Micro-fluidic chip and tumor drug sensitivity detection system
Through the multi-channel and three-dimensional culture chamber design of the microfluidic chip, high-throughput evaluation of lung cancer drug sensitivity detection is achieved, the problem of ineffective traditional Chinese medicine sensitivity detection in the existing technology is solved, more accurate drug sensitivity detection results are provided, and precise treatment of lung cancer is promoted.
Patent Information
- Application Number
- CN202411756601.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-03
- Publication Date
- 2025-03-07
AI Technical Summary
The prior art is difficult to effectively carry out the detection of lung cancer drug sensitivity in vitro, resulting in the drug resistance problem of targeted therapy and the low response rate of immunotherapy.
A microfluidic chip is adopted, including a plurality of flow channels and a three-dimensional culture chamber, each flow channel is provided with a drug delivery port and a first solenoid valve at one end, and a second solenoid valve and a biosensor at the other end. By controlling the solenoid valve and systolic pump, multiple drugs are administered and tested in three-dimensional tumor balls at the same time.
It has achieved high-throughput microtumor culture for multiple days, and can simultaneously evaluate multiple drug treatment plans and combination strategies, providing more intuitive and accurate drug sensitivity test results, and promoting the precise treatment of lung cancer.
Smart Images
Figure CN119570621A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the field of biological detection technology, and in particular to a microfluidic chip and a tumor drug sensitivity detection system. Background Art
[0002] Lung cancer, as a malignant tumor with the highest incidence and mortality rate in the world, poses a severe challenge to global public health. Therefore, the prevention and treatment of lung cancer is particularly urgent and important, as it not only affects the quality of life of individuals, but also directly affects the overall health level of society and the allocation of medical resources.
[0003] With the advancement of medical technology, the treatment of lung cancer has undergone a major transformation from traditional surgery and chemotherapy to targeted therapy and immunotherapy that have emerged in recent years. Among them, targeted therapy and immunotherapy represented by PD-1 / PD-L1 inhibitors have significantly improved the treatment effect and quality of life of lung cancer patients due to their high efficiency and low toxicity, bringing new hope to many patients. Targeted therapy achieves precise strikes by targeting specific tumor-related genes or proteins, reducing damage to normal cells; while immunotherapy achieves a revolutionary breakthrough in treatment methods by regulating the patient's own immune system and stimulating its ability to fight tumors.
[0004] However, despite the remarkable success of these new therapies, they still face two major clinical challenges: one is the drug resistance of targeted therapy, that is, over time, some patients will experience a decrease in tumor sensitivity to drugs, resulting in a weakening of the treatment effect; the other is that the response rate of immunotherapy is not high, and the efficacy varies greatly among different patients, and some patients even have no response at all. The root of these two problems lies in the high heterogeneity of lung cancer, that is, there are significant differences in the tumor microenvironment (including tumor cells themselves, surrounding blood vessels, immune cells, cytokines, etc.) of different patients. This difference leads to uncertainty in treatment response and a lack of reliable efficacy prediction indicators to guide clinical decision-making.
[0005] How to achieve drug sensitivity testing in vitro to guide personalized medication has become a technical problem that needs to be solved urgently. Summary of the invention
[0006] In view of the problems existing in the prior art, the present invention provides a microfluidic chip, comprising:
[0007] A substrate, a cover plate is covered on the substrate, and a plurality of flow channels are formed between the substrate and the cover plate, one end of each flow channel is connected to the drug delivery port and is provided with a first solenoid valve, and the other end is provided with a second solenoid valve;
[0008] A plurality of groups of three-dimensional culture chambers, each group of the three-dimensional culture chambers is sequentially arranged between the first solenoid valve and the second solenoid valve along the extension direction of the corresponding flow channel, and the flow channel flows through each of the three-dimensional culture chambers and bulges toward the cover plate in an arc shape;
[0009] Each of the three-dimensional culture chambers has an input pipe toward the first electromagnetic valve and an outlet toward the second electromagnetic valve, the input pipe and the outlet are connected to the flow channel, and the diameter of the input pipe is smaller than the diameter of the outlet.
[0010] Preferably, the drug delivery port is connected to one end of each of the flow channels through a drug delivery pipeline.
[0011] Preferably, each group of the three-dimensional culture chambers comprises a plurality of the three-dimensional culture chambers, and all the three-dimensional culture chambers are distributed in an array on each of the flow channels.
[0012] Preferably, it further comprises a flushing pipe, which is sleeved on the input pipe, one end of which is fixed to the outer wall of the input pipe, and the other end is connected to the corresponding three-dimensional culture chamber, and the inner diameter of the cross section of the flushing pipe gradually increases in the direction toward the three-dimensional culture chamber;
[0013] The side of the input pipeline is communicated with the flushing pipeline and is connected through a two-way valve.
[0014] Preferably, the two-way valve is a flow valve.
[0015] Preferably, a biosensor is disposed at the end of each flow channel located away from the three-dimensional culture chamber and located at the second solenoid valve.
[0016] Preferably, the first solenoid valve and the second solenoid valve are air pump valves.
[0017] The present invention also provides a tumor drug sensitivity detection system, which uses each of the three-dimensional culture chambers of the above-mentioned microfluidic chip to load three-dimensional tumor spheres. The tumor drug sensitivity detection system comprises:
[0018] A controller, connected to each of the first solenoid valves, the second solenoid valves and a syringe pump connected to the drug delivery port of the microfluidic chip, respectively, for sequentially controlling the first solenoid valves of each flow channel to open, the second solenoid valves to close and controlling the syringe pump to inject different drugs into different flow channels for drug sensitivity testing;
[0019] An image acquisition device, connected to the controller, for acquiring a first image and a second image of each of the three-dimensional culture chambers before and after drug sensitivity detection according to a control instruction of the controller;
[0020] The result output module is connected to the image acquisition device and is used to identify the morphological changes of the three-dimensional tumor spheres in the first image and the second image as the drug sensitivity detection results of the corresponding drugs.
[0021] Preferably, the controller controls the image acquisition device to acquire multiple frames of the second image during drug sensitivity detection;
[0022] The result output module also includes a model visualization unit, which is used to obtain the first form of the three-dimensional tumor sphere in the identified first image and the second form of the three-dimensional tumor sphere in each of the second images, and then create a virtual tumor model of the three-dimensional tumor sphere based on the digital twin technology, and visualize the first form and each of the second forms through the virtual tumor model to show the morphological change process of the three-dimensional tumor sphere during the drug sensitivity detection.
[0023] Preferably, a biosensor is arranged at the end of each flow channel located away from the three-dimensional culture chamber and located at the second solenoid valve;
[0024] The controller is also used to control the opening of the second solenoid valve after the drug sensitivity test is completed, and control the injection pump to inject a flushing solution to flush each of the three-dimensional tumor spheres out of the flow channel;
[0025] The biosensor is connected to the result output module and is used for identifying cytokines during the process of flushing out each of the three-dimensional tumor spheres;
[0026] The result output module also includes binding the morphological change recognition result of each of the three-dimensional tumor spheres in the corresponding flow channel with the recognized cytokines and the injected drug to obtain the drug sensitivity detection result of the corresponding drug.
[0027] The above technical solution has the following advantages or beneficial effects:
[0028] 1) By providing multiple flow channels through microfluidic chips, multiple drug treatment plans and combination strategies can be evaluated simultaneously, and high-throughput micro-tumor culture can be achieved for multiple days. It can be used in the fields of clinical individualized drug regimen formulation, new drug development and basic medical research, thereby promoting the precision treatment of lung cancer;
[0029] 2) Each flow channel provides multiple three-dimensional culture chambers, so that each drug regimen can act on multiple three-dimensional culture chambers at the same time, and can reflect the heterogeneity of different three-dimensional tumor cells of the same patient. The three-dimensional culture chambers of the same flow channel are interconnected, which is closer to the real environment of the human body;
[0030] 3) The flow channel passes through each three-dimensional culture cavity and is convex in an arc shape toward the cover plate, so that multiple three-dimensional culture cavities can be administered at the same time without affecting each other;
[0031] 4) The input channel has a relatively small diameter, which can more accurately control the dosage, and the outlet of the three-dimensional culture chamber has a relatively large diameter, so that the three-dimensional tumor spheres can pass smoothly, reducing the difficulty of chip flushing;
[0032] 5) By designing the flushing pipe to have a gradually increasing inner diameter of the cross section, the flushing fluid can be buffered and decompressed through the flushing pipe before entering the three-dimensional culture chamber, thereby preventing excessive flushing pressure from damaging the cells of the three-dimensional tumor spheres and affecting the subsequent cytokine detection;
[0033] 6) By setting a biosensor at the end of the flow channel, it is possible to detect cytokines in the three-dimensional tumor spheres after drug sensitivity reaction, thereby reflecting the drug sensitivity reaction results of the corresponding drugs;
[0034] 7) By using image acquisition and image recognition technology, the morphological changes of three-dimensional tumor spheres can be monitored, which can provide more intuitive and accurate drug sensitivity detection results, effectively save labor costs, and avoid the bias of human observation. BRIEF DESCRIPTION OF THE DRAWINGS
[0035] Figure 1 This is a schematic diagram of the structure of a microfluidic chip in a preferred embodiment of the present invention;
[0036] Figure 2 This is a schematic diagram of the structure of a three-dimensional culture chamber in a preferred embodiment of the present invention;
[0037] Figure 3 The figure is a schematic diagram of the structure of a tumor drug sensitivity detection system in a preferred embodiment of the present invention. DETAILED DESCRIPTION
[0038] The present invention is described in detail below in conjunction with the accompanying drawings and specific embodiments. The present invention is not limited to this embodiment, and other embodiments may also fall within the scope of the present invention as long as they conform to the gist of the present invention.
[0039] In a preferred embodiment of the present invention, based on the above problems existing in the prior art, a microfluidic chip is provided. Figure 1 and Figure 2 As shown, including:
[0040] A substrate 1, a cover plate 2 is covered on the substrate 1, and a plurality of flow channels 3 are formed between the substrate 1 and the cover plate 2, one end of each flow channel 3 is connected to a drug delivery port 4 and is provided with a first electromagnetic valve 5, and the other end is provided with a second electromagnetic valve 6;
[0041] A plurality of groups of three-dimensional culture chambers 7, each group of three-dimensional culture chambers 7 is sequentially arranged between the first solenoid valve 5 and the second solenoid valve 6 along the extension direction of the corresponding flow channel 3, and the flow channel 3 flows through each three-dimensional culture chamber 7 and bulges toward the cover plate 2 in an arc shape;
[0042] Each three-dimensional culture chamber 7 has an input pipe 71 toward the first solenoid valve 5 and an outlet 72 toward the second solenoid valve 6 . The input pipe 71 and the outlet 72 are connected to the flow channel 3 , and the diameter of the input pipe 71 is smaller than the diameter of the outlet 72 .
[0043] Specifically, in this embodiment, the substrate 1 is preferably prepared by polydimethylsiloxane (PDMS) soft etching technology, and specifically, a template including the above-mentioned flow channels 2 and the three-dimensional culture chamber 7 can be prepared by three-dimensional printing technology and soft lithography technology, and then a PDMS prepolymer is poured, and then the template is obtained after thermal curing and sealing. The cover plate 2 is made of transparent material, which is convenient for observing the morphological changes of the three-dimensional tumor spheres in the three-dimensional culture chamber 7 and the drug administration.
[0044] In actual use, the fresh tumor sample from the patient can be processed into a single cell in vitro, and then suspended and cultured in a low-adhesion culture dish using a micro-tumor-specific culture medium for 2-7 days, so that the primary tumor cells can rapidly proliferate and self-assemble with the microenvironment cells to form a three-dimensional tumor sphere with a diameter of 40-300 μm. Then, the three-dimensional tumor sphere is placed in the three-dimensional culture cavity 7, wherein the number of three-dimensional tumor spheres in each three-dimensional culture cavity 7 is preferably 30-50, and the number of three-dimensional culture cavities 7 on each flow channel 2 is not less than 3, so as to perform parallel control.
[0045] After the three-dimensional tumor sphere is placed, the drug delivery port 4 can be connected to an external injection pump through a hose, and the drug required for drug sensitivity test can be injected into the drug delivery port 4 through the injection pump, and the drug flows into the corresponding three-dimensional culture chamber 7 through the corresponding flow channel 3. Among them, for each flow channel 3, when drug injection is required, the corresponding first electromagnetic valve 5 is first controlled to open so that the drug can enter the three-dimensional culture chamber 7, and the second electromagnetic valve 6 is controlled to close so that the drug will not be flushed out of the microfluidic chip, and then the injection pump is controlled to inject the corresponding drug, so as to realize high-throughput micro-tumor continuous multi-day culture on the microfluidic chip to observe the drug sensitivity test results of the tumor cells after culture.
[0046] Among them, Figure 1 As shown, connection holes for the first solenoid valves 5 can also be provided on the side of the substrate 1 to be electrically connected to the first solenoid valves 5 . Each connection hole can be connected to a controller through an external lead to realize sequential control of each first solenoid valve 5 .
[0047] Preferably, each flow channel 3 flows through each three-dimensional culture chamber 7 in turn. When the drug is injected, it is divided into two paths when it is transported to the first three-dimensional culture chamber 7 through the front flow channel 3. One path is input into the three-dimensional culture chamber 7 through the input pipe 71, and the other path bypasses the first three-dimensional culture chamber 7 and is transported to the next three-dimensional culture chamber 7, and so on. There is no need to inject the first three-dimensional culture chamber 7 first and then inject the second three-dimensional culture chamber 7, thereby reducing the delay of drug injection in each three-dimensional culture chamber 7.
[0048] More preferably, the outlet diameter of each three-dimensional culture chamber 7 is consistent with the diameter of the flow channel 3 and is larger than the diameter of the input pipe 71, which can more accurately control the dosage while allowing the three-dimensional tumor spheres to pass through the outlet smoothly, reducing the difficulty of chip flushing after the drug sensitivity culture is completed.
[0049] In a preferred embodiment of the present invention, the drug delivery port 4 is connected to one end of each flow channel 3 through a drug delivery pipe 41 .
[0050] In a preferred embodiment of the present invention, each group of three-dimensional culture chambers 7 includes a plurality of three-dimensional culture chambers 7 , and all three-dimensional culture chambers 7 are distributed in an array on each flow channel 3 .
[0051] Specifically, in this embodiment, the three-dimensional culture chambers 7 are designed to be distributed in an array so that the three-dimensional culture chambers 7 located on different flow channels 3 can be aligned, which facilitates intuitive comparison of sensitive detection results of different drugs.
[0052] In a preferred embodiment of the present invention, a flushing pipe 8 is further included, which is sleeved on the input pipe 71, one end of the flushing pipe 8 is fixed to the outer wall of the input pipe 71, and the other end is connected to the corresponding three-dimensional culture chamber 7, and the inner diameter of the cross section of the flushing pipe 8 gradually increases in the direction toward the three-dimensional culture chamber 7;
[0053] The side of the input pipe 71 is communicated with the flushing pipe 8 and is connected through a two-way valve 9 .
[0054] Specifically, since the diameter of the input pipe 71 is relatively small, when flushing, if it is used as the flushing pipe 8, the relatively small diameter will cause the flushing liquid reaching the three-dimensional culture chamber 7 to have a higher flow rate and a higher pressure, which may easily cause damage to the three-dimensional tumor sphere after the drug sensitivity test. Based on this, in this embodiment, a flushing pipe 8 with a gradually increasing inner diameter of the cross section is designed. When it is necessary to inject drugs, the input pipe 71 and the flushing pipe 8 are isolated by a two-way valve 9, so that the drugs can only reach the corresponding three-dimensional culture chamber 7 through the input pipe 71, which will not affect the drug injection amount. When the microfluidic chip needs to be flushed after the drug sensitivity test, the input pipe 71 and the flushing pipe 8 are connected through the two-way valve 9, and the original outlet of the input pipe 71 is isolated by the two-way valve 9. At this time, the flushing solution reaches the two-way valve 9 through the input pipe 71 and then enters the flushing pipe 8. The gradually increasing inner diameter of the cross section of the flushing pipe 8 can effectively reduce the flow rate and pressure of the flushing solution to avoid excessive mechanical stress or damage to the cells.
[0055] In a preferred embodiment of the present invention, the two-way valve 9 is a flow valve.
[0056] Specifically, in this embodiment, the two-way valve 9 is designed as a flow valve, which can achieve that when the drug injection volume is detected to reach a preset threshold during drug injection, the input pipe 71 is closed, so that the corresponding three-dimensional culture chamber 7 no longer receives the drug, and all drugs are sent to the next three-dimensional culture chamber 7 through the flow channel 3 until all the flow valves reach the preset threshold, then the injection pump is controlled to be closed, and the drug injection process ends.
[0057] In a preferred embodiment of the present invention, a biosensor is disposed at the end of each flow channel 3 that is located away from the three-dimensional culture chamber 7 and is located at the second solenoid valve 6 .
[0058] Specifically, in this embodiment, the biosensor can perform cytokine detection on the three-dimensional tumor sphere after drug sensitivity detection to determine the specific point where the drug works. The cytokines here include but are not limited to IFNβ, TNF and IL-6.
[0059] Among them, IFNβ is a type of interferon (IFN), which is a low molecular weight protein (mainly glycoprotein) with multiple biological activities. It has multiple biological activities such as antiviral, anti-tumor and immunomodulatory. It does not directly kill or inhibit viruses, but induces cell surface receptors to make cells produce antiviral proteins, thereby inhibiting viral replication. In tumor treatment, IFNβ can exert anti-tumor effects by activating immune cells, inhibiting tumor angiogenesis and inducing tumor cell apoptosis. However, the efficacy of IFNβ and the patient's response may vary from individual to individual. By detecting the level of IFNβ, the patient's sensitivity to tumor drugs can be indirectly evaluated, thereby guiding the formulation of personalized treatment plans.
[0060] TNF is the abbreviation of tumor necrosis factor (TNF), which is a family of cytokines that can cause necrosis of tumor tissue cells. TNF can be divided into two types: TNF-α and TNF-β. TNF-α is mainly produced by activated monocytes and macrophages, while TNF-β is mainly produced by activated T cells. It has important biological effects such as antiviral, anti-tumor, immunomodulatory, promoting inflammatory response, pyrogenicity, and inducing cachexia, and can be used for the treatment of tumors. In particular, TNF-α plays an important role in tumor treatment. It can induce apoptosis of tumor cells, enhance the killing activity of immune cells, and promote inflammatory response, thereby exerting an anti-tumor effect. The detection of TNF is of great significance in tumor drug sensitivity testing for the following reasons:
[0061] Predicting efficacy: The level of TNF can reflect the sensitivity of tumor cells and the activity of immune cells, thereby predicting the efficacy of tumor drugs.
[0062] Monitor changes in the disease: During treatment, changes in TNF levels can reflect changes in the disease and the effectiveness of treatment, and help to adjust the treatment plan in a timely manner.
[0063] IL-6 is a type of interleukin (IL), a pleiotropic cytokine produced by various cells in the body (such as activated T cells, B cells, monocytes, endothelial cells, etc.). It participates in a variety of physiological and pathophysiological processes, especially plays an important role in inflammation and immune response. In tumor treatment, changes in IL-6 levels can reflect the proliferation, invasion and metastasis of tumor cells, as well as the activity of immune cells. Therefore, the detection of IL-6 has the following significance in tumor drug sensitivity detection:
[0064] Evaluation of tumor activity: The level of IL-6 can reflect the activity of tumor cells, thereby evaluating the malignancy and prognosis of the tumor.
[0065] Predicting drug efficacy: Changes in IL-6 levels can predict the killing effect of tumor drugs on tumor cells, thereby guiding the formulation of treatment plans.
[0066] Monitoring treatment response: During the treatment process, changes in IL-6 levels can reflect treatment response and disease changes, and help to adjust the treatment plan in a timely manner.
[0067] The detection of cytokines IFNβ, TNF, and IL-6 not only has independent predictive and monitoring value in tumor drug sensitivity testing, but also the interaction and balance between them have important clinical significance. For example, IFNβ and TNF can synergistically exert anti-tumor effects, while the increase of IL-6 may indicate the drug resistance and immune escape mechanism of tumor cells. Therefore, the comprehensive detection of the levels of these cytokines can more comprehensively evaluate the efficacy of tumor drugs and the response of patients, and provide a more accurate basis for the formulation of personalized treatment plans.
[0068] The type and specific model of the above-mentioned biosensor (not shown in the figure) are not limited, as long as it can detect the above-mentioned cytokines.
[0069] In a preferred embodiment of the present invention, the first solenoid valve 5 and the second solenoid valve 6 are air pump valves.
[0070] In summary, the microfluidic chip of the present invention can highly simulate the immune microenvironment characteristics of lung cancer, and can simultaneously evaluate multiple drug treatment regimens and combination strategies, and can be used in the fields of clinical individualized medication regimen formulation, new drug development and basic medical research, thereby promoting the precision treatment of lung cancer.
[0071] The present invention also provides a tumor drug sensitivity detection system, which uses each three-dimensional culture chamber of the above-mentioned microfluidic chip to load three-dimensional tumor spheres, such as Figure 3 As shown, the tumor drug sensitivity detection system includes:
[0072] The controller 100 is respectively connected to each first solenoid valve 5, the second solenoid valve 6 and the injection pump 200 connected to the drug delivery port of the microfluidic chip, and is used to sequentially control the first solenoid valve 5 of each flow channel 3 to open, the second solenoid valve 6 to close, and control the injection pump 200 to inject different drugs into different flow channels 3 for drug sensitivity detection;
[0073] The image acquisition device 300 is connected to the controller 100 and is used to acquire the first image and the second image of each three-dimensional culture chamber 7 before and after the drug sensitivity test according to the control instruction of the controller 100;
[0074] The result output module 400 is connected to the image acquisition device 300 and is used to identify the morphological changes of the three-dimensional tumor spheres in the first image and the second image as the drug sensitivity detection results of the corresponding drugs.
[0075] Specifically, in this embodiment, the first image is an image of the three-dimensional tumor spheres in each three-dimensional culture chamber 7 before drug injection, and the second image can be one frame or multiple frames. One frame is collected at the end of the drug sensitivity test to directly observe the changes in the three-dimensional tumor spheres before and after the drug action. Multiple frames are collected once at the end of the drug sensitivity test, and one or more frames are collected after the drug injection to the end of the drug sensitivity test to observe the changes in the three-dimensional tumor spheres during the drug action process.
[0076] Since a plurality of three-dimensional tumor spheres are placed in each three-dimensional culture chamber 7, the morphological changes of the three-dimensional tumor spheres identified above include changes in quantity and volume. For example, when the corresponding injected drug takes effect on tumor cells, the number of the corresponding three-dimensional tumor spheres will decrease or the volume will decrease. When the corresponding injected drug has no effect on tumor cells, the number of the corresponding three-dimensional tumor spheres will increase or the volume will increase. Based on this, the drug sensitivity test results can be obtained.
[0077] In a preferred embodiment of the present invention, the controller 100 controls the image acquisition device 300 to acquire multiple frames of second images during drug sensitivity detection;
[0078] The result output module 400 also includes a model visualization unit 401, which is used to obtain the first form of the three-dimensional tumor sphere in the identified first image and the second form of the three-dimensional tumor sphere in each second image, and then create a virtual tumor model of the three-dimensional tumor sphere based on the digital twin technology, and visualize the first form and the second form through the virtual tumor model to show the morphological change process of the three-dimensional tumor sphere during drug sensitivity detection.
[0079] In a preferred embodiment of the present invention, a biosensor is arranged at the end of each flow channel 3 that is located away from the three-dimensional culture chamber 7 and located at the second solenoid valve 6;
[0080] The controller 100 is also used to control the opening of the second electromagnetic valve 6 after the drug sensitivity test is completed, and control the injection pump 200 to inject a flushing solution to flush each three-dimensional tumor sphere out of the flow channel;
[0081] The biosensor connection result output module 400 is used to identify cytokines during the flushing process of each three-dimensional tumor sphere;
[0082] The result output module 400 also includes binding the morphological change recognition results of each three-dimensional tumor sphere in the corresponding flow channel with the recognized cytokines and the injected drugs to obtain the drug sensitivity detection results of the corresponding drugs.
[0083] The above description is only a preferred embodiment of the present invention, and does not limit the implementation mode and protection scope of the present invention. For those skilled in the art, it should be aware that all solutions obtained by equivalent substitutions and obvious changes made using the contents of this specification and illustrations should be included in the protection scope of the present invention.
Claims
1. A microfluidic chip, characterized in that: include: A substrate, a cover plate is covered on the substrate, and a plurality of flow channels are formed between the substrate and the cover plate, one end of each flow channel is connected to the drug delivery port and is provided with a first solenoid valve, and the other end is provided with a second solenoid valve; A plurality of groups of three-dimensional culture chambers, each group of the three-dimensional culture chambers is sequentially arranged between the first solenoid valve and the second solenoid valve along the extension direction of the corresponding flow channel, and the flow channel flows through each of the three-dimensional culture chambers and bulges toward the cover plate in an arc shape; Each of the three-dimensional culture chambers has an input pipe toward the first electromagnetic valve and an outlet toward the second electromagnetic valve, the input pipe and the outlet are connected to the flow channel, and the diameter of the input pipe is smaller than the diameter of the outlet.
2. The microfluidic chip according to claim 1, characterized in that: The drug delivery ports are respectively connected to one end of each of the flow channels through drug delivery pipes.
3. The microfluidic chip according to claim 1, characterized in that: Each group of the three-dimensional culture chambers includes a plurality of the three-dimensional culture chambers, and all the three-dimensional culture chambers are distributed in an array on each of the flow channels.
4. The microfluidic chip according to claim 1, characterized in that: It also includes a flushing pipe, which is sleeved on the input pipe, one end of the flushing pipe is fixed to the outer wall of the input pipe, and the other end is connected to the corresponding three-dimensional culture cavity, and the inner diameter of the cross section of the flushing pipe gradually increases in the direction toward the three-dimensional culture cavity; The side of the input pipeline is communicated with the flushing pipeline and is connected through a two-way valve.
5. The microfluidic chip according to claim 4, characterized in that: The two-way valve is a flow valve.
6. The microfluidic chip according to claim 1, characterized in that: A biosensor is arranged at the end of each flow channel that is located away from the three-dimensional culture chamber and is located at the second solenoid valve.
7. The microfluidic chip according to claim 1, characterized in that: The first solenoid valve and the second solenoid valve are air pump valves.
8. A tumor drug sensitivity detection system, characterized in that: The three-dimensional tumor spheres are loaded in each of the three-dimensional culture chambers of the microfluidic chip according to any one of claims 1 to 7, and the tumor drug sensitivity detection system comprises: A controller, connected to each of the first solenoid valves, the second solenoid valves and a syringe pump connected to the drug delivery port of the microfluidic chip, respectively, for sequentially controlling the first solenoid valves of each flow channel to open, the second solenoid valves to close and controlling the syringe pump to inject different drugs into different flow channels for drug sensitivity testing; An image acquisition device, connected to the controller, for acquiring a first image and a second image of each of the three-dimensional culture chambers before and after drug sensitivity detection according to a control instruction of the controller; The result output module is connected to the image acquisition device and is used to identify the morphological changes of the three-dimensional tumor spheres in the first image and the second image as the drug sensitivity detection results of the corresponding drugs.
9. The tumor drug sensitivity detection system according to claim 8, characterized in that: The controller controls the image acquisition device to acquire multiple frames of the second image during drug sensitivity detection; The result output module also includes a model visualization unit, which is used to obtain the first form of the three-dimensional tumor sphere in the identified first image and the second form of the three-dimensional tumor sphere in each of the second images, and then create a virtual tumor model of the three-dimensional tumor sphere based on the digital twin technology, and visualize the first form and each of the second forms through the virtual tumor model to show the morphological change process of the three-dimensional tumor sphere during the drug sensitivity detection.
10. The tumor drug sensitivity detection system according to claim 8, characterized in that: A biosensor is arranged at the end of each flow channel located at the second solenoid valve away from the three-dimensional culture chamber; The controller is also used to control the opening of the second solenoid valve after the drug sensitivity test is completed, and control the injection pump to inject a flushing solution to flush each of the three-dimensional tumor spheres out of the flow channel; The biosensor is connected to the result output module and is used for identifying cytokines during the process of flushing out each of the three-dimensional tumor spheres; The result output module also includes binding the morphological change recognition result of each of the three-dimensional tumor spheres in the corresponding flow channel with the recognized cytokines and the injected drug to obtain the drug sensitivity detection result of the corresponding drug.