Organ force biological reaction platform and human gait organ stress simulation method

Abstract

This invention relates to an organoid biomechanical response platform and a method for simulating the force exerted on human gait organs. The platform includes an organ-on-a-chip and a biomechanical response device. The biomechanical response device is divided into two types: simulating the force exerted on the organoid during prolonged standing and simulating the force exerted on the organoid during walking or running. The system simulating prolonged standing includes an interconnected pressure chamber base, a one-way valve, a stroke cylinder, a stroke reciprocating structure, and a motor. The system simulating walking or running includes an interconnected pressure chamber base, a stroke cylinder, a stroke reciprocating structure, and a motor. The organoid is placed within the pressure chamber base. The stroke reciprocating structure includes a connecting rod piston, a crankshaft connecting rod, and a crankshaft. The connecting rod portion of the connecting rod piston is connected to the crankshaft via the crankshaft connecting rod. The crankshaft is connected to the motor. The piston portion of the connecting rod piston extends into the stroke cylinder. Compared with existing technologies, this invention achieves stable, repeatable, and quantifiable mechanical stimulation, realistically reproducing human gait stress.

Description

Technical Field

[0001] This invention belongs to the field of biomedical engineering technology and relates to an organoid biomechanical response platform and a method for simulating the force on human gait organs. Background Technology

[0002] During daily walking, running, and various sports, bones and articular cartilage are subjected to periodic and complex mechanical loads, including pressures of varying amplitudes, gait rhythms of different frequencies, and dynamic loads of different waveforms. These mechanical stimuli not only determine the physiological homeostasis of bone and cartilage tissues (such as matrix synthesis, cell arrangement, and nutrient diffusion) but also profoundly affect various pathological processes (such as abnormal bone metabolism, cartilage degeneration, and osteoarthritis). Therefore, establishing organoid systems in vitro that can accurately simulate "physiological and pathological mechanical environments" is of great value for studying bone / cartilage formation, injury, and repair mechanisms, as well as for drug screening and biomaterial evaluation.

[0003] Existing organoid technologies can construct physiological cartilage organoids, disease organoids such as those for inflammation or hypertrophy, and bone organoids at different stages. However, their further development is still constrained by a core bottleneck: most organoid chips still rely on static or simple perfusion culture, lacking controllable, quantifiable, and programmable biomimetic mechanical stimulation devices. Existing systems cannot simulate the real mechanical environment of human walking and running. The lack of these key mechanical signals makes it difficult for organoids to closely approximate real tissues in terms of structural maturity, hierarchical tissue formation, cell behavior regulation, and the presentation of pathological features, thus limiting the application of organoids in studying mechanically related physiological processes and disease mechanisms. Therefore, there is an urgent need for a chip-based platform that can realistically reproduce human gait stress while possessing high versatility and high throughput capabilities to overcome the limitations of existing systems.

[0004] Patent CN120966629A discloses a bone organoid chip with a microelectrode array and its usage method. It uses polydimethylsiloxane material and comprises a three-layer structure: a top layer, a middle layer, and a bottom layer. The middle layer includes two vascular microchannels, two osteoblast microchannels, and one neuronal microchannel, separated by pillars and micropillars to simulate cell interactions in the bone microenvironment. The top layer has a microelectrode array for real-time monitoring of neuronal electrical activity. The bottom layer has pneumatic valves to control the opening and closing of the microchannels. However, this patent neglects the mechanical stimulation of bone organs in a real environment, such as the mechanical environment, when used for culturing bone organs.

[0005] Patent CN120796060A discloses a uniaxial adjustable mechanical stretching device and stretching culture method for organoids or cells. A fixed base is equipped with a fixed support and a guide rail via a guide rail elevation seat. A slider above the guide rail is connected to the stretching motion end via an adapter seat. The stretching motion end and the stretching fixed end are spaced apart. The lead screw of a stepper motor on the fixed support is fixed to a coupling, which is fixed to the adapter seat via a plug. Handles on both sides of the culture chamber are fixed to the stretching fixed seat and the stretching fixed end, respectively. Starting the stepper motor causes the lead screw to move, driving the adapter seat longitudinally. This longitudinal movement of the adapter seat moves the slider along the guide rail, causing the stretching motion end to move away from / close to the corresponding stretching fixed end. However, in real-world environments, bone organs are primarily under compression rather than stretching, making this patent unsuitable for simulating the real-world environment of bone organs. Summary of the Invention

[0006] The purpose of this invention is to overcome at least one of the defects of the prior art and provide an organoid biomechanical response platform and a method for simulating the force on human gait organs. This invention achieves stable, repeatable, and quantifiable mechanical stimulation, and can realistically reproduce human gait stress.

[0007] The objective of this invention can be achieved through the following technical solutions:

[0008] One of the technical solutions of the present invention is to provide an organoid biomechanical reaction platform, which includes an organ-on-a-chip and a biomechanical reaction device. The biomechanical reaction device has two forms: one simulating the force state of an organoid when a person stands for a long time, and the other simulating the force state of an organoid when a person walks or runs. The biomechanical reaction device simulating the force state of an organoid when a person stands for a long time includes a pressure chamber base, a one-way valve, a stroke air cylinder, a stroke reciprocating structure, and a motor connected to each other. The biomechanical reaction device simulating the force state of an organoid when a person walks or runs includes a pressure chamber base, a stroke air cylinder, a stroke reciprocating structure, and a motor connected to each other. The organ-on-a-chip is placed in the pressure chamber base.

[0009] The reciprocating structure includes a connecting rod piston, a crankshaft connecting rod, and a crankshaft. The connecting rod portion of the connecting rod piston is connected to the crankshaft via the crankshaft connecting rod. The crankshaft is connected to a motor. The piston portion of the connecting rod piston extends into the stroke cylinder.

[0010] Furthermore, the organ-on-a-chip has two forms: an organoid culture chip and an organoid non-destructive removal chip. The organoid culture chip includes three layers stacked in sequence: an upper chip layer, a middle chip layer, and a lower culture chip layer. The organoid non-destructive removal chip includes two layers stacked in sequence: an upper chip layer and a lower non-destructive removal chip layer.

[0011] The middle layer of the chip adopts a planar structure;

[0012] A through-hole is provided on the lower layer of the culture chip;

[0013] The chip is extracted without damage. The chip has an inlet hole, a recessed channel, and an outlet hole. The inlet hole and the outlet hole are respectively located at both ends of the recessed channel. The recessed channel at one end is connected to the inlet hole, and the recessed channel at the other end is connected to the outlet hole.

[0014] As a preferred technical solution, no holes or slots are formed in the middle layer of the chip.

[0015] As a preferred technical solution, the through-hole penetrates the upper and lower surfaces of the lower layer of the culture chip.

[0016] As a preferred technical solution, the indentation hole, the notch channel, and the outlet hole all penetrate through the upper surface of the lower layer of the chip to remove it without damage, rather than penetrating through the lower surface of the lower layer of the chip to remove it without damage.

[0017] Furthermore, the upper layer of the chip has an inlet port, an organoid culture chamber, and an outlet port. The inlet port and the outlet port are respectively located at opposite ends of the organoid culture chamber, with one end of the organoid culture chamber connected to the inlet port and the other end connected to the outlet port.

[0018] The organoid culture chamber includes interconnected organoid culture chambers and culture medium channels. Culture medium channels are provided on both sides of several organoid culture chambers, with one side of the culture medium channel connected to the inlet port and the other side of the culture medium channel connected to the outlet port.

[0019] The organoid culture chip is mainly used for the culture of organoids. The middle layer of the chip is attached to both the upper layer and the lower layer of the culture chip to form a complete organoid culture chip. The through-hole of the lower layer of the culture chip corresponds to the organoid culture chamber of the upper layer of the chip.

[0020] The organoid non-invasive removal chip is mainly used for removing cultured organoids. The upper layer of the chip is attached to the lower layer of the non-invasive removal chip to form a complete organoid non-invasive removal chip. The inlet hole of the lower layer of the non-invasive removal chip corresponds to the inlet port of the upper layer of the chip, the recessed channel of the lower layer of the non-invasive removal chip corresponds to the organoid culture chamber of the upper layer of the chip, and the outlet hole of the lower layer of the non-invasive removal chip corresponds to the outlet port of the upper layer of the chip.

[0021] As a preferred technical solution, both the inlet and outlet ports penetrate the upper and lower surfaces of the chip, while the organoid culture chamber penetrates the lower surface of the chip rather than the upper surface.

[0022] Furthermore, the pressure chamber base includes a pressure chamber and a pressure chamber inlet air cylinder. The pressure chamber is disposed in the inner cavity of the pressure chamber base, and the organ-on-a-chip is placed above the pressure chamber. The pressure chamber inlet air cylinder is disposed on the outer wall of one end of the pressure chamber base, and the outer end of the pressure chamber inlet air cylinder is provided with a pressure chamber inlet end, which is connected to the pressure chamber.

[0023] Furthermore, the pressure chamber base also includes a venting cylinder, which is disposed on the outer wall of the other end of the pressure chamber base. The venting cylinder has an axially formed pressure chamber channel and a laterally formed venting valve insertion hole. The pressure chamber channel is connected to the pressure chamber.

[0024] The biomechanical reaction device also includes a vent valve switch, which is inserted into a vent valve socket. The vent valve switch has a vent valve channel on its inner side and a switch handle on its outer end.

[0025] A sensor insertion hole is provided on one side of the outer wall of the pressure chamber base;

[0026] The biomechanical reaction device also includes a pressure sensor, which is inserted into a sensor socket, and the pressure value in the pressure chamber is read by the pressure sensor.

[0027] As a preferred technical solution, the sensor socket is provided with a pressure chamber thread, and the air pressure sensor is provided with a sensor thread. The air pressure sensor is connected to the pressure chamber base through the sensor thread and the pressure chamber thread.

[0028] Furthermore, the one-way valve includes a one-way valve positive interface air cylinder, a one-way valve side interface air cylinder, and a one-way valve inlet air cylinder. The one-way valve positive interface air cylinder and the one-way valve side interface air cylinder are arranged orthogonally and connected to each other through the one-way valve inlet air cylinder. The outer end of the one-way valve positive interface air cylinder is provided with a one-way valve positive interface end, the outer end of the one-way valve side interface air cylinder is provided with a one-way valve side interface end, and the outer end of the one-way valve inlet air cylinder is provided with a one-way valve inlet end. Both the one-way valve positive interface end and the one-way valve side interface end are connected to the one-way valve inlet end. The one-way valve positive interface air cylinder is inserted into the pressure chamber inlet air cylinder.

[0029] The positive port air cylinder of the one-way valve is equipped with a small ball and a spring. The small ball is in contact with the inner end of the positive port air cylinder of the one-way valve and is connected to the positive port end of the one-way valve through the spring. The side port air cylinder of the one-way valve is also equipped with a small ball and a spring. The small ball is in contact with the side port end of the one-way valve and is connected to the inner end of the side port air cylinder of the one-way valve through the spring.

[0030] Furthermore, one end of the stroke air cylinder is provided with a stroke air cylinder interface end, and the other end is provided with a stroke air cylinder inlet end. The stroke air cylinder interface end and the stroke air cylinder inlet end are connected. The stroke air cylinder is inserted into a one-way valve inlet air cylinder or a pressure chamber inlet air cylinder.

[0031] As a preferred technical solution, the form of the biomechanical reaction device for simulating a person standing for a long time differs from that for simulating a person walking or running in that a one-way valve is installed between the pressure chamber base and the stroke air cylinder.

[0032] When a person stands for a long time, the positive port of the one-way valve is inserted into the pressure chamber port of the pressure chamber base, the port of the stroke cylinder is inserted into the one-way valve port of the one-way valve, and the connecting rod piston of the stroke reciprocating structure is inserted into the stroke cylinder port of the stroke cylinder.

[0033] When simulating a person walking or running, the stroke air cylinder interface end of the stroke air cylinder is inserted into the pressure chamber inlet end of the pressure chamber base, and the connecting rod piston of the stroke reciprocating structure is inserted into the stroke air cylinder inlet end of the stroke air cylinder.

[0034] Furthermore, a chip insertion port is provided on one outer wall of the pressure chamber base, and a chip push port is provided on the other outer wall. Baffle slots are provided on the upper and lower sides of the chip insertion port. The organ chip is inserted into the chip insertion port, the baffle is inserted into the baffle slot to hold and fix the position of the organ chip, and the organ chip is pushed out from the chip push port.

[0035] Furthermore, the reciprocating structure also includes a pin and a support seat. The connecting rod end of the connecting rod piston is connected to one end of the crankshaft connecting rod through the pin, and the other end of the crankshaft connecting rod is connected to the crankshaft. The crankshaft is mounted on the support seat.

[0036] The crankshaft has a crankshaft flat section;

[0037] The motor includes a rotating shaft, and a rotating shaft flat section is provided on the rotating shaft;

[0038] The biomechanical reaction device also includes a coupling. The reciprocating structure is connected to the motor through the coupling. The coupling has a crankshaft mating end and a rotating shaft mating end. The coupling is connected to the crankshaft through the crankshaft mating end and the crankshaft flat fit, and is connected to the rotating shaft through the rotating shaft mating end and the rotating shaft flat fit.

[0039] One of the technical solutions of the present invention is to provide a method for simulating the force on human gait organs. This method uses the aforementioned platform to simulate the force on human gait organs, and includes the following steps:

[0040] S1. Inject organoids into an organ-on-a-chip and insert the organ-on-a-chip into the pressure chamber base.

[0041] S1.1, Turn the top layer of the chip upside down;

[0042] S1.2, The organoid culture chamber on the upper layer of the chip is used to inject organoids into the organoid culture chamber.

[0043] S1.3. Cover the chip middle layer onto the chip upper layer;

[0044] S1.4. Cover the middle layer of the culture chip with the lower layer of the culture chip to form an organoid culture chip;

[0045] S1.5. Flip the organoid culture chip so that the front side is facing up;

[0046] S1.6 Insert the organoid culture chip into the chip socket of the pressure chamber base;

[0047] S2, a pressurized biomechanical reaction device.

[0048] The drive motor rotates, and the power is first transmitted to the crankshaft through the coupling, and then transmitted to the connecting rod piston through the crankshaft connecting rod, so as to convert the rotational motion of the motor into the linear reciprocating motion of the connecting rod piston.

[0049] S3. Simulation of stress on human gait organs

[0050] S3-1. Different states inside the organ-on-a-chip during organoid culture.

[0051] During organoid culture, organoids will be in two states: no pressure and pressure.

[0052] The culture medium flows in from the inlet port on the upper layer of the organoid culture chip and flows out from the outlet port on the upper layer of the organoid culture chip.

[0053] Under pressureless conditions, organoids are not subjected to external pressure within the organoid culture chamber;

[0054] Under pressure, the middle layer of the chip is pushed upward by the air pressure, causing the organoid to be squeezed by the outside in the organoid culture chamber, thereby achieving the effect of imitating the force of the organ.

[0055] S3-2, Simulates human walking or running.

[0056] When the connecting rod piston is in the retracting motion state, the air in the pressure chamber of the pressure chamber base flows into the stroke air cylinder;

[0057] When the connecting rod piston is in the forward motion state, the air in the stroke air cylinder flows into the pressure chamber of the pressure chamber base;

[0058] Under the pressure drive of the biomechanical reaction device, the pressure inside the pressure chamber of the pressure chamber base is regularly changed. The morphology inside the organoid culture chip will change regularly between the pressureless state and the pressure state, so as to achieve regular compression of the organoid, thereby simulating the force state of the organ when a person walks or runs.

[0059] Without a check valve, the pressure chamber of the pressure chamber base is directly connected to the stroke air cylinder, and the interior is interconnected. With the total amount of air in the pressure chamber and the stroke air cylinder remaining constant, the mechanical reciprocating motion of the connecting rod piston changes the air content in the pressure chamber, thereby regularly changing the pressure in the pressure chamber. This causes the organoid to be subjected to regular force compression, which simulates the force compression state of organs when the human body is walking or running.

[0060] S3-3, Simulating a person standing for a long time.

[0061] When the connecting rod piston is in the retracting state, the small ball at the positive port of the one-way valve, under the combined action of pressure and spring, blocks the other port opposite to the positive port of the one-way valve. The small ball at the side port of the one-way valve, under the action of pressure, squeezes the spring and moves away from the side port of the one-way valve, and outside air flows into the stroke air cylinder.

[0062] When the connecting rod piston is in the forward motion state, the small ball at the one-way valve side interface end of the one-way valve is blocked by the combined action of pressure and spring. The small ball at the one-way valve positive interface end of the one-way valve is squeezed by the spring under the action of pressure and moves away from the other port opposite to the one-way valve positive interface end. The air in the stroke air cylinder flows into the pressure chamber of the pressure chamber base.

[0063] Under the pressure drive of the biomechanical reaction device, air is continuously injected into the pressure chamber of the pressure chamber base. When the morphology inside the organoid culture chip reaches the pressurized state, the biomechanical reaction device stops driving. Since the pressure chamber is a closed space, it will keep the organoid in a state of compression, thereby simulating the stress state of the organ when a person stands for a long time.

[0064] When a one-way valve is installed, atmospheric air is continuously injected into the pressure chamber of the pressure chamber base so that the pressure inside the pressure chamber reaches the required level and the atmospheric air inside the pressure chamber does not leak out. This keeps the organoid under pressure and compression, which simulates the pressure and compression state of organs when the human body stands for a long time.

[0065] S4. The organ-on-a-chip is removed from the pressure chamber base and the organoid is extracted without damage.

[0066] S4.1. Push the organoid culture chip out from the chip push port on the pressure chamber base;

[0067] S4.2 Flip the organoid culture chip so that the reverse side is facing up;

[0068] S4.3 Remove the lower and middle layers of the culture chip;

[0069] S4.4. Cover the upper layer of the non-destructive removal chip with the lower layer of the chip, and the organoid non-destructive removal chip is formed at this time.

[0070] S4.5. Remove the organoid without damage and flip the chip so that the front side is facing up;

[0071] At this point, the organoids in the organoid culture chamber will move to the area enclosed by the partition between the organoid culture chamber and the culture medium channel and the lower layer of the chip that is removed without damage, and will flow out from the outlet port of the upper layer of the chip along with the culture medium.

[0072] As a preferred technical solution, in step S2, the stroke L2 of the connecting rod piston can be changed by changing the crankshaft radius L1. The relationship between the stroke L2 and the crankshaft radius L1 is L2=2L1.

[0073] As a preferred technical solution, in step S3-1, the partition between the organoid culture chamber and the culture medium channel on the upper layer of the chip and the middle layer of the chip have a certain gap to allow the culture medium to flow.

[0074] As a preferred technical solution, in step S3-1, different degrees of compression are achieved by changing the height of the separator and the gap height on the upper layer of the chip, that is, different stress effects are achieved.

[0075] As a preferred technical solution, in step S3-2, by changing the speed of the motor, the frequency of the regular changes can be changed, thereby simulating different states of walking or running.

[0076] As a preferred technical solution, in step S3-3, by changing the number of rotations of the motor, i.e., the amount of air injected, the pressure inside the pressure chamber of the pressure chamber base is made different, thereby simulating the different pressures of a person standing for a long time.

[0077] As a preferred technical solution, the organ-on-a-chip depressurization step S3 is performed.

[0078] When the pressure is too high or pressure needs to be released, the air in the pressure chamber of the pressure chamber base is discharged through the air release valve to achieve the pressure release effect.

[0079] When the pressure relief is closed, the vent valve passage of the vent valve switch and the pressure chamber passage of the pressure chamber base are orthogonal, and the venting path is closed at this time;

[0080] When the pressure relief is activated, the pressure relief valve is rotated by turning the switch handle of the pressure relief valve.

[0081] The venting path is connected until the venting valve passage of the venting valve switch and the pressure chamber passage of the pressure chamber base are connected.

[0082] Compared with the prior art, the present invention has the following beneficial effects:

[0083] (1) The chip body of the present invention is designed as a high-throughput organoid culture structure, which can accommodate hundreds of three-dimensional organoid culture chambers in parallel; the chip is connected to a bionic gait pressure induction system, which can set the pressure magnitude and loading frequency to achieve stable, repeatable and quantifiable mechanical stimulation, and can realistically reproduce human gait pressure. It is suitable for constructing physiological organoids (promoting maturation) and pathological organoids (simulating damage), and has the versatility for multiple organoid models;

[0084] (2) The chip of the present invention is divided into a culture chip and a non-destructive extraction chip. The reason is that if the lower and middle layers of the culture chip are removed and the organoids are directly extracted from the upper layer of the chip, this process increases the risk of organoid infection and damage. However, by removing the lower and middle layers of the culture chip and then covering it with the lower layer of the non-destructive extraction chip to form a non-destructive extraction chip, the organoids can flow out with the culture medium. This operation greatly reduces the risk of infection and damage when the organoids are extracted.

[0085] (3) This invention cleverly utilizes the fluid unidirectional conduction and cut-off characteristics of a detachable one-way valve between the pressure chamber base and the stroke air cylinder to realize the simulation switching of the force environment of the human body with different gait based on a single driving source. When the one-way valve is not installed, the system is constructed as a closed cavity, and the air pressure oscillates periodically with the mechanical reciprocating motion of the connecting rod piston, which can accurately reproduce the dynamic cyclic load when the human body walks or runs. After the one-way valve is installed, the system immediately changes to a one-way air pump mode, which converts the mechanical reciprocating motion of the connecting rod piston into the unidirectional accumulation of gas, thereby quickly establishing and maintaining a constant high pressure state in the pressure chamber, effectively simulating the static continuous load when the human body stands for a long time. This design, which only switches simple structural modules, not only successfully reproduces the two key force states of "dynamic compression" and "static pressure" of the articular cartilage interface on the same platform, but also greatly reduces the equipment cost and system complexity, and significantly expands the application scenarios of organoid models in the study of mechanical pathological mechanisms such as overweight, sports injury and osteoarthritis.

[0086] (4) When simulating walking or running, the compression of the organoid is similar to the form of vibration. Through the linear reciprocating motion of the connecting rod piston, the pressure generated in the pressure chamber can make the compression of the organoid tend to the form of real human vibration. In addition, compared with the direct linear reciprocating motion of the cylinder, the use of the motor as the drive source makes it easier to control the compression effect on the organoid and more stable. Attached Figure Description

[0087] Figure 1This is a schematic diagram of the organoid biomechanical reaction platform in an embodiment of the present invention;

[0088] Figure 2 This is a schematic diagram of the exploded structure of the organoid culture chip in an embodiment of the present invention;

[0089] Figure 3 This is a schematic diagram of the exploded structure of the organoid chip for non-destructive removal in an embodiment of the present invention;

[0090] Figure 4 This is a schematic diagram of the upper layer of the chip in an embodiment of the present invention;

[0091] Figure 5 This is a schematic diagram of the structure of the lower layer of the culture chip in an embodiment of the present invention;

[0092] Figure 6 This is a schematic diagram of the structure for non-destructive removal of the lower layer of the chip in an embodiment of the present invention;

[0093] Figure 7 This is a perspective view of the organoid culture chip in an embodiment of the present invention;

[0094] Figure 8 This is a perspective view of the chip for non-invasive organoid removal in an embodiment of the present invention;

[0095] Figure 9 A schematic diagram of the mechanical-biological reaction device for simulating the stress state of organoids when a person stands for a long time in an embodiment of the present invention;

[0096] Figure 10 This is a schematic diagram of the mechanical-biological reaction device for simulating the force state of organoids when a person walks or runs, as described in an embodiment of the present invention.

[0097] Figure 11 A schematic diagram of the pressure chamber base in an embodiment of the present invention;

[0098] Figure 12 This is a schematic diagram of the structure of the vent valve switch in an embodiment of the present invention;

[0099] Figure 13 This is a schematic diagram of the structure of the digital display of the air pressure sensor in an embodiment of the present invention;

[0100] Figure 14 This is a schematic diagram of the one-way valve in an embodiment of the present invention;

[0101] Figure 15 This is a schematic diagram of the structure of the stroke air cylinder in an embodiment of the present invention;

[0102] Figure 16 This is a schematic diagram of the reciprocating structure in an embodiment of the present invention;

[0103] Figure 17 This is a schematic diagram of the coupling structure in an embodiment of the present invention;

[0104] Figure 18 This is a schematic diagram of the motor structure in an embodiment of the present invention;

[0105] Figure 19 This is a schematic diagram of the first process of injecting organoids into organ-on-a-chip and inserting the organ-on-a-chip into the pressure chamber base in an embodiment of the present invention;

[0106] Figure 20 This is a schematic diagram of the second process in an embodiment of the present invention: injecting organoids into organ-on-a-chip and inserting the organ-on-a-chip into the pressure chamber base;

[0107] Figure 21 This is a schematic diagram of the third process in an embodiment of the present invention: injecting organoids into organ-on-a-chip and inserting the organ-on-a-chip into the pressure chamber base;

[0108] Figure 22 This is a schematic diagram of the fourth process in an embodiment of the present invention: injecting organoids into organ-on-a-chip and inserting the organ-on-a-chip into the pressure chamber base;

[0109] Figure 23 This is a schematic diagram of the fifth process in an embodiment of the present invention: injecting organoids into organ-on-a-chip and inserting the organ-on-a-chip into the pressure chamber base;

[0110] Figure 24 This is a schematic diagram of the sixth process in an embodiment of the present invention, which involves injecting organoids into organ-on-a-chip and inserting the organ-on-a-chip into the pressure chamber base.

[0111] Figure 25 This is a schematic diagram of the pressurized drive state of the biomechanical reaction device in an embodiment of the present invention;

[0112] Figure 26 This is a schematic diagram of the cross-sectional structure of the organoid culture chip under pressureless state in an embodiment of the present invention;

[0113] Figure 27 This is a schematic diagram of the cross-sectional structure of the organoid culture chip under pressure in an embodiment of the present invention;

[0114] Figure 28 This is a schematic diagram showing the state of the ball and spring inside the one-way valve when the connecting rod piston is in a retracting motion state in an embodiment of the present invention;

[0115] Figure 29 This is a schematic diagram showing the state of the ball and spring inside the one-way valve when the connecting rod piston is in the forward motion state in an embodiment of the present invention;

[0116] Figure 30 This is a schematic diagram showing the interaction between the vent valve switch and the pressure chamber base when the pressure relief is closed in an embodiment of the present invention;

[0117] Figure 31 This is a schematic diagram showing the interaction between the vent valve switch and the pressure chamber base before the pressure is released in an embodiment of the present invention.

[0118] Figure 32 This is a schematic diagram showing the interaction between the vent valve switch and the pressure chamber base when the pressure is released in an embodiment of the present invention.

[0119] Figure 33 This is a schematic diagram of the first process of removing the organ-on-a-chip from the pressure chamber base and removing the organoid without damage in an embodiment of the present invention;

[0120] Figure 34 This is a schematic diagram of the second process of removing the organ-on-a-chip from the pressure chamber base and removing the organoid without damage in an embodiment of the present invention;

[0121] Figure 35 This is a schematic diagram of the third process in an embodiment of the present invention, showing the removal of the organ-on-a-chip from the pressure chamber base and the non-destructive removal of the organoid.

[0122] Figure 36 This is a schematic diagram of the fourth process in an embodiment of the present invention, in which the organ-on-a-chip is removed from the pressure chamber base and the organoid is removed without damage.

[0123] Figure 37 This is a schematic diagram of the fifth process in an embodiment of the present invention, showing the removal of the organ-on-a-chip from the pressure chamber base and the non-destructive removal of the organoid.

[0124] Figure 38 This is a schematic cross-sectional view of the chip for non-destructive removal of organoids in an embodiment of the present invention.

[0125] Explanation of markings in the diagram:

[0126] 1—Organ-on-a-chip; 2—Mechano-biological reaction device;

[0127] 1a—Organoid culture chip; 1b—Organoid non-destructive removal chip;

[0128] 11—Top layer of chip, 12—Middle layer of chip, 13—Cultivation layer of chip, 14—Removal of chip layer without damage;

[0129] 111—Inlet port, 112—Organoid culture chamber, 113—Outlet port

[0130] 131—through hole, 141—entry recess, 142—recessed passage, 143—exit recess;

[0131] 22—Pressure chamber base; 23—Relief valve switch; 24—Digital display of air pressure sensor; 25—Check valve; 26—Stroke air cylinder; 27—Stroke reciprocating structure; 28—Coupling; 29—Motor;

[0132] 221—Pressure chamber socket end; 222—Pressure chamber; 223—Chip socket; 224—Baffle slot; 225—Chip push-out; 226—Pressure chamber thread; 227—Relief valve socket; 228—Pressure chamber channel.

[0133] 231—Switch handle, 232—Relief valve passage, 241—Sensor thread.

[0134] 251—Positive interface end of check valve, 252—Side interface end of check valve, 253—Socket end of check valve.

[0135] 261—Stroke air pump interface end, 262—Stroke air pump inlet end,

[0136] 271—Connecting rod piston, 272—Pin, 273—Crankshaft connecting rod, 274—Crankshaft, 275—Support seat, 2741—Crankshaft flat position, 281—Crankshaft mating end, 282—Rotor mating end, 291—Rotor, 2911—Rotor flat position. Detailed Implementation

[0137] The present invention will now be described in detail with reference to specific embodiments. These embodiments are based on the technical solution of the present invention and provide detailed implementation methods and specific operating procedures. However, the scope of protection of the present invention is not limited to the following embodiments.

[0138] In the description of this invention, it should be noted that the terms "center," "upper," "lower," "left," "right," "vertical," "horizontal," "inner," and "outer," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are used only for the convenience of describing this invention and for simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this invention. Furthermore, the terms "first," "second," "third," etc., used to describe a common object only indicate different instances of the same object, and do not imply that the objects described in this way must be in a given order, whether temporally, spatially, sequentially, or in any other way.

[0139] In the description of this invention, it should be noted that, unless otherwise explicitly specified and limited, the terms "installation," "connection," and "linking" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection of two components. Those skilled in the art can understand the specific meaning of the above terms in this invention based on the specific circumstances.

[0140] Example 1:

[0141] An organoid biomechanical response platform, such as Figure 1 As shown, it includes an organ-on-a-chip 1 and a biomechanical reaction device 2;

[0142] like Figure 2 and Figure 3 As shown, the organ-on-a-chip 1 has two forms: organoid culture chip 1a and organoid non-destructive removal chip 1b. The organoid culture chip 1a includes three layers stacked in sequence: upper chip layer 11, middle chip layer 12, and lower culture chip layer 13. The organoid non-destructive removal chip 1b includes two layers stacked in sequence: upper chip layer 11 and non-destructive removal chip layer 14.

[0143] like Figure 4 As shown, the upper layer 11 of the chip has an inlet port 111, an organoid culture chamber 112, and an outlet port 113. Both the inlet port 111 and the outlet port 113 penetrate the upper and lower surfaces of the upper layer 11. The organoid culture chamber 112 penetrates the lower surface of the upper layer 11, but not the upper surface. The inlet port 111 and the outlet port 113 are respectively located at both ends of the organoid culture chamber 112. One end of the organoid culture chamber 112 is connected to the inlet port 111, and the other end is connected to the outlet port 113.

[0144] The organoid culture chamber 112 includes interconnected organoid culture chambers and culture medium channels. Culture medium channels are provided on both sides of several organoid culture chambers, with one side of the culture medium channel connected to the inlet port 111 and the other side of the culture medium channel connected to the outlet port 113.

[0145] The middle layer 12 of the chip adopts a flat structure without any holes or slots;

[0146] like Figure 5 As shown, a through-hole 131 is provided on the lower layer 13 of the culture chip, and the through-hole 131 penetrates the upper and lower surfaces of the lower layer 13 of the culture chip.

[0147] like Figure 6 As shown, the chip removal lower layer 14 has an inlet recess 141, a recess 142, and an outlet recess 143. The inlet recess 141, recess 142, and outlet recess 143 all penetrate the upper surface of the chip removal lower layer 14, but not the lower surface. The inlet recess 141 and outlet recess 143 are respectively located at both ends of the recess 142. One end of the recess 142 is connected to the inlet recess 141, and the other end of the recess 142 is connected to the outlet recess 143.

[0148] like Figure 7As shown, the organoid culture chip 1a is mainly used for the culture of organoids. The middle layer 12 of the chip is attached to both the upper layer 11 and the lower layer 13 of the culture chip to form a complete organoid culture chip 1a. The through-hole 131 of the lower layer 13 of the culture chip corresponds to the organoid culture chamber 112 of the upper layer 11 of the chip.

[0149] like Figure 8 As shown, the organoid non-invasive removal chip 1b is mainly used for removing cultured organoids. The upper layer 11 of the chip is attached to the lower layer 14 of the non-invasive removal chip to form a complete organoid non-invasive removal chip 1b. The inlet recess 141 of the lower layer 14 of the non-invasive removal chip corresponds to the inlet port 111 of the upper layer 11 of the chip. The notch channel 142 of the lower layer 14 of the non-invasive removal chip corresponds to the organoid culture chamber 112 of the upper layer 11 of the chip. The outlet recess 143 of the lower layer 14 of the non-invasive removal chip corresponds to the outlet port 113 of the upper layer 11 of the chip.

[0150] like Figure 9 and Figure 10 As shown, the biomechanical reaction device 2 has two forms: one is to simulate the force state of organoids when a person stands for a long time, and the other is to simulate the force state of organoids when a person walks or runs. When simulating the force state of organoids when a person stands for a long time, the biomechanical reaction device 2 includes a pressure chamber base 22, a one-way valve 25, a stroke air cylinder 26, a stroke reciprocating structure 27 and a motor 29 that are connected to each other. When simulating the force state of organoids when a person walks or runs, the biomechanical reaction device 2 includes a pressure chamber base 22, a stroke air cylinder 26, a stroke reciprocating structure 27 and a motor 29 that are connected to each other. The organ-on-a-chip 1 is placed in the pressure chamber base 22.

[0151] like Figure 11 As shown, the pressure chamber base 22 includes a pressure chamber 222 and a pressure chamber inlet air cylinder. The pressure chamber 222 is disposed in the inner cavity of the pressure chamber base 22. The organ-on-a-chip 1 is placed above the pressure chamber 222. The pressure chamber inlet air cylinder is disposed on the outer wall of one end of the pressure chamber base 22. The outer end of the pressure chamber inlet air cylinder is provided with a pressure chamber inlet end 221, which is connected to the pressure chamber 222.

[0152] A chip insertion port 223 is provided on one outer wall of the pressure chamber base 22, and a chip push port 225 is provided on the other outer wall. Baffle slots 224 are provided on the upper and lower sides of the chip insertion port 223. The organ chip 1 is inserted into the chip insertion port 223, the baffle is inserted into the baffle slot 224 to hold and fix the position of the organ chip 1, and the organ chip 1 is pushed out from the chip push port 225.

[0153] The pressure chamber base 22 also includes a venting cylinder, which is located on the outer wall of the other end of the pressure chamber base 22. The venting cylinder has an axially formed pressure chamber channel 228 and a laterally formed venting valve insertion hole 227. The pressure chamber channel 228 is connected to the pressure chamber 222.

[0154] like Figure 12 As shown, the biomechanical reaction device 2 also includes a vent valve switch 23, which is inserted into a vent valve socket 227. A vent valve channel 232 is provided on the inner side of the vent valve switch 23, and a switch handle 231 is provided on the outer end.

[0155] A sensor insertion hole is provided on one outer wall of the pressure chamber base 22, and a pressure chamber thread 226 is provided in the sensor insertion hole;

[0156] like Figure 13 As shown, the biomechanical reaction device 2 also includes a pressure sensor. The pressure sensor is inserted into a sensor socket. The pressure sensor is a digital display 24. The digital display 24 has a sensor thread 241 on its outside. The digital display 24 is connected to the pressure chamber base 22 through the sensor thread 241 and the pressure chamber thread 226. The pressure value in the pressure chamber 222 is read through the digital display 24.

[0157] like Figure 14 As shown, the one-way valve 25 includes a one-way valve positive interface air cylinder, a one-way valve side interface air cylinder, and a one-way valve inlet air cylinder. The one-way valve positive interface air cylinder and the one-way valve side interface air cylinder are arranged orthogonally and connected to each other through the one-way valve inlet air cylinder. The outer end of the one-way valve positive interface air cylinder is provided with a one-way valve positive interface end 251, the outer end of the one-way valve side interface air cylinder is provided with a one-way valve side interface end 252, and the outer end of the one-way valve inlet air cylinder is provided with a one-way valve inlet end 253. The one-way valve positive interface end 251 and the one-way valve side interface end 252 are both connected to the one-way valve inlet end 253. The one-way valve positive interface air cylinder is inserted into the pressure chamber inlet air cylinder.

[0158] A small ball and a spring are installed inside the positive port air cylinder of the one-way valve. The small ball contacts the inner end of the positive port air cylinder of the one-way valve and is connected to the positive port end 251 of the one-way valve through the spring. A small ball and a spring are installed inside the side port air cylinder of the one-way valve. The small ball contacts the side port end 252 of the one-way valve and is connected to the inner end of the side port air cylinder of the one-way valve through the spring.

[0159] like Figure 15 As shown, one end of the stroke air cylinder 26 is provided with a stroke air cylinder interface end 261, and the other end is provided with a stroke air cylinder inlet end 262. The stroke air cylinder interface end 261 and the stroke air cylinder inlet end 262 are connected. The stroke air cylinder 26 is inserted into the one-way valve inlet air cylinder or the pressure chamber inlet air cylinder.

[0160] like Figure 16As shown, the reciprocating structure 27 includes a connecting rod piston 271, a crankshaft connecting rod 273 and a crankshaft 274. The connecting rod part of the connecting rod piston 271 is connected to the crankshaft 274 through the crankshaft connecting rod 273. The crankshaft 274 is connected to the motor 29. The piston part of the connecting rod piston 271 extends into the stroke cylinder 26.

[0161] The form of the biomechanical reaction device when the simulated human stands for a long time is different from that when the simulated human walks or runs, in that a one-way valve 25 is added between the pressure chamber base 22 and the stroke air cylinder 26.

[0162] When the simulated person stands for a long time, the positive port 251 of the one-way valve 25 is inserted into the pressure chamber port 221 of the pressure chamber base 22, the port 261 of the stroke air cylinder 26 is inserted into the one-way valve port 253 of the one-way valve 25, and the connecting rod piston 271 of the stroke reciprocating structure 27 is inserted into the stroke air cylinder port 262 of the stroke air cylinder 26.

[0163] When simulating a person walking or running, the stroke cylinder interface end 261 of the stroke cylinder 26 is inserted from the pressure chamber insertion end 221 of the pressure chamber base 22, and the connecting rod piston 271 of the stroke reciprocating structure 27 is inserted from the stroke cylinder insertion end 262 of the stroke cylinder 26.

[0164] The reciprocating structure 27 also includes a pin 272 and a support seat 275. The end of the connecting rod of the connecting rod piston 271 is connected to one end of the crankshaft connecting rod 273 through the pin 272. The other end of the crankshaft connecting rod 273 is connected to the crankshaft 274. The crankshaft 274 is mounted on the support seat 275.

[0165] A crankshaft flat section 2741 is provided on the crankshaft 274;

[0166] like Figure 17 As shown, the biomechanical reaction device 2 also includes a coupling 28. The reciprocating structure 27 is connected to the motor 29 through the coupling 28. The coupling 28 has a crankshaft mating end 281 and a rotating shaft mating end 282. The coupling 28 is connected to the crankshaft 274 through the crankshaft mating end 281 and the crankshaft flat part 2741, and is connected to the rotating shaft 291 through the rotating shaft mating end 282 and the rotating shaft flat part 2911.

[0167] like Figure 18 As shown, the motor 29 includes a rotating shaft 291, and a rotating shaft flat section 2911 is provided on the rotating shaft 291.

[0168] Example 2:

[0169] A method for simulating the forces acting on human gait organs, using the platform described in Example 1, involves simulating the forces acting on human gait organs. The specific steps are as follows:

[0170] S1. Inject the organoid into organ-on-a-chip 1 and insert organ-on-a-chip 1 into the pressure chamber base 22.

[0171] S1.1, such as Figure 19 As shown, the upper layer 11 of the chip is reversed and facing upwards;

[0172] S1.2, such as Figure 20 As shown, organoids are injected into the organoid culture chamber 112 of the upper layer 11 of the chip.

[0173] S1.3, such as Figure 21 As shown, the middle layer 12 of the chip is covered on the upper layer 11 of the chip;

[0174] S1.4, such as Figure 22 As shown, the lower layer 13 of the culture chip is covered on the middle layer 12 of the chip, thus forming the organoid culture chip 1a;

[0175] S1.5, such as Figure 23 As shown, the organoid culture chip 1a is flipped so that the front side faces up;

[0176] S1.6, such as Figure 24 As shown, the organoid culture chip 1a is inserted into the chip socket 223 of the pressure chamber base 22;

[0177] S2, the mechanical-biological reaction device 2 is pressurized and driven.

[0178] like Figure 25 As shown, the drive motor 29 rotates, first transmitting power to the crankshaft 274 through the coupling 28, and then transmitting power to the connecting rod piston 271 through the crankshaft connecting rod 273, thereby converting the rotational motion of the motor 29 into the linear reciprocating motion of the connecting rod piston 271.

[0179] By changing the crankshaft radius L1 of the crankshaft 274, the stroke L2 of the connecting rod piston 271 can be changed. The relationship between the stroke L2 and the crankshaft radius L1 is L2 = 2L1.

[0180] S3. Simulation of stress on human gait organs

[0181] S3-1. Different internal states of organ-on-a-chip 1 during organoid culture.

[0182] During organoid culture, organoids will be in two states: no pressure and pressure.

[0183] The culture medium flows in from the inlet port 111 of the upper layer 11 of the organoid culture chip 1a and flows out from the outlet port 113 of the upper layer 11 of the organoid culture chip 1a.

[0184] like Figure 26 and Figure 27As shown, in the upper layer 11 of the chip, R is the culture medium inflow channel, S is the organoid culture chamber, and C is the culture medium outflow channel. The partition between the organoid culture chamber and the culture medium flow channel and the middle layer 12 of the chip have a certain gap to allow the culture medium to flow.

[0185] Under pressureless conditions, organoids are not subjected to external pressure within the organoid culture chamber S;

[0186] Under pressure, the middle layer 12 of the chip is pushed upward by the air pressure, so that the organoid is subjected to external compression in the organoid culture chamber S, thereby achieving the effect of imitating the force of the organ.

[0187] By changing the partition height h1 and gap height h2 of the upper layer 11 of the chip, different degrees of compression can be achieved, that is, different stress effects can be achieved.

[0188] S3-2, Simulates human walking or running.

[0189] When the connecting rod piston 271 is in the retracting motion state, the air in the pressure chamber 222 of the pressure chamber base 22 flows into the stroke air cylinder 26;

[0190] When the connecting rod piston 271 is in the forward motion state, the air in the stroke air cylinder 26 flows into the pressure chamber 222 of the pressure chamber base 22;

[0191] Under the pressure drive of the biomechanical reaction device 2, the pressure in the pressure chamber 222 of the pressure chamber base 22 is regularly changed, and the morphology inside the organoid culture chip 1a will change regularly between the pressureless state and the pressured state, so as to achieve regular compression of the organoid, thereby simulating the force state of the organ when a person walks or runs.

[0192] Without the one-way valve 25, the pressure chamber 222 of the pressure chamber base 22 is directly connected to the stroke air cylinder 26 and is internally connected. Under the condition that the total amount of air in the pressure chamber 222 and the stroke air cylinder 26 remains unchanged, the mechanical reciprocating motion of the connecting rod piston 271 changes the amount of air in the pressure chamber 222, thereby regularly changing the pressure in the pressure chamber 222, so that the organoid is subjected to regular force compression, which plays the role of simulating the force compression state of the organ when the human body walks or runs.

[0193] By changing the rotational speed of motor 29, the frequency of regular changes can be altered, thereby simulating different states of human walking or running.

[0194] S3-3, Simulating a person standing for a long time.

[0195] like Figure 28As shown, when the connecting rod piston 271 is in the retracting motion state, the ball at the positive port 251 of the one-way valve 25, under the combined action of pressure and spring, blocks the other port opposite to the positive port 251 of the one-way valve. The ball at the side port 252 of the one-way valve 25, under the action of pressure, squeezes the spring and moves away from the side port 252 of the one-way valve, and outside air flows into the stroke air cylinder 26.

[0196] like Figure 29 As shown, when the connecting rod piston 271 is in the forward motion state, the ball at the one-way valve side interface 252 of the one-way valve 25 blocks the one-way valve side interface 252 under the combined action of pressure and spring. The ball at the one-way valve positive interface 251 of the one-way valve 25 squeezes the spring under the action of pressure and moves away from the other port opposite to the one-way valve positive interface 251. The air in the stroke air cylinder 26 flows into the pressure chamber 222 of the pressure chamber base 22.

[0197] Under the pressure drive of the biomechanical reaction device 2, air is continuously injected into the pressure chamber 222 of the pressure chamber base 22. When the morphology inside the organoid culture chip 1a reaches the pressurized state, the biomechanical reaction device 2 stops driving. Since the pressure chamber 222 is a closed space, it will keep the organoid in a squeezed state, thereby simulating the stress state of the organ when a person stands for a long time.

[0198] When the one-way valve 25 is installed, atmospheric air is continuously injected into the pressure chamber 222 of the pressure chamber base 22, so that the pressure in the pressure chamber 222 reaches the required level and the atmospheric air in the pressure chamber 222 will not leak out, thus keeping the organoid under pressure and compression, which plays the role of simulating the pressure and compression state of the organ when the human body stands for a long time.

[0199] By changing the number of rotations of the motor 29, i.e. the amount of air injected, the pressure in the pressure chamber 222 of the pressure chamber base 22 is made different, thereby simulating the different pressures of a person standing for a long time.

[0200] S3-4, Organ-on-a-chip 1 pressure relief.

[0201] When the pressure is too high or pressure needs to be released, the air in the pressure chamber 222 of the pressure chamber base 22 is released through the air release valve switch 23 to achieve the pressure release effect.

[0202] like Figure 30 As shown, when the pressure relief is closed, the vent valve passage 232 of the vent valve switch 23 and the pressure chamber passage 228 of the pressure chamber base 22 are orthogonal, and the venting path is closed at this time.

[0203] like Figure 31 As shown, when the pressure relief is activated, the pressure relief valve switch 23 is rotated by turning the switch handle 231 of the pressure relief valve switch 23.

[0204] like Figure 32 As shown, the venting path is connected until the venting valve passage 232 of the venting valve switch 23 and the pressure chamber passage 228 of the pressure chamber base 22 are connected.

[0205] S4. Organ-on-a-chip 1 is removed from pressure chamber base 22 and the organoid is removed without damage.

[0206] S4.1, such as Figure 33 As shown, the organoid culture chip 1a is pushed out from the chip push port 225 of the pressure chamber base 22;

[0207] S4.2, such as Figure 34 As shown, the organoid culture chip 1a is flipped so that the reverse side faces up;

[0208] S4.3, such as Figure 35 As shown, the lower layer 13 and the middle layer 12 of the culture chip are removed;

[0209] S4.4, such as Figure 36 As shown, the lower layer 14 of the non-destructive removal chip is covered on the upper layer 11 of the chip, thus forming the organoid non-destructive removal chip 1b;

[0210] S4.5, such as Figure 37 As shown, the organoid chip 1b is removed without damage and flipped to face up;

[0211] like Figure 38 As shown, at this time, the organoids in the organoid culture chamber S will move to the G region enclosed by the partition between the organoid culture chamber and the culture medium channel and the lower layer 14 of the non-destructive removal chip, and flow out from the outlet port 113 of the upper layer 11 of the non-destructive removal chip 1b along with the culture medium.

[0212] The above description of the embodiments is provided to enable those skilled in the art to understand and use the invention. It will be apparent to those skilled in the art that various modifications can be made to these embodiments, and the general principles described herein can be applied to other embodiments without inventive effort. Therefore, the present invention is not limited to the above embodiments, and any improvements and modifications made by those skilled in the art based on the disclosure of the present invention without departing from the scope of the invention should be within the protection scope of the present invention.

Claims

1. An organoid biomechanical reaction platform, characterized in that, The platform includes an organ-on-a-chip (1) and a biomechanical reaction device (2). The biomechanical reaction device (2) is divided into two types: one that simulates the force state of an organoid when a person stands for a long time, and the other that simulates the force state of an organoid when a person walks or runs. The biomechanical reaction device (2) that simulates the force state of an organoid when a person stands for a long time includes a pressure chamber base (22), a one-way valve (25), a stroke air cylinder (26), a stroke reciprocating structure (27), and a motor (29) that are connected to each other. The biomechanical reaction device (2) that simulates the force state of an organoid when a person walks or runs includes a pressure chamber base (22), a stroke air cylinder (26), a stroke reciprocating structure (27), and a motor (29) that are connected to each other. The organ-on-a-chip (1) is placed inside the pressure chamber base (22). The reciprocating structure (27) includes a connecting rod piston (271), a crankshaft connecting rod (273), and a crankshaft (274). The connecting rod portion of the connecting rod piston (271) is connected to the crankshaft (274) via the crankshaft connecting rod (273). The crankshaft (274) is connected to the motor (29). The piston portion of the connecting rod piston (271) extends into the stroke cylinder (26). The pressure chamber base (22) includes a pressure chamber (222) and a pressure chamber inlet air cylinder. The pressure chamber (222) is located in the inner cavity of the pressure chamber base (22). The organ chip (1) is placed above the pressure chamber (222). The pressure chamber inlet air cylinder is located on the outer wall of one end of the pressure chamber base (22). The outer end of the pressure chamber inlet air cylinder is provided with a pressure chamber inlet end (221), which is connected to the pressure chamber (222). The one-way valve (25) includes a one-way valve positive interface air cylinder, a one-way valve side interface air cylinder, and a one-way valve inlet air cylinder. The one-way valve positive interface air cylinder and the one-way valve side interface air cylinder are arranged orthogonally and connected to each other through the one-way valve inlet air cylinder. The outer end of the one-way valve positive interface air cylinder is provided with a one-way valve positive interface end (251), the outer end of the one-way valve side interface air cylinder is provided with a one-way valve side interface end (252), and the outer end of the one-way valve inlet air cylinder is provided with a one-way valve inlet end (253). The one-way valve positive interface end (251) and the one-way valve side interface end (252) are both connected to the one-way valve inlet end (253). The one-way valve positive interface air cylinder is inserted into the pressure chamber inlet air cylinder. The positive port air cylinder of the one-way valve is equipped with a small ball and a spring. The small ball is in contact with the inner end of the positive port air cylinder of the one-way valve and is connected to the positive port end (251) of the one-way valve through the spring. The side port air cylinder of the one-way valve is equipped with a small ball and a spring. The small ball is in contact with the side port end (252) of the one-way valve and is connected to the inner end of the side port air cylinder of the one-way valve through the spring.

2. The organoid biomechanical response platform according to claim 1, characterized in that, The organ-on-a-chip (1) is divided into two types: organoid culture chip (1a) and organoid non-destructive removal chip (1b). The organoid culture chip (1a) includes three layers stacked in sequence: upper chip layer (11), middle chip layer (12), and lower culture chip layer (13). The organoid non-destructive removal chip (1b) includes two layers stacked in sequence: upper chip layer (11) and non-destructive removal chip layer (14). The middle layer (12) of the chip adopts a planar structure; A through-hole (131) is provided on the lower layer (13) of the culture chip. The chip lower layer (14) that is removed without damage has an inlet hole (141), a recessed channel (142) and an outlet hole (143). The inlet hole (141) and the outlet hole (143) are respectively located at both ends of the recessed channel (142). One end of the recessed channel (142) is connected to the inlet hole (141), and the other end of the recessed channel (142) is connected to the outlet hole (143).

3. The organoid biomechanical response platform according to claim 2, characterized in that, The upper layer (11) of the chip has an inlet port (111), an organoid culture chamber (112), and an outlet port (113). The inlet port (111) and the outlet port (113) are respectively located at both ends of the organoid culture chamber (112). One end of the organoid culture chamber (112) is connected to the inlet port (111), and the other end of the organoid culture chamber (112) is connected to the outlet port (113). The organoid culture chamber (112) includes organoid culture chambers and culture medium channels that are connected to each other. Culture medium channels are provided on both sides of several organoid culture chambers. One side of the culture medium channel is connected to the inlet port (111), and the other side of the culture medium channel is connected to the outlet port (113). The through-hole (131) of the lower layer (13) of the culture chip corresponds to the organoid culture chamber (112) of the upper layer (11) of the chip; The inlet hole (141) of the chip lower layer (14) that is removed without damage corresponds to the inlet port (111) of the chip upper layer (11), the notch channel (142) of the chip lower layer (14) that is removed without damage corresponds to the organoid culture chamber (112) of the chip upper layer (11), and the outlet hole (143) of the chip lower layer (14) that is removed without damage corresponds to the outlet port (113) of the chip upper layer (11).

4. The organoid biomechanical response platform according to claim 1, characterized in that, The pressure chamber base (22) also includes a venting cylinder, which is located on the outer wall of the other end of the pressure chamber base (22). The venting cylinder has an axially formed pressure chamber channel (228) and a laterally formed venting valve insertion hole (227). The pressure chamber channel (228) is connected to the pressure chamber (222). The biomechanical reaction device (2) also includes a vent valve switch (23), which is inserted into a vent valve socket (227). The vent valve switch (23) has a vent valve channel (232) on its inner side and a switch handle (231) on its outer end. A sensor insertion hole is provided on one side of the outer wall of the pressure chamber base (22); The biomechanical reaction device (2) also includes a pressure sensor, which is inserted into a sensor socket.

5. The organoid biomechanical response platform according to claim 1, characterized in that, One end of the stroke air cylinder (26) is provided with a stroke air cylinder interface end (261), and the other end is provided with a stroke air cylinder inlet end (262). The stroke air cylinder interface end (261) and the stroke air cylinder inlet end (262) are connected. The stroke air cylinder (26) is inserted into a one-way valve inlet air cylinder or a pressure chamber inlet air cylinder.

6. The organoid biomechanical response platform according to claim 1, characterized in that, A chip insertion port (223) is provided on one side of the outer wall of the pressure chamber base (22), and a chip push port (225) is provided on the other side of the outer wall. Baffle slots (224) are provided on the upper and lower sides of the chip insertion port (223). The organ chip (1) is inserted from the chip insertion port (223), the baffle is inserted into the baffle slot (224) to hold and fix the position of the organ chip (1), and the organ chip (1) is pushed out from the chip push port (225).

7. The organoid biomechanical response platform according to claim 1, characterized in that, The reciprocating structure (27) further includes a pin (272) and a support seat (275). The connecting rod end of the connecting rod piston (271) is connected to one end of the crankshaft connecting rod (273) through the pin (272). The other end of the crankshaft connecting rod (273) is connected to the crankshaft (274). The crankshaft (274) is mounted on the support seat (275). The crankshaft (274) has a crankshaft flat section (2741). The motor (29) includes a rotating shaft (291), and a rotating shaft flat section (2911) is provided on the rotating shaft (291). The biomechanical reaction device (2) also includes a coupling (28). The reciprocating structure (27) is connected to the motor (29) through the coupling (28). The coupling (28) has a crankshaft mating end (281) and a rotating shaft mating end (282). The coupling (28) is connected to the crankshaft (274) through the crankshaft mating end (281) and the crankshaft flat part (2741), and is connected to the rotating shaft (291) through the rotating shaft mating end (282) and the rotating shaft flat part (2911).

8. A method for simulating the force on human gait organs, characterized in that, This method uses the platform described in any one of claims 1 to 7 to simulate the forces acting on human gait organs, and the method includes the following steps: S1. Inject organoids into organ-on-a-chip (1) and insert the organ-on-a-chip (1) into the pressure chamber base (22). S1.1, Turn the upper layer (11) of the chip upwards; S1.2 Inject the organoids into the organoid culture chamber (112) of the upper layer (11) of the chip. S1.3, Cover the chip middle layer (12) onto the chip upper layer (11); S1.

4. Cover the lower layer (13) of the culture chip with the middle layer (12) of the chip to form an organoid culture chip (1a). S1.

5. Flip the organoid culture chip (1a) so that the front side is facing up; S1.6 Insert the organoid culture chip (1a) into the chip socket (223) of the pressure chamber base (22); S2, Mechanical-biological reaction device (2) pressurized drive, The drive motor (29) rotates, first transmitting power to the crankshaft (274), and then transmitting power to the connecting rod piston (271) through the crankshaft connecting rod (273), thereby converting the rotational motion of the motor (29) into the linear reciprocating motion of the connecting rod piston (271); S3. Simulation of stress on human gait organs S3-1. Different internal states of organ-on-a-chip during organoid culture (1) During organoid culture, organoids will be in two states: no pressure and pressure. The culture medium flows in from the inlet port (111) of the upper layer (11) of the organoid culture chip (1a) and flows out from the outlet port (113) of the upper layer (11) of the organoid culture chip (1a); Under pressureless conditions, organoids are not subjected to external pressure within the organoid culture chamber; Under pressure, the middle layer (12) of the chip is pushed up by air pressure, so that the organoid is squeezed by the outside in the organoid culture chamber, thereby achieving the effect of imitating the force of the organ; S3-2, Simulates human walking or running. When the connecting rod piston (271) is in the retracting motion state, the air in the pressure chamber (222) of the pressure chamber base (22) flows into the stroke air cylinder (26). When the connecting rod piston (271) is in the forward motion state, the air in the stroke air cylinder (26) flows into the pressure chamber (222) of the pressure chamber base (22). Under the pressure drive of the biomechanical reaction device (2), the pressure in the pressure chamber (222) of the pressure chamber base (22) is regularly changed, and the morphology inside the organoid culture chip (1a) will change regularly between the pressureless state and the pressured state, so as to achieve regular compression of the organoid, thereby simulating the force state of the organ when a person walks or runs. S3-3, Simulating a person standing for a long time. When the connecting rod piston (271) is in the retracting motion state, the ball at the positive port (251) of the one-way valve (25) blocks the other port opposite to the positive port (251) of the one-way valve under the combined action of pressure and spring. The ball at the side port (252) of the one-way valve (25) squeezes the spring under the action of pressure and moves away from the side port (252) of the one-way valve, and outside air flows into the stroke air cylinder (26). When the connecting rod piston (271) is in the forward motion state, the ball at the one-way valve side interface (252) of the one-way valve (25) blocks the one-way valve side interface (252) under the combined action of pressure and spring. The ball at the one-way valve positive interface (251) of the one-way valve (25) squeezes the spring under the action of pressure and moves away from the other port opposite to the one-way valve positive interface (251). The air in the stroke air cylinder (26) flows into the pressure chamber (222) of the pressure chamber base (22). Under the pressure drive of the biomechanical reaction device (2), air is continuously injected into the pressure chamber (222) of the pressure chamber base (22). When the morphology inside the organoid culture chip (1a) reaches the pressurized state, the biomechanical reaction device (2) stops driving and keeps the organoid in a squeezed state, thereby simulating the stress state of the organ when a person stands for a long time. S4. Organ-on-a-chip (1) is removed from the pressure chamber base (22) and the organoid is removed without damage. S4.

1. The organoid culture chip (1a) is pushed out from the chip push port (225) of the pressure chamber base (22); S4.2 Flip the organoid culture chip (1a) so that the reverse side is facing up; S4.3 Remove the lower layer (13) and middle layer (12) of the culture chip; S4.

4. Cover the lower layer (14) of the non-destructive removal chip with the upper layer (11) of the chip, and the non-destructive removal chip (1b) of the organoid is formed. S4.

5. Remove the organoid chip (1b) without damage and flip it so that the front side is facing up; At this time, the organoids in the organoid culture chamber will move to the area enclosed by the partition between the organoid culture chamber and the culture medium channel and the lower layer (14) of the non-destructive removal chip, and flow out from the outlet (113) of the upper layer (11) of the non-destructive removal chip (1b) of the organoid as the culture medium flows out.

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