driving member 2212. The clamping unit 221 is installed and accommodated in the accommodating member 223 through the first opening 2231 and the second opening 2232.
[0123] The receiving member 223 is further provided with a first mounting hole 2233, a second mounting hole 2234 and a third mounting hole 2235 for mounting the fixing unit 222, and the first mounting hole 2233, the second mounting hole 2234 and the third mounting hole 2235 are all arranged along the radial direction of the clamping unit 221. Fig.10 The first mounting hole 2233, the second mounting hole 2234 and the third mounting hole 2235 are radially arranged along the conical surface of the second clamping body 2211b. At least part of the first fixing member 2221 passes through the first mounting hole 2233 to enter the first opening 2231 and abuts against the clamping unit 221, at least part of the second fixing member 2222 passes through the second mounting hole 2234 to enter the first opening 2231 and abuts against the clamping unit 221, and at least part of the third fixing member 2223 passes through the third mounting hole 2235 to enter the first opening 2231 and abuts against the clamping unit 221. The elastic biasing element 2224 is located in the third mounting hole 2235 and biases the third fixing member 2223 toward the center of the first opening 2231.
[0124] In order to achieve the fixing of the first fixing member 2221 and the second fixing member 2222, the receiving member 223 is further provided with a first fixing hole 2236 and a second fixing hole 2237. The fastener fixes the first fixing member 2221 to the receiving member 223 through the first fixing hole 2236, and fixes the second fixing member 2222 to the receiving member 223 through the second fixing hole 2237. Fig.18 , the first fixing hole 2236 and the second fixing hole 2237 are arranged at intervals along the second direction S2 on the receiving member 223. The fasteners are screwed into the fixing holes and abut against the first fixing member 2221 and the second fixing member 2222, so as to achieve the fixing of the first fixing member 2221 and the second fixing member 2222 on the receiving member 223. It should be noted that the structure of the receiving member 223 can be adjusted according to the actual design and is not limited to the above structure.
[0125] When installing the clamping unit 221, loosen the first fixing member 2221 and the second fixing member 2222, take the clamping unit 221 out of the receiving member 223 along the third direction S3, install the suction and release member 21 into the clamping unit 221, repeat the above process of installing the suction and release member 21 into the clamping unit 221, and fix the suction and release member 21 to the clamping unit 221. Then, place the clamping unit 221 equipped with the suction and release member 21 into the receiving member 223 along the third direction S3, tighten the first fixing member 2221 and the second fixing member 2222, and overcome the biasing force of the third fixing member 2223 and the elastic biasing element 2224 given to the clamping unit to achieve the installation of the clamping unit 221.
[0126] It should be noted that the fixing unit 222 only needs to include one of the above fixing members. Fig.36 The fixing unit 222 includes a third fixing member 2223 and an elastic biasing element 2224, one end of the elastic biasing element 2224 is connected to the third fixing member 2223, and the third fixing member 2223 is against the clamping unit 221, so that the biasing force of the elastic biasing element 2224 is overcome to fix the clamping unit 221 to the accommodating member 223, thereby realizing the installation and fixation of the clamping unit 221.
[0127] See again Figures 4 to 6 In some embodiments, the selection moving assembly 23 is used to drive the suction and release member 21 to move relative to the main body 10 along the third direction S3 to achieve cell suction and release. The selection moving assembly 23 includes a first selection moving unit 231, and the first selection moving unit 231 includes a selection driving member 2311, a selection transmission member 2312 and a selection moving member 2313. Under the control of the control mechanism 60, the selection driving member 2311 drives the selection transmission member 2312 to rotate, thereby achieving the movement of the selection moving member 2313 in the third direction S3. Figure 8 , the accommodating member 2231 is connected to the selection moving member 2313 along the first direction S1, and under the driving of the selection driving member 2311 and the rotation of the selection transmission member 2312, the selection moving member 2313 drives the suction and release member 21 to move along the third direction S3. Specifically in the embodiment, the selection driving member 2311 is a stepping motor to achieve the quantitative movement of the suction and release member 21 and ensure the movement accuracy of the suction and release member 21. The displacement accuracy of the suction and release member 21 in this embodiment is 2 microns. The selection transmission member 2312 is a lead screw extending along the third direction S3 to achieve the movement of the suction and release member 21 along the third direction S3.
[0128] The receiving member 2231 is detachably connected to the selection moving member 2313 through a fastener. To facilitate the installation of the receiving member 2231, the selection moving member 2313 is provided with a coupling groove. The provision of the coupling groove facilitates the positioning and installation of the receiving member 2231 on the selection moving member 2313. It can be understood that as long as the selection moving assembly 23 can drive the installation assembly 22 to move, the connection method of the selection moving member 2313 and the installation assembly 22 is not limited.
[0129] In some embodiments, the first picking moving unit 231 further includes a picking guide 2314 and a picking slide 2315. The picking guide 2314 extends along the third direction S3. The picking slide 2315 is disposed on the picking guide 2314 and connected to the picking moving member 2313 to realize the movement of the picking moving member 2313 in the third direction S3. The setting of the picking guide 2314 and the picking slide 2315 facilitates the movement of the picking moving member 2313. It should be noted that the extension lengths of the picking guide 2314 and the picking transmission member 2312 are determined according to the moving stroke of the suction member and are not limited here.
[0130] In some embodiments, the first selection movement unit 231 further includes a selection displacement sensor 2316 and a selection stopper 2317. The selection displacement sensor 2316 is disposed on one side of the selection guide 2314 in the second direction S2. The setting of the selection displacement sensor 2316 facilitates obtaining the moving distance of the suction and release member 21, and helps the control mechanism 60 to control the movement of the suction and release member 21. It should be noted that as long as the transmission of the displacement signal can be achieved, the type and installation position of the selection displacement sensor 2316 are not limited.
[0131] The selection limiter 2317 extends along the third direction S3 and is connected to the selection moving member 2313. The selection limiter 2317 is arranged on one side of the selection guide member 2314 in the second direction S2. The selection limiter 2317 and the selection displacement sensor 2316 can be arranged on the same side of the selection guide member 2314, or can be arranged on both sides of the selection guide member 2314 respectively. The setting of the selection limiter 2317 limits the moving distance of the suction and release member 21 in the third direction S3. The highest position and the lowest position of the suction and release member 21 can be obtained through the selection displacement sensor 2316, which can prevent the suction and release member 21 from hitting the carrier mechanism 30 during the movement and being damaged.
[0132] Under the control of the control mechanism 60, the selection driving member 2311 drives the selection moving member 2313 to move in the third direction S3 along the selection guide member 2314, driving the suction and release member 21 connected to the selection moving member 2313 to move in the third direction S3, thereby enabling the suction and release member 21 to approach and move away from the cells to be sorted and enabling the suction and release member 21 to absorb and release the cells to be sorted.
[0133] See again Figure 8 and Fig. 9 The selection lighting unit 24 is connected to the mounting assembly 22 and is located at one end of the suction and placement member 21 away from the loading mechanism 30. The selection lighting unit 24 includes a selection light source 241 connected to the control mechanism 60. The selection light source 241 and the suction and placement member 21 are arranged along the third direction S3. The light emitted by the selection light source 241 can pass through the hollow pipe 211 of the suction and placement member 21 to form a projection of the suction and placement member 21, so as to facilitate the positioning of the suction and placement member 21. Fig.15 , the light source 241 is selected and disposed in the first accommodating cavity 2211c of the clamping body 2211.
[0134] To ensure that the suction and release member 21 can absorb and release cells, the selection light source 241 needs to be sealed and connected with the first accommodating chamber 2211c to achieve the blocking of the first accommodating chamber 2211c and the external environment. In one embodiment, the selection light source 241 is fixed in the first accommodating chamber 2211c of the first clamping body 2211a by gluing. The gluing connection is easy to operate and can ensure the sealing between the selection light source 241 and the clamping body 2211, so that the suction and release member 21 can achieve the absorption of cells under the drive of the recovery component 26. It can be understood that as long as the fixation of the selection light source 241 is achieved, the connection mode of the selection light source 241 and the clamping body 2211 is not limited.
[0135] In some embodiments, the selected light source 241 is an LED light source, which is fixedly connected to the clamping body 2211, and the central axis of the LED light source is parallel or aligned with the central axis of the suction and placement member 21, so that the light emitted by the LED light source can pass through the hollow pipe 211 of the suction and placement member 21. The LED light source has high lighting efficiency, long service life, and is easy to install, ensuring the long-term use of the cell sorting device 100. It should be noted that the position of the selected light source 241 is set according to the position of the suction and placement member 21, and the type of the selected light source 241 is not limited to an LED light source as long as it can emit light.
[0136] In a feasible embodiment, a sealing element is further provided between the selected light source 241 and the first clamping body 2211a. The sealing element needs to allow light to pass through the hollow pipe 211 of the suction and release member 21. The setting of the sealing element provides a buffer for the selected light source 241 and further ensures the sealing between the suction and release member 21 and the clamping body 2211.
[0137] In some embodiments, in combination Fig.37As shown, the cell sorting device 100 includes a suction and placement member projection recognition unit, which is used to identify the suction and placement member projection and form a suction and placement member projection map. In the suction and placement member projection map, a projection mark is provided. The suction and placement member projection can be adjusted by the first fixing member 2221 and the second fixing member 2223, thereby changing the position of the suction and placement member projection map relative to the projection mark, so that the projection mark is located at a preset position of the suction and placement member projection map to complete the calibration of the suction and placement member 21.
[0138] When in use, the control mechanism 60 controls the selected light source 241 to emit light, and the light passes through the hollow pipe 211 of the suction and release member 21 and passes through the suction and release member 21 through the suction and release port 212. The suction and release member projection is obtained according to the light passing through the suction and release port 212, and the image information (such as a circular aperture) of the suction and release member projection is obtained through the imaging mechanism 40. Based on the image information and the projection mark (such as a cross cursor) located in the image information, the first fixing member 2221 or the second fixing member 2223 is moved to adjust the position of the cross cursor located in the circular aperture, such as moving the cross cursor to the middle position of the circular aperture. After marking the position of the suction and release member projection, this position is used as a reference, so that the subsequent control mechanism 60 controls the selection moving component 23 to drive the suction and release member 21 to move in the third direction S3, so as to achieve the absorption of cells that meet the preset requirements.
[0139] See again Figure 4 and Figure 5 The cleaning component 25 is used for cleaning the suction and release part 21 before use, so that the activity of cells can be guaranteed during the cell absorption and release process without damaging the normal state of cells. The cleaning component 25 includes a driving unit 251 and a cleaning liquid unit 254. The driving unit 251 is connected to the hollow pipe 211 of the suction and release part 21 through a connecting piece 252, which can change the air pressure of the hollow pipe 211 of the suction and release part 21, thereby allowing the cleaning liquid to enter the hollow pipe 211 of the suction and release part 21, thereby cleaning the suction and release part 21. Figure 2 The driving unit 251 is disposed on the supporting plate 1221 along the first direction S1. To facilitate the absorption of the cleaning liquid, the driving unit 251 is connected to the suction and release member 21 along the third direction S3.
[0140] In some embodiments, the driving unit 251 uses a pump, and a mechanical device is used to make the diaphragm inside the pump do reciprocating motion, thereby compressing and stretching the air in the pump chamber to form a negative pressure, so that the suction and discharge port 212 of the suction and discharge member 21 produces a pressure difference with the external atmospheric pressure. Under the action of the pressure difference, the cleaning liquid is sucked into the suction and discharge member 21. Figure 4 , Fig.12 and Fig.15 The driving unit 251 is connected to the connecting hole of the clamping body 2211 , and the clamping body 2211 and the suction and release member 21 form a cleaning chamber for cleaning the hollow pipe 211 of the suction and release member 21 .
[0141] In some embodiments, see Figure 4 and Figure 5 In order to facilitate the connection between the driving unit 251 and the clamping body 2211, the cleaning assembly 25 further includes a connecting piece 252. One end of the connecting piece 252 is connected to the driving unit 251, and the other end is connected to the connecting hole of the clamping body 2211, and forms a passage with the hollow pipe 211 of the suction and release member 21, so that a pressure difference is generated at the suction and release port 212. Specifically, the connecting piece 252 can be selected from a plastic hose.
[0142] Furthermore, in order to facilitate the connection between the clamping body 2211 and the connecting piece 252, the cleaning assembly 25 further includes a passage connecting piece 253. One end of the passage connecting piece 253 is connected to the clamping body 2211 through a connecting hole, and the other end enables the connecting piece 252 to be sleeved on the passage connecting piece 253. The passage connecting piece 253 can be a pagoda joint, one end of which is threadedly connected to the clamping body 2211, and the other end is sleeved with the connecting piece 252, and has good sealing performance with the connecting piece 252.
[0143] The passage connector 253 is a hollow structure, which forms a passage together with the connecting piece 252 and the suction and release member 21. During cleaning, the cleaning liquid flows through the inner wall of the suction and release member 21, the inner wall of the clamping body 2211 and the inner wall of the passage connector 253 to clean. The passage connector 253 and the clamping body 2211 are threadedly connected. It can be understood that as long as the connection between the passage connector 253 and the clamping body 2211 can be achieved, the connection mode of the passage connector 253 and the clamping body 2211 is not limited, such as the passage connector 253 and the clamping body 2211 can be integrally formed.
[0144] In some embodiments, to facilitate the placement of the cleaning liquid, the cleaning assembly 25 also includes a holding unit 255 for holding the cleaning liquid unit 254, and the holding unit 255 is located on the carrier mechanism 30 of the cell sorting device 100. The cleaning liquid unit 254 includes a first cleaning liquid 2541 and a second cleaning liquid 2542, and the first cleaning liquid 2541 and the second cleaning liquid 2542 are different from each other. The holding unit 255 includes a first holding member 2551 and a second holding member 2552, the first holding member 2551 is used to hold the first cleaning liquid 2541, and the second holding member 2552 is used to hold the second cleaning liquid 2542. The driving unit 251 absorbs the first cleaning liquid 2541 into the hollow pipe 211 to perform a first preset number of cleanings of the suction and placement member 21 and absorbs the second cleaning liquid 2542 into the hollow pipe 211 to perform a second preset number of cleanings of the suction and placement member 21.
[0145] Specifically in the embodiment, the first cleaning liquid 2541 is ethanol, the second cleaning liquid 2542 is phosphate buffered saline (PBS), and the first holding member 2551 and the second holding member 2552 are both biological culture dishes. Ethanol is used to sterilize and disinfect the suction and release member 21, and the PBS buffer is used to provide an internal environment suitable for cell culture for cells, so that the inside of the suction and release member 21 does not affect the cell activity. It can be understood that as long as the suction and release member 21 can be cleaned, the type of cleaning liquid is not limited, such as the second cleaning liquid 2542 can also use HEPES (hydroxyethylpiperazine ethanesulfonic acid) buffer.
[0146] Furthermore, the first cleaning solution 2541 uses 75% ethanol, and the second cleaning solution 2542 uses 0.01M PBS buffer. 75% ethanol can effectively kill live bacteria and viruses. It should be noted that the first cleaning solution 2541 and the second cleaning solution 2542 of the required concentration can be obtained by configuration, or the first cleaning solution 2541 and the second cleaning solution 2542 of the required concentration can be directly used. Accordingly, the concentration of the cleaning solution can be set according to actual needs and is not limited to the above concentration.
[0147] Preferably, in order to ensure a sterile environment during the cell sorting process, the first cleaning solution 2541 and the second cleaning solution 2542 need to be filtered before use. Specifically, ethanol and PBS buffer are both filtered through 0.45 microns before use. The filtration size requirement can be set according to the experimental requirements and is not limited to 0.45 microns, such as 0.22 micron filtration. In a feasible embodiment, before cleaning, the holding part assembly and the cleaning liquid assembly are sterilized, such as by sterilization in an autoclave. As long as the sterilization and disinfection of the holding part and the cleaning liquid can be achieved, the specific sterilization method is not limited.
[0148] Before the suction and placement member 21 absorbs cells, the driving unit 251 and the suction and placement member 21 are first connected, and then the first containing member 2551 is taken, and an appropriate amount of the first cleaning liquid 2541 is added, and the first containing member 2551 with the first cleaning liquid 2541 is placed with the suction and placement member 21 along the third direction S3. Under the control of the control mechanism 60, the selection moving component 23 drives the suction and placement port 212 of the suction and placement member 21 to move into the first cleaning liquid 2541, and the driving unit 251 drives the suction and placement member 21 to absorb the first cleaning liquid 2541 into the hollow pipe 211 of the suction and placement member 21 to clean the suction and placement member 21, and drives the suction and placement member 21 to release the first cleaning liquid 2541 into the first containing member 2551. The action of absorbing and releasing the first cleaning liquid 2541 can be one or more times, and the specific number of times is determined according to the preset number of times to complete the first step of cleaning, and the hollow pipe 211 of the suction and placement member 21 is disinfected and sterilized.
[0149] Afterwards, take the second holding member 2552, add an appropriate amount of the second cleaning liquid 2542, and place the second holding member 2552 with the second cleaning liquid 2542 and the suction and release member 21 at intervals along the third direction S3. Under the control of the control mechanism 60, the selection moving component 23 drives the suction and release port 212 of the suction and release member 21 to move into the second cleaning liquid 2542, the driving unit 251 drives the suction and release member 21 to absorb the second cleaning liquid 2542 into the hollow pipe 211 of the suction and release member 21 to clean the suction and release member 21, and drives the suction and release member 21 to release the second cleaning liquid 2542 into the second holding member 2552. The action of absorbing and releasing the second cleaning liquid 2542 can be one or more times, and the specific number of times is determined according to the preset number of times to complete the second step of cleaning. The second step of cleaning cleans the first cleaning liquid 2541 on the one hand, and provides a relatively stable ionic environment and pH buffering capacity on the other hand to facilitate the survival of cells in the suction and release member 21.
[0150] After the suction and placement member 21 absorbs cells, the specific steps are opposite to those before the suction and placement member absorbs cells. Specifically, first take the second holding member 2552, add an appropriate amount of the second cleaning liquid 2542, and place the second holding member 2552 with the second cleaning liquid 2542 and the suction and placement member 21 at intervals along the third direction S3. Under the control of the control mechanism 60, the selection moving component 23 drives the suction and placement port 212 of the suction and placement member 21 to move into the second cleaning liquid 2542, the driving unit 251 drives the suction and placement member 21 to absorb the second cleaning liquid 2542 into the hollow pipe 211 of the suction and placement member 21 to clean the suction and placement member 21, and drives the suction and placement member 21 to release the second cleaning liquid 2542 into the second holding member 2552. The action of absorbing and releasing the second cleaning liquid 2542 can be one or more times, and the specific number of times is determined according to the preset number of times to complete the first step of cleaning, and the residual cells or cell buffer in the suction and placement member 21 are cleaned.
[0151] Then, take the first containing member 2551, add an appropriate amount of the first cleaning liquid 2541, and place the first containing member 2551 with the first cleaning liquid 2541 and the suction and release member 21 at intervals along the third direction S3. Under the control of the control mechanism 60, the selection moving assembly 23 drives the suction and release port 212 of the suction and release member 21 to move into the first cleaning liquid 2541, the driving unit 251 drives the suction and release member 21 to absorb the first cleaning liquid 2541 into the hollow pipe 211 of the suction and release member 21 to clean the suction and release member 21, and drives the suction and release member 21 to release the first cleaning liquid 2541 into the first containing member 2551. The action of absorbing and releasing the first cleaning liquid 2541 can be one or more times, and the specific number of times is determined according to the preset number of times to complete the second step of cleaning, on the one hand, cleaning the second cleaning liquid 2542, and on the other hand, disinfecting and sterilizing the hollow pipe 211 of the suction and release member 21.
[0152] In some embodiments, the control mechanism 60 includes a cleaning control unit 61, which is used to control the driving unit 251 to absorb the first cleaning liquid 2541 into the hollow pipe 211 to clean the suction and placement member 21 for a first preset number of times and to control the driving unit 252 to absorb the second cleaning liquid 2542 into the hollow pipe 211 to clean the suction and placement member 21 for a second preset number of times. The cleaning control unit 61 can control the driving unit 251 to make the absorbed first cleaning liquid 2541 reciprocate in the hollow pipe 211 along the third direction S3 for multiple cleanings, and then release it into the first containing member 2551; control the driving unit 251 to make the absorbed second cleaning liquid 2542 reciprocate in the hollow pipe 211 along the third direction S3 for multiple cleanings, and then release it into the second containing member 2552.
[0153] See again Figure 4 and Figure 5 , the recovery component 26 is used to absorb and release cells that meet the preset requirements. The recovery component 26 includes a driving unit 251, a connecting piece 252 and a passage connecting piece 253. The specific functional relationship and positional relationship can be referred to the description of the cleaning component 25, which will not be repeated here. Under the control of the control mechanism 60, the setting of the recovery component 26 realizes the absorption and release of cells, facilitates the cell sorting process, and improves the efficiency of cell sorting.
[0154] When the recovery component 26 is used, the cells that meet the preset requirements are moved and placed at intervals with the suction and release member 21 along the third direction S3. Under the control of the control mechanism 60, the selection moving component 23 drives the suction and release port 212 of the suction and release member 21 to move to a preset position. At this time, there is a preset distance between the suction and release port 212 and the cells that meet the preset requirements. The control mechanism 60 controls the driving unit 251 to generate a pressure difference at the suction and release port 212 of the suction and release member 21, thereby sucking the cells that meet the preset requirements into the hollow pipe 211, and completing the suction of the cells that meet the preset requirements. The preset distance is the distance that enables the suction and release member 21 to suck the cells that meet the preset requirements into the hollow pipe 211.
[0155] To facilitate the installation of the selected mobile assembly 23, refer to Figure 4, the selection mechanism 20 further includes a mounting bracket 27. The setting of the mounting bracket 27 realizes the fixed installation of the selection moving assembly 23. The selection mechanism 20 is installed on the main body 10 through the mounting bracket 27. In some embodiments, the mounting bracket 27 is connected to the imaging mechanism 40 along the third direction S3, and the imaging mechanism 40 is installed on the main body 10. It should be noted that the mounting bracket 27 can be set according to actual needs, such as the mounting bracket 27 is connected to the support plate 1221 along the first direction S1 to realize the installation of the selection mechanism 20 on the main body 10. In some embodiments, the mounting bracket 27 is provided with a first mounting seat 271 and a second mounting seat 272. The first mounting seat 271 is arranged on the mounting bracket 27 along the third direction S3, and is used for the fixed installation of the selection guide member 234. The second mounting seat 272 is arranged on the mounting bracket 27 along the first direction S1, and is perpendicular to the first mounting seat 271, and is used for the placement and fixation of the selection driving member 2311.
[0156] When the selection mechanism 20 is in use, the installation component 22 and the selection moving component 23 are connected, the suction and release component 21 is installed and fixed on the installation component 22, the selection moving component 23 drives the suction and release component 21 to move, and the suction and release component 21 is cleaned through the cleaning component 25. Then, the selection moving component 23 drives the suction and release component 21 to move, and the suction and release component 21 is made to absorb and recover cells that meet preset requirements at a preset position through the recovery component 26. Finally, after the absorption is completed, the selection moving component 23 drives the suction and release component 21 to move, and the suction and release component 21 is cleaned through the cleaning component 25.
[0157] See also Figures 4 to 6 as well as Figure 38 to Figure 43 , shows the selection mechanism in other embodiments of the present application. The selection mechanism 20 includes a suction and release member 21, a mounting assembly 22, a selection and movement assembly 23, a cleaning assembly 25 and a recovery assembly 26. It should be noted that, for the convenience of description, only the different parts of the selection mechanism and the selection mechanism in the above embodiment are described in detail below. The same parts of the selection mechanism and the selection mechanism in the above embodiment (such as the suction and release member 21) can refer to the specific structure in the above embodiment, and will not be described in detail below.
[0158] The mounting assembly 22 includes a clamping unit 221 and a receiving member 223'. The clamping unit 221 is used to clamp and release the suction and release member 21 and is connected to the suction and release member 21 along the third direction S3. Figure 7 and Fig.39One end of the suction and release member 21 is used for suction and release of cells to be sorted, and is formed with a suction and release port 212, and the other end of the suction and release member 21 is clamped or released by a clamping unit 221. Through the clamping of the clamping unit 221, the suction and release member 21 can be stably used, and through the release and clamping of the clamping unit 221, the suction and release member 21 can be replaced. The setting of the clamping unit 221 realizes the fixing or release of the suction and release member 21 without damaging the suction and release member 21.
[0159] See also Figures 38 to 40 The clamping unit 221 includes a clamping body 2211' and a first blocking unit 22190. The clamping body 2211' is a hollow structure, and a mounting channel 2211e is formed to facilitate the installation of the first blocking unit 22190 and the suction and release member 21. The first blocking unit 22190 is connected to the clamping body 2211', and the first blocking unit 22190 can block one end of the mounting channel 2211e. The first blocking unit 22190 is used to clamp the suction and release member 21, and the other end of the suction and release member 21 can enter the mounting channel 2211e.
[0160] By passing the suction and release member 21 through the first blocking unit 22190 and the clamping body 2211', the suction and release member 21 can be clamped by the first blocking unit 22190 and enter the installation channel 2211e, thereby achieving the clamping and fixation of the suction and release member 21, preventing the suction and release member 21 from loosening and falling out of the clamping unit 221, so that the suction and release member 21 can be used normally for a long time, thereby improving the sorting efficiency of the cell sorting device.
[0161] In a feasible embodiment, the first blocking unit 22190 includes a first blocking member 22191, which is connected to the clamping body 2211' and can block one end of the installation channel 2211e, and the first blocking member 22191 can clamp the suction and release member 21 through its elastic deformation in the radial direction. Optionally, the first blocking member 22191 is made of an elastic material such as rubber, and a first through hole 22191a is provided on the first blocking member 22191, and the suction and release member 21 can pass through the first through hole 22191a and be squeezed by the first blocking member 22191 under the elastic action of the rubber to achieve the clamping of the suction and release member 21.
[0162] In another feasible embodiment, the first blocking unit 22190 includes a first blocking member 22191 and a clamping member 22192. The first blocking member 22191 is connected to the clamping body 2211' and can block one end of the installation channel 2211e. The clamping member 22192 is disposed between the inner wall of the first blocking member 22191 and the outer wall of the suction and release member 21. The clamping member 22192 can clamp the suction and release member 21 by squeezing the suction and release member 21 and the first blocking member 22191. The suction and release member 21 and the first blocking member 22191 jointly squeeze the clamping member 22192 to achieve the clamping of the suction and release member 21, that is, the suction and release member 21 passes through the first through hole 22191a and is clamped by the clamping member 22192 and then enters the installation channel 2211e, which helps to improve the installation stability of the clamping member 22192. Optionally, the clamping member 22192 is an O-ring.
[0163] Specifically, the first blocking member 22191 includes a receiving hole 22191b and a first through hole 22191a which are interconnected. The radial dimension of the receiving hole 22191b is larger than the dimension of the first through hole 22191a, thereby forming a step inside the first blocking member 22191. The clamping member 22192 abuts against the step, thereby stably placing the clamping member 22192 in the first blocking member 22191 and enabling the clamping member 22192 to clamp the suction and release member 21.
[0164] Furthermore, the first blocking member 22191 can be elastically deformed in the radial direction, so that the suction and release member 21 is clamped together by the first blocking member 22191 and the clamping member 22192 to ensure the installation stability and reliability of the suction and release member 21.
[0165] The first blocking member 22191 is detachably connected to the clamping body 2211', thereby facilitating the assembly and disassembly of the first blocking member 22191 and the clamping body 2211', thereby facilitating the installation and disassembly of the suction and release member 21. Optionally, the first blocking member 22191 is connected to the clamping body 2211' by plugging, clamping, threading, etc.
[0166] In some embodiments, see Figures 38 to 40The clamping unit 221 also includes a second blocking member 22193, which is connected to the clamping body 2211' and can block the other end of the installation channel 2211e. The second blocking member 22193 is provided with a second through hole, and the second blocking member 22193 can clamp the end of the suction and release member 21 entering the installation channel 2211e. When the suction and release member 21 is installed, the end of the suction and release member 21 will pass through the first through hole 22191a, the clamping member 22192, the installation channel 2211e and the second through hole in sequence. The second blocking member 22193 and the first blocking unit 22190 realize the clamping and fixing of at least two parts of the suction and release member 21, so that the suction and release member 21 can remain stable in the installation channel 2211e, so as to improve the installation stability of the suction and release member 21.
[0167] Preferably, the first through hole 22191a of the first blocking member 22191 and the second through hole of the second blocking member 22193 are coaxially arranged, so that the suction and release member 21 can be maintained on the axial center of the installation channel 2211e, thereby ensuring that the suction and release member 21 is in a vertical state and facilitating the installation efficiency and use stability of the suction and release member 21.
[0168] Specifically, the installation channel 2211e of the clamping body 2211 includes a first accommodating cavity 2211c' and a second accommodating cavity 2211d' that are connected to each other. The radial dimension of the second accommodating cavity 2211d' is larger than the radial dimension of the first accommodating cavity 2211c', thereby forming a step shape inside the clamping body 2211.
[0169] Further, the outer diameter of the outer wall of at least part of the first blocking member 22191 is consistent with the radial dimension of the second accommodating cavity 2211d', and the outer diameter of the outer wall of at least part of the first blocking member 22191 is larger than the radial dimension of the second accommodating cavity 2211d', so that the outer wall of the first blocking member 22191 is formed with a step shape, so that part of the first blocking member 22191 can enter the second accommodating cavity 2211d' and the first blocking member 22191 can rely on the step-shaped setting to limit the movement of the first blocking member 22191. Optionally, the first blocking member 22191 is formed with an umbrella-shaped step.
[0170] At least part of the second blocking member 22193 can be installed in the first accommodating cavity 2211c'. Preferably, at least part of the second blocking member 22193 is a conical structure, and the conical second blocking member 22193 can play a guiding role, so that the second blocking member 22193 can enter the first accommodating cavity 2211c' to fix the suction and release member 21, and at least part of the second blocking member 22193 has a radial dimension greater than the radial dimension of the first accommodating cavity 2211c', so as to facilitate the removal of the second blocking member 22193 from the first accommodating cavity 2211c'. It should be noted that the present application does not limit the shape and size of the second blocking member 22193, as long as the second blocking member 22193 can be stably installed in the first accommodating cavity 2211c'.
[0171] Preferably, the end face of the suction and release member 21 entering the installation channel 2211e does not exceed the end face of the second blocking member 22193 away from the first blocking member 22191. In the third direction, the end of the suction and release member 21 is to be accommodated in the second blocking member 22193, and the suction and release member 21 can be protected by the second blocking member 22193 to avoid damage to the suction and release member 21.
[0172] The first blocking member 22191 includes a blocking body 22191c and a stopper 22191d, at least a portion of the blocking body 22191c extends into the second accommodating cavity 2211d', and the stopper 22191d extends and protrudes from the second accommodating cavity 2211d', and the stopper 22191d can block the movement of the blocking body 22191c. The setting of the stopper 22191d facilitates the operation of the first blocking member 22191, so as to facilitate the first blocking member 22191 to be placed in the second accommodating cavity 2211d', and to facilitate the first blocking member 22191 to be taken out of the second accommodating cavity 2211d', that is, to facilitate the installation and removal of the first blocking member 22191 and the clamping body 2211'.
[0173] In a feasible embodiment, the clamping unit 221 also includes a protective member 22194, which is used to protect the end of the suction and release member 21 entering the installation channel to avoid touching the end of the suction and release member 21 during installation, causing contamination of the suction and release member 21, and preventing the suction and release member 21 from being damaged during installation. On the other hand, the applicability of the suction and release member 21 can be improved. By replacing the protective member 22194, the suction and release member 21 can be applied to different second blocking members 22193. The protective member 22194 is configured between the inner wall of the second blocking member 22193 and the outer wall of the suction and release member 21. The driving unit 251 can generate negative pressure and positive pressure in the suction and release member 21 to achieve cleaning of the suction and release member 21 or absorption and release of cells to be sorted. The provision of the protective member 22194 facilitates the connection between the clamping unit 221 and the driving unit 251, so that the suction and release member 21 can absorb or release cells to be sorted.
[0174] Optionally, the protective member 22194 is sleeved on the outer periphery of the suction and release member 21, thereby determining the position of the end of the suction and release member 21, thereby facilitating the installation of the suction and release member 21 to a preset position. The protective member 22194 and the first blocking unit 22190 together form a longer positioning of the suction and release member 21, so that the suction and release member 21 and the clamping body 2211' have better concentricity, thereby preventing the suction and release member 21 from falling out of the clamping unit 221.
[0175] Preferably, the inner wall of the protective member 22194 is attached to the outer wall of the suction and release member 21 to achieve a sealed connection between the protective member 22194 and the suction and release member 21, so that the driving unit 251 can stably generate positive pressure and negative pressure in the suction and release member 21. Further, preferably, the protective member 22194 and the suction and release member 21 are interference fit or zero clearance fit, so that the protective member 22194 can also clamp the end of the suction and release member 21 to ensure the stability of the suction and release member 21 installation.
[0176] Optionally, the protective member 22194 is made of a soft and tough material such as rubber, so that the protective member 22194 can form a seal between the suction and release member 21 and the second blocking member 22193 by extrusion and protect the suction and release member 21.
[0177] The second blocking member 22193 is sleeved on the outer circumference of the protective member 22194. Preferably, the inner wall of the second through hole is in contact with the outer wall of the protective member 22194 to ensure the stability and reliability of the installation of the protective member 22194.
[0178] When the second blocking member 22193 is installed in the first accommodating cavity 2211c', the second blocking member 22193 is squeezed by the clamping body 2211', thereby squeezing the protective member 22194 to ensure the installation stability of the protective member 22194. Optionally, the material of the second blocking member 22193 is the same as that of the clamping body 2211'.
[0179] Optionally, the end face of the suction and release member 21 entering the installation channel 2211e does not exceed the end face of the protective member 22194 away from the first blocking member 22191, thereby preventing the end of the suction and release member 21 from being damaged or contaminated by the external environment. Preferably, the end face of the protective member 22194 away from the first blocking member 22191 is flush with the end face of the second blocking member 22193 away from the first blocking member 22191, thereby the installation position of the suction and release member 21 can be determined by the installation position of the protective member 22194, so that the suction and release member 21 can be accurately installed.
[0180] It should be noted that in this application, the clamping unit 221 without the suction and release member 21 can be used as the smallest unit, and the clamping unit 221 with the suction and release member 21 can also be protected as the smallest unit. That is, when the product is sold on the market, the suction and release member 21 and the clamping unit 221 can be sold as independent products or as a whole, and the clamping unit 221 with or without the suction and release member 21 is within the protection scope of this embodiment.
[0181] It should be noted that, as a same concept, when the clamping unit 221 is replaced as a whole, the clamping unit 221 can be placed in the accommodating shell 310 to protect the clamping unit 221 from damage. Fig.44 and Fig.45 The present application also provides a accommodating component 300, which includes a accommodating shell 310 and a clamping unit 221. The accommodating shell 310 forms a closed accommodating space. The clamping unit 221 is the clamping unit 221 in the above embodiment and is placed in the accommodating space of the accommodating shell 310 to protect the clamping unit 221. The clamping unit 221 can be accommodated in the accommodating space together with the suction and release member 21, or only the clamping unit 221 can be accommodated in the accommodating space.
[0182] When installing the clamping unit 221, the clamping piece 22192 can be first placed in the first blocking piece 22191, the end of the suction and release piece 21 can be passed through the first through hole 22191a and the clamping piece 22192, and then the first blocking piece 22191 and the clamping body 2211' are connected, and then the end of the suction and release piece 21 enters the installation channel 2211e and is connected to the protective piece 22194, the second blocking piece 22193 is connected to the protective piece 22194, and then the second blocking piece 22193 and the clamping body 2211' are connected.
[0183] Combination Figure 38 to Figure 43 After the clamping unit 221 is assembled, the clamping unit 221 is connected to the receiving member 223' to complete the assembly of the mounting assembly 22. Specifically, the receiving member 223' includes a first opening 2231' to install the clamping unit 221.
[0184] It is feasible that the accommodating member 223' and the clamping body 2211' are detachably connected. Specifically in this embodiment, an internal thread is provided on the inner wall of the accommodating member 223', and an external thread is provided on the outer wall of the clamping body 2211'. The connection between the internal thread and the external thread is achieved by the cooperation of the internal thread and the external thread. This connection method is simple and reliable, and is convenient for the assembly between the clamping unit 221 and the accommodating member 223'. Furthermore, a rough surface is also provided on the outer wall of the clamping body 2211', and the rough surface is used to rotate the clamping body 2211' to facilitate the operation of the connection between the clamping body 2211' and the accommodating member 223'. In other embodiments, the clamping body 2211' can also be detachably connected to the accommodating member 223' by plugging, snapping, etc.
[0185] Combination Figure 38 to Figure 43 In some other embodiments, the picking moving component 23 includes a first picking moving unit 231, a second picking moving unit 232 and a third picking moving unit 233, the first picking moving unit 231 is connected to the second picking moving unit 232, the second picking moving unit 232 is connected to the third picking moving unit 233, the third picking moving unit 233 is connected to the container, the first picking moving unit 231 can drive the second picking moving unit 232 and the third picking moving unit 233 to move along the third direction S3, the second picking moving unit 232 can drive the third picking moving unit 233 to move along the first direction S1, the third picking moving unit 233 can drive the container to move along the second direction S2, and the first direction S1, the second direction S2 and the third direction S3 are perpendicular to each other.
[0186] The first picking and moving unit 231 , the second picking and moving unit 232 and the third picking and moving unit 233 respectively drive the suction and placement member to move along the third direction S3 , the first direction S1 and the second direction S2 , so that the suction and placement member can be accurately moved to a preset position.
[0187] Specifically, the first selection moving unit 231 has the same specific structure as the first selection moving unit 231 in the above embodiment, which will not be described in detail herein.
[0188] Combination Figure 2 Under the control of the control mechanism 60, the selection driving member 2311 drives the selection moving member 2313 to move along the selection guide member 2314 in the third direction S3, driving the suction and release member 21 indirectly connected to the selection moving member 2313 to move in the third direction S3, thereby enabling the suction and release member 21 to approach and move away from the cells to be sorted and to absorb and release the cells to be sorted.
[0189] In some embodiments, see Fig.41The second selection moving unit 232 includes a first operating member 2321, a first selection fixing member 2322 and a first selection sliding member 2323. The first selection sliding member 2323 is slidably connected to the first selection fixing member 2322 and the first selection sliding member 2323 is connected to the third selection moving unit 233. The first operating member 2321 is connected to the first selection sliding member 2323 and can drive the first selection sliding member 2323 to move along the first direction S1 relative to the first selection fixing member 2322. The second selection moving unit 232 is provided so that the suction and placement member 21 can move along the first direction S1.
[0190] The third selection mobile unit 233 comprises a second operating member 2331, a second selection fixing member 2332 and a second selection sliding member 2333, the second selection fixing member 2332 is connected to the first selection sliding member 2323, the second selection sliding member 2333 is slidably connected to the second selection fixing member 2332 and the second selection sliding member 2333 is connected to the container 223', the second operating member 2331 is connected to the second selection sliding member 2333 and can drive the second selection sliding member 2333 to move along the second direction S2 relative to the second selection fixing member 2332. The third selection mobile unit 233 is provided so that the suction and release member 21 installed on the container 223' can move along the second direction S2. Through the synergistic effect of the second selection mobile unit 232 and the third selection mobile unit 233, the central axis of the suction and release member 21 can overlap with the central axis of the object lens for identification.
[0191] Specifically in this embodiment, the accommodating member 223' includes an accommodating portion 2238 and a mounting portion 2239, the accommodating portion 2238 is extended along the axial direction of the suction and placement member 21, the mounting portion 2239 is connected to the accommodating portion 2238 and is extended along the axial direction perpendicular to the suction and placement member 21, and the second selection sliding member 2333 is connected to the side of the mounting portion 2239 away from the suction and placement member 21. Through the arrangement of the mounting portion 2239 and the accommodating portion 2238, it is convenient to install and fix the accommodating member 223' and the clamping unit 221 as well as the accommodating member 223' and the third selection moving unit 233. Feasibly, the second selection moving unit 232 and the third selection moving unit 233 are configured between the accommodating portion 2238 and the selection moving member 2313.
[0192] Optionally, a first selecting sliding block is provided on one of the first selecting fixing member 2322 and the first selecting sliding member 2323 , and a first selecting sliding rail extending along the first direction S1 is provided on the other one, and the first selecting sliding block is slidably connected to the first selecting sliding rail.
[0193] A second selection slider is disposed on one of the second selection fixing member 2332 and the second selection sliding member 2333, and a second selection slide rail extending along the second direction S2 is disposed on the other, and the second selection slider is slidably connected to the second selection slide rail. The movement of the suction and placement member 21 along the first direction S1 and the second direction S2 is achieved through the cooperation of the first selection slide rail and the first selection slider, and the second selection slide rail and the second selection slider.
[0194] Optionally, the second picking moving unit 232 also includes a first locking piece 2325, and the third picking moving unit 233 includes a second locking piece not shown in the figure. The first locking piece 2325 can lock the relative positions of the first picking fixed piece 2322 and the first picking sliding piece 2323, and the second locking piece can lock the relative positions of the second picking fixed piece 2332 and the second picking sliding piece 2333, so as to avoid the movement of the suction and release piece 21 due to accidental touching of the first operating piece 2321 and the second operating piece 2331, thereby ensuring the stability and reliability of the suction and release piece 21 after movement.
[0195] Furthermore, the first operating member 2321 and the second operating member 2331 are both micrometer structures. The micrometer structure can provide micrometer-level or even nanometer-level precise adjustment, which helps to improve the movement accuracy of the suction and release member 21, so that the suction and release member 21 can accurately move to the preset position for sucking and releasing the cells to be sorted.
[0196] Generally, the micrometer structure includes a screw, a fixed sleeve, a differential cylinder and a knob. By rotating the knob and the differential cylinder of the first operating member 2321, the end of the screw is brought into contact with the first selection fixing member 2322. As the screw is extended or shortened, the fixed sleeve moves relative to the first selection fixing member 2322, and thus the first selection sliding member 2323 fixedly connected to the fixed sleeve moves relative to the first selection fixing member 2322, so as to realize the sliding of the first selection sliding member 2323 in the first direction S1, thereby driving the third selection moving unit 233 and the suction and release member 21 to move along the first direction S1. By rotating the knob and the differential cylinder of the second operating member 2331, the end of the screw rod abuts against the second selection fixing member 2332. As the screw rod is extended or shortened, the fixed sleeve moves relative to the second selection fixing member 2332. Thus, the second selection sliding member 2333 fixedly connected to the fixed sleeve moves relative to the second selection fixing member 2332, so as to realize the sliding of the second selection sliding member 2333 in the second direction S2, thereby driving the suction and release member 21 to move along the second direction S2.
[0197] In other embodiments, the first operating member 2321 and the second operating member 2331 may also be motors, etc., and the motors are used to drive the first selection sliding member 2323 to slide in the first direction S1 and the second selection sliding member 2333 to slide in the second direction S2.
[0198] Specifically, the selection moving assembly 23 further includes a matching piece 234, which is detachably connected to the selection moving piece 2312 and the first selection fixing piece 2322 through a fastener to achieve the connection between the first selection moving unit 231 and the second selection moving unit 232. It can be understood that as long as the first selection moving unit 231 can drive the second selection moving unit 232 to move, the connection method between the selection moving piece 2312 and the matching piece 234 is not limited. In this embodiment, the matching piece 234 includes a first matching portion 2341 and a second matching portion 2342 that are perpendicular to each other, the first matching portion 2341 is connected to the first selection fixing piece 2322, and the second matching portion 2342 is connected to the selection moving piece 2312.
[0199] See again Figure 4 and Figure 5 The cleaning component 25 is used for cleaning the suction and release member 21 before use, so that the activity of cells can be guaranteed during the cell suction and release process without damaging the normal state of cells. The specific structure of the cleaning component 25 can refer to the description of the above embodiment. The difference from the above embodiment is that the cleaning component 25 is combined with Figure 38 to Figure 43 In this embodiment, the connecting member 252 is connected to the containing member 223 ′, so that the driving unit 251 can generate positive pressure or negative pressure in the suction and release member 21 .
[0200] Since the clamping body 2211 is threadedly connected to one end of the first opening 2231' of the accommodating member 223', and the first opening 2231' of the accommodating member 223' is a through hole, the first opening 2231' of the accommodating member 223' can be made sealed by being connected to the other end of the first opening 2231' of the accommodating member 223' through the connecting member 252, so that the driving unit 251 can generate positive pressure or negative pressure in the suction and release member 21 through the connecting member 252 and the accommodating member 223'.
[0201] Therefore, the cleaning component 25 also includes a passage connector 253. Different from the above-mentioned embodiment, the passage connector 253 is connected to the end of the first opening 2231' of the container 223' away from the clamping unit 221. The passage connector 253 uses a valve connector, which connects the connecting member 252 and the container 223' through the valve connector, and keeps the container 223' and the connecting member 252 sealed. Specifically in this embodiment, a straight-through connector not shown in the figure is also provided in the first opening 2231' of the container 223', and the passage connector 253 and the clamping unit 221 are connected and sealed through the straight-through connector. It should be noted that the present application does not limit the type of the passage connector 253 and the specific structure in the first opening 2231' of the container 223', as long as the sealing connection between the connecting member 252 and the container 223' can be achieved.
[0202] Generally, the passage connection member 253 is a hollow structure, and forms a passage together with the connecting member 252 and the suction and release member 21. It is feasible that the passage connection member 253 and the receiving member 223' are threadedly connected to facilitate the connection and disassembly of the receiving member 223' and the cleaning assembly 25. It can be understood that as long as the connection between the passage connection member 253 and the receiving member 223' can be achieved, the connection method of the passage connection member 253 and the receiving member 223' is not limited, such as the passage connection member 253 and the receiving member 223' can be integrally formed.
[0203] The recovery component 26 is used to absorb and release cells that meet preset requirements. The recovery component 26 includes a driving unit 251, a connecting piece 252 and a passage connector 253. The specific functional relationship and positional relationship can refer to the description in the cleaning component 25. The use process of the recovery component 26 can refer to the description in the above embodiment, which will not be repeated here. Under the control of the control mechanism 60, the setting of the recovery component 26 realizes the absorption and release of cells, facilitates the cell sorting process, and improves the efficiency of cell sorting.
[0204] When the picking mechanism 20 is in use, the containing piece 223' and the picking moving component 23 are connected, the suction and release piece 21 is installed on the clamping unit 221, and then the clamping unit 221 installed with the suction and release piece 21 is connected to the containing piece 223', the first picking moving unit 231 drives the suction and release piece 21 to move, and the suction and release piece 21 is cleaned through the cleaning component 25, and then the first picking moving unit 231 drives the suction and release piece 21 to move, and the suction and release piece 21 is made to absorb and recover cells that meet preset requirements at a preset position through the recovery component 26, and finally, after the absorption is completed, the first picking moving unit 231 drives the suction and release piece 21 to move, and the suction and release piece 21 is cleaned through the cleaning component 25.
[0205] In some embodiments, see Fig.19 and Fig. 20 , shows the loading mechanism in some embodiments of the present application. The loading mechanism 30 is used to load and place the object to be sorted, and the object to be sorted contains cells to be sorted. Figure 2 The loading mechanism 30 and the selecting mechanism 20 are spaced apart from each other along the third direction S3 and are disposed between the imaging mechanism 40 and the selecting mechanism 20 .
[0206] The carrying mechanism 30 is configured to be mounted on the main body 10. In some embodiments, the carrying mechanism 30 is connected to the support seat 122 and is directly mounted on the main body 10. In some embodiments, the carrying mechanism 30 is connected to the imaging mechanism, and the imaging mechanism is mounted on the main body 10, so that the carrying mechanism 30 is indirectly mounted on the main body 10.
[0207] The carrying mechanism 30 can move the parts to be sorted to a preset position so that the cells that meet the preset requirements can be sucked and recovered under the action of the selection mechanism 20. The carrying mechanism 30 includes a carrying component 31 and a carrying and moving component 32. The carrying component 31 is used to carry the parts to be sorted, and the carrying component 31 is placed on the carrying and moving component 32. The carrying and moving component 32 can drive the carrying component 31 to move, so that the cells that meet the preset requirements in the parts to be sorted are spaced from the suction and release component 21 along the third direction S3. The setting of the carrying mechanism 30 realizes the placement and movement of the parts to be sorted, so that the cells that meet the preset requirements can be sucked and recovered, thereby improving the efficiency of cell sorting.
[0208] In some embodiments, see Fig.21 , shows a carrying assembly of a carrying mechanism 30 in some embodiments of the present application. The carrying assembly 31 includes a first carrying member 311 and a second carrying member 312. The first carrying member 311 and the second carrying member 312 are arranged at intervals along the third direction S3, the first carrying member 311 is movably connected to the second carrying member 312, the first carrying member 311 moves relative to the second carrying member 312 along the first direction S1, and the second carrying member 312 drives the first carrying member 311 to move along the second direction S2.
[0209] The first carrier 311 is used to accommodate the placement of the to-be-sorted object containing the cells to be sorted. The first carrier 311 can move along the first direction S1 relative to the base 121 of the main body 10 under the drive of the carrier moving assembly 32. The second carrier 312 is used to place the first carrier 311. The second carrier 312 can move along the second direction S2 relative to the base 121 of the main body 10 under the drive of the carrier moving assembly 32, so that the to-be-sorted object moves to the preset area relative to the base 121 of the main body 10, so as to achieve the absorption and recovery of cells that meet the preset requirements in the preset area of the to-be-sorted object. It can be understood that the moving directions of the first carrier 311 and the second carrier 312 can be set according to actual needs, and are not limited here. For example, the first carrier 311 can move along the second direction S2 under the drive of the carrier moving assembly 32, and the second carrier 312 can move along the first direction S1 under the drive of the carrier moving assembly 32.
[0210] See also Figure 2 and Fig. 22, shows the first carrier of the present application in some embodiments. The first carrier 311 is provided with a carrier portion 3111. On the one hand, the placement of the part to be sorted can be achieved through the carrier portion 3111. On the other hand, the imaging mechanism 40 can image the cells to be sorted placed in the part to be sorted through the carrier portion 3111 to obtain image information of the cells to be sorted. In order to make full use of the space of the first carrier 311 and improve the sorting efficiency of the cells to be sorted, the first carrier 311 is provided with a preset number of carrier portions 3111 to place a preset number of parts to be sorted. For example, the first carrier 311 is provided with three carrier portions 3111 spaced apart along the second direction S2 to achieve the sorting of the cells to be sorted placed in the three parts to be sorted.
[0211] In some embodiments, see Fig.21 The carrier assembly 31 further includes a third carrier 313, which is used to carry the first carrier 311 and the second carrier 312, and is spaced apart from the second carrier 312 along the third direction S3. The second carrier 312 moves relative to the third carrier 313 along the second direction S2.
[0212] In some embodiments, see Fig.21 The carrier assembly 31 further includes a storage unit 314 disposed on the first carrier 311. The storage unit 314 is used to store and hold cells that meet the preset requirements, so as to facilitate the subsequent cultivation of cells that meet the preset requirements. Figure 2 The cells that meet the preset requirements can be placed in the storage unit 314 after being sucked by the selection mechanism 20, and then the storage unit 314 is transferred to the incubator to carry out the next step of culturing the cells that meet the preset requirements.
[0213] The storage unit 314 is a porous structure as a whole. The setting of the porous structure can realize the recovery and placement of multiple cells, improve the efficiency of cell sorting, and improve the success rate and accuracy of cell sorting. For example, the storage unit 314 is provided with 96 holes. It should be noted that the number of holes in the storage unit 314 can be set according to actual needs and is not limited here.
[0214] See also Fig.25 , Fig.25The storage unit in some embodiments of the present application is shown. The storage unit 314 includes a support frame 3141 and a reaction tube 3142. The support frame 3141 can be reused, and the reaction tubes 3142 are arranged on the support frame 3141 at intervals along the second direction S2, and can be recovered and cultured separately. Preferably, the distances between the reaction tubes 3142 are the same. For example, the support frame 3141 has 8 reaction tubes 3142 equidistantly arranged along the first direction S1, and 12 reaction tubes 3142 equidistantly arranged along the second direction S2. It should be noted that as long as the recovery and culture of cells can be achieved, the material of the storage unit 314 is not limited, and different materials can be selected according to actual needs, such as the materials of the support frame 3141 and the storage portion 3142a component can be the same or different.
[0215] The support frame 3141 is provided with a through hole, and the reaction tube 3142 passes through the through hole to be combined with the support frame 3141. In order to facilitate the placement of the support frame 3141 and the determination of the position of the storage portion 3142a component, one of the corners of the support frame 3141 is set as a positioning chamfer. The other corners of the support frame 3141 except the positioning chamfer are set as rounded corners. The setting of the rounded corners can prevent the corners of the support frame 3141 from being sharp, which is convenient for the recovery and cultivation of the storage unit 314. The support frame 3141 is circumferentially provided with a skirt structure extending along the third direction S3. The setting of the skirt structure can strengthen the structural strength of the support frame 3141 itself and prevent the support frame 3141 from twisting and deforming. Furthermore, the skirt structure is stepped to facilitate the placement of the support frame 3141.
[0216] See also Fig.26 , Fig.26 Schematic diagram of the reaction tube 3142 in some embodiments of the present application is shown. The reaction tube 3142 includes a receiving portion 3142a and a placement platform 3142b for placing the receiving portion 3142a. The placement platform 3142b is provided with a placement hole corresponding to the receiving portion 3142a. The receiving portion 3142a is provided to provide a place for accommodating and culturing cells in accordance with preset requirements. Fig.24 The placement holes on the placement platform 3142b and the through holes of the support frame 3141 all correspond to the receiving portions 3142a one by one. The number of the receiving portions 3142a matches the number of the through holes.
[0217] One end of the storage portion 3142a extends along the third direction S3, and the size of at least part of the tube body gradually increases along the third direction S3 to form a cone, and the other end is set as an opening to achieve the placement of cells that meet the preset requirements. The cone-shaped design facilitates the recovery of cells. In some embodiments, the storage portion 3142a is a transparent storage portion 3142a, which helps to observe the cells that meet the preset requirements later.
[0218] The placement platform 3142b is in the shape of a square sheet, and positioning holes that are not on the same axis are set at both ends of the placement platform 3142b along the first direction S1. This arrangement facilitates the determination of the positions of different receiving portions 3142a. In some embodiments, the placement platform 3142b and the receiving portion 3142a are injection molded separately, and then connected by thermosetting to form the reaction tube 3142.
[0219] Specifically in the embodiment, each reaction tube 3142 includes a preset number of storage portions 3142a arranged in the first direction S1. The number of reaction tubes 3142 to be installed can be selected according to specific usage requirements, which is conducive to improving the flexibility of use of the storage unit 314, and is also conducive to further reducing consumables and avoiding waste. For example, the support frame 3141 has 96 mounting through holes. If a certain experiment requires the use of 32 storage portions 3142a, only 4 reaction tubes 3142 can be installed in the support frame 3141. It should be noted that the preset number of storage portions 3142a in each reaction tube 3142 can also be set to other arrangements, such as a plurality of storage portions 3142a array distribution or a plurality of storage portions 3142a rectangular distribution, etc.
[0220] See also Figure 19 to Figure 22 , a placement groove 3112 for placing the storage unit 314 is provided on the first carrier 311. The storage unit 314 is placed on the first carrier 311 through the placement groove 3112, so that the storage unit 314 is placed and fixed. Specifically, the storage unit 314 is placed on the first carrier 311 by matching the step skirt structure of the support frame 3141 with the placement groove 3112. The shape and size of the placement groove 3112 match the shape and size of the support frame 3141. Because the storage unit 314 and the to-be-selected parts are spaced apart along the first direction S1, correspondingly, the placement groove 3112 provided on the first carrier 311 is spaced apart from the carrier 3111 along the first direction S1. It can be understood that as long as the absorption and recovery of cells that meet the preset requirements can be achieved, the positions of the parts to be sorted and the storage unit 314 are not limited, such as the parts to be sorted and the storage unit 314 are arranged at intervals along the second direction S2 or the storage unit 314 is arranged at intervals along the circumference of the parts to be sorted.
[0221] Furthermore, in order to better fix the first carrier 311, the first carrier 311 is further provided with an elastic buffer 3113, which is provided at at least one corner of the placement groove 3112, and the storage unit 314 is fixed to the first carrier 311 through the elastic buffer 3113. Fig.25 and Fig.26In order to prevent the storage portion 3142a from touching the first carrier 311 and affecting the recovery of cells that meet the preset requirements, the first carrier 311 is provided with a through hole connected to the placement groove 3112. The size of the through hole is smaller than the size of the placement groove 3112, and a step is formed between the through hole and the placement groove 3112 to achieve the placement of the storage unit 314. As long as the normal placement of the storage portion 3142a can be guaranteed, the size of the through hole is not limited.
[0222] See again Fig.19 and Fig. 20 The loading and moving assembly 32 can drive the loading assembly 31 to move, thereby driving the to-be-sorted object to move, so that the cells that meet the preset requirements in the to-be-sorted object can be sucked, and then driving the storage unit 314 to move, so that the sucked cells that meet the preset requirements can be released into the storage unit 314. Figure 2 The control mechanism 60 can carry the moving component 32 to move, and control the selection mechanism 20 to absorb and release, so as to achieve the absorption and release of cells that meet the preset requirements.
[0223] In some embodiments, the loading and moving assembly 32 includes a first loading and moving unit 321 and a second loading and moving unit 322. The first loading and moving unit 321 is used to drive the loading assembly 31 to move along the first direction S1, and the second loading and moving unit 322 is used to drive the loading assembly 31 to move along the second direction S2. Specifically, the first loading and moving unit 321 is used to drive the first carrier 311 to move along the first direction S1, and the second loading and moving unit 322 is used to drive the second carrier 312 to move along the second direction S2.
[0224] In some embodiments, the first carrying and moving unit 321 includes a first carrying driving member 3211, a first carrying transmission member 3212, and a first carrying and moving member 3213. The first carrying driving member 3211 can drive the first carrying transmission member 3212 to rotate so as to realize the movement of the first carrying and moving member 3213 in the first direction S1. The first carrying and moving member 3213 is connected to the first carrying member 311, and the first carrying transmission member 3212 extends along the first direction S1. Under the drive of the first carrying driving member 3211, the first carrying and moving member 3213 drives the first carrying member 311 to move along the first direction S1.
[0225] Specifically, the first carrier driving member 3211 can use a stepping motor to achieve quantitative movement of the first carrier 311, thereby controlling the first carrier 311 and the to-be-selected parts and the storage unit 314 disposed on the first carrier 311 to move a preset distance in the first direction S1. It can be understood that as long as the movement of the carrier assembly 31 along the first direction S1 can be achieved, the type of the first carrier driving member 3211 is not limited.
[0226] Preferably, the first carrier drive member 3211 uses a five-phase stepper motor. The five-phase stepper motor can achieve high-precision positioning of the first carrier member 311, and the static angle error during micro-step drive control can achieve high precision that is basically unchanged compared to full-step drive. Compared with other stepper motors, the five-phase stepper motor also achieves low vibration and low noise drive. The five-phase stepper motor helps to achieve high-precision automatic movement of the carrier assembly 31.
[0227] In some embodiments, in order to facilitate the first carrier 311 to move along the first direction S1, the first carrier moving unit 321 further includes a first carrier guide 3214. The first carrier guide 3214 extends along the first direction S1 so that the first carrier 311 moves along the first direction S1. The first carrier guides 3214 are arranged at intervals on both sides of the second carrier 312 along the second direction S2. The first carrier guides 3214 arranged at intervals can ensure the stability of the first carrier 311 when moving along the first direction S1. It should be noted that the extension lengths of the first carrier transmission member 3212 and the first carrier guide 3214 are determined by the movement stroke of the first carrier 311.
[0228] To facilitate the installation of the first loading guide 3214, refer to Fig.23 , shows the second carrier and the first carrier moving unit in some embodiments of the present application. The second carrier 312 is provided with a first carrier guide groove 3121, and the first carrier guide 3214 is provided in the first carrier guide groove 3121 to ensure the stability of the first carrier 311 when moving. It can be understood that the first carrier guide 3214 can also be provided on the surface of the second carrier 312.
[0229] In some embodiments, the first loading and moving unit 321 further includes a first loading sliding member 3215. The first loading sliding member 3215 is disposed on the first loading guide 3214 and connected to the first loading member 311. The first loading sliding member 3215 slides on the first loading guide 3214, driving the first loading member 311 to move along the first direction S1. The provision of the first loading sliding member 3215 reduces the loss when the first loading member 311 moves, and helps to improve the movement stability and displacement accuracy of the first loading member 311. Further, each first loading guide 3214 is provided with a preset number of first loading sliding members 3215, and the first loading sliding members 3215 are arranged at intervals on the first loading guide 3214 along the first direction S1. The preset number of first loading sliding members 3215 further ensures the stability of the first loading member 311 when it moves.
[0230] In some embodiments, the first loading and moving unit 321 also includes a displacement sensor not shown in the figure. The setting of the displacement sensor can obtain the position information of the to-be-sorted parts and the storage unit 314, so that the control mechanism 60 can control the automatic movement of the loading assembly 31 to improve the efficiency of cell sorting. Specifically, the displacement sensor adopts a grating displacement sensor. The grating displacement sensor has high measurement accuracy and resolution, good stability, strong anti-interference ability, is easy to interface with a microcomputer, and is suitable for long-distance transmission. It can be understood that as long as the position information of the loading assembly 31 can be obtained, the type of displacement sensor is not limited.
[0231] In some embodiments, see Fig.19 and Fig. 20 The second carrying and moving unit 322 includes a second carrying driving member 3221, a second carrying transmission member 3222 and a second carrying and moving member 3223. The second carrying driving member 3221 can drive the second carrying transmission member 3222 to rotate and thus realize the movement of the second carrying and moving member 3223 in the second direction S2. The second carrying and moving member 3223 is connected to the second carrying member 312, and the second carrying transmission member 3222 extends along the second direction S2. Under the drive of the second carrying driving member 3221, the second carrying member 312 is realized to move along the second direction S2.
[0232] Specifically, the second carrier drive member 3221 is a stepper motor, which realizes the quantitative movement of the second carrier member 312, thereby controlling the to-be-sorted parts and the storage unit 314 to move a preset distance in the second direction S2. It can be understood that as long as the movement of the carrier assembly 31 along the second direction S2 can be achieved, the type of the second carrier drive member 3221 is not limited. Preferably, the second carrier drive member 3221 is also a five-phase stepper motor. The setting of the five-phase stepper motor is more conducive to realizing the high-precision automatic movement of the carrier assembly 31. The movement accuracy of the carrier assembly 31 must meet the movement requirements of the to-be-sorted parts, that is, the absorption of adjacent cells that meet the preset requirements is not disturbed, such as the movement accuracy of the carrier assembly 31 is 2 microns.
[0233] In some embodiments, the second carrying moving unit 322 further includes a second carrying guide 3224, which extends along the second direction S2 and is arranged on the third carrying member 313 at intervals along the first direction S1. The second carrying guide 3224 is arranged to facilitate the movement of the second carrying member 312. It should be noted that the extension length of the second carrying transmission member 3222 and the second carrying guide 3224 is determined by the movement stroke of the second carrying member 312.
[0234] See also Fig.24, shows the third carrier and the second carrier moving unit in some embodiments of the present application. The third carrier 313 is provided with a second carrier guide groove 3131, and the second carrier guide 3224 is provided in the second carrier guide groove 3131 to ensure the stability of the second carrier 312 when moving. It can be understood that the second carrier guide 3224 and the second carrier guide groove 3131 can also be provided inversely, that is, the second carrier guide 3224 is provided on the third carrier 313, and the second carrier guide groove 3131 is provided on the second carrier.
[0235] In some embodiments, the second loading and moving unit 322 further includes a second loading sliding member 3225. The second loading sliding member 3225 is disposed on the second loading guide 3224 and connected to the second loading member 312. The second loading sliding member 3225 slides on the second loading guide 3224 to drive the second loading member 312 to move, reduce the wear of the second loading member 312 during movement, and improve the stability and position accuracy of the second loading member 312 during movement. Further, each second loading guide 3224 is provided with a preset number of second loading sliding members 3225, and the second loading sliding members 3225 are arranged at intervals on the second loading guide 3224 along the first direction S1. The preset number of second loading sliding members 3225 further ensures the stability of the second loading member 312 during movement.
[0236] In some embodiments, the second loading and moving unit 322 further includes a displacement sensor. The displacement sensor adopts a proximity displacement sensor. The proximity displacement sensor has a simple structure, is stable and reliable, and has high measurement accuracy and sensitivity. It can be understood that as long as the displacement information of the second loading member 312 can be obtained, the type and installation position of the displacement sensor are not limited.
[0237] See also Fig.23 and Fig.24 The first loading and moving unit 321 is disposed on one side of the second loading member 312 in the second direction S2, and the second loading and moving unit 322 is disposed on one side of the third loading member 313 in the first direction S1. It should be noted that as long as the first loading member 311 can move along the first direction S1 and the second loading member 312 can move along the second direction S2, the installation positions of the first loading and moving unit 321 and the second loading and moving unit 322 are not limited.
[0238] See again Fig.19 The loading mechanism 30 further includes a loading limiter assembly 33. The loading limiter assembly 33 is disposed on the loading assembly 31 and is used to fix the object to be sorted on the loading assembly 31. The loading limiter assembly 33 includes an elastic member 331 and a biasing connecting member 332. The elastic member 331 is configured to surround the surface of the object to be sorted and bias the object to be sorted in the radial direction of the object to be sorted. Fig. 20, the biasing connecting member 332 is arranged on the first carrier 311 at intervals along the second direction S2, and the elastic member 331 is sleeved on the biasing connecting member 332. Specifically in the embodiment, the biasing connecting member 332 is arranged along the circumference of the carrying portion 3111 of the first carrier 311, so that the elastic member 331 can bias and limit the part to be selected placed on the first carrier 311. After the part to be selected is placed on the first carrier 311, the elastic member 331 is pulled from one side of the carrying portion 3111 to the other side of the carrying portion 3111, biased to the part to be selected, so that the part to be selected is against the carrying portion 3111, to ensure the stability of the part to be selected during placement and subsequent movement.
[0239] In some embodiments, the loading and limiting assembly 33 further includes a limiting member 333. The setting of the limiting member 333 enables the to-be-selected parts of different sizes to be fixed in the loading part 3111. The shape and size of the inner diameter of the limiting member 333 are substantially consistent with the shape and size of the outer diameter of the to-be-selected part, so that the outer wall of the to-be-selected part fits the inner wall of the limiting member 333, and the shape and size of the outer diameter of the limiting member 333 are substantially consistent with the shape and size of the limiting groove in the loading part 3111, and the outer wall of the limiting member 333 fits the limiting groove in the loading part 3111, so as to realize the limiting of the to-be-selected part on the first loading part 311.
[0240] Further to the embodiment, combined with Fig. 22 , the limiter 333 can be made of silicone material. The setting of the limiter 333 increases the friction between the part to be sorted and the carrier 3111, making the part to be sorted more stable. The elastic member 331 can be biased on the limiter to provide a buffer for the part to be sorted, avoid or reduce the damage of the elastic member 331 to the part to be sorted, and ensure the normal use of the part to be sorted. It can be understood that the material, shape and size of the limiter 333 can be set according to actual needs and are not limited here.
[0241] In other embodiments, the limiting member 333 may also be a clamping member, and a preset number of clamping members are arranged at intervals on the limiting groove of the loading portion 3111. By setting the clamping member, the position of the part to be sorted in the loading portion 3111 is limited. The clamping member may be a spring, a spring pin, etc. When the part to be sorted is placed in the loading portion 3111, the part to be sorted presses the clamping member in the loading portion 3111, and the clamping member is compressed and exerts pressure on the part to be sorted, thereby fixing the part to be sorted in the loading portion 3111. It can be understood that the number and position of the clamping members can be set according to actual needs and are not limited here.
[0242] In some feasible embodiments, the position limiting member 333 may be a fastener, and the member to be selected is fixed in the loading portion 3111 by arranging the fastener on the inner wall of the loading portion 3111. The position limiting member may also be a clamping member, and the member to be selected is fixed in the loading portion 3111 by arranging the clamping member on the peripheral side of the loading portion 3111. It can be understood that as long as the member to be selected can be fixed in the loading portion 3111, the combination of the position limiting member and the member to be selected is not limited.
[0243] When the loading mechanism 30 is working, the object to be sorted is placed on the loading component 31, and the object to be sorted is limited by the loading limit component 33. The loading moving component 32 drives the object to be sorted to move to achieve the absorption of cells that meet the preset requirements, and then drives the storage unit 314 to move to achieve the recovery and cultivation of cells that meet the requirements.
[0244] Specifically, when sucking cells that meet the preset requirements, under the control of the control mechanism 60, the first loading and moving unit 321 drives the to-be-sorted member to move in the first direction S1, and the second loading and moving unit 322 drives the to-be-sorted member to move in the second direction S2, until the cells that meet the preset requirements are spaced apart from the suction and placement member 21 in the third direction S3. The selection moving assembly 23 drives the suction and placement member 21 to move to a preset position, and the driving unit 251 drives the suction and placement member 21 to suck the cells that meet the preset requirements into the hollow pipe 211, thereby completing the suction of the cells that meet the preset requirements.
[0245] Afterwards, the selection moving assembly 23 drives the suction and release opening 212 of the suction and release member 21 to move upward, the first loading moving unit 321 drives the storage unit 314 to move in the first direction S1, and the second loading moving unit 322 drives the storage unit 314 to move in the second direction S2, until the corresponding storage portion 3142a is spaced apart from the suction and release member 21 in the third direction S3. The selection moving assembly 23 drives the suction and release member 21 to move to a preset position, and the driving unit 251 drives the suction and release member 21 to release cells that meet the preset requirements into the storage unit 314, completing the recovery and cultivation of cells that meet the preset requirements.
[0246] In some embodiments, see Fig. 27 and Fig.28 , shows an imaging mechanism in some embodiments of the present application. The imaging mechanism 40 is used for imaging the cells to be sorted and obtaining image information of the cells to be sorted, so as to select cells that meet the preset requirements. The imaging mechanism 40 includes an imaging lighting unit 41, an optical path component 42, a fluorescent component 43 and a detection component 44.
[0247] The imaging lighting unit 41 provides a bright field lighting source for the cells to be sorted and the optical path component 42, irradiates the cells to be sorted with transmitted light, and the transmitted light reaches the detection component 44 through the optical path component 42, and the image information of the cells to be sorted is obtained through the detection component 44. Figure 2 and Fig. 9 The imaging lighting unit 41 is spaced apart from the optical path component 42 along the third direction S3, and the part to be sorted is arranged between the imaging lighting unit 41 and the optical path component 42 along the third direction S3, so that the transmitted light emitted by the imaging lighting unit 41 enters the optical path component 42 after passing through the part to be sorted, thereby realizing the imaging of the cells to be sorted.
[0248] See again Figure 8 and Fig. 9 The imaging lighting unit 41 is used to illuminate the cells to be sorted, providing a certain observation brightness for the cells to be sorted. The imaging lighting unit 41 is connected to the mounting assembly 22 along the third direction S3. Figure 2 and Fig. 9 , the imaging lighting unit 41 is connected to the accommodating member 223 along the third direction S3. The imaging lighting unit 41 is closer to the suction and release opening 212 of the suction and release member 21 than the selection lighting unit 24. The imaging lighting unit 41 and the selection lighting unit 24 are spaced apart along the axial direction of the suction and release member 21 and the third direction S3.
[0249] In some embodiments, the imaging lighting unit 41 includes an imaging light source 411, a shading member 412, and a light-transmitting member 413. The light emitted by the imaging light source 411 passes through the shading member 412 and the light-transmitting member 413 to the cells to be sorted, and illuminates the cells to be sorted along the periphery of the suction and release member 21. The imaging light source 411 is connected to the mounting assembly 22 along the third direction S3, so that the light can be transmitted to the imaging mechanism 40 to meet the lighting requirements of the imaging mechanism 40. It should be noted that the position of the imaging light source 411 is set according to actual conditions.
[0250] The imaging light source 411 is provided with a central hole for the suction and placement member 21 to pass through, so that the suction and placement member 21 can pass through the imaging light source 411. Fig.12 and Fig.13 The first clamping driving member 2212 is connected to the imaging light source 411 through a central hole, and the diameter of the central hole is slightly larger than the outer diameter of the second clamping driving portion 2212c of the first clamping driving member 2212. The central axis of the imaging light source 411 in the third direction S3 coincides with or is parallel to the central axis of the suction and placement member 21 in the third direction S3, so as to facilitate the illumination of the imaging light source 411.
[0251] In some embodiments, the imaging light source 411 is a ring light source, which provides bright and uniform illumination for a large visual field. Further, the imaging light source 411 is an LED light source. The ring LED light source can adopt the entire ring light source, or it can be obtained by circumferentially evenly arranging multiple light sources, so that the imaging light source 411 irradiates the cell area to be sorted from the radial periphery of the suction and release member 21. It should be noted that the type of the ring light source is not limited to an LED light source.
[0252] Further to some embodiments, see Fig. 9 The imaging light source 411 and the receiving member 223 are detachably connected. The detachable connection facilitates the installation and replacement of the suction and placement member 21, preventing the suction and placement member 21 from touching the imaging light source 411 during installation and replacement, thereby causing damage to the suction and placement member 21; on the other hand, it facilitates the installation and replacement of the imaging light source 411.
[0253] In some embodiments, when the cell sorting device 100 is used, the suction and release member 21 is first installed on the clamping unit 221, and then the clamping unit 221 is placed in the receiving member 223, and finally the imaging lighting unit 41 is passed through the suction and release member 21 along the third direction S3 and connected to the receiving member 223 to avoid the suction and release member 21 hitting the imaging lighting unit 41 during installation, causing damage to the suction and release member 21.
[0254] Specifically in the embodiment, the imaging light source 411 and the container 223 are connected magnetically. In one embodiment, a magnet is provided on the end face of the imaging light source 411, and the container 223 is made of metal. The light source cover and the container 223 are connected magnetically by magnets adsorbing the metal material. In a feasible embodiment, the container 223 is made of non-metallic material, and a magnetic metal part is provided on the container 223, and the magnetic connection between the light source cover and the container 223 is achieved by magnets adsorbing the magnetic metal part. It can be understood that the positions of the magnets and the magnetic metal parts can be interchanged and the specific setting positions are not limited. For example, the light source cover is provided with a magnetic metal part, and the container 223 is provided with a magnet to achieve the connection between the light source cover and the container 223. The magnetic connection makes it easy to disassemble the connection between the mounting assembly 22 and the lighting assembly 24, which is convenient for the installation and replacement of the suction and release member 21. At the same time, the magnetic connection does not destroy the structure of the mounting assembly 22 and the lighting assembly 24, which is reliable and stable, convenient and fast, and does not require precise alignment.
[0255] In an embodiment not shown in the figure, the imaging light source 411 is provided with a groove, and the receiving member 223 is provided with a protrusion for matching with the groove. The combination of the groove and the protrusion realizes the detachable connection between the mounting assembly 22 and the lighting assembly 24. It can be understood that as long as the connection between the imaging light source 411 and the receiving member 223 can be realized, the connection method between the imaging light source 411 and the receiving member 223 is not limited to a detachable connection, such as the imaging light source 411 being glued to the receiving member 223.
[0256] In some embodiments, the light-transmitting member 413 and the light-shielding member 412 jointly limit the scattering of the light of the imaging light source 411. The light-shielding member 412 is arranged between the imaging light source 411 and the light-transmitting member 413 along the third direction S3. The light-shielding member 412 is a hollow cylindrical shape as a whole, extending along the third direction S3 to realize the penetration of the suction and release member 21. The outer diameter size of the light-shielding member 412 matches the outer diameter size of the imaging light source 411. The light-transmitting member 413 is a transparent ring as a whole, and is provided with a center hole. The outer diameter size of the light-transmitting member 413 matches the outer diameter size of the imaging light source 411, and the shape and size of the center hole match the outer diameter shape and size of the suction and release member 21, which is used for the penetration of the suction and release member 21. The light-transmitting member 413 can be made of an acrylic plate. It can be understood that as long as the scattering of light and the transmission of light can be limited, the shape, size and material of the light-shielding member 412 and the light-transmitting member 413 are not limited.
[0257] In some embodiments, the light-transmitting member 413, the light-shielding member 412 and the imaging light source 411 are detachably connected. The detachable connection facilitates maintenance and replacement. Specifically, the light-transmitting member 413, the light-shielding member 412 and the imaging light source 411 are all coaxially provided with threaded holes in the third direction S3, and the light-transmitting member 413, the opaque member 413 and the imaging light source 411 are connected by fasteners through the threaded holes. It should be noted that the imaging light source 411, the light-shielding member 412 and the light-transmitting member 413 are not limited to detachable connections, and the connection between the imaging light source 411, the light-shielding member 412 and the light-transmitting member 413 can also be achieved by gluing.
[0258] In the case where the imaging light source 411 is a light source for transmitted light, the imaging light source 411 can be any light source as long as it emits light containing a wavelength that can be absorbed or reflected by the cells to be sorted. As the imaging light source 411, various lamps such as halogen lamps, light emitting diodes, and various lasers can be used. The image from the cells to be sorted can be image information such as a bright field image or a dark field image. Further, in some embodiments, the brightness of the imaging light source 411 can be adjusted, so that the imaging light source 411 can be applied to more occasions and facilitates brightness adjustment of image information.
[0259] In some other feasible embodiments, combined with Figure 38 to Figure 43In order to prevent the imaging lighting unit 2 from causing damage to the suction and release member 21 during installation, the cell sorting device 100 also includes an avoidance mechanism for the suction and release member. The avoidance mechanism for the suction and release member includes the container 223', the imaging lighting unit 41 and the avoidance unit 80 in the above-mentioned embodiment. The imaging lighting unit 41 and the container 223' are arranged at intervals along the axial direction of the suction and release member 21. The imaging lighting unit 41 includes a first imaging lighting unit 414 and a second imaging lighting unit 415. The first imaging lighting unit 414 has a first bonding surface 4141, and the second imaging lighting unit 415 has a second bonding surface 4151. The first bonding surface 4141 and the second bonding surface 4151 are arranged opposite to each other. The avoidance unit 80 is connected to the first imaging lighting unit 414 and the second imaging lighting unit 415 and can drive the first imaging lighting unit 414 and the second imaging lighting unit 415 to move.
[0260] The imaging lighting unit 41 has an open state and a closed state. In the open state, the avoidance unit 80 can drive the first joint surface 4141 and the second joint surface 4151 to separate from each other, so that the suction and release member 21 can pass through the imaging lighting unit 41, that is, when the suction and release member 21 is installed, the imaging lighting unit 41 can avoid the suction and release member 21 to avoid damage to the suction and release member 21. In the closed state, the avoidance unit 80 can drive the first joint surface 4141 and the second joint surface 4151 to fit each other, so that the imaging lighting unit 41 can operate normally.
[0261] The first coupling surface 4141 of the first imaging lighting unit 414 and the second coupling surface 4151 of the second imaging lighting unit 415 are driven to separate by the avoidance unit 80, so that when the suction and release member 21 is installed to the receiving member 223' along with the clamping unit 221, the suction and release member 21 can be installed without touching the imaging lighting unit 41, thereby effectively avoiding damage to the suction and release member 21 during the installation process, improving the installation reliability of the suction and release member 21, and thus helping to improve the efficiency of cell sorting.
[0262] In a feasible embodiment, the avoidance unit 80 includes a first avoidance member 81 and a second avoidance member 82, one end of the first avoidance member 81 is rotatably connected to the accommodating member 223', the other end of the first avoidance member 81 is connected to the first imaging lighting unit 414, one end of the second avoidance member 82 is rotatably connected to the accommodating member 223', the other end of the first avoidance member 81 is connected to the first imaging lighting unit 414, the first avoidance member 81 is engaged with the second avoidance member 82, and the first avoidance member 81 and the second avoidance member 82 can drive the first joint surface 4141 and the second joint surface 4151 to separate or fit together when rotating relative to the accommodating member 223'.
[0263] The first avoidance member 81 rotates relative to the accommodating member 223' and drives the second avoidance member 82 engaged with the first avoidance member 81 to rotate relative to the accommodating member 223'. Since the rotation directions of the first avoidance member 81 and the second avoidance member 82 are opposite, the first bonding surface 4141 and the second bonding surface 4151 can be separated from or attached to each other.
[0264] In other embodiments, the first imaging lighting unit 414 and the second imaging lighting unit 415 may be driven to move respectively by a motor or other structure, thereby providing an avoidance space for the installation of the suction and release member 21 .
[0265] In some embodiments, the accommodating member 223' is provided with a first opening 2231'2231 for installing the clamping unit 221, and the imaging lighting unit 41 is provided with a avoidance hole 416 for fixing the suction and release member 21, and the first opening 2231'2231 and the avoidance hole 416 are coaxially arranged. The coaxial arrangement of the first opening 2231'2231 and the avoidance hole 416 contributes to the accuracy and reliability of the installation of the clamping unit 221, and in the closed state, the suction and release member 21 can be accommodated in the avoidance hole 416, thereby avoiding damage to the suction and release member 21 by the imaging lighting unit 41.
[0266] Specifically in this embodiment, the accommodating member 223' includes an accommodating portion 2238 and a mounting portion 2239. The accommodating portion 2238 is extended along the axial direction of the suction and release member 21 and is corresponding to the imaging lighting unit 41. The mounting portion 2239 is connected to the accommodating portion 2238 and is extended along the axial direction perpendicular to the suction and release member 21. The first avoidance member 81 and the second avoidance member 82 are both rotatably connected to the mounting portion 2239. The mounting portion 2239 and the accommodating portion 2238 are arranged to facilitate the installation and fixation of the clamping unit 221 and the avoidance unit 80. Fig.41 In this embodiment, the side of the mounting portion 2239 facing the suction and release member 221 is connected to the avoidance unit 80 , and the side of the mounting portion 2239 facing away from the suction and release member 221 is connected to the third selection moving unit 233 .
[0267] Specifically, the first imaging lighting unit 414 includes a first imaging light source 4142, and the second imaging lighting unit 415 includes a second imaging light source 4152. In a closed state, the first imaging light source 4142 and the second imaging light source 4152 can be arranged together around the periphery of the suction and placement member 21, so that the light emitted by the first imaging light source 4142 and the second imaging light source 4152 can illuminate the cells to be sorted along the periphery of the suction and placement member 21. The illumination of the cells to be sorted is achieved by the first imaging light source 4142 and the second imaging light source 4152.
[0268] The first imaging lighting unit 414 further includes a first light shielding member 4143 and a first light transmitting member 4144, and the second imaging lighting unit 415 further includes a second light shielding member 4153 and a second light transmitting member 4154. Light emitted by the first imaging light source 4142 and the second imaging light source 4152 passes through the passages of the first light shielding member 4143 and the second light shielding member 4153 and the passages of the first light transmitting member 4144 and the second light transmitting member 4154 to provide illumination for the cells to be sorted. The arrangement of the first light shielding member 4143 and the first light transmitting member 4144 and the second light shielding member 4153 and the second light transmitting member 4154 reduces the scattering of light.
[0269] Further, the first imaging lighting unit 414 further includes a first combining member 4146, and the first imaging lighting unit 414 further includes a second combining member 4156. The first combining member 4146 is connected to the first light shielding member 4143 and is extended along the axial direction perpendicular to the suction and release member 21. One end of the first avoidance member 81 is connected to the first combining member 4146, and the second combining member 4156 is connected to the second light shielding member 4153 and is extended along the axial direction perpendicular to the suction and release member 21. One end of the second avoidance member 82 is connected to the second combining member 4156. The first combining member 4146 and the second combining member 4156 are provided to facilitate the connection between the avoidance unit 80 and the imaging lighting unit 41, so that the avoidance unit 80 can drive the first imaging lighting unit 414 and the second imaging lighting unit 415 to move. Optionally, the first combining member 4146 and the first light shielding member 4143 are integrally formed, and the second combining member 4156 and the second light shielding member 4153 are integrally formed.
[0270] Furthermore, a first operating portion 4145 protruding from the first imaging lighting unit 414 is provided on the first light shielding member 4143 of the first imaging lighting unit 414, and a second operating portion 4155 protruding from the second imaging lighting unit 415 is provided on the second light shielding member 4153 of the second imaging lighting unit 415. The first operating portion 4145 is used to drive the first avoidance member 81 to rotate relative to the accommodating member 223', and the second operating portion 4155 is used to drive the second avoidance member 82 to rotate relative to the accommodating member 223'. The first operating portion 4145 and the second operating portion 4155 are provided to facilitate the rotation of the avoidance unit 80, thereby improving the convenience of operation of the avoidance unit 80.
[0271] The functions and connection methods of the first imaging light source 4142, the first light shading member 4143 and the first light transmitting member 4144 and the second imaging light source 4152, the second light shading member 4153 and the second light transmitting member 4154 can refer to the functions and connection methods of the imaging light source 411, the light shading member 412 and the light transmitting member 413 in the above-mentioned embodiments.
[0272] Preferably, the first imaging lighting unit 414 and the second imaging lighting unit 415 and the first avoidance member 81 and the second avoidance member 82 are symmetrically arranged on both sides of the central axis of the suction and release member 21 to ensure that the first imaging lighting unit 414 and the second imaging lighting unit 415 have the same movement stroke in the open state, so as to ensure that in the closed state, the first joint surface 4141 can be stably and accurately attached to the second joint surface 4151, so that the imaging lighting unit 41 can be used normally. Feasibly, the first imaging lighting unit 414 and the second imaging lighting unit 415 have the same structure and size, and the first avoidance member 81 and the second avoidance member 82 have the same structure and size.
[0273] When the cell sorting device 100 is in use, the first operating part 4145 is first used to drive the first imaging lighting unit 414 to move in a preset direction, so that the first avoidance member 81 rotates relative to the accommodating member 223', and drives the second avoidance member 82 to rotate in the opposite direction, and the second avoidance member 82 drives the second imaging lighting unit 415 to move in a direction opposite to the preset direction, so that the first combining surface 4141 and the second combining surface 4151 are separated, or the second operating part 4155 is first used to drive the second imaging lighting unit 415 to move in a preset direction, so that the second avoidance member 82 rotates relative to the accommodating member 223', and drives the first avoidance member 81 to rotate in the opposite direction, and the first avoidance member 81 drives the first imaging lighting unit 414 to move in a direction opposite to the preset direction, so that the first combining surface 4141 and the second combining surface 4151 are separated, so that the imaging lighting unit 41 is in an on state.
[0274] Then, the suction and placement member 21 is installed to the clamping unit 221 , and the clamping unit 221 is installed in the receiving member 223 ′.
[0275] Finally, the first operating part 4145 is used to drive the first imaging lighting unit 414 to move in a direction opposite to the preset direction, so that the first avoidance member 81 rotates relative to the accommodating member 223', and drives the second avoidance member 82 to rotate in the opposite direction, and the second avoidance member 82 drives the second imaging lighting unit 415 to move in the preset direction, so that the first combining surface 4141 and the second combining surface 4151 are fitted together, and the suction and release member 21 is accommodated in the avoidance hole 416; or the second operating part 4155 is used to drive the second imaging lighting unit 415 to move in a direction opposite to the preset direction, so that the second avoidance member 82 rotates relative to the accommodating member 223', and drives the first avoidance member 81 to rotate in the opposite direction, and the first avoidance member 81 drives the first imaging lighting unit 414 to move in the preset direction, so that the first combining surface 4141 and the second combining surface 4151 are fitted together, and the suction and release member 21 is accommodated in the avoidance hole 416. This installation method can effectively prevent the suction and placement member 2121 from being damaged due to collision with the imaging lighting unit 4141 during installation.
[0276] In some embodiments, see Fig.28 , the optical path component 42 is used to form the optical path of the imaging mechanism 40, and is configured with an optical element for forming a transmission optical path to realize the imaging of the cells to be sorted. The optical path component 42 includes an objective lens 421 and a first imaging lens 422. The objective lens 421 has a certain focal length, and the preset area of the object to be sorted is spaced apart from the objective lens 421 along the third direction S3, and the objective lens 421 images the cells to be sorted in the preset area. The objective lens 421 and the first imaging lens 422 are spaced apart along the third direction S3 to form the transmission light path of the imaging mechanism 40. The transmission light emitted by the imaging light source 411 passes through the cells to be sorted, the objective lens 421 and the first imaging lens 422 in sequence to the detection component 44. Specifically, the objective lens 421 can be selected as a 10x objective lens 421. It should be noted that the multiple of the objective lens 421 can be set according to actual needs and is not limited here. In other embodiments, the optical path component 42 may include multiple objective lenses 421 to obtain image information of the cells to be sorted at different multiples. Since the objective lens 421 and the first imaging lens 422 are disposed on one side of the cells to be sorted in the third direction S3, the light generated by the imaging light source 411 at the cells to be sorted may not be transmitted light but reflected light.
[0277] In some embodiments, see Fig. 27 and Fig.28 The optical path assembly 42 further includes an objective lens moving unit 423. The objective lens moving unit 423 is used to focus the objective lens 421, change the focal length between the objective lens 421 and the object to be sorted, so that the imaging of the cells to be sorted is clear, and the imaging mechanism 40 obtains clear image information of the cells to be sorted. The objective lens moving unit 423 can drive the objective lens 421 to move along the third direction S3 relative to the object to be sorted, so that the image information of the cells to be sorted is clear.
[0278] In some embodiments, the objective lens moving unit 423 includes a first rotating member 4231 and a second rotating member not shown in the figure, and the first rotating member 4231 and the second rotating member are arranged relatively along the second direction S2. The first rotating member 4231 and the second rotating member can both move the objective lens 421 along the third direction S3 to achieve the focusing of the objective lens 421, wherein the second rotating member can realize the automatic movement of the objective lens 421 under the control of the control mechanism 60, and the first rotating member 4231 is not controlled by the control mechanism 60, and can realize the movement of the objective lens 421 under the action of an external force. The arrangement of the first rotating member 4231 and the second rotating member enables the objective lens 421 to adjust the focus automatically or manually, thereby improving the applicability of the cell sorting device 100.
[0279] In some embodiments, the objective lens moving unit 423 further includes an objective lens driving member 4232. The objective lens driving member 4232 is connected to the control mechanism 60, and can drive the second rotating member to rotate, so that the objective lens 421 moves along the third direction S3, and adjusts the distance between the objective lens 421 and the cells to be sorted to achieve the focusing of the objective lens 421, and obtains high-definition image information of the cells to be sorted. The objective lens driving member 4232 can use a stepping motor to accurately control the moving distance of the objective lens 421, and achieve coarse adjustment and fine adjustment during the focusing process of the objective lens 421.
[0280] In some embodiments, the objective lens moving unit 423 further includes a displacement sensor not shown. The arrangement of the displacement sensor facilitates the control of the displacement of the objective lens 421, and helps to achieve automatic focusing of the objective lens 421. In this embodiment, the displacement sensor is a grating displacement sensor. It can be understood that as long as the position information of the carrier assembly 31 can be obtained, the type of the displacement sensor is not limited.
[0281] In some embodiments, the objective lens moving unit 423 also includes an objective lens limiter not shown in the figure. The setting of the objective lens limiter limits the moving range of the objective lens 421. Combined with the displacement sensor, the highest position and the lowest position of the objective lens 421 can be obtained to prevent the objective lens 421 from colliding with the loading mechanism 30 and damaging the objective lens 421, thereby facilitating the automatic movement of the objective lens 421 to achieve focusing.
[0282] Combination Figure 19 to Figure 22 , the first carrier 311 is set as a step-like structure in the third direction S3, on the one hand, to prevent the second carrier 312 from colliding with the storage unit 314, and on the other hand, to provide a moving distance for focusing for the objective lens 421, to prevent the objective lens 421 from colliding with the first carrier 311 during the focusing process, and to damage the objective lens 421. Further, the mirror surface of the objective lens 421 is arranged between the first carrier 311 and the second carrier 312 in the third direction S3, so as to better realize the focusing of the objective lens 421 and ensure that the image information of the cells to be sorted is clear. The third carrier 313 is provided with an observation hole 3132, so as to facilitate the focusing of the objective lens 421 and prevent the objective lens 421 from colliding with the third carrier 313. The second carrier 312 is provided with a through hole for the focusing of the objective lens 421 to pass through, and the size of the through hole should ensure that the movement of the second carrier 312 will not collide with the objective lens 421, so as to ensure the normal use of the cell sorting device 100.
[0283] Combination Figure 2 In some embodiments, the objective lens 421 is coincident or parallel to the central axis of the suction and placement member 21 in the third direction S3. The coincidence or parallelism of the central axis of the objective lens 421 and the suction and placement member 21 is conducive to improving the accuracy of the suction and placement member 21 in sucking cells that meet the preset requirements, and improving the sorting efficiency of the cell sorting device 100.
[0284] See again Fig. 27 and Fig.28 , the fluorescent component 43 is used to make the cells to be sorted emit fluorescence, and find the cells that meet the preset requirements through the fluorescent image information of the cells to be sorted. The fluorescent component 43 and the optical path component 42 are arranged on the same side of the cells to be sorted. The fluorescent component 43 includes an excitation light source 431 and a filter unit 432. The excitation light source 431 is used to irradiate the cells to be sorted and make the cells to be sorted emit fluorescence. The excitation light source 431 can be any light source that can make the cells to be sorted emit fluorescence. As the excitation light source 431, lamps such as xenon lamps, mercury lamps, various lasers such as argon lasers, and light-emitting diodes can be used.
[0285] The filter unit 432 is a core component of the imaging mechanism 40 for realizing fluorescence imaging. In some embodiments, the filter unit 432 is arranged between the objective lens 421 and the first imaging lens 422 along the third direction S3, and includes a first beam splitter 4321. The first beam splitter 4321 can reflect the light emitted by the excitation light source 431, and can allow the transmitted light and fluorescence of the cells to be sorted to pass through, so that the detection component 44 obtains the image information of the cells to be sorted. The first beam splitter 4321 can separate the wavelength of the imaging light source 411 from the wavelength of the fluorescence generated by the cells to be sorted, such as by using a dichroic mirror, a dichroic mirror, etc. The first beam splitter 4321 is arranged between the objective lens 421 and the first imaging lens 422 along the third direction S3, and the first beam splitter 4321 is arranged at an angle with the third direction S3. The first beam splitter 4321 is arranged at intervals with the excitation light source 431 along the second direction S2 to reflect the light emitted by the excitation light source 431 to the cells to be sorted, thereby causing the cells to be sorted to emit fluorescence.
[0286] In some embodiments, the filter unit 432 further includes a first filter 4322. The first filter 4322 is disposed between the first beam splitter 4321 and the excitation light source 431 along the second direction S2. The first filter 4322 is used to filter the excitation light source 431 so that light of a wavelength band that satisfies the cells to be sorted to emit fluorescence reaches the first beam splitter 4321.
[0287] The observation light path in the imaging mechanism 40 includes an illumination light path obtained by light emitted by the imaging light source 411 passing through the cells to be sorted, a guiding light path that guides light emitted by the excitation light source 431 to the cells to be sorted, and a fluorescence light path generated by the cells to be sorted.
[0288] In some embodiments, the fluorescent component 43 further includes a filter switching unit 433. The filter switching unit 433 is used to switch different filter units 432, and obtain excitation light of different wavelengths after passing through different filter units 432, so that the cells to be sorted emit different fluorescence, so that the imaging mechanism 40 can meet the culture requirements of the cells to be sorted in various situations, and increase the applicability of the cell sorting device 100.
[0289] In some embodiments, the cells to be sorted are specifically screened by adding a culture medium with a preset type of fluorescent dye, and accordingly, different fluorescent dyes can produce different fluorescence under the action of the excitation light. For example, the cells to be sorted are cultured with three fluorescent dyes, and the excitation light passes through the first filter unit 432 to make the cells to be sorted emit a first fluorescence, the excitation light passes through the second filter unit 432 to make the cells to be sorted emit a second fluorescence, and the excitation light passes through the third filter unit 432 to make the cells to be sorted emit a third fluorescence.
[0290] Specifically in the embodiment, the cells to be sorted are specifically screened by adding a culture medium containing a fluorescent dye capable of generating blue fluorescence, a fluorescent dye capable of generating green fluorescence, and a fluorescent dye capable of generating red fluorescence. Short-wavelength light can excite the generation of long-wavelength light. Therefore, ultraviolet excitation generates blue light, blue light excitation generates green light, and green light excitation generates red light. The cells to be sorted cultured with a fluorescent dye capable of generating blue fluorescence use an ultraviolet filter unit 432, and the excitation light causes the cells to be sorted to emit blue fluorescence; the cells to be sorted cultured with a fluorescent dye capable of generating green fluorescence use a blue light filter unit 432, and the excitation light causes the cells to be sorted to emit green fluorescence; the cells to be sorted cultured with a fluorescent dye capable of generating red fluorescence use a green light filter unit 432, and the excitation light causes the cells to be sorted to emit red fluorescence. The cells to be sorted are specifically screened by a preset type of fluorescent dye, which helps to more accurately select cells that meet the preset requirements. It can be understood that different filter units 432 are selected according to different fluorescent dyes, and the types of fluorescent dyes and filter units 432 are not limited.
[0291] In some embodiments, the filter switching unit 433 includes a switching driver 4331. The switching driver 4331 is connected to the filter unit 432 and can drive the filter unit 432 to move, thereby switching between different filter units 432. The switching driver 4331 is disposed on one side of the objective lens 421 along the second direction S2, and the filter units 432 connected to the switching driver 4331 can be moved to the observation light path of the imaging mechanism 40, such as between the objective lens 421 and the first imaging lens 422 in the third direction S3. Figure 2 The control mechanism 60 can control the filter switching unit 433 to switch different filter units 432 to excite different fluorescent dyes to produce different fluorescence.
[0292] In some embodiments, the filter unit 432 is configured with a first filter 4322, a second filter, and a third filter. The first filter 4322, the second filter, and the third filter are different from each other. The filter switching unit 433 switches the first filter 4322, the second filter, and the third filter. When the filter switching unit 433 switches to the first filter 4322, the light emitted by the excitation light source 431 can cause the cells to be sorted to emit a first fluorescence through the first filter 4322. When the filter switching unit 433 switches to the second filter, the light emitted by the excitation light source 431 can cause the cells to be sorted to emit a second fluorescence through the second filter. When the filter switching unit 433 switches to the third filter, the light emitted by the excitation light source 431 can cause the cells to be sorted to emit a third fluorescence through the third filter. It should be noted that the number of filters can be set according to the fluorescence emitted by the cells to be sorted.
[0293] In some embodiments, the filter switching unit 433 includes a switching driver 4331 connected to the control mechanism 60. The switching driver 4331 is connected to the excitation light source 431, and the cells to be sorted can emit different fluorescence by switching the excitation light source 431. For example, three groups of excitation light sources 431 that can excite different fluorescence can be switched into the observation light path, and different excitation light sources 431 emit excitation light of different wavelengths, such as ultraviolet LED light sources, blue LED light sources, green LED light sources, etc., so that the cells to be sorted emit different fluorescence. It should be noted that the filter switching unit 433 can switch different light sources to switch in and out of the light path, switch different filter units 432, or switch different filters in and out of the light path, and can also be automatically switched manually. The specific setting method can be set according to actual needs, and the switching method of the excitation light source 431 is not limited here.
[0294] In some embodiments, the filter unit 432 further includes a fourth filter 4323. The fourth filter 4323 is disposed along the third direction S3 between the first beam splitter 4321 and the first imaging lens 422. The fourth filter 4323 is used to filter the fluorescence emitted by the cells to be sorted, so that the fluorescence image information of the cells to be sorted reaching the detection component 44 is not affected by other light.
[0295] The filter unit 432 plays an important role in the fluorescence imaging of the imaging mechanism 40: after the light emitted from the excitation light source 431 hits the first filter 4322, the first filter 4322 selects the excitation light source 431 of a certain wavelength band to excite the sample and blocks light of other wavelengths; the light passing through the first filter 4322 passes through the first beam splitter 4321, and the first beam splitter 4321 reflects the filtered excitation light, which is then focused by the objective lens 421 and irradiated to the cells to be sorted, so that the cells to be sorted emit corresponding fluorescence, which is collected by the objective lens 421, passes through the first beam splitter 4321, and reaches the fourth filter 4323. When the first beam splitter 4321 is tilted at 45 degrees to the excitation light source 431, the filtered excitation light is vertically directed to the objective lens 421, and at this time the objective lens 421 directly acts as a condenser. In a feasible embodiment, the first filter element 4322 , the fourth filter element 4323 and the first beam splitter 4321 are integrally provided to obtain a filter unit 432 .
[0296] See also Fig.28 , the detection component 44 is connected to the display mechanism 50 for image observation and processing, and the detection component 44 is used to detect the image information formed by the transmitted light and fluorescence of the cells to be sorted emitted by the optical path component 42, and process the obtained image information, and transmit the obtained image information to the display mechanism 50. In one embodiment, the detection component 44 includes a CCD sensor 441, and in another embodiment, the detection component 44 includes a CMOS sensor 441. The CMOS sensor 441 or the CCD sensor 441 can both obtain the bright field image information and the fluorescence image information of the cells to be sorted. So as to facilitate subsequent processing and screening. Further, the detection component 44 also includes a cooling unit not shown in the figure, and the CMOS sensor 441 or the CCD sensor 441 is cooled by a cooling unit such as liquid nitrogen, a Peltier element, etc., so as to improve the signal-to-noise ratio and reduce the noise of the image information.
[0297] In some embodiments, the detection component 44 includes a bright field image information detector 442 and a fluorescent image information detector 443. The bright field image information detector 442 is used to detect image information based on the transmitted light and reflected light of the imaging light source 411 through the cells to be sorted. The fluorescent image information detector 443 is used to detect fluorescent image information based on the cells to be sorted, and both the bright field image information detector 442 and the fluorescent image information detector 443 are connected to the CMOS sensor 441 or the CCD sensor 441.
[0298] In some embodiments, the optical path component 42 is provided with a second beam splitter 424 and a second imaging lens 425. The second beam splitter 424 is spaced apart from the first beam splitter 4321 along the third direction S3, and is disposed between the first beam splitter 4321 and the first imaging lens 422. The transmitted light from the microscopic cells that passes through the first beam splitter 4321 passes through the second beam splitter 424 and the first imaging lens 422, and is emitted to the bright field image information detector 442. Furthermore, a filter (not shown) is disposed between the first imaging lens 422 and the bright field image information detector 442 to allow the transmitted light to be incident on the bright field image information detection unit 442 without interfering with the excitation light source 431 and the fluorescence.
[0299] The second imaging lens 425 is disposed between the second beam splitter 424 and the fluorescence image information detector 443. The fluorescence from the cells to be sorted that has passed through the first beam splitter 4321 is reflected by the second beam splitter 424 and passes through the second imaging lens 425, and then is emitted to the fluorescence image information detector 443. Furthermore, a filter (not shown) is disposed between the imaging lens and the fluorescence image information detector 443 to allow the fluorescence to enter the fluorescence image information detector 443 without interfering with the excitation light source 431 and the transmitted light.
[0300] The first imaging lens 422 used in the bright field image information detector 442 and the second imaging lens 425 used in the fluorescent image information detector 443 may be the same lens or different lenses. For example, the magnification of the first imaging lens 422 used in the bright field image information detector 442 may be reduced, while the magnification of the second imaging lens 425 used in the fluorescent image information detector 443 may be increased. In this case, the field of view of the image of the transmitted light acquired by the bright field image information detector 442 can be expanded, and a more expanded fluorescent image of the cells to be sorted can be obtained in the fluorescent image information detector 443.
[0301] In some embodiments, in combination Figure 2 and Fig. 27 The imaging mechanism 40 further includes a protective housing 45, which is used to protect the internal components of the imaging mechanism 40 and to prevent the optical path of the imaging mechanism 40 from being affected by external light, thereby ensuring that the image information of the cells to be sorted is accurate and clear. The protective housing 45 is connected to the bottom plate 1211 through a fastener. The bottom plate 1211 is also provided with a fixing protrusion for fixing the protective housing 45, so that the protective housing 45 is limited by a plurality of fixing protrusions, thereby ensuring that the imaging mechanism 40 is stably placed.
[0302] Before using the imaging mechanism 40, the imaging lighting unit 41, the cells to be sorted and the objective lens 421 are arranged along the third direction S3. When in use, the bright field image information of the cells to be sorted is obtained, and the specific operation is as follows: turn on the imaging lighting unit 41, so that the light emitted by the imaging light source 411 enters the bright field image information detector 442 through the cells to be sorted, the objective lens 421, the filter unit 432 and the first imaging lens 422, and the bright field image information detector 442 transmits the acquired image information of the cells to be sorted to the display mechanism 50. According to the image information displayed by the display mechanism 50, the objective lens moving unit 423 is controlled to move the objective lens 421 along the third direction S3, so that the image information of the cells to be sorted is clear, and is recorded by the CMOS sensor 441 or a CMOS sensor for subsequent processing.
[0303] The fluorescent image information of the cells to be sorted is obtained by the following specific operations: the imaging light source 411 is turned off, and the excitation light source 431 is turned on. The light emitted by the excitation light source 431 passes through the filter unit 432 and the objective lens 421 to the cells to be sorted, so that the cells to be sorted that have been specifically screened by the fluorescent dye emit fluorescence, and the fluorescence enters the fluorescent image information detector 443 through the objective lens 421, the filter unit 432 and the second imaging lens 425. The fluorescent image information detector 443 transmits the fluorescent image information of the cells to be sorted to the display mechanism 50. The objective lens moving unit 423 is controlled by the image information obtained by the display mechanism 50 to move the position of the objective lens 421 to make the image information clear, and then the image information is recorded by the CCD sensor 441 or the CMOS sensor. Different filter units 432 are replaced by the filter switching unit 433, and the above operation is repeated to transmit different fluorescent image information of the cells to be sorted to the display mechanism 50. By analyzing the acquired bright field image information and fluorescent image information of the cells to be sorted, cells that meet the preset requirements are found.
[0304] It should be noted that the switching between the imaging light source 411 and the excitation light source 431 can be achieved through the control mechanism 60 or through manual switching.
[0305] The to-be-sorted cells can be automatically moved under the control of the control mechanism 60. The fluorescent component 43 is provided with different filter units 432. Automatic switching is achieved through the filter switching unit 433. Automatic focusing is achieved through the objective lens moving unit 423. The automatic scanning of the imaging mechanism 40 can be achieved. A large number of cells to be sorted can be automatically scanned and imaged, which greatly improves the working efficiency of the cell sorting device 100 and expands its application range. And by comparing and analyzing a variety of fluorescent image information and bright field image information before and after selection, the cell sorting can be more accurately achieved.
[0306] See also Fig.29In some embodiments, the control mechanism 60 is used to control the cell sorting device 100 to achieve automatic cell sorting, improve the efficiency of cell sorting, and achieve high-throughput sorting. The control mechanism 60 can control the selection drive 2311, thereby controlling the movement and stop of the suction and release member 21 in the third direction S3; the control mechanism 60 can control the opening and closing of the selection light source 241 to achieve the observation and alignment of the suction and release member 21; the control mechanism 60 can control the drive unit 251 to achieve the cleaning of the suction and release member 21 and control the suction and release member 21 to absorb or release cells that meet the preset requirements; the control mechanism 60 can control the first carrier drive 3211 and the second carrier drive 3221, thereby controlling the movement and stop of the carrier assembly 31; control The mechanism 60 can control the on and off of the imaging light source 411, provide a transmitted light source for the cells to be sorted, and obtain bright field image information of the cells to be sorted; the control mechanism 60 can control the on and off of the excitation light source 431, provide an excitation light source 431 for the cells to be sorted, and obtain fluorescent image information of the cells to be sorted; the control mechanism 60 can control the objective lens driver 4232 to achieve the focusing of the objective lens 421 and obtain clear image information of the cells to be sorted; the control mechanism 60 can control the switching driver 4331 to excite the cells to be sorted to emit different fluorescence.
[0307] In some embodiments, the control mechanism 60 is disposed on the main body 10, including a power module, a switch module, a switching module, a voltage module, etc. (not shown). It can be understood that as long as it is used to control the functional components of the cell sorting device 100, it belongs to the control mechanism 60, and the control mechanism 60 can select corresponding control elements according to the settings of the components of the cell sorting device 100.
[0308] In some embodiments, the cell sorting device 100 further includes a lighting assembly. The lighting assembly is used to illuminate the hollow tube 211 of the suction and placement member 21 on one hand, and to illuminate the imaging mechanism 40 on the other hand, so as to achieve observation and alignment of the suction and placement member 21 on the display mechanism 50. The lighting assembly includes one or both of the above-mentioned selection lighting unit 24 and imaging lighting unit 41.
[0309] In some embodiments, the method of operating the cell sorting device 100 comprises the following steps:
[0310] Install the suction and release member 21 to the mounting assembly 22. Specifically, first move the first housing 111 and open the cell sorting device 100. In one embodiment, loosen the first fixing member 2221 and the second fixing member 2222, remove the clamping unit 221, loosen the first clamping driver 2212, and be careful not to completely separate the first clamping driver 2212 from the clamping body 2211. Put the end of the suction and release member 21 that is opposite to the suction and release port 212 into the clamping unit 221, tighten the first clamping driver 2212 to the clamping mark 2218, and do not tighten it too hard to cause damage to the suction and release member 21. Put the clamping unit 221 fixed with the suction and release member 21 back into the accommodating member 223. Tighten the first fixing member 2221 and the second fixing member 2222, fix the clamping unit 221, and complete the installation of the suction and release member 21 to the mounting assembly 22.
[0311] In another embodiment, the clamping piece 22192 is first placed in the first blocking piece 22191, the end of the suction and release piece 21 is passed through the first through hole 22191a and the clamping piece 22192, and then the first blocking piece 22191 and the clamping body 2211' are connected, and then the end of the suction and release piece 21 enters the installation channel 2211e and is connected to the protective piece 22194, the second blocking piece 22193 is connected to the protective piece 22194, and then the second blocking piece 22193 and the clamping body 2211' are connected to complete the connection between the suction and release piece 21 and the clamping unit 221. Then, the first operating part 4145 is used to drive the first imaging lighting unit 414 to move in a preset direction, so that the first avoidance member 81 rotates relative to the accommodating member 223', and drives the second avoidance member 82 to rotate in the opposite direction, and the second avoidance member 82 drives the second imaging lighting unit 415 to move in a direction opposite to the preset direction, so that the first combining surface 4141 and the second combining surface 4151 are separated, or the second operating part 4155 is used to drive the second imaging lighting unit 415 to move in a preset direction, so that the second avoidance member 82 rotates relative to the accommodating member 223', and drives the first avoidance member 81 to rotate in the opposite direction, and the first avoidance member 81 drives the first imaging lighting unit 414 to move in a direction opposite to the preset direction, so that the first combining surface 4141 and the second combining surface 4151 are separated, so that the imaging lighting unit 41 is in an open state, and the clamping unit 221 is installed in the accommodating member 223'. Finally, the first operating part 4145 is used to drive the first imaging lighting unit 414 to move in a direction opposite to the preset direction, so that the first avoidance member 81 rotates relative to the accommodating member 223', and drives the second avoidance member 82 to rotate in the opposite direction, and the second avoidance member 82 drives the second imaging lighting unit 415 to move in the preset direction, so that the first combining surface 4141 and the second combining surface 4151 are fitted together, and the suction and release member 21 is accommodated in the avoidance hole 416; or the second operating part 4155 is used to drive the second imaging lighting unit 415 to move in a direction opposite to the preset direction, so that the second avoidance member 82 rotates relative to the accommodating member 223', and drives the first avoidance member 81 to rotate in the opposite direction, and the first avoidance member 81 drives the first imaging lighting unit 414 to move in the preset direction, so that the first combining surface 4141 and the second combining surface 4151 are fitted together, and the suction and release member 21 is accommodated in the avoidance hole 416. This installation method can effectively prevent the suction and placement member 2121 from being damaged due to collision with the imaging lighting unit 4141 during installation.
[0312] Demarcate the position of the suction and release member 21. Specifically, under the control of the control mechanism 60, turn on the selection light source 241, and the first selection mobile unit 231 drives the suction and release member 21 to move along the third direction S3 until the image information of the suction and release member projection is clearly presented on the display mechanism 50. In one embodiment, the suction and release member 21 is fine-tuned by the first fixing member 2221 and the second fixing member 2222 so that the projection mark is located at the preset position of the suction and release member projection mapping. In another embodiment, the position of the suction and release member 21 is fine-tuned by the second selection mobile unit 232 and the third selection mobile unit 233 so that the projection mark is located at the preset position of the suction and release member projection mapping. Afterwards, the to-be-sorted member that is not provided with the to-be-sorted cells is placed in the fixing groove of the first carrier 311. The first selection mobile unit 231 drives the suction and release member 21 to move along the third direction S3 until the image information of the suction and release port 212 is clearly presented on the display mechanism 50. The position information of the suction and release member 21 at this time is recorded to complete the position calibration of the suction and release member 21.
[0313] Clean the suction and release member 21 for the first time. Specifically, first take the first containing member 2551, add an appropriate amount of the first cleaning liquid 2541, and place the first containing member 2551 with the first cleaning liquid 2541 on the first carrier 311, so that the first containing member 2551 and the suction and release member 21 are spaced apart along the third direction S3. Under the control of the control mechanism 60, the driving member 2311 is selected to drive the suction and release port 212 of the suction and release member 21 to move into the first cleaning liquid 2541, the driving unit 251 drives the suction and release member 21 to absorb the first cleaning liquid 2541 into the hollow pipe 211 of the suction and release member 21 for cleaning, and then drives the suction and release member 21 to release the first cleaning liquid 2541 into the first containing member 2551, and repeats several times to complete the first step of cleaning for the first preset number of times. Then take the second holding component 2552, add an appropriate amount of second cleaning liquid 2542, place the second holding component 2552 with the second cleaning liquid 2542 on the first carrier 311, so that the second holding component 2552 and the suction and release component 21 are spaced apart along the third direction S3, select the driving component 2311 to drive the suction and release component 21 to move into the second cleaning liquid 2542, the driving unit 251 drives the suction and release component 21 to absorb the second cleaning liquid 2542 into the hollow pipe 211 of the suction and release component 21 for cleaning, and then drive the suction and release component 21 to release the second cleaning liquid 2542 into the second holding component 2552, repeat several times, and complete the second step of cleaning for the second preset number of times.
[0314] Place the object to be sorted and the storage unit 314. Place the object to be sorted with the cells to be sorted in the loading part 3111 of the first loading part 311, pull the elastic member 331 on one side of the loading part 3111 to the other side of the loading part 3111, so that the elastic member 331 is biased against the object to be sorted, so as to place and fix the object to be sorted on the first loading part 311. Place the storage unit 314 with an appropriate amount of culture fluid in the placement groove 3112 of the first loading part 311. The cells to be sorted are specifically screened by the culture medium containing fluorescent dye.
[0315] Find cells that meet the preset requirements. Under the control of the control mechanism 60, the imaging light source 411 is turned on, the first loading and moving unit 321 and the second loading and moving unit 322 drive the cells to be sorted that need to be observed in the to-be-sorted part to be arranged along the third direction S3 with the second light source and the objective lens 421, and the objective lens moving unit 423 drives the objective lens 421 to move until the image information of the cells to be sorted that need to be observed is clearly presented on the display mechanism 50, and the bright field image information of the cells to be sorted is recorded. The imaging light source 411 is turned off, the excitation light source 431 is turned on, the light emitted by the excitation light source 431 passes through the first filter unit 432, the cells to be sorted emit the first fluorescence, the first fluorescence image information of the cells to be sorted is recorded, the filter switching unit 433 is controlled to switch to the second filter unit 432, the cells to be sorted emit the second fluorescence, the second fluorescence image information of the cells to be sorted is recorded, the filter switching unit 433 is controlled to switch to the third filter unit 432, the cells to be sorted emit the third fluorescence, and the third fluorescence image information of the cells to be sorted is recorded. Then, the excitation light source 431 is turned off and the imaging light source 411 is turned on. The first loading and moving unit 321 and the second loading and moving unit 322 drive the to-be-sorted cells to move to the preset area, and replace the to-be-sorted cells to be observed. Repeat the above process to record the bright field image information and fluorescent image information of the to-be-sorted cells in different areas. The acquired bright field image information and fluorescent image information of the to-be-sorted cells are processed and analyzed to find cells that meet the preset requirements.
[0316] Absorb and recover cells that meet preset requirements. Under the control of the control mechanism 60, the selection moving component 23 drives the suction and release component 21 to move along the third direction S3 until the suction and release component 21 reaches a position where cells can be absorbed, which is marked as the preset position, and pre-absorption is completed. The second loading moving unit 322 drives the second loading component 312 to move in the second direction S2, and the first loading moving unit 321 drives the first loading component 311 to move in the first direction S1 until the cells that meet the preset requirements are spaced apart from the suction and release component 21 along the third direction S3. The selection moving component 23 drives the suction and release component 21 to move to the preset position in the third direction S3. The driving unit 251 generates appropriate negative pressure in the hollow pipe 211 of the suction and release component 21 to absorb cells into the hollow pipe 211 of the suction and release component 21. The selection moving component 23 drives the suction and release component 21 to move in the direction away from the loading component 31. The second loading and moving unit 322 drives the second loading member 312 to move in the second direction S2, and the first loading and moving unit 321 drives the first loading member 311 to move in the first direction S1, until the storage portion 3142a for recovering and culturing cells that meet the preset requirements is spaced from the suction and release member 21 along the third direction S3. The selection and moving assembly 23 drives the suction and release member 21 to move in the third direction S3, so that there is a preset distance between the suction and release port 212 and the storage portion 3142a, and the preset distance is the distance that satisfies the suction and release member 21 to release the cells that meet the preset requirements to the storage portion 3142a. The first driving unit drives the suction and release member 21 to release the cells that meet the preset requirements sucked into the hollow tube 211 into the storage portion 3142a through positive pressure. The selection and moving assembly 23 drives the suction and release member 21 to move in a direction away from the loading assembly 31. Repeat the above process to make different cells that meet the preset requirements be absorbed and released and recovered into different storage parts 3142a until all cells that meet the preset requirements in the object to be sorted are absorbed and released. The object to be sorted is recovered and stored, and the storage unit 314 is transferred to the incubator for further cultivation.
[0317] Clean the suction and release member 21 for the second time. Specifically, first take the second containing member 2552, add an appropriate amount of the second cleaning liquid 2542, place the second containing member 2552 with the second cleaning liquid 2542 on the first carrier 311, so that the second containing member 2552 and the suction and release member 21 are spaced apart along the third direction S3, select the driving member 231 to drive the suction and release member 21 to move into the second cleaning liquid 2542, the driving unit 251 drives the suction and release member 21 to absorb the second cleaning liquid 2542 into the hollow pipe 211 of the suction and release member 21 for cleaning, and then drive the suction and release member 21 to release the second cleaning liquid 2542 into the second containing member 2552, repeat several times, and complete the first step of cleaning for a preset number of times. Then, take the first containing member 2551, add an appropriate amount of the first cleaning liquid 2541, and place the first containing member 2551 with the first cleaning liquid 2541 on the first carrier 311, so that the first containing member 2551 and the suction and placement member 21 are spaced apart along the third direction S3. Under the control of the control mechanism 60, the driving member 2311 is selected to drive the suction and placement port 212 of the suction and placement member 21 to move into the first cleaning liquid 2541, and the driving unit 251 drives the suction and placement member 21 to absorb the first cleaning liquid 2541 into the hollow pipe 211 of the suction and placement member 21 for cleaning, and then drives the suction and placement member 21 to release the first cleaning liquid 2541 into the first containing member 2551, and repeats several times to complete the second step of cleaning for a preset number of times.
[0318] Furthermore, the operating method of the cell sorting device 100 further includes:
[0319] Obtain the bright field image information of the cells to be sorted after absorbing. Specifically, before the suction and release part 21 is cleaned for the second time, after absorbing and recovering the cells that meet the preset requirements, under the control of the control mechanism 60, the imaging light source 411 is turned on, the first loading mobile unit 321 and the second loading mobile unit 322 drive the cells to be sorted that need to be observed in the part to be sorted and the second light source and the object lens 421 are arranged along the third direction S3, and the object lens moving unit 423 drives the object lens 421 to move until the image information of the cells to be sorted that need to be observed is clearly presented on the display mechanism 50, and the bright field image information of the cells to be sorted is recorded. The first loading mobile unit 321 and the second loading mobile unit 322 drive the part to be sorted to move to the preset area, and replace the cells to be sorted that need to be observed. Repeat the above process until the bright field image information of the cells to be sorted in different areas is all obtained and recorded. Compare the bright field image information of the cells to be sorted before and after absorbing, and obtain the acquisition situation of the cells that meet the preset requirements.
[0320] The cell sorting device 100 is used to selectively absorb and release cells that meet the preset requirements from the objects to be sorted into the corresponding storage portion 3142a of the storage unit 314. This process is automatically completed under the control of the control mechanism 60, thereby improving the efficiency of cell sorting, avoiding damage to the absorption and release member 21 and cells that meet the preset requirements due to manual operation, ensuring the biological activity of cells that meet the preset requirements, and realizing high-throughput cell sorting.
[0321] The biological culture chip 200 makes full use of microscopic technology or nanotechnology to complete precise control of cell capture, fixation, and culture on the chip, and through miniaturized chemical analysis methods, it achieves research purposes such as high-throughput, multi-parameter, in-situ signal detection of cell samples and physical and chemical analysis of cell components.
[0322] The biological culture chip 200 is introduced in detail below.
[0323] Figure 30 to Figure 32 A schematic diagram of a biological culture chip in some embodiments of the present application is shown.
[0324] In some embodiments, see Figure 30 to Figure 32 The biological culture chip 200 includes a matrix 201 and a receiving cavity 202, wherein the matrix 201 is formed of a matrix material, the receiving cavity 202 is formed on the surface of the matrix 201, and the receiving cavity 202 is open on the surface of the matrix 201, wherein the receiving cavity 202 defines a biological culture space for culturing cell biological materials. The structure and size of the receiving cavity 202 are not particularly limited, as long as it can provide a culture or growth expansion space for a single cell. The receiving cavity 202 can present a structure such as a cuboid, a cube, or a cylinder.
[0325] In some embodiments, the matrix material is selected from a microporous soft matrix with good biocompatibility, cell culture medium compatibility and mechanical tension, which can more efficiently capture and culture cells (including single cells and multi-cells with controllable number of aggregations). The soft matrix is easy to be affinity and fused with different extracellular matrix environments, providing cells with a uniform and fused three-dimensional culture space, thereby creating a microenvironment for the cells of the two-dimensional array that is conducive to survival, proliferation, migration, protein expression and secretion, stem cell differentiation, etc., as well as conducive to the detection of biological functions of array cells. It should be noted that the specific type of matrix material that can be used is not particularly limited, and hard matrix materials such as glass, silicon wafers, plastics, etc. are also within the scope of protection of this application.
[0326] In some embodiments, see Fig.32, the opening diameter of the accommodating cavity 202 is smaller than the bottom diameter of the accommodating cavity 202. Thus, it is convenient to capture single cells for culture without cell escape during the culture process. Specifically, the opening diameter of the accommodating cavity 202 is at most 80%, preferably 50%, of the bottom diameter of the accommodating cavity 202. The term "diameter" used is defined as the diameter of the circle with the largest area that the opening or bottom can accommodate. The term "depth" of the accommodating cavity 202 used refers to the shortest distance between the opening cross section and the bottom cross section of the accommodating cavity 202. In a feasible embodiment, the opening diameter of the accommodating cavity 202 is 8-25 microns and the depth is 15-35 microns. It should be noted that different opening diameters can be set for different cells, for example, if the biological material is a B cell, the opening diameter is 8-12 microns; if the biological material is a hybridoma cell or a tumor cell, the opening diameter is 15-25 microns.
[0327] In some embodiments, the biological culture chip 200 may include a plurality of cavities 202, and the cavities 202 are discretely distributed. The cavities 202 form a predetermined pattern, and the distance between two adjacent cavities 202 is 10-100 microns. Thus, the culture of multiple single cells can be processed in batches. When the distance between the cavities 202 is 10-100 microns, the cells cultured in the cavities 202 will not interfere with each other between the cavities 202, thereby improving the uniformity of batch processing, improving the accuracy and efficiency of cell biological function detection, and facilitating high-throughput acquisition and analysis of cell signal data. The cavities 202 on the biological culture chip 200 can form an array, for example, there are tens of thousands of cavities 202 or even hundreds of thousands and more cavities 202 arrays on a chip 200.
[0328] In some embodiments, positioning marks may be further provided on the biological culture chip 200, and the positioning marks are formed on the matrix 201. Thus, the multiple cavities 202 may be positioned by these positioning marks. The form of the positioning marks is not particularly limited. According to the embodiments of the present application, positioning marks of fluorescent materials may be provided so as to enable automatic and accurate positioning, or coordinate lines may be provided to position each cavity 202. When cells meeting the preset requirements are observed, each cavity 202 in which cells meeting the preset requirements are placed may be quickly positioned and recorded. This further facilitates the subsequent separation of cells or other components meeting the preset requirements in the cavities 202.
[0329] In some embodiments, the method of using the biological culture chip 200 is as follows:
[0330] Place the chip 200 in the chip holder 71. Because the biological culture chip 200 needs to be placed in a low-temperature environment for preservation, such as in an environment of 0-5°C. Therefore, before use, the biological culture chip 200 needs to be left at room temperature for a period of time to restore the temperature to room temperature. Because the biological culture chip 200 is thin, the material is soft and brittle, it is usually placed in the chip holder 71. After the outside of the chip holder 71 with the biological culture chip 200 is sterilized, it is transferred to a sterile environment, the chip preservation solution is removed with a pipette, and it is washed several times with sterile 0.01M PBS buffer. It should be noted that the biological culture chip 200 should not be touched during the cleaning process.
[0331] Add cells. Add the cells to be sorted prepared in advance to the chip holder 71 containing the biological culture chip 200. Preferably, in order to ensure the best single-cell array efficiency, the ratio of the number of cells to the chip flux is between 5:1 and 10:1, and the volume of the cell suspension is 1.5 ml. If the chip flux is 100,000, the array is performed with a cell suspension containing 500,000 to 1,000,000 cells. Let it stand in the cell culture incubator for a preset time, such as 15 minutes, so that the cells to be sorted form an array in the biological culture chip 200, and the containing cavity 202 of the biological culture chip 200 is set as an array.
[0332] First separation. Use a pipette to recover the cell suspension after the array is completed, and then wash it several times with 0.01M PBS buffer to remove the residual cells. The chip holder 71 can be properly tilted for washing. The whole process should be operated gently to separate the cells that have not formed an array. After washing, observe the array status of the chip 200 with cell array under a microscope.
[0333] Prepare screening medium. Pre-select and prepare complete cell culture medium, add preset types of fluorescent dyes to the complete cell culture medium according to the required dilution multiples, shake at low speed, mix thoroughly, and add substances such as antigens pre-labeled with fluorescent dyes to the fully mixed complete culture medium according to a certain dilution ratio as needed, shake at low speed, mix thoroughly, and obtain screening culture medium.
[0334] Add screening medium. Add pre-configured screening medium to the chip 200 behind the cell array, and then place the chip 200 behind the cell array in a cell incubator for incubation. The substances in the screening medium are specifically combined with the secretory substances of the cells to be sorted after the array is completed. The incubation time is set according to different projects, such as 3-8 hours for cell line development projects and no less than 8 hours for antibody discovery.
[0335] Second separation: After the incubation is completed, the screening culture medium is recovered, and the chip is washed 3-5 times with 0.01M PBS buffer until all suspended cells are basically removed, and the cells to be sorted after being cultured with fluorescent dye are obtained in the biological culture chip 200 .
[0336] Fig.33 A schematic diagram of a chip fixing assembly in some embodiments of the present application is shown. Fig.34 A schematic diagram of a pressure-applying member in some embodiments of the present application is shown.
[0337] In some embodiments, see Fig.19 and Fig.33 Since the biological culture chip 200 is thin, soft and brittle, it is difficult to directly fix it in the cell sorting device 100. Therefore, the cell sorting device further includes a chip fixing component 70. The chip fixing component 70 can be placed on the loading mechanism 30. The chip fixing component includes a chip container 71. The chip container 71 is used to hold the biological culture chip 200. First, the biological culture chip 200 is fixed in the chip container 71, and then the chip container 71 is placed on the loading component 31 of the cell sorting device 100.
[0338] In some embodiments, see Fig.33 , the chip fixing assembly 70 is used to fix the biological culture chip 200 to the chip container 71, and the chip fixing assembly 70 also includes a pressure member 72 supported by the chip container 71. The pressure member 72 can apply pressure to the biological culture chip 200 along the third direction S3, so that the biological culture chip 200 is stably placed in the chip container 71. The pressure member 72 is a cylindrical shape with two ends open, and applies pressure to the corners of the biological culture chip 200, so that the biological culture chip 200 is stably placed in the chip container 71. Applying pressure to the corners of the biological culture chip 200 can increase the number of effective accommodating cavities 202 in the biological culture chip 200, and increase the number of cells to be sorted. It can be understood that as long as the fixation of the biological culture chip 200 can be achieved, the pressure position of the pressure member 72 is not limited, such as the pressure member 72 applying pressure to the edge of the biological culture chip 200. Furthermore, in order to better fix the organism culture chip 200 in the chip container 71223 , the corners of the organism culture chip 200 abut against the inner wall of the chip container 71 .
[0339] To facilitate the placement and removal of the pressure member 72 and the biological culture chip 200, refer to Fig.34 The pressure member 72 includes a pressure portion 721 and a taking portion 722. Fig.33The pressure-applying portion 721 is accommodated in the chip container 71 and is used to apply pressure to the biological culture chip 200. The shape and size of the pressure-applying portion 721 match the shape and size of the chip container 71. The pick-up portion 722 is used to pick up the pressure-applying member 72, and is used to place and pick up the pressure-applying member 72. One end of the pressure-applying portion 721 away from the biological culture chip 200 extends along the circumferential direction to form the pick-up portion 722, and the pick-up portion 722 protrudes from the chip container 71 along the circumferential direction of the chip container 71, that is, at least part of the pick-up portion 722 is larger than the size of the chip container 71, so as to facilitate the pick-up of the pressure-applying member 72.
[0340] In some embodiments, the pressure member 72 can apply pressure to the biological culture chip 200 through the pressure member 72 body. Specifically, the pressure member 72 is made of a metal material that is heavier than the biological culture chip 200, such as copper or aluminum. The biological culture chip 200 is pressurized by the gravity of the pressure member 72. The mass of the pressure member 72 is set according to actual needs and is not limited here. The material of the pressure member 72 should ensure that it will not contaminate the biochip, and the pressure member 72 needs to be disinfected before and after use.
[0341] In some embodiments, the pressure member 72 can apply pressure to the biological culture chip 200 by transmitting external pressure. Specifically, the pressure member 72 is made of a light material, and is provided with a clamping portion, and the chip container 71 is provided with a clamped portion. Through the combination of the clamping portion and the clamped portion, the pressure member 72 is connected to the chip container 71, and the pressure member 72 generates pressure applied to the biological culture chip 200 through the clamping, so that the biological culture chip 200 is fixed in the chip container 71. It can be understood that as long as the biological culture chip 200 can be fixed in the chip container 71, the pressure application method of the pressure member 72 is not limited.
[0342] In some embodiments, to ensure the normal use of the biological culture chip 200 in the cell sorting device 100, the cell sorting device 100 further includes a fixing mechanism, which includes a chip fixing component 70 and a loading and limiting component 33. The chip fixing component 70 is used to fix the biological culture chip 200 in the chip container 71, and the loading and limiting component 33 is used to fix the chip container 71 on the loading mechanism 30. The use of the biological culture chip 200 improves the sorting efficiency and accuracy of the cell sorting device 100.
[0343] In some embodiments, when the biological culture chip 200 that has undergone cell-specific screening is used as a to-be-sorted object, the biological culture chip 200 is first fixed, the metal pressure piece 72 is disinfected and sterilized, and the metal pressure piece 72 is placed in the chip container 71, so that the pre-prepared biological culture chip 200 with cells to be sorted is fixed in the chip container 71. Then fix the chip container 71, put the chip container 71 into the loading part 3111 of the first loading part 311, the loading part 3111 is formed with a through hole and a limiting wall formed around the through hole, the elastic member 331 is arranged on the outer surface of the chip container 71, the elastic member 331 on one side of the loading part 3111 is pulled to the other side of the loading part 3111, so that the elastic member 331 is biased against the outer surface of the chip container 71, and the outer surface of the chip container 71 is biased and limited to the limiting wall, so that the chip container 71 is fixed on the first loading part 311, and the biological culture chip 200 is fixed on the cell sorting device 100. Then repeat the above-mentioned operation method of the cell sorting device 100 to achieve cell sorting.
[0344] In a feasible embodiment, the placement and limiting assembly further includes a limiting member 333, such as a silicone sleeve, etc. The chip container 71 is placed in the limiting member 333, and then the limiting member 333 is placed in the placement portion 3111. The elastic member 331 is biased against the outer surface of the limiting member 333 to achieve the fixation of the chip container 71 on the first placement portion 311. It is understandable that the limiting member 333 can also be placed in the placement portion 3111 first, and then the chip container 71 is placed in the limiting member 333.
[0345] During suction, the loading moving component 32 drives the receiving chamber 202 of the biological culture chip 200 in which the cells meeting the preset requirements are placed to move until the receiving chamber 202 and the suction and release member 21 are spaced apart along the third direction S3. The selection moving component 23 drives the suction and release member 21 to move along the third direction S3 until there is a preset distance between the suction and release port 212 and the receiving chamber 202, and the preset distance enables the driving unit 251 to drive the suction and release member 21 to suck the cells meeting the preset requirements into the hollow pipe 211 of the suction and release member 21. Preferably, the cells meeting the preset requirements are single cells disposed in the receiving chamber 202 of the biological culture chip 200.
[0346] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.
[0347] The above-described embodiments only express several implementation methods of the present application, and the descriptions thereof are relatively specific and detailed, but they cannot be construed as limiting the scope of the patent application. It should be pointed out that, for a person of ordinary skill in the art, several variations and improvements can be made without departing from the concept of the present application, and these all belong to the protection scope of the present application. Therefore, the protection scope of the patent application shall be subject to the attached claims.
Claims
1. A selection mechanism for a cell sorting device, characterized in that: The selection agencies include: A clamping unit, used for clamping the suction and release parts; a receiving member, the receiving member being used to receive the clamping unit; and A selection moving component is connected to the receiving member, and the selection moving component can drive the receiving member to move so that the suction and placement member moves to a preset position.
2. The selection mechanism for a cell sorting device according to claim 1, characterized in that: The picking moving assembly includes a first picking moving unit, a second picking moving unit and a third picking moving unit, the first picking moving unit is connected to the second picking moving unit, the second picking moving unit is connected to the third picking moving unit, the third picking moving unit is connected to the receiving member, the first picking moving unit can drive the second picking moving unit and the third picking moving unit to move along a third direction, the second picking moving unit can drive the third picking moving unit to move along a first direction, the third picking moving unit can drive the receiving member to move along a second direction, and the first direction, the second direction and the third direction are perpendicular to each other.
3. The selection mechanism for a cell sorting device according to claim 2, characterized in that: The first picking movable unit comprises a picking driving member, a picking transmission member and a picking movable member, wherein the picking driving member can drive the picking transmission member to rotate, the picking transmission member can drive the picking movable member to move, and the picking movable member is connected to the second picking movable unit and can drive the second picking movable unit to move along the third direction.
4. The selection mechanism for a cell sorting device according to claim 3, characterized in that: The second picking moving unit includes a first operating member, a first picking fixed member and a first picking sliding member, the first picking sliding member is slidably connected to the first picking fixed member and the first picking sliding member is connected to the third picking moving unit, the first operating member is connected to the first picking sliding member and can drive the first picking sliding member to move along the first direction relative to the first picking fixed member.
5. The selection mechanism for a cell sorting device according to claim 4, characterized in that: The third picking moving unit includes a second operating member, a second picking fixing member and a second picking sliding member, the second picking fixing member is connected to the first picking sliding member, the second picking sliding member is slidably connected to the second picking fixing member and the second picking sliding member is connected to the accommodating member, the second operating member is connected to the second picking sliding member and can drive the second picking sliding member to move along the second direction relative to the second picking fixing member.
6. The selection mechanism for a cell sorting device according to claim 5, characterized in that: A first selection slide block is provided on one of the first selection fixing member and the first selection sliding member, and a first selection slide rail extending along the first direction is provided on the other member, and the first selection slide block is slidably connected to the first selection slide rail; A second selecting slide block is provided on one of the second selecting fixing member and the second selecting sliding member, and a second selecting slide rail extending along the second direction is provided on the other member, and the second selecting slide block is slidably connected to the second selecting slide rail.
7. The selection mechanism for a cell sorting device according to claim 5, characterized in that: The first operating member and the second operating member are both micrometer structures.
8. The selection mechanism for a cell sorting device according to claim 1, characterized in that: The clamping unit includes a clamping body, and the clamping body is detachably connected to the receiving member.
9. The selection mechanism for a cell sorting device according to claim 1, characterized in that: The clamping body is threadedly connected to the receiving member.
10. A cell sorting device, characterized in that: The cell sorting device comprises the selection mechanism as described in any one of claims 1-9.