Biological organ culture device

Abstract

The invention discloses a biological organ culture device. The biological organ culture device is characterized in that a plurality of culture chamber placement grooves for mounting culture chambers are formed in a culture chamber support; the eight-way pipe heads of the first liquid path slip ring and the second liquid path slip ring are respectively connected with the first end and the second end of the culture chamber support; in a working state, the culture chamber is mounted in the culture chamber placement groove of the culture chamber support, an outlet of the nutrient solution tank is connected to an inlet of the peristaltic pump, an outlet of the peristaltic pump is connected to a liquid inlet of the oxygenator, a fluid inlet of the culture chamber is communicated with a liquid outlet of the oxygenator through the first liquid path slip ring, and a fluid outlet of the culture chamber is communicated with a liquid outlet of the oxygenator through the second liquid path slip ring. A fluid outlet of the culture chamber is connected into the nutrient solution tank through a second liquid path slip ring to form a circulating liquid path; the culture chamber support driving device is in driving connection with the culture chamber support and drives the culture chamber support to rotate so as to realize suspension culture of cells in the culture chamber.

Description

Technical Field

[0001] The present application belongs to the field of biomedical engineering, and specifically relates to a biological organoid culture device. Background Art

[0002] With the continuous progress of biomedical research, organoid technology has gradually become an important tool for simulating and studying the structure and function of human organs. Organoids are tiny organ-like structures formed by stem cells or organ-specific cells in a three-dimensional culture environment. They can simulate a variety of physiological and pathological states of real organs, so they have broad application prospects in disease research, drug screening, personalized medicine and other fields. However, traditional organoid culture methods have certain limitations. For example, the culture environment is unstable, and organoids are easy to settle or adhere to the wall of the culture container, making it difficult to maintain a suspended state. In addition, the gas exchange efficiency is low and cannot meet the metabolic needs of organoids, resulting in unsatisfactory culture effects. These problems seriously affect the culture efficiency and quality of organoids, limiting their wide application in biomedical research and applications. Microgravity suspension culture technology has significant advantages in organoid culture and can promote the uniform growth and differentiation of organoids, but the existing devices still need to be improved in terms of liquid supply system, gas exchange, etc. to improve culture efficiency and quality. Existing devices are usually only capable of single-channel operation and cannot culture multiple organoids at the same time; the liquid supply system is complex and it is difficult to accurately control the flow rate and flow rate; the gas exchange efficiency is low and cannot meet the oxygen and carbon dioxide needs of organoids. Summary of the invention

[0003] Purpose: In view of at least one of the above technical problems, the present application provides a biological organoid culture device, which provides an efficient, stable and flexible biological organoid culture device by combining microgravity suspension culture, multi-channel liquid supply and efficient gas exchange technologies.

[0004] Technical solution: To solve the above technical problems, the technical solution adopted in this application is: According to a first aspect of the present application, a fluid path slip ring is provided, comprising: an eight-way pipe head, an eight-way pipe pipeline, a snap ring, a first bearing, an eight-way pipe sleeve, and a second bearing; The eight-way pipe and the eight-way pipe head are connected to form an eight-way pipe through a snap ring; the two ends of the eight-way pipe sleeve are respectively mounted on the eight-way pipe through a first bearing and a second bearing to rotate relative to each other; The outer circumference of the eight-way tube is provided with eight annular liquid storage grooves at intervals in the circumferential direction, and eight first openings are respectively opened at corresponding positions on the eight-way tube sleeve, and are respectively connected with the corresponding liquid storage grooves; eight first internal pipes are correspondingly arranged inside the eight-way tube; eight second openings are correspondingly arranged on the outer circumference of the eight-way tube head, and eight second internal pipes are correspondingly arranged inside the eight-way tube head, and the second internal pipes are respectively connected with the corresponding second openings; one end of the first internal pipe is connected with the corresponding liquid storage groove, and the other end is connected with the corresponding second internal pipe.

[0005] In some embodiments, the fluid circuit slip ring further includes a positioning pin and an end face sealing gasket, the eight-way pipe and the eight-way pipe head are positioned and connected via the positioning pin, and the first internal pipe and the corresponding second internal pipe are sealed and connected via the end face sealing gasket.

[0006] In some embodiments, the fluid circuit sliding ring further comprises a bearing retaining ring, and the bearing retaining ring is arranged at the outer end of the second bearing.

[0007] In some embodiments, the end of the eight-way tube head is provided with a dovetail groove structure for mating with a culture chamber support.

[0008] According to a second aspect of the present application, a biological organ culture device is provided, the biological organ culture device comprising a cell culture device base box, a nutrient solution tank, a peristaltic pump, an oxygenator, a first liquid path slip ring, a culture chamber, a second liquid path slip ring, a culture chamber support, and a culture chamber support drive device; the first liquid path slip ring and the second liquid path slip ring are the liquid path slip rings described in the first aspect; The culture chamber support is provided with a plurality of culture chamber placement slots for installing the culture chambers in parallel; The octagonal tube head of the first fluid path sliding ring is relatively fixedly connected to the first end of the culture chamber support, and the octagonal tube head of the second fluid path sliding ring is relatively fixedly connected to the second end of the culture chamber support; the first fluid path sliding ring, the culture chamber support and the second fluid path sliding ring are installed on the base box of the cell culture device; In the working state, the culture chamber is installed in the culture chamber placement groove of the culture chamber support, and the fluid inlet of each culture chamber is connected to the second port corresponding to the octagonal tube head of the first liquid path sliding ring through a pipeline, and the fluid outlet of each culture chamber is connected to the second port corresponding to the octagonal tube head of the second liquid path sliding ring through a pipeline; The nutrient solution tank stores nutrient solution required by the corresponding cells in the culture chamber, and the outlet of the nutrient solution tank is connected to the inlet of the peristaltic pump through a pipeline, so as to provide nutrient solution circulation power through the peristaltic pump; the outlet of the peristaltic pump is connected to the liquid inlet of the oxygenator through a pipeline, so as to oxygen-enrich the nutrient solution passing through the oxygenator, and the liquid outlet of the oxygenator is connected to the first port on the octagonal tube sleeve of the first liquid path slip ring through a pipeline; the first port on the octagonal tube sleeve of the second liquid path slip ring is connected to the nutrient solution tank, so as to form a circulating liquid path; The culture chamber support driving device is drivingly connected to the culture chamber support and is used to drive the culture chamber support to rotate so as to realize suspension culture of cells in the culture chamber.

[0009] In some embodiments, the culture chamber support driving device includes a motor, a connecting rod, and a connecting rod synchronous belt; the connecting rod is provided with an intermediate synchronous pulley and two connecting rod synchronous pulleys at both ends; the power output end of the motor is engaged with the intermediate synchronous pulley through the motor synchronous belt to provide rotational power; the eight-way tube head is connected to an eight-way tube synchronous pulley, and each connecting rod synchronous pulley is respectively engaged with the corresponding eight-way tube synchronous pulley through the same connecting rod synchronous belt, driving the two eight-way tubes and the culture chamber support to rotate synchronously.

[0010] In some embodiments, the base box of the cell culture device includes a cell culture device support plate, a synchronous pulley bearing bracket is connected below the cell culture device support plate, and a connecting rod bearing seat is installed on the synchronous pulley bearing bracket; both ends of the connecting rod are installed on the connecting rod bearing seat through bearings and can rotate around the connecting rod.

[0011] In some embodiments, two upper support plates are connected above the support plate of the cell culture device, and are used to install the eight-way pipe sleeves of the first liquid path sliding ring and the second liquid path sliding ring respectively; Furthermore, the eight-way tube sleeves of the first liquid path sliding ring and the second liquid path sliding ring are provided with flanges for connecting with the corresponding upper support plates on the support plate of the cell culture device through the flanges.

[0012] In some embodiments, the biological organ culture device further includes a bearing support and a third bearing, wherein the bearing support is connected to the corresponding upper support plate, the third bearing is installed inside the bearing support, the outer ring of the third bearing is connected to the bearing support, and the inner ring of the third bearing is connected to the corresponding eight-way tube synchronous pulley, which is used to guide and position the eight-way tube synchronous pulley to prevent axial movement.

[0013] In some embodiments, the end of the eight-way tube head is provided with a dovetail groove structure for cooperating with a culture chamber support, and the two ends of the culture chamber support are respectively provided with dovetail tenon structures cooperating with the dovetail groove structure; the eight-way tube head and the culture chamber support are connected through the dovetail groove structure and the dovetail tenon structure.

[0014] In some embodiments, the cell culture chamber includes a chamber body and a chamber end cover connected to each other, the chamber body having a cylindrical accommodating cavity with an opening on one side and a fluid inlet and a fluid outlet connected to the accommodating cavity, and the chamber end cover is detachably sealed and connected to the open end of the chamber body.

[0015] The chamber end cover is a square structure, and the opening end of the chamber body is provided with an end cover groove matching with the chamber end cover, and the chamber end cover is connected to the end cover groove through a connecting piece.

[0016] In some embodiments, threaded countersunk holes are provided at the four corners of the end cover groove, and through holes are opened at corresponding positions of the chamber end cover, which are used to pass set screws through the through holes and then be threadedly connected to the threaded countersunk holes, so that the chamber end cover can be detachably connected to the chamber body.

[0017] In some embodiments, an outer side of the chamber end cap is flush with a corresponding side on the chamber body.

[0018] In some embodiments, the cell culture chamber further comprises a sealing ring, which is disposed between the chamber end cover and the chamber body to seal the open end of the chamber body.

[0019] In some embodiments, the fluid inlet and the fluid outlet are provided with connectors, respectively. Further, the connectors are Luer connectors.

[0020] In some embodiments, the fluid inlet and the fluid outlet are arranged perpendicular to each other.

[0021] In some embodiments, the chamber body and the chamber end cover are made of transparent materials to facilitate observation of the cell culture conditions in the containing chamber.

[0022] In some embodiments, the chamber body is provided with a ball groove for cooperating with a ball on a culture chamber support, so as to fix the cell culture chamber on the culture chamber support through the ball and the ball groove.

[0023] Beneficial effects: The biological organoid culture device provided by the present application has the following advantages: it can culture different types of organoid cells in different cell culture chambers to form an organic joint culture system; it can also culture multiple organoid cells of the same type at the same time to obtain a large number of samples at one time, which is suitable for a variety of biomedical research and applications. By combining microgravity suspension culture, multi-channel liquid supply and efficient gas exchange technologies, the device achieves efficient, stable and flexible culture of organoids. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 This is a schematic diagram of the overall structure of the biological organoid culture device according to an embodiment of the present application; Figure 2 This is a schematic diagram of the structure in which the base box of the biological organ culture device in the embodiment of the present application is disassembled; Figure 3 In the embodiment of this application Figure 1 A vertical cross-sectional diagram of ; Figure 4 This is a schematic diagram of the structure of the liquid circuit slip ring in the embodiment of the present application; Figure 5 This is a schematic diagram of the assembly of the fluid circuit slip ring in the embodiment of the present application; Figure 6 This is a vertical cross-sectional schematic diagram of a fluid path slip ring in an embodiment of the present application; Figure 7 This is a schematic diagram of the structure of the culture chamber support in the embodiment of the present application; Figure 8 This is a schematic diagram of the fluid connection of each component of the biological organoid culture device in the embodiment of the present application; Fig. 9 Schematic diagram of the structure of the culture chamber in the embodiment of the present application.

[0025] In the figure: liquid circuit slip ring 1: eight-way pipe head 101, second port 101a, second internal pipe 101b, dovetail groove structure 101c, eight-way pipe pipe 102, liquid storage groove 102a, first internal pipe 102b, snap ring 103, eight-way pipe sleeve 104, first port 104a, first bearing 105, second bearing 106, positioning pin 107, end face sealing gasket 108, bearing retaining ring 109; Cell culture device base box 2, cell culture device support plate 201, synchronous pulley bearing bracket 202, connecting rod bearing seat 203, upper support plate 204, vertical plate 206, Nutrient solution filling 3, peristaltic pump 4, oxygenator 5; Culture chamber 6, chamber body 601, end cover groove 601a, chamber end cover 602, accommodating cavity 603, fluid inlet 604 and fluid outlet 605, set screw 606, sealing ring 607, joint 608, ball groove 609; Culture chamber support 7, culture chamber placement slot 701, dovetail structure 702, bead 703; Culture chamber support driving device 8; motor 801, connecting rod 802, connecting rod synchronous belt 803, intermediate synchronous pulley 804, connecting rod synchronous pulley 805, eight-way pipe synchronous pulley 806, bearing support 807, third bearing 808, motor synchronous belt 809. DETAILED DESCRIPTION

[0026] The following will be combined with the drawings in the embodiments of the present application to clearly and completely describe the technical solutions in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all of the embodiments. The following description of at least one exemplary embodiment is actually only illustrative and is by no means intended to limit the present application and its application or use. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

[0027] Unless otherwise specifically stated, the relative arrangement, numerical expressions and numerical values ​​of the parts and steps set forth in these embodiments do not limit the scope of the present application. At the same time, it should be understood that, for ease of description, the sizes of the various parts shown in the accompanying drawings are not drawn according to the actual proportional relationship. The technology, method and equipment known to those of ordinary skill in the relevant field may not be discussed in detail, but in appropriate cases, the technology, method and equipment should be considered as a part of the authorization specification. In all examples shown and discussed here, any specific value should be interpreted as being merely exemplary, rather than as a limitation. Therefore, other examples of exemplary embodiments may have different values. It should be noted that similar reference numerals and letters represent similar items in the following drawings, so that once a certain item is defined in an accompanying drawing, it does not need to be further discussed in subsequent drawings.

[0028] In the description of the present application, it should be understood that the terms "center", "longitudinal", "lateral", "up", "down", "front", "back", "left", "right", "inside", "outside", etc., indicating the orientation or position relationship, are based on the orientation or position relationship shown in the drawings, and are only used to explain the relative position relationship, movement, etc. between the components in a certain posture. If the specific posture changes, the directional indication will also change accordingly. It 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 to the present application.

[0029] In addition, the terms "first", "second", etc. are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Thus, a feature defined as "first", "second", etc. may explicitly or implicitly include one or more of the feature. In the description of this application, unless otherwise specified, "plurality" means two or more.

[0030] In the description of this application, it should be noted that, unless otherwise clearly specified and limited, the terms "installed", "connected", and "connected" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection, or it can be indirectly connected through an intermediate medium, or it can be the internal communication of two components. For ordinary technicians in this field, the specific meanings of the above terms in this application can be understood by specific circumstances.

[0031] Example 1: Figures 4 to 6 As shown, this embodiment provides a fluid path slip ring 1, comprising: an eight-way pipe head 101, an eight-way pipe pipeline 102, a snap ring 103, an eight-way pipe sleeve 104, a first bearing 105, and a second bearing 106; The eight-way pipe 102 and the eight-way pipe head 101 are connected to form an eight-way pipe through a snap ring 103; the two ends of the eight-way pipe sleeve 104 are respectively installed on the eight-way pipe 102 through a first bearing 105 and a second bearing 106 to rotate relative to each other; like Figures 5 and 6 As shown, eight annular liquid storage grooves 102a are circumferentially spaced apart on the outer circumference of the eight-way tube pipeline 102, and eight first ports 104a are respectively opened at corresponding positions on the eight-way tube sleeve 104, and are respectively connected with the corresponding liquid storage grooves 102a; eight first internal pipes 102b are correspondingly arranged inside the eight-way tube pipeline 102; eight second ports 101a are correspondingly arranged on the outer circumference of the eight-way tube head 101, and eight second internal pipes 101b are correspondingly arranged inside the eight-way tube head 101, and the second internal pipes 101b are respectively connected with the corresponding second ports 101a; one end of the first internal pipe 102b is connected with the corresponding liquid storage groove 102a, and the other end is connected with the corresponding second internal pipe 101b.

[0032] In some embodiments, Figures 5 and 6 As shown, the fluid path slip ring also includes a positioning pin 107 and an end face sealing gasket 108. The eight-way pipe 102 and the eight-way pipe head 101 are positioned and connected via the positioning pin 107, and the first internal pipe 102b and the corresponding second internal pipe 101b are sealed and connected via the end face sealing gasket 108.

[0033] In some embodiments, Figures 4 to 6 As shown, the fluid path sliding ring further includes a bearing retaining ring 109 , and the bearing retaining ring 109 is arranged at the outer end of the second bearing 106 .

[0034] In some embodiments, Figures 5 and 6 As shown, the end of the eight-way tube head 101 is provided with a dovetail groove structure 101c for cooperating with the culture chamber support.

[0035] In some embodiments, the first bearing 105 adopts a 6205 bearing, and the second bearing 106 adopts a 6202 bearing.

[0036] Example 2: Figures 1 to 9 As shown, this embodiment provides a biological organ culture device, including a cell culture device base box 2, a nutrient solution tank 3, a peristaltic pump 4, an oxygenator 5, a first liquid path slip ring, a culture chamber 6, and a second liquid path slip ring; a culture chamber support 7, and a culture chamber support drive device 8; the first liquid path slip ring and the second liquid path slip ring are the liquid path slip ring 1 described in Example 1; The culture chamber support 7 is provided with a plurality of culture chamber placement slots 701 for installing the culture chamber 6 in parallel; The octagonal tube head of the first liquid path sliding ring is relatively fixedly connected to the first end of the culture chamber support 7, and the octagonal tube head of the second liquid path sliding ring is relatively fixedly connected to the second end of the culture chamber support 7; the first liquid path sliding ring, the culture chamber support 7 and the second liquid path sliding ring are installed on the base box 2 of the cell culture device; In the working state, the culture chamber 6 is installed in the culture chamber placement slot 701 of the culture chamber support 7, and a parallel connection mode can be adopted: the fluid inlet of each culture chamber is connected to the second port corresponding to the octagonal tube head of the first liquid circuit slip ring through a joint and a pipeline, and the fluid outlet of each culture chamber is connected to the second port corresponding to the octagonal tube head of the second liquid circuit slip ring through a joint and a pipeline; or a series connection mode is adopted: the fluid inlet of the first culture chamber is connected to the second port corresponding to the octagonal tube head of the first liquid circuit slip ring through a joint and a pipeline, the fluid outlet and fluid inlet of the adjacent culture chamber are connected in turn through a joint and a pipeline, and the fluid outlet of the last one is connected to the second port corresponding to the octagonal tube head of the second liquid circuit slip ring through a joint and a pipeline; The nutrient solution tank 3 stores the nutrient solution required by the corresponding cells in the culture chamber. The outlet of the nutrient solution tank 3 is connected to the inlet of the peristaltic pump 4 through a pipeline, which is used to provide nutrient solution circulation power through the peristaltic pump; the outlet of the peristaltic pump 4 is connected to the liquid inlet of the oxygenator 5 through a pipeline, which is used to oxygen-enrich the nutrient solution passing through the oxygenator, and the liquid outlet of the oxygenator 5 is connected to the first port on the octagonal tube sleeve of the first liquid path slip ring through a pipeline; the first port on the octagonal tube sleeve of the second liquid path slip ring is connected to the nutrient solution tank 3 to form a circulating liquid path; The culture chamber support driving device 8 is drivingly connected to the culture chamber support 7 and is used to drive the culture chamber support to rotate, so as to realize suspension culture of cells in the culture chamber 6 .

[0037] In some embodiments, Figures 1 to 3 As shown, the culture chamber support driving device 8 includes a motor 801, a connecting rod 802, and a connecting rod synchronous belt 803; the connecting rod 802 is provided with an intermediate synchronous pulley 804 and two connecting rod synchronous pulleys 805 located at both ends; the power output end of the motor 801 is engaged with the intermediate synchronous pulley 804 through the motor synchronous belt 809 to provide rotational power; the head of the eight-way tube is connected to an eight-way tube synchronous pulley 806, and each connecting rod synchronous pulley 805 is respectively engaged with the corresponding eight-way tube synchronous pulley 806 through the same connecting rod synchronous belt 803, driving the two eight-way tubes and the culture chamber support 7 to rotate synchronously.

[0038] In some embodiments, Figures 1 to 3 As shown, the cell culture device base box 2 includes a cell culture device support plate 201, a synchronous pulley bearing bracket 202 is connected below the cell culture device support plate, and a connecting rod bearing seat 203 is installed on the synchronous pulley bearing bracket; both ends of the connecting rod 802 are installed on the connecting rod bearing seat 203 through bearings, and can rotate around the connecting rod.

[0039] In some embodiments, Figures 1 to 3 As shown, two upper support plates 204 are connected above the cell culture device support plate 201, which are used to install the eight-way pipe sleeves of the first liquid path sliding ring and the second liquid path sliding ring respectively.

[0040] In some embodiments, Figures 1 to 6 As shown, the eight-way tube sleeves of the first liquid circuit sliding ring and the second liquid circuit sliding ring are provided with flanges, which are used to be connected to the corresponding upper support plate 204 on the support plate of the cell culture device through the flanges and connecting pieces (bolts).

[0041] In some embodiments, Figures 1 to 3As shown, the biological organ culture device also includes a bearing support 807 and a third bearing 808. The bearing support 807 is connected to the corresponding upper support plate. The third bearing 808 is installed inside the bearing support. The outer ring of the third bearing 808 is connected to the bearing support 807, and the inner ring of the third bearing 808 is connected to the corresponding eight-way tube synchronous pulley 806, which is used to guide and position the eight-way tube synchronous pulley 806 to prevent axial movement.

[0042] In some embodiments, bearing covers 205 connected to the upper support plate 204 are respectively provided on the left and right sides. The flange of the eight-way pipe sleeve, the bearing support 807, and the eight-way pipe synchronous pulley 806 are located therein through the upper support plate 204 and the bearing cover 205 to play a protective role.

[0043] In this embodiment, if Figures 1 to 3 As shown, the cell culture device base box 2 is composed of six plates, namely, front, rear, left and right side plates, a bottom plate and a cell culture device support plate 201, and each plate is connected and fixed by bolts; the vertical plate 206 is fixed to the cell culture device support plate 201 by bolts; an oxygenator assembly support plate is provided on the vertical plate 206, and the oxygenator 3 is fixed to the oxygenator assembly support plate by bolts; a peristaltic pump assembly hole is opened on the vertical plate 206, and the peristaltic pump 4 and the peristaltic pump motor are fixed to the vertical plate by bolts.

[0044] In some embodiments, Figure 6 , Figure 7 As shown, the end of the eight-way pipe head 101 is provided with a dovetail groove structure 101c for matching with the culture chamber support, and the two ends of the culture chamber support 7 are respectively provided with dovetail tenon structures 702 matching with the dovetail groove structure; the eight-way pipe head 101 and the culture chamber support 7 are connected by mortise and tenon through the dovetail groove structure 101c and the dovetail tenon structure 702. Figure 7 As shown, the culture chamber support 7 is provided with beads 703 on both sides of the culture chamber placement groove 701, respectively, so as to fix the culture chamber 6 placed in the culture chamber placement groove 701 through the beads 703 structure.

[0045] In this embodiment, Figure 7 As shown, the culture chamber support 7 is divided into eight parallel culture chamber placement slots 701 by a partition in the length direction; corresponding positions on both sides in the width direction are provided with shifting beads 703. No dovetail structures 702 are provided at both ends of the culture chamber support 7 in the length direction.

[0046] On this basis, in some embodiments, such as Figure 8 , Fig. 9As shown, the culture chamber 6 includes a chamber body 601 and a chamber end cover 602 connected to each other, the chamber body 601 has a cylindrical accommodating cavity 603 with an opening on one side, and a fluid inlet 604 and a fluid outlet 605 connected to the accommodating cavity 603, and the chamber end cover 602 is detachably sealed and connected to the open end of the chamber body 601.

[0047] In some embodiments, the chamber end cap 602 is a square structure, and the open end of the chamber body 601 is provided with an end cap groove 601a that matches the chamber end cap 602, and the chamber end cap 602 is connected to the end cap groove 601a through a connector. In this embodiment, the end cap groove 601a is a square structure.

[0048] Furthermore, in some embodiments, threaded countersunk holes are provided at the four corners of the end cover groove 601a, and through holes are opened at corresponding positions of the chamber end cover 602, which are used to pass the set screws 606 through the through holes and then be threadedly connected to the threaded countersunk holes, so that the chamber end cover 602 can be detachably connected to the chamber body 601.

[0049] Furthermore, in some embodiments, the outer side of the chamber end cover 602 is flush with the corresponding side on the chamber body 601 .

[0050] Furthermore, in some embodiments, the culture chamber further includes a sealing ring 607, and the sealing ring 607 is disposed between the chamber end cover 602 and the chamber body 601 to seal the open end of the chamber body.

[0051] In some embodiments, the fluid inlet 604 and the fluid outlet 605 are respectively provided with connectors 608. Furthermore, in this embodiment, the connectors are Luer connectors.

[0052] In some embodiments, the fluid inlet 604 and the fluid outlet 605 are arranged perpendicular to each other.

[0053] In some embodiments, the chamber body 601 and the chamber end cover 602 are made of transparent materials to facilitate observation of the cell culture conditions in the accommodating chamber.

[0054] In some embodiments, Fig. 9 As shown, the chamber body 6 is provided with a ball groove 609 for cooperating with the ball 703 on the culture chamber support, so as to fix the culture chamber on the culture chamber support through the ball and the ball groove 609.

[0055] In some embodiments, the motor 801 is a stepper motor.

[0056] In some embodiments, the working principle of a biological organoid culture device provided by the present application is as follows: it is divided into two stages: cell aggregation and suspension culture.

[0057] In the first stage, the motor 801 drives the connecting rod to rotate through the motor synchronous belt 809 and the middle synchronous pulley 804, and the connecting rod synchronous pulleys 805 on the left and right sides of the connecting rod drive the eight-way pipe synchronous pulley 806 on the upper support plate 204 to rotate through the connecting rod synchronous belt 803. The eight-way pipe synchronous pulley 806 rotates through the internal regular hexagon to drive the eight-way pipe to rotate, and the eight-way pipe drives the culture chamber support 7 to rotate through the dovetail groove structure 101c of the eight-way pipe head 101, while the eight-way pipe sleeve 104 is fixed; The stepper motor connected to the peristaltic pump 4 drives the peristaltic pump to rotate and pump the nutrient solution out of the nutrient solution tank 3 and start circulation: the nutrient solution flows into the first port 104a of the left eight-way tube sleeve 104 after passing through the oxygenator 5, and the liquid enters the eight-way tube pipeline 102 on the eight-way tube sleeve, and then flows into each culture chamber; after the culture chamber is filled with nutrient solution, the nutrient solution flows into the right eight-way tube pipeline through the right outlet, and then flows from the eight-way tube pipeline through the eight-way tube sleeve back to the nutrient solution tank, so as to achieve recycling. The rotation of the culture chamber support promotes the full aggregation of cultured cells. This process can ensure that the cells form a tight cell aggregate during the rotation process, thereby fully preparing for the second stage of suspension culture. At the same time, the continuous operation of the peristaltic pump and the circulation of the nutrient solution ensure that the cells are fully supplied with nutrients during the aggregation stage, which is conducive to the initial growth and aggregation of cells. In the second stage, the culture chamber support stops rotating and enters the static suspension culture stage. At this time, the peristaltic pump continues to circulate the nutrient solution to ensure that the nutrient solution in each culture chamber is continuously renewed, and the nutrient solution is continuously enriched with oxygen through the oxygenator to ensure that the cells have sufficient oxygen supply during the suspension culture process. The suspension culture stage is designed to allow cells to grow freely in an environment without adhesion, avoiding the risk of cells adhering to the walls of the culture chamber. This suspension culture method not only improves the growth rate and vitality of cells, but also makes the cultured cells closer to the natural state in the body, providing high-quality cell materials for subsequent biomedical research and applications. In addition, the continuous circulation and oxygen enrichment of the nutrient solution can effectively prevent cell death due to hypoxia during the culture process, and improve the success rate and yield of cell culture. This comprehensive cell culture device creates an ideal cell culture environment by precisely controlling the flow rate and oxygen content of the nutrient solution, allowing cells to grow healthily and rapidly in a suspended state.

[0058] Application Example 1: Single Cell Parallel Culture Inject different types of cell nutrient solutions into eight different culture chambers, start the culture device, set the culture parameters, and start the cell suspension culture. The specific implementation steps are as follows: Step S1: Preparation, clean and sterilize all culture chambers, hoses and nutrient solution tanks. Prepare the cell nutrient solution and ensure that it contains the required nutrients and oxygen.

[0059] Step S2: Device setup, install the culture chamber on the culture chamber support, and fix the position of the culture chamber by the bead on the culture chamber support and the bead groove on the side of the culture chamber. Connect the inlet pipe, discharge pipe, oxygenator and peristaltic pump, connect the inlet of each culture chamber to the outlet of the left eight-way pipe, and connect the outlet of each culture chamber to the inlet of the right eight-way pipe, so that eight different cells can be cultured in eight culture chambers at the same time, and ensure that each hose is connected correctly. Connect the nutrient solution tank to the liquid supply system to ensure no leakage.

[0060] Step S3: Cell inoculation: inject the cell suspension into each cell culture chamber. Ensure that the cells are evenly distributed in the nutrient solution. Close the injection port of the cell culture chamber to ensure airtightness.

[0061] Step S4: Start the device, start the motor, and drive the culture chamber support to rotate through the synchronous pulley structure to start the first stage of cell aggregation. Adjust the speed of the peristaltic pump to make the nutrient solution circulate and ensure that the cells get enough nutrition.

[0062] Step S5: During the culture process, the culture chamber support is rotated continuously in the first stage to fully aggregate the cells. In the second stage, the rotation is stopped and static suspension culture is started. At this time, the peristaltic pump keeps the nutrient solution circulating. Gas exchange is performed to ensure that the oxygenator continues to work and oxygenates the nutrient solution to meet the oxygen demand of the cells.

[0063] Step S6: Data recording, recording various parameters during the culture process, such as temperature, pH value, oxygen concentration, etc. Collect and store image data and sensor data of cell growth for subsequent analysis.

[0064] Step S7: End the culture. When the predetermined culture time is reached or the cells reach the expected growth state, stop the device operation, open the cell culture chamber, and take out the cells for further experiments or analysis.

[0065] Application Example 2: Multi-cell Serial Culture This embodiment involves culturing multiple types of cells simultaneously in the same device, injecting multiple types of cell nutrient solutions into different culture chambers, and co-culturing multiple organoid cells in series, and adjusting the flow rate and parameters of the solution according to demand to achieve synergistic effects of metabolites among multiple organoid cells. The specific implementation steps are as follows: Step S1: Preparation: Clean and sterilize all culture chambers, hoses, and nutrient solution tanks to ensure a sterile environment. Prepare nutrient solutions for various cells and ensure that they contain the required nutrients and oxygen. Adjust the formula of the nutrient solution according to the needs of different cells.

[0066] Step S2: Device setup: Install multiple culture chambers on the culture chamber support, and ensure that each chamber is firmly fixed. Connect the inlet pipe, the drain pipe and the oxygenator, and ensure that each hose is connected correctly and leak-free. Connect the nutrient solution tank to the liquid supply system and ensure that the system is well sealed.

[0067] Step S3: Cell inoculation: Inject different types of cell suspensions into each cell culture chamber to ensure that the cells in each chamber are evenly distributed. Close the injection port of the cell culture chamber to ensure airtightness to prevent external contamination.

[0068] Step S4: Start the device: Start the motor to drive the culture chamber support to rotate through the synchronous pulley to start the first stage of cell aggregation. Adjust the speed of the peristaltic pump to make the nutrient solution circulate and ensure that all types of cells get enough nutrition.

[0069] Step S5: Cultivation process: Phase 1: The culture chamber support rotates continuously to allow different types of cells to fully aggregate and form tight cell aggregates. Phase 2: Stop the rotation and start static suspension culture. The peristaltic pump keeps the nutrient solution circulating to ensure that the nutrient solution is constantly updated. Ensure that the oxygenator continues to work, enrich the nutrient solution with oxygen, and maintain the oxygen concentration to always meet the oxygen needs of the cells. Regularly check and record the temperature, pH value and other parameters of the nutrient solution.

[0070] Step S6: Data recording: During the entire culture process, various parameter data are recorded, such as temperature, pH value, oxygen concentration, nutrient solution flow rate, etc. Microscopes and camera equipment are used to collect image data of cell growth, and sensor data is recorded to facilitate subsequent analysis and evaluation of cell growth conditions.

[0071] Step S7: End of culture: When the predetermined culture time is reached or the cells reach the expected growth state, the device is stopped, the cell culture chamber is opened, and various cells are taken out for further experiments or analysis.

[0072] In summary, the biological organoid culture device provided in the present application provides an efficient, stable and flexible biological organoid culture solution by combining microgravity suspension culture, multi-channel liquid supply and efficient gas exchange technologies. Microgravity rotary perfusion suspension culture can be achieved: the rotation of the culture chamber support is achieved by the synchronous pulley control, and the cells are cultured in a microgravity environment by the rotation of the support. The rotation speed is controlled by controlling the stepper motor, which significantly improves the stability of the biological organoid suspension culture, thereby solving the limitation that organoid biological cells are easy to settle or adhere to the wall of the culture container, making it difficult to maintain a suspended state. Microgravity rotary perfusion suspension culture provides technical support for achieving efficient biological organoid suspension culture.

[0073] As a preferred technical solution of the present invention, gas exchange and blood oxygen balance can be achieved: the biological organoid culture device is equipped with an oxygenator assembly, and adopts an efficient gas exchange design to achieve gas exchange and blood oxygen balance. By using a breathable silicone rubber tube and adjusting the silicone rubber tube process, the rubber tube has good permeability and barrier properties, and a sufficient exchange area is designed to achieve efficient exchange of carbon dioxide and oxygen, achieve blood oxygen balance, and meet the metabolic needs of the organoid.

[0074] As a preferred technical solution of the present invention, it is possible to achieve the connection and synergy of multiple organoids: the culture chamber support is provided with a culture chamber placement groove for placing the cell culture chamber, which can simultaneously place eight culture chambers, each culture chamber can be connected in parallel or in series, and the synergy of organoid metabolites can be achieved by adjusting the flow rate to form an organic joint culture system. At the same time, independent perfusion microgravity suspension culture is adopted, and a liquid path slip ring is designed to achieve independent liquid supply to each chamber under the rotating state, and by adjusting the rotation speed, it is ensured that the organoids of the eight channels can be effectively suspended. When connected in series, the inlet of the first cell culture chamber is connected to the eight-way pipe, and the outlet of the eighth cell culture chamber is connected to the eight-way pipe, so that one nutrient solution passes through eight culture chambers; when connected in parallel, the inlet and outlet of each cell culture chamber are connected to the eight-way pipe, so that each culture chamber is independently supplied with liquid.

[0075] Compared with the existing technology, the advantages of the present invention are: it can culture different types of organoid cells in different cell culture chambers to form an organic joint culture system; it can also culture multiple organoid cells of the same type at the same time to obtain a large number of samples at one time, which is suitable for a variety of biomedical research and applications. By combining microgravity suspension culture, multi-channel liquid supply and efficient gas exchange technologies, the device achieves efficient, stable and flexible culture of organoids.

[0076] The technical means disclosed in the present application are not limited to the technical means disclosed in the above implementation mode, but also include technical solutions composed of any combination of the above technical features. The present application has been disclosed in the above preferred embodiments, but it is not used to limit the present application. Any technical solution obtained by equivalent replacement or equivalent transformation falls within the protection scope of the present application.

Claims

1. A fluid circuit slip ring, It is characterized in that include: An eight-way pipe head, an eight-way pipe pipe, a snap ring, a first bearing, an eight-way pipe sleeve, and a second bearing; The eight-way pipe and the eight-way pipe head are connected to form an eight-way pipe through a snap ring; the two ends of the eight-way pipe sleeve are respectively mounted on the eight-way pipe through a first bearing and a second bearing to rotate relative to each other; The outer circumference of the eight-way tube is provided with eight annular liquid storage grooves at intervals in the circumferential direction, and eight first openings are respectively opened at corresponding positions on the eight-way tube sleeve, and are respectively connected with the corresponding liquid storage grooves; eight first internal pipes are correspondingly arranged inside the eight-way tube; eight second openings are correspondingly arranged on the outer circumference of the eight-way tube head, and eight second internal pipes are correspondingly arranged inside the eight-way tube head, and the second internal pipes are respectively connected with the corresponding second openings; one end of the first internal pipe is connected with the corresponding liquid storage groove, and the other end is connected with the corresponding second internal pipe.

2. The fluid circuit slip ring according to claim 1, It is characterized in that It also includes a positioning pin and an end face sealing gasket. The eight-way pipe and the eight-way pipe head are positioned and connected through the positioning pin, and the first internal pipe and the corresponding second internal pipe are sealed and connected through the end face sealing gasket.

3. The fluid circuit slip ring according to claim 1, It is characterized in that A bearing retaining ring is also included, and the bearing retaining ring is arranged at the outer end of the second bearing.

4. A biological organoid culture device, It is characterized in that The biological organ culture device comprises a cell culture device base box, a nutrient solution tank, a peristaltic pump, an oxygenator, a first liquid path sliding ring, a culture chamber, a second liquid path sliding ring, a culture chamber support, and a culture chamber support drive device; the first liquid path sliding ring and the second liquid path sliding ring are the liquid path sliding rings according to any one of claims 1 to 3; The culture chamber support is provided with a plurality of culture chamber placement slots for installing the culture chambers in parallel; The octagonal tube head of the first fluid path sliding ring is relatively fixedly connected to the first end of the culture chamber support, and the octagonal tube head of the second fluid path sliding ring is relatively fixedly connected to the second end of the culture chamber support; the first fluid path sliding ring, the culture chamber support and the second fluid path sliding ring are installed on the base box of the cell culture device; In the working state, the culture chamber is installed in the culture chamber placement groove of the culture chamber support, and the fluid inlet of each culture chamber is connected to the second port corresponding to the octagonal tube head of the first liquid path sliding ring through a pipeline, and the fluid outlet of each culture chamber is connected to the second port corresponding to the octagonal tube head of the second liquid path sliding ring through a pipeline; The nutrient solution tank stores nutrient solution required by the corresponding cells in the culture chamber, and the outlet of the nutrient solution tank is connected to the inlet of the peristaltic pump through a pipeline, so as to provide nutrient solution circulation power through the peristaltic pump; the outlet of the peristaltic pump is connected to the liquid inlet of the oxygenator through a pipeline, so as to oxygen-enrich the nutrient solution passing through the oxygenator, and the liquid outlet of the oxygenator is connected to the first port on the octagonal tube sleeve of the first liquid path slip ring through a pipeline; the first port on the octagonal tube sleeve of the second liquid path slip ring is connected to the nutrient solution tank, so as to form a circulating liquid path; The culture chamber support driving device is drivingly connected to the culture chamber support and is used to drive the culture chamber support to rotate so as to realize suspension culture of cells in the culture chamber.

5. The biological organoid culture device according to claim 4, It is characterized in that The culture chamber support driving device includes a motor, a connecting rod, and a connecting rod synchronous belt; the connecting rod is provided with an intermediate synchronous pulley and two connecting rod synchronous pulleys at both ends; the power output end of the motor is engaged with the intermediate synchronous pulley through the motor synchronous belt to provide rotational power; the eight-way tube head is connected to an eight-way tube synchronous pulley, and each connecting rod synchronous pulley is respectively engaged with the corresponding eight-way tube synchronous pulley through the same connecting rod synchronous belt, driving the two eight-way tubes and the culture chamber support to rotate synchronously.

6. The biological organoid culture device according to claim 5, It is characterized in that The base box of the cell culture device includes a cell culture device support plate, a synchronous pulley bearing bracket is connected below the cell culture device support plate, and a connecting rod bearing seat is installed on the synchronous pulley bearing bracket; both ends of the connecting rod are installed on the connecting rod bearing seat through bearings and can rotate around the connecting rod.

7. The biological organoid culture device according to claim 6, It is characterized in that Two upper support plates are connected above the support plate of the cell culture device and are used to install the eight-way pipe sleeves of the first liquid path sliding ring and the second liquid path sliding ring respectively; The eight-way pipe sleeves of the first liquid path sliding ring and the second liquid path sliding ring are provided with flanges for connecting with the corresponding upper support plates on the support plate of the cell culture device through the flanges.

8. The biological organoid culture device according to claim 7, It is characterized in that It also includes a bearing support and a third bearing, the bearing support is connected to the corresponding upper support plate, the third bearing is installed inside the bearing support, the outer ring of the third bearing is connected to the bearing support, and the inner ring of the third bearing is connected to the corresponding eight-way tube synchronous pulley, which is used to guide and position the eight-way tube synchronous pulley to prevent axial movement.

9. The biological organoid culture device according to claim 7, It is characterized in that The end of the eight-way tube head is provided with a dovetail groove structure for connecting with the culture chamber support, and the two ends of the culture chamber support are respectively provided with dovetail tenon structures matching with the dovetail groove structure; the eight-way tube head and the culture chamber support are connected by mortise and tenon joints through the dovetail groove structure and the dovetail tenon structure.

10. The biological organoid culture device according to claim 1, It is characterized in that The cell culture chamber comprises a chamber body and a chamber end cover connected to each other, wherein the chamber body has a cylindrical accommodating cavity with an opening on one side and a fluid inlet and a fluid outlet connected to the accommodating cavity, and the chamber end cover is detachably sealed and connected to the open end of the chamber body.

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