Organoid 3d printer temperature control system

Abstract

The application discloses an organoid 3D printer temperature control system, which comprises a first liquid guide assembly, a first driving assembly, a hole plate and a first temperature control assembly. The first liquid guide assembly has a first liquid guide end for guiding out biological ink. The first driving assembly is connected to the first liquid guide assembly and is used for driving the first liquid guide assembly to move. The hole plate is arranged below the first liquid guide assembly and comprises an upper wall and a lower wall. The upper wall is concave and is provided with a plurality of accommodating grooves. Each accommodating groove is used for accommodating the biological ink guided out by the first liquid guide end. The first temperature control assembly is attached to the lower wall and is used for adjusting the temperature value of the hole plate to a first preset range. The application collects the accommodating grooves on the hole plate. The temperature of the solution in each accommodating groove can be conducted to each other through the hole plate. Therefore, the design of the application can make the temperature of each accommodating groove tend to be average, so that the printing, culture and other operations of a large number of organs can be more efficiently and accurately performed.

Description

Technical Field

[0001] This invention relates to the field of organoid and cell culture technology, and in particular to a temperature control system for an organoid 3D printer. Background Technology

[0002] In today's industrial production and technological applications, containers, as a fundamental component, are widely used in numerous fields. However, with continuous technological advancements and increasing application demands, existing container designs are gradually revealing some shortcomings.

[0003] Specifically, existing container designs are often stand-alone units. While this design is simple and easy to manufacture, it presents numerous problems in practical use. Especially in applications requiring heating or reactions, stand-alone containers often struggle to achieve uniform heating, leading to low reaction efficiency and potentially even safety issues.

[0004] For example, in chemical laboratories or industrial production lines, it is often necessary to heat substances inside containers to trigger chemical reactions. However, due to the independent nature of existing containers, heat is difficult to transfer evenly to each container, resulting in some containers overheating while others remain underheated. This uneven heating not only affects the efficiency of the reaction but may also trigger unnecessary side reactions and even create safety hazards. Summary of the Invention

[0005] The main objective of this invention is to propose a temperature control system for organoid 3D printers, which can perform large-scale organoid manufacturing, reaction testing, and other operations more efficiently and accurately.

[0006] To achieve the above objectives, some embodiments of the present invention provide a temperature control system for an organoid 3D printer, comprising: The first liquid guiding assembly has a first liquid guiding end for discharging bio-ink; A first driving component is connected to a first liquid guiding component and is used to drive the first liquid guiding component to move. An orifice plate is located below the first liquid guiding component. The orifice plate includes an upper surface wall and a lower surface wall. The upper surface wall is recessed with multiple receiving grooves, each of which is used to receive the bio-ink discharged from the first liquid guiding end. The first temperature control component is attached to the lower surface wall and is used to adjust the temperature value of the orifice plate to a first preset range.

[0007] In some embodiments, the temperature control system of the organoid 3D printer includes a placement platform, a perforated plate and a first temperature control component respectively disposed on opposite sides of the placement platform; The mounting platform is recessed to form a first recessed portion, which is used to accommodate the perforated plate. The side of the mounting platform opposite to the first recessed portion is recessed in the opposite direction of the first recessed portion to form a second recessed portion, which is used to accommodate the first temperature control component.

[0008] In some embodiments, the first temperature control component includes a first temperature control device and a second temperature control device. The first temperature control device is fixed to the mounting platform and is in contact with the lower surface wall of the orifice plate to adjust the temperature of the orifice plate. The second temperature control device is movably connected to the mounting platform to regulate the local temperature of the orifice plate.

[0009] In some embodiments, the first temperature control component includes a drive device connected to a second temperature control device, the drive device being configured to drive the second temperature control device to move relative to the orifice plate to regulate the temperature of the area of ​​the orifice plate containing bio-ink.

[0010] In some embodiments, the mounting platform includes a plurality of upwardly projecting stops, each of which abuts against the edge of the perforated plate.

[0011] In some embodiments, the temperature control system of the organoid 3D printer further includes a temperature probe connected to the placement platform and located on the side of the placement platform away from the perforated plate.

[0012] In some embodiments, the temperature control system of the organoid 3D printer includes a second temperature control component connected to a first liquid guiding component, and the second temperature control component is used to adjust the temperature of the bio-ink exported by the first liquid guiding component to a second preset range.

[0013] In some embodiments, the temperature control system of the organoid 3D printer includes a first driving component, which is connected to a first liquid guiding component, and the first driving component is used to drive the first liquid guiding component to move along a first preset path. The first driving component is configured to first move the liquid guiding component toward the solution to be treated until the bio-ink at the first liquid guiding end adheres to the solution to be treated, and then move the first liquid guiding component away from the solution to be treated until the bio-ink detaches from the first liquid guiding end.

[0014] In some embodiments, the temperature control system of the organoid 3D printer further includes a second liquid guiding component and a second driving component. The second liquid guiding component has a second liquid guiding end for discharging culture medium. The second driving component is connected to the second liquid guiding component and drives the second liquid guiding component to move along a second preset path to inject the culture medium into the receiving tank.

[0015] In some embodiments, the temperature control system of the organoid 3D printer further includes a housing assembly having an inner chamber capable of sealingly accommodating a first fluid guiding assembly, a first drive assembly, an orifice plate, and a first temperature control assembly.

[0016] According to the above embodiments, the beneficial effects of the present invention are: The organoid 3D printer temperature control system of the present invention includes a first liquid guiding assembly, a first driving assembly, a well plate, and a first temperature control assembly. The first liquid guiding assembly has a first liquid guiding end for dispensing bio-ink, the design of which allows the bio-ink to be uniformly dripped into the various receiving slots of the well plate. A first driving assembly is connected to the first liquid guiding assembly and functions to drive the first liquid guiding assembly to make precise movements, ensuring that the bio-ink is accurately dripped into designated positions. The well plate is disposed below the first liquid guiding assembly and consists of an upper surface wall and a lower surface wall. Multiple receiving slots are recessed on the upper surface wall. The layout of these receiving slots is designed to maximize the space for cell growth while ensuring the uniform distribution of bio-ink, thereby improving the culture efficiency of the organoid 3D printer temperature control system. The first temperature control assembly is mounted close to the lower surface wall of the well plate to adjust the temperature of the well plate to a first preset range suitable for cell growth. This structural design ensures that cells grow in a suitable temperature environment, thereby improving the efficiency and quality of the biological reaction.

[0017] This invention integrates reservoirs onto an orifice plate, with the reservoirs connected by the orifice plate. Heat received by the orifice plate can be conducted between the reservoirs, or the temperatures of the solutions within each reservoir can be conducted and influence each other through the orifice plate. Therefore, the design of this application enables the temperature of each reservoir to tend towards uniformity. This design helps ensure that the solution in each reservoir has the same environmental conditions (such as temperature), enabling more efficient and precise large-scale organoid printing, reaction testing, and other operations.

[0018] Additional aspects and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. Attached Figure Description

[0019] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the structures shown in these drawings without creative effort.

[0020] Figure 1 This is a schematic diagram of the temperature control system of an organoid 3D printer according to one embodiment of the present invention; Figure 2 yes Figure 1 Exploded structural diagram of the temperature control system in a 3D printer for organoids; Figure 3 yes Figure 2 Enlarged view of point A in the middle; Figure 4 A schematic diagram of the temperature control system of an organoid 3D printer, viewed from another perspective, in one embodiment of the present invention; Figure 5 yes Figure 4 A schematic diagram of the cross-sectional structure of the temperature control system of the organoid 3D printer cut by the aa plane; Figure 6 This is a schematic diagram of the structure of the temperature control system of the organoid 3D printer hidden behind the outer door panel in one embodiment of the present invention; Figure 7 yes Figure 6 A schematic diagram of the cross-sectional structure of the temperature control system of the organoid 3D printer cut by the bb plane; Figure 8 This is a partial structural schematic diagram of the first liquid guiding component and the second liquid guiding component in one embodiment of the present invention; Figure 9 It is to observe from another perspective Figure 8 Schematic diagram of the structure of the first and second liquid guiding components; Figure 10 This is a schematic diagram of the structure of a cultivation platform unit in one embodiment of the present invention; Figure 11 yes Figure 10 A schematic diagram of the cross-sectional structure of the culture platform unit cut by the cc plane.

[0021] Explanation of icon numbers: Housing assembly 10; filter fan 101; high-efficiency filter screen 102; microscope display screen 103; outer door panel 104; rear support of cabinet 105; machine support unit 106; load-bearing feet 107; lower support of cabinet 108; Second liquid guiding assembly 20; Vertical precision lead screw motor 201; Motor slider 202; Hydraulic block 203; Liquid injection pump 204; Liquid filling enclosure 205; Liquid filling device holder 206; Microscope 207; Microscope slide 208. Culture platform unit 30; well plate holder 301; placement platform 302; temperature probe 303; first temperature control device 304; second temperature control device 305; First liquid guiding assembly 40; Vertical precision lead screw motor 401; Motor slider 402; Sampling pressure block 403; Sampling injection pump 404; Sampling encapsulation shell 405; Sampling circulating water cooling generator 406; Temperature probe 407; Sampling device holder 408. Second temperature control component 50; First temperature control component 60; First drive component 70; Second drive component 80; Orifice plate 90; receiving groove 910.

[0022] The realization of the objective, functional features and advantages of the present invention will be further explained in conjunction with the embodiments and with reference to the accompanying drawings. Detailed Implementation

[0023] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0024] It should be noted that if the embodiments of the present invention involve directional indicators (such as up, down, left, right, front, back, etc.), the directional indicators are only used to explain the relative positional relationship and movement of the components in a specific posture. If the specific posture changes, the directional indicators will also change accordingly.

[0025] Furthermore, if the embodiments of this invention involve descriptions such as "first" or "second," these descriptions are for descriptive purposes only and should not be construed as indicating or implying their relative importance or implicitly specifying the number of technical features indicated. Therefore, a feature defined with "first" or "second" may explicitly or implicitly include at least one of those features. Additionally, the use of "and / or," "and / or," or "and / or" throughout the text implies three parallel solutions. For example, "A and / or B" includes solution A, solution B, or a solution where both A and B are satisfied simultaneously. Furthermore, the technical solutions of the various embodiments can be combined with each other, but this must be based on the ability of those skilled in the art to implement them. When the combination of technical solutions is contradictory or impossible to implement, it should be considered that such a combination of technical solutions does not exist and is not within the scope of protection claimed by this invention.

[0026] In today's industrial production and technological applications, the manufacturing process of organoids often involves temperature control, including temperature control during extrusion and temperature control in porous containers to ensure successful manufacturing and shaping.

[0027] Specifically, the preparation of organoid precursors often involves mixing and extruding cells with hydrogels such as matrigel. During the mixing process, the cells and matrigel are kept at a low temperature to ensure a fluid state conducive to extrusion. After extrusion, the matrigel must be cured within a temperature range of 35°C-45°C while maintaining cell viability to promote organoid development and maturation. Current printing devices lack a dedicated temperature control module for the organoid manufacturing process. In particular, there is a lack of design and devices for temperature control during extrusion, the overall ambient temperature, and the stage of the porous container. This prevents organoids from forming during manufacturing and hinders the maintenance of cell viability in the prepared organoid precursors after formation.

[0028] The following is for reference. Figures 1 to 11 This describes a temperature control system for an organoid 3D printer according to an embodiment of the present invention. (Refer to...) Figures 1 to 3 as well as Figure 10 and Figure 11 In some embodiments, the temperature control system of the organoid 3D printer includes a first liquid guiding assembly 40, a first driving assembly 70, a well plate 90, and a first temperature control assembly 60. The first liquid guiding assembly 40 has a first liquid guiding end for discharging bio-ink, designed to allow the bio-ink to drip evenly into the various receiving slots 910 of the well plate 90. The first driving assembly 70 is connected to the first liquid guiding assembly 40 and functions to drive the first liquid guiding assembly 40 to move precisely, ensuring that the bio-ink is accurately dripped into designated locations. The well plate 90 is disposed below the first liquid guiding assembly 40 and consists of an upper surface wall and a lower surface wall. The upper surface wall has multiple recessed receiving slots 910, the layout of which is designed to maximize space for cell growth while ensuring uniform distribution of the bio-ink, thereby improving the culture efficiency of the organoid 3D printer temperature control system. The first temperature control assembly 60 is mounted close to the lower surface wall of the well plate 90 and adjusts the temperature of the well plate 90 to a first preset range suitable for cell growth via an electric heating or cooling element. The first preset range can be 32°C to 42°C to simulate the human body environment, such as 33°C, 36°C, 37°C, 39°C, and 42°C, with 37°C being preferred. This structural design ensures that cells grow in a suitable temperature environment, thereby improving the efficiency and quality of biological reactions.

[0029] This invention integrates containment tanks 910 onto a perforated plate 90, with the tanks 910 connected to each other via the perforated plate 90. Heat received by the perforated plate 90 can be conducted between the tanks 910, or the temperatures of the solutions within each tank 910 can be conducted and influence each other through the perforated plate 90. Therefore, the design of this application enables the temperature of each tank 910 to tend towards uniformity. This design helps ensure that the solution in each tank 910 has the same environmental conditions (such as temperature), enabling more precise and efficient large-scale organoid printing, culture, and reaction testing.

[0030] Understandably, in some embodiments, the first liquid guiding assembly 40 may be equipped with a flow control valve to precisely control the flow rate of the bio-ink, thereby better adapting to different experimental needs. Furthermore, the first driving assembly 70 may employ a stepper motor or a servo motor, which possesses high-precision position control capabilities, enabling fine-tuning of the bio-ink titration position to ensure that the bio-ink is accurately dripped into each receiving slot 910 of the well plate 90.

[0031] In some embodiments, the material of the orifice plate 90 may be selected from materials with excellent biocompatibility and thermal conductivity, such as glass and polystyrene. This not only helps cell adsorption and growth, but also effectively transfers the heat generated by the first temperature control component 60 and maintains the temperature uniformity of the orifice plate 90.

[0032] In some embodiments, the first temperature control component 60, in addition to electric heating, can be combined with a water bath circulation system to remove or replenish heat through water flow. This method is particularly suitable for experimental scenarios requiring rapid temperature changes. For example, the first temperature control component 60 itself is a cavity with the function of containing coolant, and the first temperature control component 60 is recessed to accommodate the orifice plate 90. The peripheral wall of the first temperature control component 60 fits against the peripheral wall of the orifice plate 90 to increase the contact area between the first temperature control component 60 and the orifice plate 90, thereby improving heat exchange efficiency. The first temperature control component 60 can also be a heat exchange pipe, which wraps around the outer periphery of the orifice plate 90 to achieve heat exchange between the coolant inside the first temperature control component 60 and the orifice plate 90. In addition, to further improve the accuracy of temperature control, multiple temperature sensors can be arranged inside or on the surface of the orifice plate 90 to monitor temperature changes at various points in real time, so as to adjust the temperature control strategy in a timely manner.

[0033] It is understood that, in some embodiments, the number and arrangement of the wells 910 on the well plate 90 can be adjusted according to experimental requirements. For example, the well plate 90 can be designed with 96 wells, 24 wells, or 6 wells to accommodate experiments of different scales. The shape and size of the wells 910 can also be optimized according to cell type and culture conditions, such as circular, square, or elliptical.

[0034] The well plate 90 can be equipped with a lid to prevent external contaminants from entering the containment tank 910, maintaining a sterile environment. The lid can be designed with a breathable material to allow gas exchange but prevent microbial entry. Furthermore, the well plate 90 can be equipped with a marking system, such as numerical or alphanumeric markings, to facilitate quick location and recording of the position and contents of each containment tank 910 by laboratory personnel.

[0035] The orifice plate 90 can be manufactured using injection molding or blow molding to ensure dimensional accuracy and surface quality. The edges of the orifice plate 90 can be designed with a wavy or serrated shape to increase grip and facilitate operation by laboratory personnel. The orifice plate 90 can also be equipped with a support to maintain its stability on the laboratory bench.

[0036] Reference Figure 3 , Figure 10 and Figure 11 In some embodiments, the temperature control system of the organoid 3D printer includes a mounting platform 302, a perforated plate 90, and a first temperature control component 60, respectively mounted on opposite sides of the mounting platform 302. The mounting platform 302 is recessed to form a first recess that can accommodate the perforated plate 90. Because this recessed structure shortens the distance between the perforated plate 90 and the first temperature control component 60, this design ensures stable placement of the perforated plate 90 while also helping to maintain close contact between the perforated plate 90 and the first temperature control component 60, thus improving the speed at which the first temperature control component 60 regulates the temperature of the perforated plate 90. On the side of the mounting platform 302 opposite to the first recess, a second recess is formed along the opposite direction of the first recess's recess direction, and this second recess is used to mount the first temperature control component 60. This design not only saves space but also shortens the distance between the first temperature control component 60 and the perforated plate 90, ensuring that the first temperature control component 60 can effectively and quickly heat or cool the perforated plate 90, guaranteeing high efficiency and stability in temperature control.

[0037] It is understood that, in some embodiments, the mounting platform 302 can be designed with a modular structure, allowing users to replace orifice plates 90 or temperature control components of different specifications according to experimental needs, thereby improving the system's flexibility and applicability. For example, orifice plates 90 and temperature control components can be quickly installed and removed via slide rails or snap-fit ​​mechanisms, facilitating maintenance and cleaning.

[0038] The material of the placement platform 302 can be selected to have good corrosion resistance and thermal stability to cope with the chemical substances and temperature changes that may occur during the biological reaction. Furthermore, in some embodiments, a layer of thermal insulation material can be added to the bottom of the placement platform 302 to prevent heat loss and improve energy utilization efficiency. In some cases, the placement platform 302 can also be equipped with a temperature monitoring system that uses integrated temperature sensors to monitor the temperature of the orifice plate 90 and the temperature control components in real time, ensuring that the entire system operates at its optimal condition.

[0039] Reference Figure 3 , Figure 10 and Figure 11 In some embodiments, the first temperature control component 60 includes a first temperature control device 304 and a second temperature control device 305. The first temperature control device 304 is fixed to the placement platform 302 and conforms to the lower surface wall of the well plate 90, used to regulate the overall temperature of the well plate 90. The second temperature control device 305 is movably connected to the placement platform 302 and can regulate the local temperature of the well plate 90. This design allows for precise adjustment of the local temperature while maintaining overall temperature control of the well plate 90, thereby better meeting the needs of different cell growth. It is understood that the movable connection of the second temperature control device 305 allows it to be configured to promptly compensate for areas of temperature imbalance. For example, if the temperature of a certain container 910 deviates from a preset value during the reaction, the second temperature control device 305 can be moved to that area to adjust the temperature of the solution in that container 910, thus correcting the reaction process in a timely manner. Of course, in some embodiments, only a portion of the orifice plate 90 is injected with bio-ink or the solution to be treated. In this case, it is only necessary to drive the second temperature control device 305 to move to the area where the container tank 910 containing the bio-ink or the solution to be treated is located, and only the temperature of this area needs to be adjusted, thereby saving power and reducing energy consumption.

[0040] Understandably, in some embodiments, the first temperature control device 304 may employ an electric heating element or a cooling element. These elements have high thermal response speed and temperature control accuracy, enabling rapid adjustment of the temperature of the orifice plate 90 to the desired range. The second temperature control device 305 may employ a small heating rod or cooling rod, achieving temperature regulation of localized areas of the orifice plate 90 by precisely controlling its position and power. For example, the second temperature control device 305 may be designed as a movable module, moving across the surface of the orifice plate 90 via a slide rail or robotic arm to cover different localized areas.

[0041] In some embodiments, the second temperature control device 305 may be equipped with a temperature sensor to monitor temperature changes in a local area in real time, ensuring the accuracy and stability of temperature control. To improve the reliability and durability of the system, the connection between the first temperature control device 304 and the second temperature control device 305 may be designed to be waterproof and dustproof to prevent liquids or dust from entering and affecting the temperature control effect.

[0042] Reference Figure 3 , Figure 10 and Figure 11In some embodiments, the first temperature control component 60 includes a drive device connected to the second temperature control device 305. The drive device is configured to move the second temperature control device 305 relative to the well plate 90 to control the temperature of the area of ​​the well plate 90 containing bio-ink. This design allows the second temperature control device 305 to move flexibly on the surface of the well plate 90, achieving localized temperature control in different areas, thus better adapting to the needs of different cell growth. Furthermore, this design can compensate for areas with excessively low or high temperatures. It is understood that when only a localized temperature adjustment of the well plate 90 is needed, only the second temperature control device 305 needs to be controlled to regulate the temperature of the corresponding area, saving power and making the temperature control system of the organoid 3D printer of this application more environmentally friendly.

[0043] Understandably, in some embodiments, the drive unit may employ a stepper motor or a servo motor, which possesses high-precision position control capabilities and significant driving force, enabling precise movement of the second temperature control device 305 to the desired position. The drive unit may be equipped with a closed-loop control system, adjusting the motor's position and speed in real time via feedback signals to ensure the motion accuracy and stability of the second temperature control device 305. Furthermore, the drive unit may be designed with a modular structure for easy maintenance and replacement. For example, the drive unit may include a detachable motor module and a slide rail module, with the slide rail module mounted on the mounting platform 302. The motor module drives the second temperature control device 305 along the slide rail via a belt or lead screw. To improve system reliability and safety, the drive unit may be equipped with overload protection and emergency stop functions to prevent damage or accidents caused by unforeseen circumstances.

[0044] To facilitate the operation of the drive unit, in some embodiments, the mounting platform 302 may be equipped with guide grooves or positioning pins to ensure the stability of the second temperature control device 305 during movement, avoiding temperature control deviations caused by vibration or collisions. Furthermore, wireless communication technology can be used between the drive unit and the second temperature control device 305 to achieve remote control and monitoring, improving the system's intelligence level.

[0045] Reference Figure 3 , Figure 10 and Figure 11 In some embodiments, the mounting platform 302 includes multiple upwardly protruding stops that abut against the edges of the orifice plate 90. The design of the stops ensures the stability and precise positioning of the orifice plate 90 on the mounting platform 302, preventing displacement or tilting of the orifice plate 90 during operation. This structural design not only improves the installation accuracy of the orifice plate 90 but also enhances the overall stability of the system.

[0046] Understandably, in some embodiments, the stop can be made of an elastic material, such as silicone or rubber, to better adapt to changes in the size of the orifice plate 90, while providing a cushioning effect and reducing wear on the orifice plate 90 during installation and use. Furthermore, the stop can be designed as an adjustable structure, fixed to the mounting platform 302 by screws or clips, allowing the user to adjust the position of the stop according to different orifice plate 90 specifications to ensure precise installation. The height and shape of the stop can also be optimized according to the edge design of the orifice plate 90; for example, the stop can be designed in an L-shape or U-shape to provide better support and fixation. To further improve system reliability, anti-slip pads can be added to the surfaces of the stop that contact the orifice plate 90 to prevent the orifice plate 90 from sliding during operation. In addition, the material selection for the stop should consider biocompatibility and chemical resistance to accommodate various chemicals that may be generated during biological reactions.

[0047] Reference Figure 3 , Figure 10 and Figure 11 In some embodiments, the temperature control system of the organoid 3D printer further includes a temperature probe 303, which is connected to the placement platform 302 and located on the side of the placement platform 302 opposite to the well plate 90. The temperature probe 303 is designed to monitor the temperature of the well plate 90 in real time, ensuring that the temperature of the well plate 90 remains within a first preset range. The temperature probe 303 is connected to the temperature control system controller, which can provide real-time temperature data feedback. The controller adjusts the operating state of the first temperature control component 60 based on the feedback data, thereby achieving precise temperature control. This design ensures the stability and reliability of the temperature of the well plate 90, providing an ideal environment for cell growth.

[0048] Understandably, in some embodiments, the temperature probe 303 may employ a high-precision thermocouple or resistance temperature detector (RTD). These sensors offer high temperature measurement accuracy and response speed, enabling real-time and accurate monitoring of temperature changes in the orifice plate 90. The temperature probe 303 may be designed with a detachable structure for easy periodic calibration and maintenance, ensuring its long-term accuracy and reliability. Furthermore, multiple temperature probes 303 may be deployed at different locations on the orifice plate 90 to monitor the overall temperature distribution of the orifice plate 90, ensuring temperature uniformity. Communication between the temperature probe 303 and the controller can be wired or wireless; wireless communication reduces wiring complexity and improves system flexibility.

[0049] In some embodiments, to prevent the temperature probe 303 from being affected by the external environment, a protective cover can be added around the temperature probe 303 to protect it from interference from contaminants such as dust and liquids. Furthermore, the installation position of the temperature probe 303 should be as close as possible to the lower surface wall of the orifice plate 90 to ensure the accuracy and real-time nature of temperature measurement. The material selection for the temperature probe 303 should consider biocompatibility and high-temperature resistance to adapt to the potentially high-temperature environment during biological reactions.

[0050] Reference Figures 1 to 7 In some embodiments, the temperature control system of the organoid 3D printer further includes a housing assembly 10 having an inner chamber for housing a first fluid guiding assembly 40, a first drive assembly 70, a perforated plate 90, and a first temperature control assembly 60. The design of the housing assembly 10 ensures the sealing and sterile environment of the entire system. The housing assembly 10 includes a filter fan 101, which includes a filter screen and airflow ducts adapted to connect the inner chamber to the external environment to ensure a sterile environment within the inner chamber. This design not only protects the internal components from contamination but also provides ideal environmental conditions for cell growth.

[0051] Understandably, in some embodiments, the housing assembly 10 may be made of materials with excellent biocompatibility and chemical resistance, such as stainless steel or polypropylene, to ensure stability and reliability during long-term use. The internal chamber design may include multiple vents and sealed doors. The vents are used to install the filter fan 101, and the sealed doors facilitate user replacement or maintenance of internal components under sterile conditions. The filter screen of the filter fan 101 may use HEPA high-efficiency filter media to ensure effective filtration of airborne particulate matter and microorganisms. The design of the airflow duct should ensure uniform airflow and avoid eddies or dead zones, thereby improving the quality of the sterile environment.

[0052] In some embodiments, the housing assembly 10 may be equipped with pressure sensors and temperature and humidity sensors to monitor the environmental parameters of the internal chamber in real time, ensuring that it is always in optimal condition. To improve the automation level of the system, the housing assembly 10 may also integrate an automatic disinfection function, which periodically disinfects the internal chamber using ultraviolet lamps or chemical disinfectants to further ensure a sterile environment. The bottom of the housing assembly 10 may be designed with a drainage structure to facilitate cleaning and discharging of wastewater generated during the cleaning process.

[0053] Reference Figure 8 and Figure 9In some embodiments, the temperature control system of the organoid 3D printer includes a second temperature control component 50, which is connected to a liquid guiding component and used to regulate the temperature of the bio-ink discharged from the first liquid guiding component 40 to a second preset range. This design ensures that the bio-ink is at a suitable temperature before discharge, thereby improving cell survival rate and the efficiency of biological reactions. The second temperature control component 50 can be an independent temperature control unit connected to the first liquid guiding component 40 via a pipe to ensure the temperature stability of the bio-ink during transport.

[0054] Understandably, in some embodiments, the second temperature control component 50 may employ a water bath circulation system or an electric heating / cooling element. These temperature control elements have high temperature control accuracy and response speed, enabling them to quickly adjust the temperature of the bio-ink to the required range. A water bath circulation system uses circulating water to remove or replenish heat, making it suitable for scenarios requiring long-term stable temperatures, while an electric heating / cooling element is suitable for scenarios requiring rapid temperature changes.

[0055] In some embodiments, the second temperature control component 50 may be equipped with a temperature sensor to monitor the temperature changes of the bio-ink in real time, ensuring the accuracy and stability of temperature control. To improve the reliability and safety of the system, the second temperature control component 50 may be designed with a modular structure for easy maintenance and replacement. For example, the temperature control unit may be designed as a detachable module, connected to the liquid delivery component via a quick connector, facilitating regular inspection and maintenance by the user. Furthermore, the second temperature control component 50 may be equipped with a flow control valve to further optimize the temperature control effect by adjusting the flow rate. To prevent contamination of the bio-ink during transmission, the connecting pipe between the liquid delivery component and the second temperature control component 50 may be a disposable sterile conduit, ensuring sterility for each use. The second temperature control component 50 may also be equipped with data logging and transmission functions, transmitting temperature data to the central control system in real time via wireless communication technology, facilitating remote monitoring and management by the user.

[0056] Reference Figure 8 and Figure 9In some embodiments, the first drive assembly 70 includes a motor, a transmission mechanism, and a guide rail. The motor is installed in the inner cavity of the housing assembly 10, the transmission mechanism connects the motor and the first liquid guiding assembly 40, and the guide rail guides the movement of the first liquid guiding assembly 40. When the motor starts, the transmission mechanism drives the first liquid guiding assembly 40 to move along the guide rail along a predetermined path. First, the first liquid guiding assembly 40 is driven to move towards the solution to be processed, so that the first liquid guiding end contacts the solution to be processed. At this time, the bio-ink will adhere to the surface of the solution to be processed due to capillary action. Subsequently, the motor reverses, and the transmission mechanism pulls the first liquid guiding assembly 40 back, causing the bio-ink to fall off from the first liquid guiding end, completing the fixed-point and quantitative dispensing of bio-ink. This structural design ensures that the bio-ink can be accurately placed at the target position, while avoiding bio-ink residue. Therefore, it can further accurately control the volume of bio-ink in the receiving tank 910, improving the accuracy of the temperature control system of the organoid 3D printer.

[0057] The temperature control system for the organoid 3D printer proposed in this application can also be used in various application scenarios such as drug screening, screening of different growth and development factors, exploration of cell mechanisms, and manufacturing of diverse tissues.

[0058] In some embodiments, the first liquid guiding assembly 40 includes a linear pump and a first liquid guiding end. The linear pump is used to store and extrude bio-ink, and the first liquid guiding end is connected to the linear pump. When the linear pump is operating, the bio-ink is ejected from the first liquid guiding end through the reciprocating motion of an internal piston. The design of the first liquid guiding assembly 40 allows for precise control of the amount of bio-ink discharged, ensuring that the volume of bio-ink discharged each time is consistent.

[0059] The first drive assembly 70, connected to the first liquid guiding assembly 40, consists of a motor and a lead screw. The motor drives the lead screw to rotate, and the lead screw drives the first liquid guiding assembly 40 to move along a first preset path. The first drive assembly 70 drives the first liquid guiding assembly 40 to move so that the bio-ink droplets suspended at the first liquid guiding end come into contact with and adhere to the previously discharged bio-ink surface. Then, the first drive assembly 70 drives the first liquid guiding assembly 40 away from the previously discharged bio-ink surface, thereby smoothly drawing the bio-ink droplets previously suspended at the first liquid guiding end away from the first liquid guiding end. This design avoids droplet residue and can precisely control the volume of bio-ink discharged by the first liquid guiding assembly 40.

[0060] It is understandable that the solution discharged by the first liquid delivery component 40 can be bio-ink. Bio-ink can include cell suspension, cell-mixed hydrogel, cell spheres, cell tissue blocks, cell fibers, cell clusters, hydrogels, DNA, etc. The corresponding material is selected according to the actual application. Through the culture device of this application, the volume of these materials discharged can be controlled more precisely, that is, the amount of materials participating in the reaction can be controlled more precisely.

[0061] It is understood that in some embodiments, the linear pump of the first liquid guiding assembly 40 can employ different driving methods, such as a pneumatic pump or an electric pump, as long as it can achieve precise dispensing of the bio-ink. For example, the parameters of the linear pump of the first liquid guiding assembly 40 can be configured as 100ul, 200ul, 500ul, 1ml, 2ml, 5ml, 10ml, 50ml, 100ml, etc., and the first liquid guiding end can be a needle with a diameter of 0.1mm, 0.2mm, 0.3mm, or 0.5mm.

[0062] It is understood that the volume of the bio-ink droplet discharged from the first liquid guide end is determined by the cross-sectional area and lead of the outlet. Therefore, in some embodiments, the first liquid guide end can be designed with different shapes and sizes to adapt to different types of bio-inks and experimental needs. For example, the first liquid guide end can be designed as an elongated shape to facilitate the formation of small bio-ink droplets, or as a flat shape to facilitate the formation of larger bio-ink droplets.

[0063] The motion control of the first liquid guiding component 40 by the first driving component 70 to avoid droplet residue at the first liquid guiding end can be either compensating or hovering. For example, when configured as compensating, the first driving component 70 continuously drives the first liquid guiding component 40 to move away from the surface of the bio-ink, that is, the liquid guiding component moves upward while dripping, until at the last moment, the dripped bio-ink is pulled by the surface of the bio-ink and breaks off from the first liquid guiding end, thereby achieving the effect of precisely controlling the volume of bio-ink. When configured as hovering, the first driving component 70 only needs to drive the first liquid guiding end to a preset height. As bio-ink is injected, the surface of the bio-ink rises. When it approaches the preset height, the surface of the bio-ink will contact the bio-ink droplet suspended at the first liquid guiding end, thereby breaking off the bio-ink droplet from the first liquid guiding end. Understandably, the volume of bio-ink in the container is determined by the volume of the last drop of bio-ink discharged from the first liquid guide end. The finer the volume of the last drop of bio-ink discharged from the first liquid guide end, the finer the volume of bio-ink in the container, i.e., the higher the precision. Therefore, regardless of whether a compensation-type or hovering-type system is used, it is only necessary to ensure that the last drop of bio-ink discharged from the first liquid guide end is torn off from the first liquid guide end by adsorption from the surface of the previous bio-ink liquid, thereby detaching from the first liquid guide end.

[0064] To precisely control the amount of bio-ink in the container 910, it is necessary to precisely control the height of the first liquid guide end from the surface of the bio-ink or the orifice plate 90. In some embodiments, this height is precisely controlled by a grating ruler to ensure that the accuracy of the culture device achieves the preset effect.

[0065] In some embodiments, the first temperature control component 60 includes a water-cooling generator, which can employ various cooling media, such as water, ethanol, or other coolants, to meet different temperature regulation requirements. The liquid cooling pipes can be designed in a serpentine or spiral shape to increase the contact area between the coolant and the bio-ink, thereby improving cooling efficiency. Furthermore, the first temperature control component 60 can also be equipped with a temperature sensor to monitor the temperature of the bio-ink in real time, ensuring that the temperature remains within a first preset range. In some embodiments, the first preset range is 4 degrees Celsius to 8 degrees Celsius; for example, the temperature can be selected as 4 degrees Celsius, 5 degrees Celsius, 6 degrees Celsius, 7 degrees Celsius, or 8 degrees Celsius.

[0066] The motor of the first drive assembly 70 can be a stepper motor or a servo motor to achieve high-precision motion control. The lead screw can be designed with different pitches to adjust the moving speed and distance of the first fluid guiding assembly 40. The first drive assembly 70 can also be equipped with an encoder to provide real-time feedback on the position information of the first fluid guiding assembly 40, ensuring that it accurately reaches the predetermined position.

[0067] Reference Figures 6 to 9 In some embodiments, the culture apparatus further includes a second liquid guiding component 20 and a second driving component 80. The second liquid guiding component 20 has a second liquid guiding end for discharging culture medium, and the second driving component 80 is connected to the second liquid guiding component 20. The second driving component 80 drives the second liquid guiding component 20 to move along a second preset path to inject the culture medium into the receiving groove 910 of the orifice plate 90.

[0068] The second liquid guiding assembly 20 is designed similarly to the first liquid guiding assembly 40, including a liquid storage container and a liquid guiding conduit. The liquid storage container is used to store the culture medium, and the liquid guiding conduit connects the liquid storage container and the second liquid guiding end. An internal pump operates to discharge the culture medium from the second liquid guiding end. The design of the second liquid guiding end ensures accurate discharge of the culture medium, avoiding over- or under-discharge.

[0069] The second drive assembly 80 consists of a motor and a lead screw. The motor drives the lead screw to rotate, and the lead screw drives the second liquid guiding assembly 20 to move along a second preset path. When the second liquid guiding assembly 20 reaches the predetermined position, the culture medium is discharged from the second liquid guiding end and injected into the receiving groove 910 of the well plate 90. This design ensures precise distribution of the culture medium and improves the efficiency and accuracy of the experiment.

[0070] It is understood that, in some embodiments, the reservoir of the second liquid-conducting assembly 20 can be made of different materials, such as stainless steel or plastic, to accommodate different types of culture media. The capacity of the reservoir can be adjusted according to experimental needs to meet experiments of different scales. The liquid-conducting conduit can be designed with different diameters and lengths to accommodate different flow rates and distances.

[0071] The motor of the second drive assembly 80 can be a stepper motor or a servo motor to achieve high-precision motion control. The lead screw can be designed with different pitches to adjust the moving speed and distance of the second fluid guiding assembly 20. The second drive assembly 80 can also be equipped with an encoder to provide real-time feedback on the position information of the second fluid guiding assembly 20, ensuring that it accurately reaches the predetermined position.

[0072] In some embodiments, the second liquid guiding assembly 20 may further include a flow divider plate having multiple flow dividers, each flow divider corresponding to a receiving tank 910. The design of the flow divider plate allows the culture medium to be injected into multiple receiving tanks 910 simultaneously, improving experimental efficiency. The shape and size of the flow dividers can be optimized according to the dimensions of the receiving tanks 910 to ensure uniform distribution of the culture medium.

[0073] In some embodiments, heating or cooling functions can be integrated into the second liquid guiding assembly 20 to regulate the temperature of the culture medium, ensuring that it reaches the required temperature conditions before being injected into the well plate 90. These improvements further enhance the reliability of the system and the accuracy of experimental results.

[0074] In some embodiments, regarding the temperature control system of the organoid 3D printer of this application, refer to... Figures 1 to 11 , specifically, refer to Figures 1 to 3 The temperature control system of the organoid 3D printer mainly consists of a shell assembly 10, a second liquid guiding assembly 20, a culture platform unit 30, a first liquid guiding assembly 40, a first temperature control assembly 60, and a second temperature control assembly 50.

[0075] The shell assembly 10 in the extrusion-type organoid 3D printer of the present invention, refer to Figure 4 and Figure 5 The housing assembly 10 includes a filter fan 101, a high-efficiency filter screen 102, a microscope display screen 103, an outer door panel 104, a rear support for the cabinet 105, a machine support unit 106, load-bearing feet 107, and a lower support for the cabinet 108.

[0076] The filter fan 101 in this invention's extrusion-type organoid 3D printer features a special FFU structure, a guided airflow duct, and a uniform airflow system design. This reduces eddies, eliminates noise, guides airflow evenly through the filter, and allows for controllable airflow speed. Combined with a high-efficiency filter, it achieves a sterile environment throughout the entire internal structure for a short period. The microscope display screen 103 connects to the microscope via cable, allowing real-time transmission of captured video and images to the screen. The outer door panel 104 consists of two panels, made of semi-transparent black acrylic, providing a semi-transparent effect to the machine's internal structure. The rear support 105 provides structural support and features regularly spaced ventilation holes for heat dissipation. Support units 106 are designed with central cutouts to reduce machine weight and support components, ensuring stable operation. Load-bearing feet 107 are located at the four corners of the machine, allowing for slight height adjustment of the operating platform. The lower cabinet support 108 connects to the rear cabinet support 105, and the cabinet features symmetrically distributed ventilation holes for heat dissipation.

[0077] The second liquid guiding component 20 in the bioreactor of the present invention, as shown in the figure Figure 9 The second liquid guiding assembly includes a vertical precision lead screw motor 201, a motor slider 202, a hydraulic block 203, a liquid injection pump 204, a liquid filling enclosure 205, a liquid filling device holder 206, a microscope 207, and a microscope stage 208. The vertical precision lead screw motor 201 provides precise transmission, powering the liquid filling assembly's vertical movement. Transmission methods include, but are not limited to, belts, chains, and gears. The motor slider 202 is tightly fitted to the vertical precision lead screw motor 201; the forward and reverse rotation of the lead screw motor enables the slider to slide up and down. One end of the hydraulic block 203 is connected to the liquid injection pump, and the other end is connected to the liquid filling power unit. When tightly fitted with the liquid injection pump 204, the downward movement of the hydraulic block 203 causes the liquid to be injected to be squeezed out from the injection needle. The liquid injection pump 204 consists of a liquid injection push rod, a liquid injection pump housing, and an injection needle, and has good sealing properties. The size of the liquid injection pump 204 can be adjusted according to the liquid volume. The liquid filling enclosure 205 serves as a fixing unit for the liquid filling injection pump 204, providing support. The liquid filling device holder 206 serves as a fixing plate for the second liquid guiding assembly 20, and is equipped with another set of power units for pressing the liquid filling block a203, located on the back of the fixing plate.

[0078] The microscope 207 in the extrusion-type organoid 3D printer of this invention can observe the sample application and liquid addition in real time and provide real-time feedback to the system control unit. It can also perform supplementary sample application for individual wells that were not sampled. The microscope slide 208 can slide up and down and then be fixed, allowing adjustment of the microscope's imaging area.

[0079] The first liquid guiding component 40 in the bioreactor of the present invention, as shown in the figure Figure 9The first liquid guiding assembly includes a vertical precision lead screw motor 401, a motor slider 402, a sampling pressure block 403, a sampling injection pump 404, a sampling enclosure 405, a sampling circulating water cooling generator 406, a temperature probe 407, and a sampling device holder 408. The vertical precision lead screw motor 401 provides precision transmission and power for the up-and-down movement of the sampling assembly. Transmission methods include, but are not limited to, belts, chains, and gears. The motor slider 402 works closely with the vertical precision lead screw motor 401; the forward and reverse rotation of the lead screw motor enables the slider to slide up and down. The sampling pressure block 403 is connected to the sampling injection pump at one end and to the sampling power unit at the other. When in close contact with the sampling injection pump, the downward movement of the sampling pressure block 403 causes the sampling material to be squeezed out from the injection needle. The sampling injection pump 404 consists of a sampling push rod, a sampling pump housing, and an injection needle, and has good sealing properties. The size of the sampling injection pump can be adjusted according to the sampling volume. The sample dispensing enclosure 405 serves as the fixing unit for the sample dispensing injection pump 404, providing support and transferring temperature. The other end of the sample dispensing circulating water-cooling generator 406 is connected to a water pump, which removes excess heat through water circulation. The temperature probe 407 monitors the temperature of the dispensing area in real time. When the predetermined temperature range is reached, the temperature control module stops working; otherwise, it activates when the temperature is outside the predetermined range. The normal temperature setting is around 4 to 8 degrees Celsius. The sample dispensing device holder 408 serves as the fixing plate for the first liquid guiding assembly 40, and it houses the power unit for another set of sample dispensing pressure blocks 403, located on the back of the fixing plate.

[0080] The culture platform unit 30 in the bioreactor of this invention, as shown in the figure Figure 10 and Figure 11 The cultivation platform unit includes a perforated plate holder 301, a placement platform 302, a temperature probe 303, a circulating water cooler, and a semiconductor temperature controller. The first temperature control device 304 can be configured as a circulating water cooler, and the second temperature control device 305 can be configured as a semiconductor temperature controller; alternatively, the two can be configured in reverse. The perforated plate holder 301 can hold perforated plates of different sizes and numbers of holes, fixing their positions through surrounding holes. The placement platform 302 houses the perforated plate holder 301 on top and connects to the first temperature control component 60 below. Its material has good thermal conductivity, allowing it to promptly transmit the temperature regulated by the first temperature control component 60 to the perforated plate 90. The temperature probe 303 monitors the temperature of the placement platform 302 in real time. When the predetermined temperature range is reached, the first temperature control component 60 stops working; otherwise, if the temperature is outside the predetermined range, the temperature control module activates. The normal temperature setting is around 37 degrees Celsius. The other end of the circulating water cooler is connected to a water pump, which circulates water to remove excess heat. The semiconductor temperature controller has a cooling function on one end and a heating function on the other. The heating surface can be attached to the mounting platform 302 to transfer the temperature to the orifice plate 90.

[0081] The above are merely preferred embodiments of the present invention and do not limit the scope of the patent. Any equivalent structural transformations made using the contents of the specification and drawings of the present invention under the inventive concept of the present invention, or direct / indirect applications in other related technical fields, are included within the scope of patent protection of the present invention.

Claims

1. A temperature control system for an organoid 3D printer, characterized in that, The temperature control system of the organoid 3D printer includes: The first liquid guiding assembly has a first liquid guiding end for discharging bio-ink; A first driving component is connected to the first liquid guiding component and is used to drive the first liquid guiding component to move. An orifice plate is disposed below the first liquid guiding component. The orifice plate includes an upper surface wall and a lower surface wall. The upper surface wall is recessed with a plurality of receiving grooves, each of which is used to receive the bio-ink discharged from the first liquid guiding end. A first temperature control component is attached to the lower surface wall, and the first temperature control component is used to adjust the temperature value of the orifice plate to a first preset range; The first temperature control component includes a first temperature control device and a second temperature control device. The first temperature control device is fixed to the mounting platform and is attached to the lower surface wall of the orifice plate to adjust the temperature of the orifice plate. The second temperature control device is movably connected to the mounting platform to adjust the local temperature of the orifice plate; The temperature control system of the organoid 3D printer includes a first driving component, which is connected to the first liquid guiding component. The first driving component is used to drive the first liquid guiding component to move along a first preset path. The first driving component is configured to first move the first liquid guiding component toward the solution to be treated until the bio-ink at the first liquid guiding end adheres to the solution to be treated, and then move the first liquid guiding component away from the solution to be treated until the bio-ink detaches from the first liquid guiding end.

2. The temperature control system for the organoid 3D printer according to claim 1, characterized in that, The temperature control system of the organoid 3D printer includes a placement platform, with the perforated plate and the first temperature control component respectively disposed on opposite sides of the placement platform; The mounting platform is recessed to form a first recess, which is used to accommodate the perforated plate. The side of the mounting platform opposite to the first recess is recessed in the opposite direction of the first recess to form a second recess, which is used to accommodate the first temperature control component.

3. The temperature control system for the organoid 3D printer according to claim 1, characterized in that, The first temperature control component includes a drive device connected to the second temperature control device, the drive device being configured to drive the second temperature control device to move relative to the orifice plate to regulate the temperature of the area of ​​the orifice plate containing bio-ink.

4. The temperature control system for the organoid 3D printer according to claim 2, characterized in that, The mounting platform includes multiple upwardly protruding stops, each of which abuts against the edge of the perforated plate.

5. The temperature control system for the organoid 3D printer according to claim 2, characterized in that, The temperature control system of the organoid 3D printer also includes a temperature probe, which is connected to the placement platform and is located on the side of the placement platform away from the perforated plate.

6. The temperature control system for the organoid 3D printer according to claim 1, characterized in that, The temperature control system of the organoid 3D printer includes a second temperature control component, which is connected to the first liquid guiding component. The second temperature control component is used to adjust the temperature of the bio-ink exported by the first liquid guiding component to a second preset range.

7. The temperature control system for the organoid 3D printer according to claim 1, characterized in that, The temperature control system of the organoid 3D printer further includes a second liquid guiding component and a second driving component. The second liquid guiding component has a second liquid guiding end for discharging culture medium. The second driving component is connected to the second liquid guiding component and drives the second liquid guiding component to move along a second preset path to inject the culture medium into the receiving tank.

8. The temperature control system for the organoid 3D printer according to claim 1, characterized in that, The temperature control system of the organoid 3D printer also includes a housing assembly having an inner chamber that can sealably accommodate the first liquid guiding assembly, the first driving assembly, the orifice plate, and the first temperature control assembly.

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