Organ chip for co-culture of multiple tissues
By designing an organ-on-a-chip for multi-tissue co-culture, integrating a spiral PDMS main channel and a porous membrane separator, the problem that traditional single-tissue culture models cannot simulate the complex physiological environment in vivo has been solved. This enables dynamic co-culture of multiple tissues and real-time monitoring of physiological parameters, thereby improving the accuracy of drug screening.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Utility models(China)
- Current Assignee / Owner
- SICHUAN DIYA BIOTECHNOLOGY GRP CO LTD
- Filing Date
- 2025-04-29
- Publication Date
- 2026-04-21
AI Technical Summary
In existing technologies, single-tissue culture models cannot fully simulate the complex physiological environment in vivo. Traditional single-channel chips are difficult to achieve precise spatial distribution of multiple tissues, have a high rate of cross-contamination, and cannot fully reflect the interactions and functional changes between organs.
An organ-on-a-chip for multi-tissue co-culture is designed, comprising a vascular main channel module, branch culture chambers, and a connection box. It is made of polydimethylsiloxane material, with collagen on the inner wall, and integrates a helical PDMS main channel and a porous membrane separator. Combined with a microfluidic system, it realizes dynamic co-culture of multiple tissues and real-time monitoring of physiological parameters.
It enables dynamic co-culture of multiple tissues, simulating human microcirculation, reducing cross-contamination, improving the comparability of experimental results and the accuracy of drug screening, and enabling real-time monitoring of drug distribution and metabolism in different tissues.
Smart Images
Figure CN224148069U_ABST
Abstract
Description
Technical Field
[0001] This utility model relates to the field of organ-on-a-chip technology, specifically to an organ-on-a-chip for multi-tissue co-culture. Background Technology
[0002] Toxicity testing of different organs or entire systems in the human body is a crucial part of pharmacokinetic and pharmacodynamic studies. Traditional methods primarily rely on animal experiments and two-dimensional cell culture models. While these methods have yielded significant achievements, they are limited by factors such as time constraints, cost, accuracy, and ethical concerns, making it difficult to predict human responses to various drugs. For instance, current cell culture experiments using animal models are time-consuming and costly. Furthermore, animal tissues and organs differ considerably from human tissues and organs, making animal models unreliable for predicting human drug responses and failing to meet the needs of in vitro human toxicity and efficacy testing. Secondly, while two-dimensional cell culture is employed, it remains a single-cell study, lacking a systematic approach and failing to comprehensively analyze mechanisms of action and toxic effects on other tissues.
[0003] Human organ-on-a-chip technology, combining methods from cell biology, engineering, and biomaterials, simulates the microenvironments of various living cells, tissues, and organs in vitro. It can reflect the main structural and functional characteristics of human tissues and organs, accurately control multiple system parameters, and better reflect the real human condition compared to traditional toxicological animal experiments. It also demonstrates greater specificity in new drug screening. Therefore, using microfabrication technology to create biomimetic systems that more closely resemble the human environment has become a research hotspot in in vitro physiological models.
[0004] However, with the development of organ-on-a-chip technology, its application still has certain limitations. For example, although three-dimensional cell culture can construct three-dimensional chip structures of organ tissues and provide new models for drug development, it is still a static study of a single organ. Single organ chips cannot fully reflect the complexity, functional changes and integrity of organ functions, cannot summarize the multicellular structure, tissue interface and related physical microenvironment of key functional units of living organs, and cannot simulate the absorption of nutrients and drugs by the human body through blood circulation and vascular filtration, or the real environment of human tumor metastasis and invasion.
[0005] CN218932175U discloses an organ-on-a-chip for multi-tissue co-culture, comprising a sealing layer, a culture layer, and a connecting layer stacked sequentially. The connecting layer is provided with a connecting inlet group and a connecting outlet group; the culture layer is provided with a culture inlet group, a culture outlet group, an extravascular tissue flow channel group, a first culture chamber, and a vascular culture chamber; the sealing layer is provided with an intravascular inlet, an intravascular outlet, and an intravascular flow channel group; the connecting inlet group, culture inlet group, extravascular tissue flow channel group, vascular culture chamber, first culture chamber, culture outlet group, and connecting outlet group form an extravascular tissue culture channel; the connecting inlet group, culture inlet group, intravascular inlet, intravascular flow channel group, artificial blood vessel, intravascular outlet, culture outlet group, and connecting outlet group form an intravascular culture channel;
[0006] In existing technologies, traditional single-tissue culture models cannot fully simulate the complex physiological environment in vivo, while multi-tissue co-culture can better reflect the interaction between organs. Traditional single-channel chips are difficult to achieve spatially accurate distribution of more than 3 types of tissues, and the cross-contamination rate is greater than 20%. Therefore, this device provides an organ-on-a-chip for multi-tissue co-culture. Utility Model Content
[0007] The purpose of this invention is to address the shortcomings of existing technologies by providing an organ-on-a-chip for multi-tissue co-culture, thereby solving the aforementioned technical problems.
[0008] The present invention adopts the following technical solution: an organ-on-a-chip for multi-tissue co-culture, comprising a vascular main channel module, wherein a transmission branch is provided at the top of the vascular main channel module, and a connection box is provided below the vascular main channel module, wherein two branch culture chambers are fixedly installed at the top of the connection box.
[0009] A stem cell culture area is provided at the top center of the branch culture chamber, a cardiomyocyte culture area is provided at the front of the top of the branch culture chamber, and an immune cell migration channel is provided at the rear of the top of the branch culture chamber.
[0010] Preferably, two connecting insertion tubes are fixedly installed on the rear side of the main vascular channel module, and an installation block is fixedly installed on the inner side of the connecting insertion tubes, and a locking rod is slidably installed on the inner side of the installation block.
[0011] Preferably, a limiting block is fixedly installed on the outer side of one end of the locking rod, and a first spring is fixedly installed between one side of the limiting block.
[0012] Preferably, two connecting blocks are fixedly installed at the bottom of the main blood vessel channel module, a control frame is slidably installed on the inner side of the connecting box, a sliding plate is fixedly installed on one side of the control frame, a second spring is fixedly installed on one side of the sliding plate, one end of the second spring is fixedly installed on the inner wall of one side of the connecting box, and an insertion block is fixedly installed on one side of the sliding plate.
[0013] Preferably, a limiting groove is provided on the inner side of the connecting box, the second spring is fixedly installed on the inner side of the limiting groove, the control frame, the sliding plate and the insertion block are slidably installed on the inner side of the limiting groove, and a through groove is provided on one side of the connecting block, and the insertion block fits into the through groove.
[0014] Preferably, the main vascular channel module is made of polydimethylsiloxane, and the inner wall of the main vascular channel module is provided with collagen.
[0015] The above-mentioned technical solutions adopted in the embodiments of this utility model can achieve the following beneficial effects:
[0016] 1. The drug solution above the main vascular channel module flows through the transfer branches to different chambers above the branch culture chambers. The branch culture chambers on both sides can be used for comparative experiments, making the experimental results comparable. This organ-on-a-chip integrates a spiral PDMS main channel to simulate the human microcirculation of 0.1-10 mm / s, 6-unit radial branch culture chambers containing 0.4 μm porous membrane separators and oxygen sensors, as well as a sodium alginate-gelatin scaffold for hepatocytes, a microelectrode array for myocardium, and a dual-entry immune migration channel, to achieve dynamic co-culture of multiple tissues and real-time monitoring of physiological parameters.
[0017] 2. The connecting block slides into the inside of the connecting box. The sliding plate and the insertion block can be slid by the second spring. The insertion block can slide into the inside of the connecting block. After the connecting insertion tube slides into the inside of the connecting box, it can be locked in the inside of the connecting box by the cooperation of the first spring and the locking rod, which can realize the quick assembly and disassembly of the main blood vessel channel module. Attached Figure Description
[0018] The accompanying drawings, which are included to provide a further understanding of the present invention and constitute a part of this invention, illustrate exemplary embodiments of the present invention and, together with the description thereof, serve to explain the present invention and do not constitute an undue limitation thereof. In the drawings:
[0019] Figure 1 This is a three-dimensional structural diagram of the present invention;
[0020] Figure 2 This is a partial three-dimensional structural diagram of the stem cell culture area, cardiomyocyte culture area, and immune cell migration channel in this utility model.
[0021] Figure 3 for Figure 2 Enlarged view of point A in the middle;
[0022] Figure 4 This is a three-dimensional structural diagram of the exploded portion of the connecting block in this utility model;
[0023] Figure 5 This is a partial structural diagram of the sliding plate and the insertion block in this utility model.
[0024] Figure Labels
[0025] 1. Main vascular channel module; 2. Transmission branch; 3. Connection box; 4. Branch culture chamber; 5. Stem cell culture area; 6. Cardiac cell culture area; 7. Immune cell migration channel; 8. Connection insertion tube; 9. Mounting block; 10. Locking rod; 11. Limiting block; 12. First spring; 13. Connection block; 14. Control frame; 15. Second spring; 16. Sliding plate; 17. Insertion block. Detailed Implementation
[0026] To make the objectives, technical solutions, and advantages of this utility model clearer, the technical solutions of this utility model will be clearly and completely described below in conjunction with specific embodiments and corresponding drawings. Obviously, the described embodiments are only a part of the embodiments of this utility model, and not all of them. Based on the embodiments of this utility model, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this utility model.
[0027] The technical solutions provided by the various embodiments of this utility model are described in detail below with reference to the accompanying drawings.
[0028] This utility model embodiment provides an organ-on-a-chip for multi-tissue co-culture, including a vascular main channel module 1, a transmission branch 2 opened at the top of the vascular main channel module 1, a connection box 3 arranged below the vascular main channel module 1, and two branch culture chambers 4 fixedly installed on the top of the connection box 3.
[0029] A stem cell culture area 5 is provided at the top center of the branch culture chamber 4, a cardiomyocyte culture area 6 is provided at the front of the top of the branch culture chamber 4, and an immune cell migration channel 7 is provided at the rear of the top of the branch culture chamber 4.
[0030] Furthermore, the system enables rapid assembly and disassembly of the main vascular channel module 1, facilitating the flow of medication from above the module through the transfer branch 2 to different chambers above the branch culture chamber 4. Comparative experiments can be conducted on both sides of the branch culture chamber 4, allowing for comparative analysis of experimental results. The chip-integrated sensor array simultaneously monitors environmental parameters such as glucose concentration, pH, and temperature, and correlates these parameters with cellular functional data, such as albumin secretion and cardiomyocyte beating frequency, through algorithms. This closed-loop feedback system ensures that culture conditions are consistently maintained within physiological limits, avoiding experimental errors caused by parameter drift in traditional static culture.
[0031] In a further preferred embodiment of the present invention, two connecting insertion tubes 8 are fixedly installed on the rear side of the main blood vessel channel module 1, an installation block 9 is fixedly installed on the inner side of the connecting insertion tube 8, and a locking rod 10 is slidably installed on the inner side of the installation block 9.
[0032] Furthermore, a locking groove is provided on one side of the connecting box 3, allowing the connecting insertion tube 8 to be inserted into the locking groove. The locking groove can position the connecting insertion tube 8, allowing the locking rod 10 to slide into the inside of the connecting insertion tube 8 via the first spring 12 after insertion. Two slots are provided on the upper inner wall of the locking groove. After the connecting insertion tube 8 is fully slid in, the locking rod 10 can slide into the inside of the slot via the first spring 12, making it easier to connect the main vascular channel module 1 and the branch culture chamber 4 quickly and tightly.
[0033] In a further preferred embodiment of the present invention, a limiting block 11 is fixedly installed on the outer side of one end of the locking rod 10, and a first spring 12 is fixedly installed on one side of the limiting block 11.
[0034] Furthermore, the limiting block 11 prevents the locking lever 10 from sliding out from the inside of the mounting block 9 during the sliding process.
[0035] In a further preferred embodiment of this utility model, two connecting blocks 13 are fixedly installed at the bottom of the main blood vessel channel module 1, a control frame 14 is slidably installed on the inner side of the connecting box 3, a sliding plate 16 is fixedly installed on one side of the control frame 14, a second spring 15 is fixedly installed on one side of the sliding plate 16, one end of the second spring 15 is fixedly installed on the inner wall of one side of the connecting box 3, and an insertion block 17 is fixedly installed on one side of the sliding plate 16.
[0036] Furthermore, the connecting insertion tube 8 is inserted into the inside of the connecting box 3, and the connecting block 13 is slid into the inside of the connecting box 3. The sliding plate 16 and the insertion block 17 can be slid by the second spring 15. The insertion block 17 can be slid into the inside of the connecting block 13. After the connecting insertion tube 8 is slid into the inside of the connecting box 3, it can be locked in the inside of the connecting box 3 by the cooperation of the first spring 12 and the locking rod 10, which can realize the quick assembly and disassembly of the main blood vessel channel module 1.
[0037] In a further preferred embodiment of the present invention, a limiting groove is provided on the inner side of the connecting box 3, the second spring 15 is fixedly installed on the inner side of the limiting groove, the control frame 14, the sliding plate 16 and the insertion block 17 are slidably installed on the inner side of the limiting groove, a through groove is provided on one side of the connecting block 13, and the insertion block 17 is in contact with the through groove.
[0038] Furthermore, the limiting groove facilitates the limiting of the control frame 14, the second spring 15, and the insertion block 17, allowing them to slide more stably.
[0039] In a further preferred embodiment of this utility model, the main vascular channel module 1 is made of polydimethylsiloxane, and the inner wall of the main vascular channel module 1 is provided with collagen.
[0040] Furthermore, this organ-on-a-chip integrates a spiral PDMS main channel to simulate the 0.1-10 mm / s human microcirculation, a 6-unit radially branched culture chamber containing 0.4 μm porous membrane separators and oxygen sensors, a sodium alginate-gelatin scaffold for hepatocytes, a microelectrode array for myocardium, and a dual-entry immune migration channel. This enables dynamic co-culture of multiple tissues and real-time monitoring of physiological parameters. Combined with the flow rate regulation capabilities of a microfluidic system, it can simulate the pharmacokinetic process of drugs in vivo. For example, by simulating clinical intravenous injection with a pulsed flow rate of 0.5 mm / s for 1 hour, the distribution and metabolism of drugs in different tissues can be monitored in real time, significantly improving the accuracy and efficiency of drug screening. This chip provides a novel platform for multi-organ interaction research and can be used to elucidate the crosstalk mechanism between liver and adipose tissue in metabolic diseases such as diabetes, or to explore the dynamic evolution of immunosuppression in the tumor microenvironment.
[0041] Specifically, when it is necessary to detect interactions between organs and drug use, the main vascular channel module 1 can be positioned and installed above the connecting box 3 via the connecting insertion tube 8. When the main vascular channel module 1 is connected to the connecting box 3, the connecting insertion tube 8 can be inserted into the inside of the connecting box 3, and the connecting block 13 can be slid into the inside of the connecting box 3. The sliding plate 16 and the insertion block 17 can be slid by the second spring 15. The insertion block 17 can slide into the inside of the connecting block 13, and after the connecting insertion tube 8 slides into the inside of the connecting box 3, it can be locked inside the connecting box 3 by the cooperation of the first spring 12 and the locking rod 10. This allows for rapid assembly and disassembly of the main vascular channel module 1, facilitating the flow of medication above the module through the transfer branch 2 to different chambers above the branch culture chamber 4. The two branch culture chambers 4 on either side can be used for comparative experiments, ensuring the comparability of results. This organ-on-a-chip integrates a spiral PDMS main channel simulating 0.1-10 mm / s human microcirculation, 6 radial branch culture chambers containing 0.4 μm porous membrane separators and oxygen sensors, a sodium alginate-gelatin scaffold for hepatocytes, a microelectrode array for myocardium, and a dual-entry immune migration channel, enabling dynamic co-culture of multiple tissues and real-time monitoring of physiological parameters.
[0042] The above description is merely an embodiment of this utility model and is not intended to limit the scope of this utility model. Various modifications and variations can be made to this utility model by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principle of this utility model should be included within the scope of the claims of this utility model.
Claims
1. An organ-chip for multi-tissue co-culture, characterized by: include; The main vascular channel module (1) has a transmission branch (2) at its top and a connection box (3) at its bottom. Two branch culture chambers (4) are fixedly installed on the top of the connection box (3). A stem cell culture area (5) is provided at the top center of the branch culture chamber (4), a cardiomyocyte culture area (6) is provided at the front of the top of the branch culture chamber (4), and an immune cell migration channel (7) is provided at the rear of the top of the branch culture chamber (4).
2. The organ-chip for multi-tissue co-culture of claim 1, wherein: Two connecting insertion tubes (8) are fixedly installed on the rear side of the main vascular channel module (1). An installation block (9) is fixedly installed on the inner side of the connecting insertion tube (8), and a locking rod (10) is slidably installed on the inner side of the installation block (9).
3. The organ-chip for multi-tissue co-culture of claim 2, wherein: A limiting block (11) is fixedly installed on the outer side of one end of the locking rod (10), and a first spring (12) is fixedly installed between one side of the limiting block (11).
4. The organ-chip for multi-tissue co-culture of claim 1, wherein: Two connecting blocks (13) are fixedly installed at the bottom of the main vascular channel module (1). A control frame (14) is slidably installed on the inner side of the connecting box (3). A sliding plate (16) is fixedly installed on one side of the control frame (14). A second spring (15) is fixedly installed on one side of the sliding plate (16). One end of the second spring (15) is fixedly installed on the inner wall of one side of the connecting box (3). An insertion block (17) is fixedly installed on one side of the sliding plate (16).
5. An organ-chip for multi-tissue co-culture according to claim 4, wherein: The inner side of the connecting box (3) is provided with a limiting slide groove, the second spring (15) is fixedly installed on the inner side of the limiting slide groove, the control frame (14), the sliding plate (16) and the insertion block (17) are slidably installed on the inner side of the limiting slide groove, a through groove is provided on one side of the connecting block (13), and the insertion block (17) is in contact with the through groove.
6. An organ-on-a-chip for multi-tissue co-culture as described in claim 1, characterized in that: The main vascular channel module (1) is made of polydimethylsiloxane, and the inner wall of the main vascular channel module (1) is provided with collagen.