Orifice plate device for organoid sphere culture
By introducing an oxygen delivery network, heating device and sensor system into the orifice plate device, the problems of hypoxia and temperature instability in organoid culture are solved, and an appropriate oxygen and temperature environment is achieved, and the healthy growth of organoid cell spheres is promoted.
Patent Information
- Application Number
- CN202421963340.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Utility models(China)
- Current Assignee / Owner
- Filing Date
- 2024-08-14
- Publication Date
- 2025-08-05
- Estimated Expiration
- 2034-08-14
AI Technical Summary
Existing orifice plate devices are prone to form an hypoxic environment in the culture of organoid cell spheres and do not have the function of temperature regulation, resulting in slow cell growth or damage.
An orifice plate device is designed, including an oxygen delivery pipe network, a heating device and a thermal conduction plate. It provides oxygen through the oxygen delivery pipe network, maintains a constant temperature environment with the heating device, discharges carbon dioxide from the exhaust passage, and sensors monitor and adjust the temperature and oxygen concentration.
It provides an appropriate oxygen concentration and temperature environment to ensure the healthy growth of organoid cell spheres, avoid the problems of hypoxia and temperature instability, and is suitable for the cultivation of a variety of organoids.
Smart Images
Figure CN223189205U_ABST
Abstract
Description
Technical Field
[0001] The utility model relates to the technical field of biological cell culture, and more particularly to a well plate device for organoid sphere culture. Background Art
[0002] Organoids are multicellular, three-dimensional structures cultivated in vitro that resemble the microanatomical features of their source organs. The primary cell types used for organoid development are tissue-specific pluripotent stem cells or precursor cells. To date, organoids have been developed from a variety of organs, including the brain, intestine, stomach, tongue, thyroid, thymus, testis, liver, pancreas, skin, lung, kidney, heart, and retina. In addition to organoids derived from healthy tissue, a wide range of disease models, including tumor models, are also emerging. Key characteristics of organoids include cell-type-based self-organization and spatially restricted, directed differentiation, similar to in vivo developmental processes. They contain a variety of organ-specific cells, whose spatial organization and arrangement resemble those of the source organ. Therefore, organoids are not only useful for drug toxicity testing, efficacy evaluation, and new drug screening, but also for establishing disease models to study genetic diseases, infectious diseases, and cancer. They can also be used for precision medicine, studying tissue and organ development, and for transplantation and repair.
[0003] The existing culture plates used for organoid spheroid culture have covers that are almost sealed over the culture plates with multiple culture wells, creating a nearly "fully" enclosed state and prone to hypoxia. For organoid spheroids with high oxygen requirements, hypoxia can lead to slow cell growth and, in severe cases, extensive cell damage. The culture of some organoids requires a suitable temperature, and existing well plate devices lack heating capabilities. Consequently, existing well plate devices cannot provide a good culture environment. Utility Model Content
[0004] The purpose of the utility model is to provide a well plate device for culturing organoid spheroids, by providing through holes on the well plate device to supply oxygen to the interior of the well plate device, and providing a heating device and a heat conducting plate, so that the heat provided by the heating device is introduced into the interior of the well plate device through the heat conducting plate to ensure a suitable constant temperature environment.
[0005] The above technical objectives of the present utility model are achieved through the following technical solutions: a well plate device for organoid spheroid culture, comprising a well plate base, a culture well unit and a well plate cover; a cavity is provided on the well plate base, a raised placement seat is provided inside the cavity, an oxygen outlet is provided on the side of the placement seat, and the culture well unit is embedded in the placement seat in the cavity; an oxygen supply pipe network is provided inside the well plate base, and the oxygen supply pipe network is provided with an oxygen supply channel connected to the oxygen outlet in the cavity; an air inlet is provided on one side of the well plate base, and an exhaust channel is provided on the other side thereof; a bottom groove of the well plate cover, a heating pipe is provided in the groove, and a heat conduction plate for closed heat conduction is provided in the groove.
[0006] The utility model is further configured as follows: a limiting ring is provided in the cavity, and a connecting rod is provided on the side surface of the limiting ring opposite to the inner wall of the cavity through the connecting rod.
[0007] The utility model is further configured as follows: the exhaust channel is L-shaped, the two ends of the exhaust channel are respectively located at the top and the side of the orifice plate base, and dustproof nets are provided at both ends of the exhaust channel.
[0008] The utility model is further configured as follows: a heat insulation layer is laid inside the groove.
[0009] The utility model is further configured as follows: a temperature sensor and an oxygen sensor are provided at the bottom of the orifice plate cover.
[0010] The utility model is further configured as follows: the orifice plate cover is provided with a power supply compartment, a battery is provided in the power supply compartment, the battery is a rechargeable storage battery, and a charging port is provided on the side of the orifice plate cover.
[0011] The utility model is further configured as follows: a display and control panel is provided on the top of the orifice plate cover, and the display and control panel includes a display screen and function buttons.
[0012] The utility model is further configured as follows: a valve is provided at the air inlet.
[0013] In summary, the present invention has the following beneficial effects: 1. A groove is provided at the bottom of the orifice plate cover and a heating pipe is provided in the groove for heating. An insulation layer is provided inside the groove, and a heat conducting plate is provided to seal the groove so that heat can only be transferred out through the heat conducting plate. The temperature inside the orifice plate device is changed to maintain a stable temperature, so that a suitable set temperature can be provided, which is beneficial to the culture of organoids. 2. An oxygen supply network is provided below the cavity inside the orifice plate base. The oxygen outlet on the side of the placement seat inside each cavity is connected to the oxygen supply network through the provided oxygen supply channel. Oxygen is supplied to the interior through the air inlet and discharged from the oxygen outlet after passing through the oxygen supply network, maintaining the stability of the internal oxygen concentration content, which is beneficial to the culture of organoids. 3. The exhaust channel is L-shaped, and the channel openings at both ends are respectively located at the top and side of the orifice plate base, which can effectively and quickly discharge gases such as carbon dioxide inside the orifice plate device. A dust net is provided near the two ports of the exhaust channel to effectively prevent external dust and the like from entering the orifice plate device and causing culture failure. 4. Temperature and oxygen sensors enable real-time monitoring of the temperature and oxygen concentration inside the well plate during the culture process. 5. This device can provide heat to the heat-conducting plate via a heating tube, which is then transferred to the culture well unit, providing a suitable temperature environment for the organoids. It can also supply oxygen to the well plate via an oxygen supply network and exhaust gases such as carbon dioxide through an exhaust channel, making it suitable for the culture of a variety of organoids. BRIEF DESCRIPTION OF THE DRAWINGS
[0014] Figure 1 This is a schematic diagram of the orifice plate device in the embodiment of the present utility model;
[0015] Figure 2 This is a schematic diagram of the orifice plate device in the embodiment of the present utility model;
[0016] Figure 3 This is a schematic diagram of the orifice plate cover structure in an embodiment of the present utility model;
[0017] Figure 4 This is a schematic diagram of the structure of the orifice plate base in the embodiment of the present utility model;
[0018] Figure 5 yes Figure 4 A magnified schematic diagram of the structure in the middle.
[0019] In the figure: 1. Orifice plate base; 2. Orifice plate cover; 3. Support foot; 4. Display and control panel; 5. Power compartment; 6. Charging port; 7. Exhaust channel; 8. Cavity; 9. Culture well unit; 10. Air inlet; 11. Valve; 12. Heat conduction plate; 13. Temperature sensor; 14. Oxygen sensor; 15. Insulation layer; 16. Heating tube; 17. Battery; 18. Limiting ring; 19. Oxygen supply network; 20. Connecting rod; 21. Oxygen supply channel; 22. Placement seat; 23. Oxygen outlet; 24. Dust net; 41. Display screen; 42. Function buttons. DETAILED DESCRIPTION
[0020] The following is combined with Figure 1-5 The utility model is described in further detail.
[0021] Example: A well plate device for culturing organoid spheroids, such as Figure 1-Figure 5 As shown, it includes a well plate base 1, a culture well unit 9 and a well plate cover 2; a cavity 8 is provided on the well plate base 1, a raised placement seat 22 is provided inside the cavity 8, an oxygen outlet 23 is provided on the side of the placement seat 22, and the number of oxygen outlets 23 is 1-2, and the culture well unit 9 is embedded in the placement seat 22 in the cavity 8; an oxygen supply pipe network 19 is provided inside the well plate base 1, and the oxygen supply pipe network 19 is provided with an oxygen supply channel 21 connected to the oxygen outlet 23 in the cavity 8; an air inlet 10 is provided on one side of the well plate base 1, and an exhaust channel 7 is provided on the other side thereof; the bottom groove of the well plate cover 2 is provided with a heating pipe 16 in the groove, and the groove is provided with a heat conduction plate 12 for closed heat conduction.
[0022] By adopting the above technical solution, a plurality of cavities 8 distributed in an array are provided on the orifice plate base 1 for embedding and placing the culture well units 9. A raised placement seat 22 is provided at the inner bottom of the cavity 8, and an oxygen outlet 23 is provided on the side of the placement seat 22. An oxygen supply network 19 is provided inside the orifice plate base 1 below the cavity 8. The oxygen outlet 23 on the side of the placement seat 22 inside each cavity 8 is connected to the oxygen supply network 19 through the provided oxygen supply channel 21. An air inlet 10 is provided on the side of the orifice plate base 1 to connect to the oxygen supply network 19. Oxygen is supplied to the interior through the air inlet 10 and then discharged from the oxygen outlet 23 after passing through the oxygen supply network 19. An exhaust channel 7 is provided on the opposite side of the air inlet 10 of the orifice plate base 1 to discharge gases such as carbon dioxide generated during the culture process. A groove is provided at the bottom of the orifice plate cover 2 and a heating tube 16 is provided in the groove for heating, so as to change the temperature inside the orifice plate device and maintain the temperature stable. A heat conducting plate 12 is installed at the bottom of the groove to seal the groove. The heat generated by the heating tube 16 is transferred to the cavity 8 through the heat conducting plate 12 to stabilize the temperature inside the orifice plate device, so as to provide a suitable set temperature, which is beneficial to the culture of some types of internal organoids. When in use, the culture well unit 9 is placed on the placement seat 22 inside the cavity 8, and the orifice plate cover 2 is covered on the orifice plate base 1. The heating tube 16 is used to heat and maintain the temperature stability so that the temperature remains stable in a temperature range suitable for organoid sphere culture. For organoid cell spheres with a large oxygen demand, an appropriate amount of oxygen is provided to the interior of the cavity 8 through the air inlet 10, the oxygen supply network 19 and the oxygen outlet 23, so as to facilitate the culture of organoid cell spheres.
[0023] It is further configured as follows: a limiting ring 18 is provided in the cavity 8 , and a connecting rod 20 is provided on the side of the limiting ring 18 opposite to the inner wall of the cavity 8 via the connecting rod 20 .
[0024] By adopting the above technical solution, a limiting ring 18 is set in the cavity 8. The limiting ring 18 is fixedly installed by being connected to the inner wall of the cavity 8 through connecting rods 20 relatively fixedly connected on both sides. When in use, the culture hole unit 9 is placed in the cavity 8 and the culture hole unit 9 is limited by the limiting ring 18 to avoid damage to the culture hole unit 9 caused by violent shaking.
[0025] It is further configured as follows: the exhaust channel 7 is L-shaped, the number of exhaust channels 7 can be 1-3, the two ends of the exhaust channel 7 are respectively located at the top and the side of the orifice plate base 1, and dustproof nets 24 are provided at both ends of the exhaust channel 7.
[0026] By adopting the above technical solution, the number of exhaust channels 7 in the orifice plate base 1 can be designed to be 1-3 according to actual needs, enabling the effective and rapid exhaust of gases such as carbon dioxide from within the orifice plate assembly, thereby preventing low oxygen concentrations. The exhaust channels 7 are L-shaped, with their openings located at the top and side of the orifice plate base 1, respectively. Dust screens 24 are installed near the two ports of the exhaust channels 7, effectively preventing external dust and other gases from entering the orifice plate assembly and causing culture failures.
[0027] The groove is further configured with an insulating layer 15, a temperature sensor 13, and an oxygen sensor 14 at the bottom of the orifice plate cover 2. The orifice plate cover 2 has a power supply compartment 5, which houses a rechargeable battery 17. A charging port 6 is provided on the side of the orifice plate cover 2. A display panel 4 is provided on the top of the orifice plate cover 2, including a display screen 41 and function buttons 42. A valve 11 is provided at the air inlet 10, and support legs 3 are provided around the bottom of the orifice plate base 1.
[0028] By adopting the above technical solution, a heat-insulating layer 15 is laid inside the groove. The heat-insulating layer 15 can be sprayed on the inside of the groove using a heat-insulating coating, or laid inside the groove using a heat-insulating material, which plays a role in heat insulation and prevents the temperature of the orifice plate cover 2 from rising and the heat from being transmitted to the inside of the orifice plate device through the orifice plate cover 2. The temperature sensor 13 and the oxygen sensor 14 can monitor the temperature and oxygen concentration inside the orifice plate device during the cultivation process. A rechargeable battery 17 is provided in the power supply compartment 5 of the orifice plate cover 2, and is charged through the charging port 6 on the side of the orifice plate cover 2. The battery 17 supplies power to the heating tube 16, the temperature sensor 13, the oxygen sensor 14 and the display and control panel 4. The display and control panel 4 includes a display screen 41 and function buttons 42. The function buttons 42 include multiple buttons with multiple functions. The display and control panel 4 can realize the display and setting of temperature, time, oxygen concentration, etc. When in use, the valve 11 at the air inlet 10 is opened, and the air inlet 10 can be connected to an external oxygen supply device to supply an appropriate amount of oxygen to the inside of the orifice plate device.
[0029] Working principle: When in use, the culture well unit 9 is embedded and placed in the cavity 8, and the well plate cover 2 is covered. When suitable temperature culture is required, the temperature value is set through the display control panel 4, and then the heating tube 16 is started to heat and generate heat. The generated heat is transmitted to the internal gap of the well plate device through the heat conduction plate 12 to change the temperature and stabilize the temperature, and the real-time temperature is monitored in real time by the temperature sensor 13 and displayed on the display screen 41. The oxygen sensor 14 monitors the internal oxygen concentration in real time and displays it on the display screen 41. For organoid cell spheres with a large oxygen demand, when the oxygen concentration inside the monitored well plate device is low, the valve 11 at the air inlet 10 is opened, and the air inlet 10 can be connected to an external oxygen supply device to supply an appropriate amount of oxygen to the inside of the well plate device to maintain the stability of the oxygen concentration inside the well plate device.
[0030] This specific embodiment is merely an explanation of the present invention and is not a limitation of the present invention. After reading this specification, those skilled in the art may make non-creative modifications to the present embodiment as needed. However, as long as they are within the scope of the claims of the present invention, they are protected by patent law.
Claims
1. A well plate device for culturing organoid spheroids, characterized by: The invention comprises a well plate base (1), a culture well unit (9) and a well plate cover (2); the well plate base (1) is provided with a cavity (8), the cavity (8) is provided with a raised placement seat (22), the side of the placement seat (22) is provided with an oxygen outlet (23), and the culture well unit (9) is embedded in the placement seat (22) in the cavity (8); the well plate base (1) is provided with an oxygen supply pipe network (19), the oxygen supply pipe network (19) is provided with an oxygen supply channel (21) connected to the oxygen outlet (23) in the cavity (8); one side of the well plate base (1) is provided with an air inlet (10), and the other side thereof is provided with an exhaust channel (7); the bottom groove of the well plate cover (2) is provided with a heating pipe (16) in the groove, and the groove is provided with a heat conduction plate (12) for closed heat conduction.
2. The well plate device for organoid spheroid culture according to claim 1, characterized in that: A limiting ring (18) is provided in the cavity (8), and a connecting rod (20) is provided on the side of the limiting ring (18) opposite to the inner wall of the cavity (8) via the connecting rod (20).
3. The well plate device for organoid spheroid culture according to claim 1, characterized in that: The exhaust channel (7) is L-shaped, and the two ends of the exhaust channel (7) are respectively located at the top and the side of the orifice plate base (1), and dustproof nets (24) are provided in both ends of the exhaust channel (7).
4. The well plate device for organoid spheroid culture according to claim 1, characterized in that: A heat insulation layer (15) is laid inside the groove.
5. The well plate device for organoid spheroid culture according to claim 1, characterized in that: A temperature sensor (13) and an oxygen sensor (14) are provided at the bottom of the orifice plate cover (2).
6. The well plate device for organoid spheroid culture according to claim 1, characterized in that: The orifice plate cover (2) is provided with a power supply compartment (5), a battery (17) is provided in the power supply compartment (5), and the battery (17) is a rechargeable storage battery (17). A charging port (6) is provided on the side of the orifice plate cover (2).
7. The well plate device for organoid spheroid culture according to claim 1, characterized in that: A display and control panel (4) is provided on the top of the orifice plate cover (2), and the display and control panel (4) comprises a display screen (41) and function buttons (42).
8. The well plate device for organoid spheroid culture according to claim 1, characterized in that: A valve (11) is provided at the air inlet (10).