A liver cancer organoid drug evaluation device for rapid drug screening

Abstract

The utility model discloses a kind of liver cancer organoid drug evaluation devices of rapid drug screening, specifically related to biomedical and engineering cross technical field, including drug screening plating, the inner cavity rectangular array of drug screening plating is provided with several incubation tubes, the top of drug screening plating is provided with transparent plastic cover plate, the bottom rectangular array of transparent plastic cover plate is fixedly installed with several plug blocks connected with incubation tube, the top rear side of drug screening plating is provided with classified adding mechanism.The utility model relates to a kind of liver cancer organoid drug evaluation devices of rapid drug screening, by setting up rectangular array incubation tube and combining the classified adding mechanism of turnover, the rapid, zoned, accurate addition to multiple organoid samples is realized, effectively avoid cross contamination, simultaneously, by centralized adding mechanism, culture medium can be synchronously injected to all incubation tubes at a time, improve operating efficiency and experimental flux, meet the demand of high-throughput drug screening.

Description

Technical Field

[0001] This utility model relates to the field of biomedical and engineering interdisciplinary technology, and in particular to a rapid drug screening device for evaluating organoid drugs for liver cancer. Background Technology

[0002] In the fields of biomedicine and drug development, the liver, as a key organ for drug metabolism and toxicity, directly impacts the success rate and clinical safety of new drug development due to the reliability of its in vitro evaluation models. Currently, commonly used drug evaluation models mainly include two-dimensional cultured human hepatocyte cell lines and in vivo animal models. However, 2D cultured cells are prone to losing their original functions during long-term culture, exhibiting significant differences from the actual physiological state of humans in terms of morphology, biological function, and genetic expression, leading to insufficient accuracy in drug response prediction. Animal models, due to differences in drug metabolism pathways between species, cannot accurately reflect the human response to drugs, especially in hepatotoxicity assessment. The existing technologies have the following problems: 2D cultured hepatocytes are prone to losing their specific functions during long-term culture, exhibiting significant differences from the physiological state of the human liver in terms of morphology, biological function, and gene expression. This leads to insufficient accuracy in predicting drug responses based on 2D models. Furthermore, animal models, due to inherent differences in drug metabolism enzyme profiles, transporters, and immune responses among species, struggle to accurately predict human responses to drugs, particularly in assessing drug hepatotoxicity. In addition, current organoid drug screening procedures largely rely on manual pipetting, which is cumbersome, has low throughput, and is prone to cross-contamination. Moreover, the lack of precise temperature control in the culture medium means that adding room-temperature medium directly can affect organoid activity, resulting in poor experimental reproducibility and reduced reliability. Utility Model Content

[0003] The main objective of this invention is to provide a rapid drug screening device for evaluating organoid drugs in liver cancer, which can effectively solve the problems of low drug screening throughput, cumbersome operation, insufficient automation, and imprecise control of culture environment in the existing technology.

[0004] To achieve the above objectives, the technical solution adopted by this utility model is as follows: A rapid drug screening device for evaluating organoid drugs in liver cancer includes a drug screening plate. A rectangular array of culture tubes is arranged within the inner cavity of the drug screening plate. A transparent plastic cover is positioned above the drug screening plate. A rectangular array of plugs that engage with the culture tubes is fixedly installed at the bottom of the transparent plastic cover. A classification and addition mechanism is located on the rear top side of the drug screening plate. A centralized addition mechanism is located on the left side of the drug screening plate. A preheating mechanism is located on the right side of the drug screening plate. The classification and addition mechanism includes a rotating shaft, which is fixedly installed on the rear bottom side of the drug screening plate. A plurality of movable rods are evenly and movably mounted on the outer wall of the rotating shaft. Each movable rod corresponds to a plurality of longitudinally arranged culture tubes, and each movable rod has an organoid addition extension tube mounted adjacent to its front end above the longitudinally arranged culture tubes. A funnel is fixedly connected to the top of each organoid addition extension tube.

[0005] Preferably, a baffle is fixedly installed at the rear end of the drug sieve plate, and the organoid extension tube can be flipped backward to abut against the baffle for limiting position.

[0006] Preferably, the centralized addition mechanism includes an L-shaped rotating plate, one end of which is hinged to the left side of the drug sieve plate, and the other end of which is fixedly installed with a culture medium addition box. The bottom of the culture medium addition box is fixedly connected with a rectangular array of connecting pipes penetrating its inner cavity, and the connecting pipes are respectively engaged with a number of culture tubes.

[0007] Preferably, a pressure plate is slidably installed in the inner cavity of the culture medium addition box, a lifting rod is fixedly installed on the top of the pressure plate, and several sealing pressure rods are fixedly installed in a rectangular array at the bottom of the pressure plate for squeezing the culture medium in the connecting tube into the inner cavity of the culture tube. A cross-shaped valve is fixedly installed at the bottom of the inner ring of several connecting tubes.

[0008] Preferably, the preheating mechanism includes an extension plate, a snap-fit ​​frame is fixedly installed on the top of the extension plate, a heating resistance plate is provided in the inner ring of the snap-fit ​​frame, and a culture medium preheating box is provided above the heating resistance plate and snaps into the inner ring of the snap-fit ​​frame. The volume of the culture medium preheating box is the same as the sum of the volumes of a plurality of connecting tubes, and the volumes of the plurality of connecting tubes are respectively the same as the volumes of a plurality of culture tubes.

[0009] Preferably, the power input wire of the heating resistance plate is connected to a thermostat for controlling the heating temperature, and the heating resistance plate is provided with a heating wire for converting electrical energy into heat energy.

[0010] Compared with the prior art, the present invention has the following beneficial effects: 1. This utility model provides a rapid drug screening device for liver cancer organoids. By setting up a rectangular array of culture tubes and combining it with a flip-out classification and addition mechanism, it realizes rapid, partitioned, and precise addition of multiple organoid samples, effectively avoiding cross-contamination. At the same time, the centralized addition mechanism can inject culture medium into all culture tubes at one time, improving operational efficiency and experimental throughput, and meeting the needs of high-throughput drug screening.

[0011] 2. This utility model provides a rapid drug screening device for evaluating organoid drugs in liver cancer. By setting up an independent preheating mechanism and using a temperature controller to precisely heat the culture medium in the culture medium preheating box, it ensures that the culture medium injected into the culture tube is always within the physiological temperature range, avoiding the adverse effects of temperature fluctuations on organoid activity, thereby improving the repeatability and data reliability of drug reaction experiments, and making the evaluation results closer to the real situation in vivo. Attached Figure Description

[0012] Figure 1 This is a schematic diagram of the overall structure of this utility model; Figure 2 Add a schematic diagram of the mechanism structure for the classification of this utility model; Figure 3 This is a schematic diagram of the centralized addition mechanism structure of this utility model; Figure 4 This is a schematic diagram of the cross-sectional structure of the butt joint pipe of this utility model; Figure 5 This is a schematic diagram of the preheating mechanism of this utility model.

[0013] In the diagram: 1. Drug sieve plate; 11. Culture tube; 12. Transparent plastic cover; 121. Plug; 13. Baffle; 2. Classification and addition mechanism; 21. Rotating shaft; 22. Movable rod; 23. Organoid addition extension tube; 24. Funnel; 3. Centralized addition mechanism; 31. L-shaped rotating plate; 32. Culture medium addition box; 33. Connecting tube; 331. Cross valve; 34. Pressure plate; 35. Lifting rod; 36. Sealing pressure rod; 4. Preheating mechanism; 41. Extension plate; 42. Snap-fit ​​frame; 43. Heating resistance plate; 44. Culture medium preheating box. Detailed Implementation

[0014] To make the technical means, creative features, objectives and effects of this utility model easier to understand, the present utility model will be further described below in conjunction with specific embodiments.

[0015] like Figure 1 , Figure 2As shown, a rapid drug screening device for evaluating organoids of liver cancer includes a drug screening plate 1. A rectangular array of culture tubes 11 is arranged inside the drug screening plate 1. A transparent plastic cover 12 is positioned above the drug screening plate 1. A rectangular array of plugs 121 that engage with the culture tubes 11 are fixedly installed at the bottom of the transparent plastic cover 12. A classification and addition mechanism 2 is located on the rear top side of the drug screening plate 1. A centralized addition mechanism 3 is located on the left side of the drug screening plate 1. A preheating mechanism 4 is located on the right side of the drug screening plate 1. The classification and addition mechanism 2 includes a rotating shaft 2. 1. A rotating shaft 21 is fixedly installed on the bottom rear side of the medicine sieve plate 1. Several movable rods 22 are evenly and movably installed on the outer wall of the rotating shaft 21. Several movable rods 22 correspond to several longitudinally arranged culture tubes 11 respectively. The front ends of several movable rods 22 are adjacent to organoid addition extension tubes 23 located above the longitudinally arranged culture tubes 11. A funnel 24 is fixedly connected to the top of the organoid addition extension tube 23. A baffle 13 is fixedly installed at the rear end of the medicine sieve plate 1. The organoid addition extension tube 23 can be flipped backward to abut against the baffle 13 for limitation. In use, the transparent plastic cover 12 on the top of the drug sieve plate 1 can be removed first. The plug 121 at the bottom of the transparent plastic cover 12 can be engaged with the culture tube 11 to improve the sealing of the transparent plastic cover 12 to the culture tube 11. After removing the transparent plastic cover 12, all the movable rods 22 rotating on the outer wall of the rotating shaft 21 can be flipped forward, so that several organoid addition extension tubes 23 from back to front and from short to tall are respectively located above several culture tubes 11 arranged longitudinally. Thus, the active small cell clusters obtained by tissue washing and tissue disruption can be inserted into the funnel 24 at the top of the organoid addition extension tube 23 through the injection tube and quickly injected into the inner cavity of the culture tube 11, reducing the alignment time. After all the culture tubes 11 are injected with active small cell clusters, several organoid addition extension tubes 23 can be flipped backward until they stop against the baffle 13.

[0016] like Figure 3 , Figure 4 As shown, the centralized addition mechanism 3 includes an L-shaped rotating plate 31. One end of the L-shaped rotating plate 31 is hinged to the left side of the drug sieve plate 1. The other end of the L-shaped rotating plate 31 is fixedly installed with a culture medium addition box 32. The bottom rectangular array of the culture medium addition box 32 is fixedly connected with several connecting tubes 33 that penetrate its inner cavity. The several connecting tubes 33 are respectively snapped into several culture tubes 11. The inner cavity of the culture medium addition box 32 is slidably installed with a pressure plate 34. The top of the pressure plate 34 is fixedly installed with a lifting rod 35. The bottom rectangular array of the pressure plate 34 is fixedly installed with several sealing pressure rods 36, which are used to squeeze the culture medium in the connecting tubes 33 into the inner cavity of the culture tubes 11. The bottom of the inner ring of each of the several connecting tubes 33 is fixedly installed with a cross valve 331. The culture medium addition box 32 is flipped from the left side of the drug sieve plate 1 to the bottom of the drug sieve plate 1 using an L-shaped rotating plate 31 until several connecting tubes 33 are inserted into the inner cavity of several culture tubes 11. By pressing down the pressure plate 34 with the sealing pressure rod 36 aligned with several culture tubes 11, and because the sealing pressure rod 36 is engaged with the culture tubes 11, the culture medium can be injected into the inner cavity of the culture tubes 11 through the cross valve 331 to mix with the cell clusters. The height of the pressure plate 34 is consistent with the height of the inner cavity of the culture medium addition box 32. When pressing down, the pressure plate 34 extends beyond the height above the culture medium addition box 32, which can control the volume of injected culture medium and avoid completely filling the culture tubes 11, leaving space for drug addition. Half of the culture medium can be injected here, which facilitates secondary injection.

[0017] like Figure 5 As shown, the preheating mechanism 4 includes an extension plate 41, a snap-fit ​​frame 42 is fixedly installed on the top of the extension plate 41, a heating resistance plate 43 is provided in the inner ring of the snap-fit ​​frame 42, a culture medium preheating box 44 is provided above the heating resistance plate 43 and snaps into the inner ring of the snap-fit ​​frame 42, the volume of the culture medium preheating box 44 is the same as the sum of the volumes of several connecting pipes 33, and the volumes of several connecting pipes 33 are respectively the same as the volumes of several culture tubes 11, the power input wire of the heating resistance plate 43 is connected to a thermostat for controlling the heating temperature, and an electric heating wire is provided inside the heating resistance plate 43 for converting electrical energy into heat energy. While injecting cells into the lumen of culture tube 11, culture medium can be injected into the lumen of culture medium preheating box 44. The preheating box is heated by the heating resistance plate 43 within the inner ring of the snap-fit ​​frame 42, maintaining it at room temperature or 37 degrees Celsius. When the L-shaped rotating plate 31 is above culture tube 11, the culture medium preheating box 44 can be removed, and the preheated culture medium poured into the lumen of the L-shaped rotating plate 31. Since the volume of the culture medium preheating box 44 is consistent with that of several connecting tubes 33, the culture medium can quickly flow into the lumens of several connecting tubes 33, and leakage is prevented by the cross valve 331. After the culture medium injection is completed, several combined organoid extension tubes 23 can be flipped back above culture tube 11, and different mixed drug solutions can be injected according to the longitudinal arrangement. This facilitates rapid observation of the reactions of different drugs with cell clusters within the same drug sieve plate 1, allowing for evaluation of different drugs and meeting the clinical needs for evaluating liver cancer using various drugs, including single and combined drugs of small molecules and large molecules. The working principle of this rapid drug screening organoid drug evaluation device for liver cancer will be explained in detail below.

[0018] like Figure 1-5As shown, during use, the transparent plastic cover 12 on top of the drug sieve plate 1 can be removed first. The plug 121 at the bottom of the transparent plastic cover 12 can be engaged with the culture tube 11 to improve the sealing of the transparent plastic cover 12 to the culture tube 11. After removing the transparent plastic cover 12, all the movable rods 22 rotating on the outer wall of the rotating shaft 21 can be flipped forward, so that several organoid addition extension tubes 23, arranged from back to front and from short to tall, are respectively positioned above several longitudinally arranged culture tubes 11. Thus, the active small cell clusters obtained by optimizing the tissue washing solution and breaking down the tissue can be quickly injected through the injection tube aligned with the funnel 24 at the top of the organoid addition extension tube 23. After injecting viable small cell clusters into all culture tubes 11, reduce alignment time. Then, flip several organoid extension tubes 23 backward until they stop against the baffle 13. At this point, use the L-shaped rotating plate 31 to flip the culture medium addition box 32 from the left side of the drug sieve plate 1 to the bottom of the drug sieve plate 1 until several connecting tubes 33 are inserted into the lumens of several culture tubes 11. While injecting cells into the lumens of the culture tubes 11, inject culture medium into the lumen of the culture medium preheating box 44. Use the heating resistance plate 43 on the inner ring of the snap-fit ​​frame 42 to heat it and keep it at room temperature or 37 degrees Celsius. When the culture tube 11 is positioned above the culture tube 11, the culture medium preheating box 44 can be removed, and the preheated culture medium can be poured into the inner cavity of the L-shaped transfer plate 31. Since the volume of the culture medium preheating box 44 is consistent with that of several connecting tubes 33, the culture medium can quickly flow into the inner cavity of several connecting tubes 33, and is prevented from leaking through the cross valve 331. At this time, the pressure plate 34 is then pressed down with the sealing pressure rod 36 aligned with several culture tubes 11. Because the sealing pressure rod 36 is engaged with the culture tube 11, the culture medium can be injected into the inner cavity of the culture tube 11 through the cross valve 331 to mix with the cell clusters. The height of the pressure plate 34 is consistent with the height of the inner cavity of the culture medium addition box 32. When the pressure plate 34 is pressed down, it extends beyond the height above the culture medium addition box 32, thus controlling the volume of injected culture medium and avoiding completely filling the culture tube 11. This leaves space for drug addition, allowing for partial injection and facilitating secondary injection. After the culture medium is injected, several combined organoid addition extension tubes 23 can be flipped back above the culture tube 11, and different mixed drug solutions can be injected according to the vertical arrangement. This allows for rapid observation of the reaction between different drugs and cell clusters within the same drug sieve plate 1, enabling evaluation of different drugs and meeting the clinical needs for evaluating liver cancer using various drugs, including single and combined drugs of small molecules and large molecules.

[0019] The foregoing has shown and described the basic principles, main features, and advantages of this utility model. Those skilled in the art should understand that this utility model is not limited to the above embodiments. The embodiments and descriptions in the specification are merely illustrative of the principles of this utility model. Various changes and modifications can be made to this utility model without departing from its spirit and scope, and all such changes and modifications fall within the scope of the claims. The scope of protection of this utility model is defined by the appended claims and their equivalents.

Claims

1. A rapid drug screening device for evaluating organoids of liver cancer, comprising a drug screening plate (1), wherein a plurality of culture tubes (11) are arranged in a rectangular array within the cavity of the drug screening plate (1), a transparent plastic cover plate (12) is provided above the drug screening plate (1), and a plurality of plugs (121) that engage with the culture tubes (11) are fixedly installed in a rectangular array at the bottom of the transparent plastic cover plate (12), characterized in that: A classification and addition mechanism (2) is provided on the top rear side of the drug sieve plate (1), a centralized addition mechanism (3) is provided on the left side of the drug sieve plate (1), and a preheating mechanism (4) is provided on the right side of the drug sieve plate (1). The classification and addition mechanism (2) includes a rotating shaft (21). The rotating shaft (21) is fixedly installed on the bottom rear side of the drug sieve plate (1). Several movable rods (22) are evenly and movably installed on the outer wall of the rotating shaft (21). Several movable rods (22) correspond to several longitudinally arranged culture tubes (11). The front ends of several movable rods (22) are adjacent to each other and are located above several longitudinally arranged culture tubes (11). A funnel (24) is fixedly connected to the top of the organoid addition extension tube (23).

2. The rapid drug screening device for evaluating organoid drugs for liver cancer according to claim 1, characterized in that: A baffle (13) is fixedly installed at the rear end of the drug sieve plate (1), and the organoid extension tube (23) can be flipped backward to abut against the baffle (13) for limitation.

3. The rapid drug screening device for evaluating organoid drugs for liver cancer according to claim 1, characterized in that: The centralized addition mechanism (3) includes an L-shaped rotating plate (31), one end of which is hinged to the left side of the drug sieve plate (1), and the other end of which is fixedly installed with a culture medium addition box (32). The bottom rectangular array of the culture medium addition box (32) is fixedly connected with several connecting pipes (33) that penetrate its inner cavity, and the several connecting pipes (33) are respectively snapped into several culture tubes (11).

4. The rapid drug screening device for evaluating organoid drugs for liver cancer according to claim 3, characterized in that: The inner cavity of the culture medium addition box (32) is slidably fitted with a pressure plate (34), the top of the pressure plate (34) is fixedly fitted with a lifting rod (35), and the bottom of the pressure plate (34) is fixedly fitted with a rectangular array of sealing pressure rods (36) for squeezing the culture medium in the connecting tube (33) into the inner cavity of the culture tube (11). The bottom of the inner ring of each of the connecting tubes (33) is fixedly fitted with a cross valve (331).

5. The rapid drug screening device for evaluating organoid drugs for liver cancer according to claim 1, characterized in that: The preheating mechanism (4) includes an extension plate (41), a snap-fit ​​frame (42) is fixedly installed on the top of the extension plate (41), a heating resistance plate (43) is provided in the inner ring of the snap-fit ​​frame (42), and a culture medium preheating box (44) is provided above the heating resistance plate (43) and snap-fits with the inner ring of the snap-fit ​​frame (42). The volume of the culture medium preheating box (44) is the same as the volume of a number of connecting tubes (33) added together, and the volume of the number of connecting tubes (33) is the same as the volume of a number of culture tubes (11).

6. The rapid drug screening device for evaluating organoid drugs for liver cancer according to claim 5, characterized in that: The power input wire of the heating resistance plate (43) is connected to a thermostat to control the heating temperature. The heating resistance plate (43) is equipped with a heating wire to convert electrical energy into heat energy.

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