A multi-organ chip system with double perfusion mode

Abstract

The utility model relates to organ chip technical field provides a kind of multi-organ chip system with double perfusion mode, including multi-cultivation unit support, chip placement slot and organ chip main part, the top of multi-cultivation unit support is equipped with several chip placement slots, organ chip main part is placed in chip placement slot, organ chip main part includes first layer component, second layer component and third layer component, the bottom of first layer component is provided with second layer component, the bottom of second layer component is provided with third layer component, the utility model is equipped with threaded perfusion interface in the liquid storage tank of organ chip, so that single organ chip can simultaneously adapt gravity perfusion and pump perfusion two kinds of driving mode, when needing to switch perfusion mode in experimental process, without replacing new chip, also without reseeding cell, effectively reduce the repeated investment of experimental consumables, avoid the time cost of repeated cell culture, improve the economy and operating efficiency of experimental procedure.

Description

Technical Field

[0001] This utility model relates to the field of organ-on-a-chip technology, and in particular to a multi-organ-on-a-chip system with dual perfusion methods. Background Technology

[0002] Organ-on-a-chip technology is a rapidly developing in vitro biomimetic model that uses microchannels, microcavities, and supporting functional components to precisely control parameters such as flow rate, shear force, and substance concentration gradient, thereby simulating the physiological microenvironment of human organs. It has significant application value in fields such as drug screening, disease model construction, and chemical safety evaluation.

[0003] Based on the perfusion drive method, the current mainstream organ-on-a-chip can be divided into two categories: gravity perfusion type and pump perfusion type. Among them, gravity perfusion organ-on-a-chip does not require complex external drive equipment, and the culture medium flow can be driven by the liquid level difference generated by the tilt of the shaker; when multiple gravity perfusion organ-on-a-chips are placed synchronously on the shaker platform, consistent fluid conditions can be obtained, which is suitable for high-throughput parallel experiments; However, gravity-perfusion organ-on-a-chip systems cannot be interconnected and are limited by height differences, offering a narrow range of flow rates that may not meet the needs of certain cells. Pump perfusion, on the other hand, connects the organ-on-a-chip to a driving pump via tubing. This pump provides highly controllable fluid perfusion with a wide range of flow rates, and organ-on-a-chip systems can be connected via tubing for multi-organ studies. However, pump perfusion organ-on-a-chip systems are limited by pump throughput, preventing high-throughput experiments. Utility Model Content

[0004] The purpose of this invention is to provide a multi-organ-on-a-chip system with dual perfusion modes, which solves the above-mentioned problems when used in operation.

[0005] To solve the above-mentioned technical problems, this utility model provides the following technical solution: a multi-organ-on-a-chip system with dual perfusion mode, including a multi-culture unit scaffold, a chip placement slot and an organ-on-a-chip body. The top of the multi-culture unit scaffold is provided with several chip placement slots, and the organ-on-a-chip body is placed in the chip placement slots. The organ-on-a-chip body includes a first layer component, a second layer component and a third layer component. The second layer component is provided at the bottom of the first layer component, and the third layer component is provided at the bottom of the second layer component. Four perfusion connectors are fixed at the top of the first layer component, and the inner sidewall of the perfusion connector is provided with internal threads.

[0006] Preferably, two injection connectors are provided on each side of the top of the first layer component, and the four injection connectors are symmetrically distributed on both sides of the center line of the top of the first layer component.

[0007] Preferably, a first liquid storage tank and a fourth liquid storage tank are provided on one side of the bottom of the first layer component, with the first liquid storage tank located at the front end of the fourth liquid storage tank. A second liquid storage tank and a third liquid storage tank are provided on the other side of the bottom of the first layer component, with the second liquid storage tank located at the front end of the third liquid storage tank. Four filling connectors are located directly above the first liquid storage tank, the second liquid storage tank, the third liquid storage tank, and the fourth liquid storage tank, respectively, and are connected to them.

[0008] Preferably, an upper flow channel one is provided at the middle position of the bottom of the first layer component, and upper flow channels two are provided on both sides of the upper flow channel one.

[0009] Preferably, the first upper flow channel is connected to the third and fourth liquid storage tanks through two second upper flow channels respectively.

[0010] Preferably, a through hole one is provided on one side of the interior of the second layer component, and a through hole two is provided on the other side of the interior of the second layer component. The through hole one is located directly below and opposite the first liquid storage tank, and the through hole two is located directly below and opposite the second liquid storage tank.

[0011] Preferably, a lower flow channel one is provided at the middle position of the top of the third layer component, and lower flow channels two are provided on both sides of the lower flow channel one.

[0012] Preferably, the lower flow channel is located directly below the upper flow channel, and the first liquid storage tank, the second liquid storage tank, the third liquid storage tank, the fourth liquid storage tank, the first through hole, and the second through hole have the same size.

[0013] Preferably, the second upper flow channel is symmetrically distributed on both sides of the centerline of the first upper flow channel, and the second lower flow channel is symmetrically distributed on both sides of the centerline of the first lower flow channel.

[0014] Compared with the prior art, the beneficial effects of this utility model are as follows: 1. This utility model provides a multi-organ-on-a-chip system with dual perfusion modes. By setting a threaded perfusion interface in the reservoir of the organ-on-a-chip, a single organ-on-a-chip can be adapted to both gravity perfusion and pump perfusion modes simultaneously. When it is necessary to switch the perfusion mode during the experiment, there is no need to replace the chip or re-seed the cells, which effectively reduces the repeated investment in experimental consumables, avoids the time cost of repeated cell culture, and improves the economy and operational efficiency of the experimental process.

[0015] 2. The present invention provides a multi-organ-on-a-chip system with dual perfusion modes. When using gravity perfusion mode, it can be paired with a multi-culture unit support placed on an inclined shaker to achieve high-throughput experiments with multiple chips in parallel. When using pump perfusion mode, it can be driven by an external pump through an adapter and pipeline to achieve precise flow rate control and multi-chip interconnection, meeting the needs of multi-organ interaction research and covering a wider range of experimental scenarios. Attached Figure Description

[0016] Figure 1 This is a schematic diagram of the multi-culture unit scaffold and organ-on-a-chip structure of this utility model. Figure 1 ; Figure 2 This is a schematic diagram of the multi-culture unit scaffold and organ-on-a-chip structure of this utility model. Figure 2 ; Figure 3 This is a schematic diagram of the organ-on-a-chip structure of this utility model; Figure 4 Disassembly of the organ-on-a-chip structure of this utility model Figure 1 ; Figure 5 Disassembly of the organ-on-a-chip structure of this utility model Figure 2 ; Figure 6 This is a schematic diagram of gravity injection of this utility model; Figure 7 A schematic diagram of a standard connector structure adapted to the threaded interface of this utility model; Figure 8 This is a schematic diagram of the pump injection structure of this utility model.

[0017] The following are the annotations in the figure: 1. Multi-culture unit scaffold; 2. Chip placement slot; 3. Organ-on-a-chip main body; 31. First layer component; 311. Perfusion connector; 312. First reservoir; 313. Second reservoir; 314. Third reservoir; 315. Fourth reservoir; 316. Upper flow channel one; 317. Upper flow channel two; 32. Second layer component; 321. Through hole one; 322. Through hole two; 33. Third layer component; 333. Lower flow channel one; 334. Lower flow channel two. Detailed Implementation

[0018] The technical solutions of the present utility model will be clearly and completely described below with reference to the accompanying drawings of the embodiments. Obviously, the described embodiments are only some embodiments of the present utility model, and not all embodiments. Based on the embodiments of the present utility model, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the protection scope of the present utility model.

[0019] To further understand the content of this utility model, a detailed description of this utility model will be provided in conjunction with the accompanying drawings.

[0020] Combination Figures 1 to 8As shown, this utility model discloses a multi-organ-on-a-chip system with dual perfusion methods, including a multi-culture unit support 1, a chip placement slot 2, and an organ-on-a-chip body 3. The top of the multi-culture unit support 1 is provided with several chip placement slots 2, and the organ-on-a-chip body 3 is placed in the chip placement slots 2. The organ-on-a-chip body 3 includes a first layer component 31, a second layer component 32, and a third layer component 33. The second layer component 32 is provided at the bottom of the first layer component 31, and the third layer component 33 is provided at the bottom of the second layer component 32. Four perfusion connectors 311 are fixed at the top of the first layer component 31, and the inner sidewall of the perfusion connector 311 is provided with internal threads.

[0021] Two injection connectors 311 are respectively provided on both sides of the top of the first layer component 31, and the four injection connectors 311 are symmetrically distributed on both sides of the center line of the top of the first layer component 31.

[0022] Specifically, the first layer component 31, the second layer component 32, and the third layer component 33 are all made of materials with high transparency, low adsorption, and biocompatibility. The first layer component 31 and the third layer component 33 can be one of glass, 3D printing resin, polystyrene (PS), polypropylene (PP), and cyclic olefin copolymer (COC). The second layer component 32 is a porous membrane, which can be made of polyethylene terephthalate (PET) or polycarbonate (PC). The three layers can be sealed and bonded together using methods such as hot pressing, ultrasonic waves, laser, or double-sided adhesive.

[0023] like Figures 1 to 8 As shown, a first liquid storage tank 312 and a fourth liquid storage tank 315 are provided on one side of the bottom of the first layer component 31. The first liquid storage tank 312 is located at the front end of the fourth liquid storage tank 315. A second liquid storage tank 313 and a third liquid storage tank 314 are provided on the other side of the bottom of the first layer component 31. The second liquid storage tank 313 is located at the front end of the third liquid storage tank 314. Four filling connectors 311 are located directly above the first liquid storage tank 312, the second liquid storage tank 313, the third liquid storage tank 314 and the fourth liquid storage tank 315 respectively and are connected to them respectively.

[0024] Specifically, the methods for providing fluid supply to the organ-on-a-chip body 3 include two types: gravity perfusion and pump perfusion. The implementation process and applicable scenarios for the two types of solutions are as follows: 1. Gravity infusion When using gravity perfusion, first manually inject culture medium into the flow channel, ensuring no air bubbles remain, then add an appropriate amount of culture medium to the reservoir; subsequently, place the organ-on-a-chip main body 3 into the reservoir. Figure 6 The tilted shaker plate is marked at point a. During the tilting process, multiple liquid reservoirs within the organ-on-a-chip body 3 create a liquid level difference, and the culture medium flows towards the opposite liquid reservoir under the action of gravity, creating a fluid microenvironment for the cells in the middle channel.

[0025] For high-throughput experiments, the device can be placed on an inclined shaker. Figure 1 The multi-culture unit scaffold 1 shown can hold up to 12 organ-on-a-chip bodies 3 in a single multi-culture unit scaffold 1, which can meet the requirements of parallel experiments with multiple groups of samples.

[0026] 2. Pump priming Pump infusion requires matching the appropriate connectors and tubing according to the interface thread specifications and drive pump type. Commonly used drive pumps in the organ-on-a-chip field include three types: peristaltic pumps, pressure pumps, and injection pumps.

[0027] 1 Single-chip injection pump infusion solution The internal thread specification of the perfusion connector 311 is 1 / 4-28UNF, and an injection pump is selected as the drive source for independent perfusion scenarios of a single organ-on-a-chip. For example... Figure 7 As shown, the internal thread of this specification is compatible with a variety of adapters and can be used with both rigid and flexible tubing. Therefore, a tapered connector with a 1 / 4-28UNF external thread is selected to work with the rigid tubing to achieve the connection between the infusion pump and the organ-on-a-chip, providing a stable fluid environment for the cells.

[0028] 2. Multi-organ circulation peristaltic pump perfusion scheme When conducting multi-organ-on-a-chip (MOA) interactions, a culture medium circulation system needs to be constructed. Therefore, a pagoda-shaped connector with 1 / 4-28 UNF external threads is used in conjunction with tubing to interconnect multiple organ-on-a-chip units and connect the OCA unit to the peristaltic pump. Additionally, a reservoir bottle is added to the tubing, such as... Figure 8 As shown, this facilitates the addition, replacement, and other reagent addition operations of the entire circulation system.

[0029] like Figures 3 to 5 As shown, an upper flow channel 316 is provided at the middle position of the bottom of the first layer component 31, and upper flow channels 317 are provided on both sides of the upper flow channel 316.

[0030] The upper flow channel 316 is connected to the third liquid storage tank 314 and the fourth liquid storage tank 315 through two upper flow channels 317 respectively.

[0031] A through hole 321 is provided on one side of the interior of the second layer component 32, and a through hole 322 is provided on the other side of the interior of the second layer component 32. The through hole 321 is located directly below and opposite the first liquid storage tank 312, and the through hole 322 is located directly below and opposite the second liquid storage tank 313.

[0032] The third layer component 33 has a lower flow channel 333 at the middle of its top, and lower flow channels 334 are provided on both sides of the lower flow channel 333.

[0033] Specifically, the culture medium is injected into the organ-on-a-chip through four perfusion connectors 311. In terms of structural layout, the first reservoir 312 is directly connected to the first through hole 321, and the second reservoir 313 is directly connected to the second through hole 322.

[0034] Among them, the two filling connectors 311, which are directly opposite the positions of the first liquid storage tank 312 and the second liquid storage tank 313, can respectively introduce the culture medium into the lower flow channel 333 and the lower flow channel 334 through the through hole 1 321 and the through hole 2 322.

[0035] Driven by the inclined shaking plate, the culture medium in the lower flow channel 333 and the lower flow channel 334 flows in opposite directions through the lower flow channel 333 and the lower flow channel 334; simultaneously, the culture medium in the third storage tank 314 and the fourth storage tank 315 flows in opposite directions through the upper flow channel 316 and the upper flow channel 317.

[0036] like Figures 3 to 5 As shown, the lower flow channel 333 is located directly below the upper flow channel 316. The first liquid storage tank 312, the second liquid storage tank 313, the third liquid storage tank 314, the fourth liquid storage tank 315, the first through hole 321, and the second through hole 322 have the same size.

[0037] Upper flow channel 2 317 is symmetrically distributed on both sides of the centerline of upper flow channel 1 316, and lower flow channel 2 334 is symmetrically distributed on both sides of the centerline of lower flow channel 1 333.

[0038] Specifically, the lower flow channel 333 and the upper flow channel 316 are separated by a second layer component 32, thereby enabling independent cell culture between the two layers; the two layers exchange substances through a porous membrane, and its permeability effect is similar to the physiological function of the human blood vessel wall.

[0039] It should be noted that, in this document, relational terms such as "first" and "second" are used only to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus.

[0040] Although embodiments of the present invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the present invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A multi-organ-on-a-chip system with dual perfusion mode, comprising a multi-culture unit scaffold (1), chip placement slots (2), and an organ-on-a-chip body (3), wherein the top of the multi-culture unit scaffold (1) is provided with a plurality of chip placement slots (2), and the organ-on-a-chip body (3) is placed in the chip placement slots (2), characterized in that: The organ-on-a-chip body (3) includes a first layer component (31), a second layer component (32) and a third layer component (33). The second layer component (32) is provided at the bottom of the first layer component (31), and the third layer component (33) is provided at the bottom of the second layer component (32). Four infusion connectors (311) are fixed at the top of the first layer component (31), and the inner sidewall of the infusion connector (311) is provided with internal threads.

2. The multi-organ-on-a-chip system with dual perfusion mode according to claim 1, characterized in that: Two injection connectors (311) are respectively provided on both sides of the top of the first layer component (31), and the four injection connectors (311) are symmetrically distributed on both sides of the center line of the top of the first layer component (31).

3. A multi-organ-on-a-chip system with dual perfusion mode according to claim 1, characterized in that: A first liquid storage tank (312) and a fourth liquid storage tank (315) are provided on one side of the bottom of the first layer component (31). The first liquid storage tank (312) is located at the front end of the fourth liquid storage tank (315). A second liquid storage tank (313) and a third liquid storage tank (314) are provided on the other side of the bottom of the first layer component (31). The second liquid storage tank (313) is located at the front end of the third liquid storage tank (314). The four filling connectors (311) are located directly above the first liquid storage tank (312), the second liquid storage tank (313), the third liquid storage tank (314) and the fourth liquid storage tank (315) respectively and are connected to them respectively.

4. A multi-organ-on-a-chip system with dual perfusion mode according to claim 3, characterized in that: The first layer component (31) has an upper flow channel one (316) at the middle position of the bottom, and upper flow channels two (317) are opened on both sides of the upper flow channel one (316).

5. A multi-organ-on-a-chip system with dual perfusion mode according to claim 4, characterized in that: The first upper flow channel (316) is connected to the third liquid storage tank (314) and the fourth liquid storage tank (315) through the two second upper flow channels (317).

6. A multi-organ-on-a-chip system with dual perfusion mode according to claim 4, characterized in that: A through hole 1 (321) is provided on one side of the interior of the second layer component (32), and a through hole 2 (322) is provided on the other side of the interior of the second layer component (32). The through hole 1 (321) is located directly below and opposite to the first liquid storage tank (312), and the through hole 2 (322) is located directly below and opposite to the second liquid storage tank (313).

7. A multi-organ-on-a-chip system with dual perfusion mode according to claim 6, characterized in that: The third layer component (33) has a lower flow channel one (333) at the middle position of the top, and lower flow channels two (334) are opened on both sides of the lower flow channel one (333).

8. A multi-organ-on-a-chip system with dual perfusion mode according to claim 7, characterized in that: The lower flow channel (333) is located directly below the upper flow channel (316), and the first liquid storage tank (312), the second liquid storage tank (313), the third liquid storage tank (314), the fourth liquid storage tank (315), the first through hole (321), and the second through hole (322) have the same size.

9. A multi-organ-on-a-chip system with dual perfusion mode according to claim 7, characterized in that: The upper flow channel 2 (317) is symmetrically distributed on both sides of the center line of the upper flow channel 1 (316), and the lower flow channel 2 (334) is symmetrically distributed on both sides of the center line of the lower flow channel 1 (333).

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