A magnetically controlled cell dynamic mechanical stimulation culture device and a cell dynamic mechanical stimulation method

Abstract

A magnetically controlled cell dynamic mechanical stimulation culture device and a cell dynamic mechanical stimulation method, wherein the magnetically controlled cell dynamic mechanical stimulation culture device is provided with a main body outer frame, a cell culture module and an electromagnetic module for generating a magnetic field for the cell culture module, the cell culture module and the electromagnetic module are respectively assembled on the main body outer frame, and the cell culture module is electromagnetically connected to the electromagnetic module. The present invention generates a magnetic field to the cell culture module through the electromagnetic module, thereby generating a mutation force, so it can better simulate cell dynamic mechanics. Therefore, when the electromagnetic module exerts an effect on the cell culture module by generating a magnetic field, because the distribution of the magnetic field is not blocked, the electromagnetic module and the cell culture module can be completely separated, thereby reducing the probability of bacterial contamination in the culture chamber.

Description

Technical Field

[0001] The invention belongs to the field of biomechanical instruments, and in particular relates to a magnetically controlled cell dynamic mechanical stimulation culture device and a cell dynamic mechanical stimulation method. Background Art

[0002] The cells of natural skeletal muscle, myocardium, nerves and other tissues and organs all have the characteristic of oriented arrangement. This structural feature is the basis for these tissues and organs to perform certain important physiological functions, such as skeletal muscle can contract and relax in a certain direction, and nerves can conduct action potentials in a certain direction. In addition, in mature tissues in the body, most cells are highly differentiated and express characteristic functional proteins. For example, mature skeletal muscle expresses myosin heavy chain, and mature nerve cells express microtubule-associated proteins. In recent years, with the advancement of life science research, when researchers construct functional in vitro bionic models of the above-mentioned tissues and organs, they urgently need methods that can effectively reproduce the orientation characteristics of natural tissues and induce their cells to differentiate and express functional proteins.

[0003] Cell biomechanics is a cutting-edge branch of biomechanics, involving the study of the changing laws and mechanisms of cell states under mechanical loads. Existing reports show that mechanical stimulation plays an important regulatory role in promoting cell orientation, inducing maturation and differentiation, and the expression of related proteins.

[0004] Existing cell biomechanical loading devices are specifically divided into mechanical loading devices and pneumatic loading devices according to the generation and conduction methods of the force.

[0005] The mechanical loading device directly connects the force-bearing part (such as a material or tissue block with cells) to the transmission rod, and then drives the transmission rod through a motor to cyclically load the mechanical force to the force-bearing part. This mechanical loading device is currently adopted by the mainstream scientific research, but it also has the following disadvantages: 1. The force-bearing part is loaded with a continuously changing force in a manner similar to gear transmission. However, the changing patterns of physiological processes such as natural skeletal muscle, myocardium, smooth muscle generating muscle force, bone or cartilage cells bearing compressive stress, and nerve cells generating action potentials are dynamic and sudden, so the continuously changing force cannot achieve good bionics. 2. In the process of pulling the transmission rod back and forth, it is easy to bring bacteria outside the cell culture module into the culture chamber, causing contamination. 3. Because the existence of the transmission rod is integrated with the loading force source and the control system, it is not conducive to the modular partition management of each part. For example, when replacing the culture chamber, the transmission rod has to be removed; when repairing the motor, the problem of contamination of the culture chamber must be taken into account.

[0006] The pneumatic loading device connects the two ends of the force-bearing part to the airbag respectively, and then changes the expansion amplitude of the airbag by ventilating the airbag, thereby driving the deformation of the force-bearing part. However, this setting also has the following disadvantages: 1. It can only load continuously changing forces by inhaling and deflating, and cannot achieve good bionics. 2. Because the expansion amplitude of the airbag is limited, the strain amplitude of the force-bearing part is limited. For example, the tensile strain of the commercially available Flexcell5000 is only in the range of 0% to 33%, which cannot meet the experimental requirements of higher strains.

[0007] Therefore, in view of the technical deficiencies of existing cell dynamic mechanical stimulation culture devices, it is necessary to provide a magnetically controlled cell dynamic mechanical stimulation culture device and a cell dynamic mechanical stimulation method to solve the technical deficiencies of the existing technology. Summary of the invention

[0008] One of the purposes of the present invention is to avoid the shortcomings of the prior art and provide a magnetically controlled cell dynamic mechanical stimulation culture device. The magnetically controlled cell dynamic mechanical stimulation culture device can produce sudden changes and a large strain range of stretching or compression, so as to better simulate the dynamic and sudden physiological processes such as natural skeletal muscle, cardiac muscle, smooth muscle to generate muscle force, bone or cartilage cells to withstand compression stress, and bionic nerve cells to generate action potentials, and the probability of bacterial infection is low.

[0009] The above-mentioned purpose of the present invention is achieved by the following technical measures:

[0010] A magnetically controlled cell dynamic mechanical stimulation culture device is provided, which is provided with a main body outer frame, a cell culture module and an electromagnetic module for generating a magnetic field for the cell culture module. The cell culture module and the electromagnetic module are respectively assembled on the main body outer frame, and the cell culture module is electromagnetically connected to the electromagnetic module.

[0011] The cell culture module is provided with a culture chamber and a strain component that generates strain under the magnetic force of the electromagnetic module. The culture chamber is assembled on the outer frame of the main body, and the strain component can be detachably assembled inside the culture chamber. The strain component is electromagnetically connected to the electromagnetic module, and the electromagnetic module is located outside the culture chamber.

[0012] Preferably, the strain assembly is provided with a stator, a magnetic actuator and a force-bearing part for inoculating cells, one side of the force-bearing part is fixedly connected to the stator, the other side of the force-bearing part is fixedly connected to the magnetic actuator, and the stator and the magnetic actuator are arranged opposite to each other, the stator is fixedly assembled inside the culture chamber, and the magnetic actuator moves inside the culture chamber.

[0013] Preferably, the stator is a stator with a hollow structure, and one side edge of the force-bearing portion is fixedly embedded in the hollow structure of the stator.

[0014] Preferably, the magnetic mover is a magnetic mover with a hollow structure, and the other side of the force-bearing portion is fixedly embedded in the hollow structure of the magnetic mover.

[0015] Preferably, the outer surface of the magnetically attracted mover is wrapped with a first elastic layer, and one side edge of the force-bearing portion is integrally connected to the first elastic layer.

[0016] Preferably, the outer surface of the stator is wrapped with a second elastic layer, and the second elastic layer on the other side of the force-bearing portion is integrally connected.

[0017] Preferably, the cell culture module is also configured to suspend the magnetic actuator on the buoyancy portion and the cover of the culture chamber, the buoyancy portion floats on the surface of the culture fluid contained in the culture chamber, the strain assembly is detachably assembled inside the culture chamber, and the cover is buckled on the upper bottom surface of the culture chamber.

[0018] Preferably, the buoyancy portion is provided with a buoyancy dish and a positioning iron block, the buoyancy dish floats inside the culture chamber, the positioning iron block is placed at the center of the buoyancy dish, and the positioning iron block is magnetically connected to the magnetic mover.

[0019] Preferably, the above-mentioned culture chamber is provided with a fixed groove, a stretching groove and a liquid exchange groove, which are all located on the inner surface of the culture chamber, and the stretching groove and the liquid exchange groove are respectively connected to the fixed groove, the stator is detachably embedded in the fixed groove, and the magnetic actuator moves in the stretching groove.

[0020] The sum of the lengths of the stretching groove and the fixing groove is defined as A, and the length of the strain component in the original state is defined as B. 1cm≤1.5B≤A≤3B exists.

[0021] Preferably, the above-mentioned culture chamber is also provided with a magnetic conductive part and a placement groove for conducting the magnetic field of the electromagnetic module to the stretching groove, the magnetic conductive part is embedded in the culture chamber, and the position of the magnetic conductive part corresponds to the stretching groove, the magnetic conductive part abuts against the side of the electromagnetic module, and the magnetic conductive part is electromagnetically connected to the electromagnetic module, the placement groove is located on the outer surface of the culture chamber, the electromagnetic module is located on the outer side surface of the placement groove, and the magnetic conductive part is assembled in the placement groove.

[0022] The magnetically controlled cell dynamic mechanical stimulation culture device of the present invention is also provided with an intelligent control circuit module for controlling the size of the electromagnetic field via Bluetooth. The intelligent control circuit module is electrically connected to the electromagnetic module, and the intelligent control circuit module can be detachably assembled on the main body outer frame.

[0023] Preferably, the electromagnetic module is provided with an electromagnet L1 and a variable resistance potentiometer R1, which are electrically connected to the intelligent control circuit module, the electromagnet L1 is electrically connected to the variable resistance potentiometer R1, the electromagnet L1 abuts against the magnetic conductive part, and the magnetic conductive part is electromagnetically connected to the electromagnet L1.

[0024] Preferably, the above-mentioned intelligent control circuit module is provided with a relay module K1, a control chip U1, a Bluetooth chip U2, a DC power supply BT1, a coupling capacitor C1, a coupling capacitor C2, a coupling capacitor C3 and an LED1, the RXD end of the Bluetooth chip U2 is connected to the D1 / TX end of the control chip U1, the TXD end of the Bluetooth chip U2 is connected to the D0 / RX end of the control chip U1, the GND end of the Bluetooth chip U2 is grounded, the VCC end of the Bluetooth chip U2 is connected to the VCC end of the relay module K1, the D8 end of the control chip U1 is connected to the IN end of the relay module K1, the GND end of the control chip U1 is grounded, and the 5V end of the control chip U1 is connected to the relay module K1. 1, the positive electrode of the coupling capacitor C1, the positive electrode of the coupling capacitor C2, the positive electrode of the coupling capacitor C3 and the positive electrode of the LED1 are all connected to the VCC end of the relay module K1, the negative electrode of the coupling capacitor C1, the negative electrode of the coupling capacitor C2, the negative electrode of the coupling capacitor C3 and the negative electrode of the LED1 are all grounded, the GND end of the relay module K1 is grounded, the COM end of the relay module K1 is connected to the negative electrode of the DC power supply BT1, the NO end of the relay module K1 is connected to a fixed end and an adjustment end of the variable resistance potentiometer R1, the other fixed end of the variable resistance potentiometer R1 is connected to one side of the electromagnet L1, and the other end of the electromagnet L1 is connected to the positive electrode of the DC power supply BT1.

[0025] Preferably, the model of the above-mentioned control chip U1 is Arduino UNO R3 chip, Arduino UNO R2 chip, Arduino NANO chip, Arduino MEGA chip or Arduino Leonardo chip, the model of the relay module K1 is Relay Module V4.0, the model of the Bluetooth chip U2 is HC-06, HC-05 or a PCBA board with Bluetooth transmission function, the capacitance values ​​of the coupling capacitors C1, C2 and C3 are all 4.7 microfarads, the voltage value of the DC power supply BT1 is 12V, the variable resistance potentiometer R1 is a mechanical or digitally controlled potentiometer, and the maximum resistance value of the variable resistance potentiometer R1 is 10 ohms to 5000 ohms, the maximum suction force of the electromagnet L1 is 5Kg to 500Kg, and the shape of the electromagnet L1 is a round or square electromagnet L1.

[0026] Preferably, the magnetically attracted mover is a neodymium iron boron magnet.

[0027] Preferably, the stator is a silica gel stator.

[0028] Preferably, the force-bearing part is an elastic membrane or a 3D-printed bionic tissue.

[0029] Preferably, the above-mentioned culture chamber is a glass culture chamber, an acrylic culture chamber, a photosensitive resin culture chamber or a transparent silica gel culture chamber.

[0030] Preferably, the first elastic layer and the second elastic layer are both silicone layers.

[0031] The magnetically controlled cell dynamic mechanical stimulation culture device of the present invention is also provided with a microscope component for observing cells in the force-bearing part and a positioning embedding instrument for embedding the force-bearing part into the stator and the magnetically attracted mover. The microscope component is arranged below the culture chamber and corresponds to the position of the stretching groove, and the positioning embedding instrument is an independent structure.

[0032] Another object of the present invention is to provide a magnetically controlled cell dynamic mechanical stimulation method to avoid the shortcomings of the prior art. The magnetically controlled cell dynamic mechanical stimulation method can produce sudden changes and tensile or compressive effects with a large strain range, thereby better biomimetic natural skeletal muscle, cardiac muscle, smooth muscle to generate muscle force, bone or cartilage cells to withstand compressive stress, and biomimetic nerve cells to generate action potentials and other dynamic and sudden physiological processes, and the probability of bacterial infection is low.

[0033] The above-mentioned purpose of the present invention is achieved by the following technical measures:

[0034] A magnetically controlled cell dynamic mechanical stimulation method is provided, which is performed using the magnetically controlled cell dynamic mechanical stimulation culture device.

[0035] The present invention discloses a magnetically controlled cell dynamic mechanical stimulation culture device and a cell dynamic mechanical stimulation method, wherein the magnetically controlled cell dynamic mechanical stimulation culture device is provided with a main body outer frame, a cell culture module and an electromagnetic module for generating a magnetic field for the cell culture module, the cell culture module and the electromagnetic module are respectively assembled on the main body outer frame, and the cell culture module is electromagnetically connected to the electromagnetic module; the cell culture module is provided with a culture chamber and a strain component that generates strain under the control of the magnetic force of the electromagnetic module, the culture chamber is assembled on the main body outer frame, the strain component can be detachably assembled inside the culture chamber, the strain component is electromagnetically connected to the electromagnetic module, and the electromagnetic module is located outside the culture chamber. The beneficial effects of the present invention compared with the prior art are: (1) a technical solution of applying biomechanical loads by magnetic field is adopted. Because the distribution of the magnetic field is not blocked by the culture chamber, the stretching power source and the culture chamber can be completely separated, which reduces the probability of bacterial contamination of the culture chamber and is also conducive to the modular partition management and work of the entire instrument. (2) The present invention uses an electromagnetic module to generate a magnetic field for applying a biomechanical load. Therefore, by controlling the current size and direction of the electromagnetic module, the strength, polarity and change mode of the magnetic field can be instantly controlled, so that the mechanical control is more convenient and effective. (3) The biomechanical load applied by the present invention can better meet the requirements of bionics. (4) The biomechanical load applied by the present invention can ensure a strain application range of -30% to 100%. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] The present invention is further described with reference to the accompanying drawings, but the contents in the accompanying drawings do not constitute any limitation to the present invention.

[0037] Figure 1 This is a schematic diagram of the structure of the culture chamber.

[0038] Figure 2 This is a schematic diagram of the structure after the strain assembly and the magnetic conductive part are assembled in the culture chamber.

[0039] Figure 3 Schematic diagram of the structure of the cell culture module.

[0040] Figure 4 It is a structural schematic diagram of the positioning embedding instrument.

[0041] Figure 5 The figure is a schematic diagram of the structure of the strain assembly when the positioning embedding instrument is assembled to the strain assembly.

[0042] Figure 6 for Figure 5 Schematic diagram of the decomposition.

[0043] Figure 7 This is the orientation and differentiation effect of C2C12 cells seeded at low density (20%-30%) after culturing for 5 days without stretching stimulation.

[0044] Figure 8 This is the orientation and differentiation effect of C2C12 cells seeded at high density (50%-70%) after culturing for 5 days without stretching stimulation.

[0045] Fig. 9 This is the orientation and differentiation effect of C2C12 cells seeded at a low density (20% to 30%) after culturing for 5 days after the initial stretching stimulation in Example 1.

[0046] Fig.10 This is the orientation and differentiation effect of C2C12 cells seeded at high density (50% to 70%) after culturing for 5 days after the initial stretching stimulation in Example 1.

[0047] Fig.11 This is a schematic diagram of the structure of a magnetically controlled cell dynamic mechanical stimulation culture device according to Example 2.

[0048] Fig.12 It is the circuit diagram of the intelligent control circuit module and the electromagnetic module.

[0049] Fig.13 for Fig.12 An enlarged view of the relay module in Figure 2.

[0050] Fig.14 for Fig.12 A magnified image of the control chip in Figure 2.

[0051] Fig.15 This is a schematic diagram of the structure of a magnetically controlled cell dynamic mechanical stimulation culture device according to Example 3.

[0052] exist Figures 1 to 15 Including:

[0053] Main body outer frame 100,

[0054] Cell culture module 200,

[0055] Culture chamber 210, fixing tank 2111, stretching tank 2112, liquid exchange tank 2113, placement tank 2114, buoyancy part 212, buoyancy dish 2121, positioning iron block 2122,

[0056] Strain assembly 220, stator 221, magnetic mover 222, force receiving part 223,

[0057] The magnetic conductive part 230,

[0058] Electromagnetic module 300, electromagnet 310, variable resistance potentiometer 320,

[0059] Microscope assembly 400,

[0060] Intelligent control circuit module 500, relay module 510, control chip 520, Bluetooth chip 530,

[0061] Positioning and embedding instrument 600, frame 610, fixture 620, Z-axis lifting adjustment unit 630, XY-axis translation adjustment unit 640,

[0062] Silicone mold 700. DETAILED DESCRIPTION

[0063] The technical solution of the present invention is further described in conjunction with the following embodiments.

[0064] Example 1.

[0065] A magnetically controlled cell dynamic mechanical stimulation culture device, such as Figures 1 to 3 As shown, a main body outer frame 100, a cell culture module 200 and an electromagnetic module 300 for generating a magnetic field for the cell culture module 200 are provided. The cell culture module 200 and the electromagnetic module 300 are respectively assembled on the main body outer frame 100, and the cell culture module 200 is electromagnetically connected to the electromagnetic module 300.

[0066] The cell culture module 200 is provided with a culture chamber 210 and a strain component 220 that generates strain under the magnetic force of the electromagnetic module 300. The culture chamber 210 is assembled on the main outer frame 100, and the strain component 220 is detachably assembled inside the culture chamber 210. The strain component 220 is electromagnetically connected to the electromagnetic module 300, and the electromagnetic module 300 is located outside the culture chamber 210.

[0067] The strain assembly 220 is provided with a stator 221, a magnetic mover 222 and a force-bearing part 223 for inoculating cells, one side of the force-bearing part 223 is fixedly connected to the stator 221, the other side of the force-bearing part 223 is fixedly connected to the magnetic mover 222, and the stator 221 and the magnetic mover 222 are arranged opposite to each other, the stator 221 is fixedly assembled inside the culture chamber 210, and the magnetic mover 222 moves inside the culture chamber 210.

[0068] It should be noted that the strain assembly 220 of the present invention stretches or compresses the plane where the force-bearing part 223 is located at the two opposite sides of the force-bearing part 223, and the magnetic actuator 222 and the stator 221 are only fixed at the two opposite sides of the force-bearing part 223, and the volume of the magnetic stator 221 is not limited by the size of the force-bearing part 223. The cross-section of the force-bearing part 223 is obtained along the stretching or compression direction of the force-bearing part 223. When the electromagnetic module 300 generates a magnetic field on the magnetic actuator 222, the magnetic actuator 222 transmits the force from one side of the force-bearing part 223 to the other side of the force-bearing part 223 along the cross-section. The area of ​​the cross-section is much smaller than the surface area of ​​the force-bearing part 223, so the pressure of the force in the cross-section is relatively large, so that a larger strain can be achieved.

[0069] It has been verified by multiple experiments that the biomechanical load strain range of the present invention can reach -30% to 100%. The tensile strain range of the present invention is comparable to that of the mechanical loading device in the prior art, and is significantly better than that of the pneumatic loading device.

[0070] The stator 221 of the present invention is a stator 221 with a hollow structure, and one side of the force-bearing portion 223 is fixedly embedded in the hollow structure of the stator 221; the magnetic mover 222 is a magnetic mover 222 with a hollow structure, and the other side of the force-bearing portion 223 is fixedly embedded in the hollow structure of the magnetic mover 222.

[0071] It should be noted that the stator 221 and the magnetic mover 222 of the present invention are both hollow structures, and both sides of the force-bearing portion 223 are fixedly embedded in the two hollow structures. The purpose of this is to increase the contact area between the stator 221 and the magnetic mover 222 and the force-bearing portion 223, thereby improving the firmness between the force-bearing portion 223 and the stator 221 and the magnetic mover 222 when stretched or compressed.

[0072] It should be noted that the force bearing part 223 of the present invention can be an elastic film, a 3D printed bionic tissue or tissue block, etc., wherein the elastic film is specifically a PDMS film. The culture chamber 210 can be made of non-cytotoxic materials such as glass, acrylic, photosensitive resin or transparent silica gel.

[0073] The outer surface of the magnetic mover 222 of the present invention is wrapped with a first elastic layer, and one side of the force-bearing part 223 is integrally connected to the first elastic layer. The outer surface of the stator 221 is wrapped with a second elastic layer, and the other side of the force-bearing part 223 is integrally connected to the second elastic layer.

[0074] It should be noted that the two side edges of the force-bearing portion 223 of the present invention are fixed to the magnetic mover 222 and the stator 221 respectively through the first elastic layer and the second elastic layer.

[0075] The cell culture module 200 is also configured to suspend the magnetic actuator 222 on the buoyancy portion 212 and the cover of the culture chamber 210, the buoyancy portion 212 floats on the surface of the culture fluid contained in the culture chamber 210, the strain assembly 220 can be detachably assembled inside the culture chamber 210, and the cover is buckled on the upper bottom surface of the culture chamber 210.

[0076] The cover of the present invention is a commercially available 100×100 mm square polystyrene cell culture dish cover.

[0077] The buoyancy portion 212 of the present invention is provided with a buoyancy dish 2121 and a positioning iron block 2122 . The buoyancy dish 2121 floats inside the culture chamber 210 . The positioning iron block 2122 is placed at the center of the buoyancy dish 2121 , and the positioning iron block 2122 is magnetically connected to the magnetic mover 222 .

[0078] The culture chamber 210 is provided with a fixed groove 2111, a stretching groove 2112 and a liquid exchange groove 2113, which are all located on the inner surface of the culture chamber 210, and the stretching groove 2112 and the liquid exchange groove 2113 are respectively connected to the fixed groove 2111, the stator 221 is detachably embedded in the fixed groove 2111, and the magnetic mover 222 moves in the stretching groove 2112.

[0079] It should be noted that when the culture chamber 210 is filled with culture fluid, the buoyancy dish 2121 can float inside the culture chamber 210. At this time, the positioning iron block 2122 is magnetically connected to the magnetic mover 222, and the buoyancy dish 2121 simultaneously generates buoyancy on the positioning iron block 2122 and the magnetic mover 222. Therefore, the magnetic mover 222 can be suspended in the culture fluid, and the magnetic mover 222 will not contact the bottom surface of the culture chamber 210, thereby reducing the friction between the magnetic mover 222 and the culture chamber 210, so as to ensure the smooth extension or compression and elastic reset under the action of the magnetic field.

[0080] The sum of the lengths of the stretching groove 2112 and the fixing groove 2111 is defined as A, and the length of the strain component 220 in the original state is defined as B. There exists 1cm≤1.5B≤A≤3B.

[0081] It should be noted that the function of the liquid replacement tank 2113 of the present invention is to replace the culture medium inside the stretching tank 2112 without contacting the stretching tank 2112 where the force-applying object is located.

[0082] When the length of the stretching groove 2112 is greater than or equal to 1.5 times the length of the strain assembly 220 in the original state, sufficient movement distance can be provided for the magnetically attracted mover 222 .

[0083] The culture chamber 210 is also provided with a magnetic conductive part 230 and a placement groove 2114 for conducting the magnetic field of the electromagnetic module 300 to the stretching groove 2112. The magnetic conductive part 230 is embedded in the culture chamber 210, and the position of the magnetic conductive part 230 corresponds to the stretching groove 2112. The magnetic conductive part 230 abuts against the side of the electromagnetic module 300, and the magnetic conductive part 230 is electromagnetically connected to the electromagnetic module 300. The placement groove 2114 is located on the outer surface of the culture chamber 210, and the electromagnetic module 300 is located on the outer side of the placement groove 2114. The magnetic conductive part 230 is assembled in the placement groove 2114.

[0084] The function of the magnetic conductive part 230 of the present invention is to conduct the magnetic field of the electromagnetic module 300 to the magnetic attraction mover 222 to ensure the smooth progress of magnetic stretching or compression.

[0085] The magnetic mover 222 of the present invention is a N52, N48 or N44 neodymium iron boron magnet, the stator 221 is a silicone stator 221, and the magnetic conductive part 230 is a magnetic conductive core. The first elastic layer and the second elastic layer are both PDMS layers and silicone layers.

[0086] The magnetically controlled cell dynamic mechanical stimulation culture device of the present invention is further provided with a positioning embedding instrument 600 for embedding the force-bearing part 223 into the stator 221 and the magnetically attracted mover 222. The positioning embedding instrument 600 is provided with a frame 610, a clamp 620 for fixing the force-bearing part 223, the stator 221 or the magnetically attracted mover 222, a Z-axis lifting adjustment part 630 and an XY-axis translation adjustment part 640, wherein the clamp 620 is assembled on the frame 610, and the XY-axis translation adjustment part 640 is fixedly assembled on the upper bottom surface of the Z-axis lifting adjustment part 630, as shown in FIG. Figure 4 .

[0087] It should be noted that the Z-axis lifting adjustment part 630, the XY-axis translation adjustment part 640 and the fixture 620 of the present invention are all obtained through commercial channels.

[0088] The method of using the magnetically controlled cell dynamic mechanical stimulation culture device of the present invention is as follows: take a 0.08mm PDMS film, cut the required shape, and then fix the force-bearing part 223 with the magnetic actuator 222 and the stator 221 to obtain the strain component 220. Then use 75% ethanol to soak for 30 minutes to disinfect the strain component 220, and place it in the clean bench to dry and prepare. Use 75% ethanol to soak for 30 minutes to disinfect the culture chamber 210, and after drying the culture chamber 210 in the clean bench, the stator 221 of the strain component 220 is loaded into the fixed groove 2111 of the culture chamber 210. Then the cells are inoculated on the surface of the force-bearing part 223. In this embodiment, C2C12 mouse myoblasts within 10 generations of trypsin digestion are used as specific cells. Finally, the electromagnetic module 300 generates a magnetic field for the magnetic actuator 222, so that the magnetic actuator 222 stretches or compresses the force-bearing part 223. After the experiment, remove the PDMS membrane, stain it with Live / Dead, and observe it under a fluorescence microscope.

[0089] Among them, the present invention uses C2C12 mouse myoblasts within 10 generations of trypsin digestion to inoculate the cell inoculation method of the present invention, which is specifically as follows: C2C12 mouse myoblasts within 10 generations of trypsin digestion are centrifuged, and after the whole culture is resuspended, the whole culture is diluted to a cell inoculation density of 20% to 30% or 50% to 70%, and 200 microliters are dripped on the force-bearing part 223 to complete the cell inoculation. Then, after standing at 37°C for 3 hours, the cells complete the initial attachment. Continue to add 50ml to 60ml of the whole culture solution, install the buoyancy dish 2121 and the positioning iron block 2122 under sterile operation, and cover the culture chamber 210 lid. After the magnetic conductive part 230 is embedded in the placement groove 2114, the cell culture chamber 210 is placed in the incubator as a whole, and is left to stand for 12 hours at 37°C and 5% CO2 to allow the cells to complete adhesion. When C2C12 mouse myoblasts within 10 generations of pancreatic enzyme digestion were used as inoculated cells, the tensile strain of the force-bearing portion 223 was set at 20% to 50% by the electromagnetic module 300 of this embodiment. Figures 7 to 10 shown.

[0090] It should be noted that the inoculated cells of this embodiment can also be PC12 adrenal medullary pheochromoma cells digested with trypsin for 25 generations. When PC12 adrenal medullary pheochromoma cells digested with trypsin for 25 generations are used as inoculated cells, the electromagnetic module 300 of the present invention makes the tensile strain of the force-bearing part 223 between 20% and 50%.

[0091] The specific fixing method of the force bearing part 223, the magnetic mover 222 and the stator 221 of the present invention is as follows:

[0092] In the first step, the surface of the force-bearing part 223 is coated with protein, and then one side of the force-bearing part 223 is clamped in the clamp 620, and the other end of the force-bearing part 223 is freely drooped under the action of gravity;

[0093] The second step is to place the magnetic actuator 222 into the prefabricated PDMS silicone mold 700, and then place the two on the XY axis translation adjustment part 640, and adjust the XY axis translation adjustment part 640 and the Z axis lifting adjustment part 630 so that the force-bearing part 223 is exactly in the center of the hollow structure of the magnetic actuator 222;

[0094] The third step is to pour uncured PDMS into the prefabricated PDMS silicone mold 700 so that one side of the force-bearing portion 223 and the magnetic actuator 222 are completely submerged in the PDMS;

[0095] In the fourth step, the fixture 620, the force-bearing part 223, the magnetic actuator 222 and the PDMS silicone mold 700 are placed in a 60-degree oven for one hour to complete the PDMS curing, so that one side of the magnetic actuator 222 and the force-bearing part 223 is completely embedded in the prefabricated PDMS silicone mold 700, and then the PDMS silicone mold 700 is removed. After curing, the PDMS is the first elastic layer;

[0096] Step 5: The magnetic actuator 222 with an elastic layer on its surface is clamped in the fixture 620, and the other end of the force-bearing part 223 is freely drooped under the action of gravity;

[0097] Step 6: Place the stator 221 into the prefabricated PDMS silicone mold 700, and then place the two on the XY axis translation adjustment part 640, and adjust the XY axis translation adjustment part 640 and the Z axis lifting adjustment part 630 so that the other side of the force-bearing part 223 is exactly at the center of the hollow structure of the stator 221;

[0098] Step 7: Pour uncured PDMS into the prefabricated PDMS silicone mold 700, so that the other side of the force-bearing portion 223 and the stator 221 are completely submerged in the PDMS. Figure 5 and 6 ;

[0099] In the eighth step, the fixture 620, the force-bearing part 223, the magnetic mover 222, the stator 221 and the PDMS silicone mold 700 are placed in a 60-degree oven for one hour to complete the PDMS curing. Figure 5 and 6 , so that the stator 221 and the other side of the force-bearing part 223 are completely embedded in the prefabricated PDMS silicone mold 700, and then the PDMS silicone mold 700 is removed. After curing, the PDMS becomes the second elastic layer, and the strain assembly 220 is obtained.

[0100] The magnetically controlled cell dynamic mechanical stimulation culture device generates a magnetic field on the cell culture module 200 through the electromagnetic module 300, thereby generating a mutation force, so it can better simulate cell dynamic mechanics. Therefore, when the electromagnetic module 300 exerts an effect on the cell culture module 200 by generating a magnetic field, because the distribution of the magnetic field is not blocked, the electromagnetic module 300 and the cell culture module 200 can be completely separated, reducing the probability of bacterial contamination in the culture chamber 210.

[0101] Specifically, compared with the prior art, the present invention has the following beneficial effects:

[0102] (1) The present invention adopts a technical solution of applying biomechanical loads by means of a magnetic field. Since the distribution of the magnetic field is not blocked by the culture chamber 210, the stretching power source and the culture chamber 210 can be completely separated, which reduces the probability of bacterial contamination in the culture chamber 210 and is also beneficial to the modular partition management and operation of the entire instrument. The existing biomechanical stimulation cell culture device adopts a technical solution based on mechanical loading, with a motor providing power, and a transmission rod passing through the wall of the culture chamber 210 to apply a biomechanical load. Because in the process of pulling the transmission rod back and forth, it is easy to bring bacteria outside the cell culture chamber 210 into the culture chamber 210, increasing the probability of bacterial contamination. The culture chamber 210 becomes an integral whole with the loading force source and the control system due to the existence of the transmission rod, which is not conducive to the modular partition management of each part.

[0103] (2) The present invention uses the electromagnetic module 300 to generate the magnetic field for applying the biomechanical load. Therefore, by controlling the current size and direction of the electromagnetic module 300, the strength, polarity and change mode of the magnetic field can be instantly controlled, so that the mechanical control is more convenient and effective. Compared with the prior art, the present invention can control the electromagnetic module 300 to produce a variety of stretching methods, such as inching stretching, by applying the biomechanical load, which is not achievable by the prior art.

[0104] (3) The changing patterns of physiological processes such as natural skeletal muscle, cardiac muscle, smooth muscle generating muscle force, bone or cartilage cells bearing compressive stress, and nerve cells generating action potentials are all dynamic and sudden changes. The present invention can produce sudden changes and a large strain range of stretching or compression, so that the application of biomechanical loads can better meet the requirements of bionics. The existing mechanical loading scheme cannot simulate this feature well, but the present invention can generate point stretching by controlling the electromagnetic module 300. The applied tensile load can reach the set value at the moment of current passing, and the applied tensile load can disappear at the moment of current stopping, which is similar to the above-mentioned dynamic and sudden physiological processes.

[0105] (4) The biomechanical load applied by the present invention can ensure a strain application range of -30% to 100%, which is comparable to the traditional mechanical loading scheme and significantly better than the pneumatic loading scheme.

[0106] (5) The main outer frame 100 and the cell culture module 200 of the magnetically controlled cell dynamic mechanical stimulation culture device of the present invention are processed by emerging manufacturing methods such as 3D printing and CNC cutting. Therefore, the overall design of the cell dynamic mechanical stimulation culture device complies with the principle of modular work management and supports tool-free disassembly, assembly, and expansion. The cell dynamic mechanical stimulation culture device is small in size and easy to disinfect, so that the use requirements match the actual experimental conditions of the existing cell culture room. However, the biomechanical stimulation cell culture device in the prior art does not support tool-free disassembly and assembly, and some biomechanical stimulation cell culture devices require a relatively high level of sterility for use.

[0107] (6) The types of the force-bearing part 223 of the present invention are various, such as elastic film materials of the type of silica gel, resin, rubber, etc.; elastic block materials of the type of hydrogel, protein gel, etc.; elastic natural tissue blocks and tissue-engineered tissue organs, etc. The types of cells seeded in the force-bearing part 223 of the present invention are also various, such as skeletal muscle and cardiac myoblasts, nerve cells, fibroblasts, etc.

[0108] Example 2.

[0109] A magnetically controlled cell dynamic mechanical stimulation culture device, such as Figures 11 to 14 As shown, other features are the same as those of Example 1, and also have the following characteristics: an intelligent control circuit module 500 is also provided for controlling the size of the electromagnetic field via Bluetooth, the intelligent control circuit module 500 is electrically connected to the electromagnetic module 300, and the intelligent control circuit module 500 can be detachably assembled on the main body outer frame 100.

[0110] It should be noted that, because the magnetic field is a force field distributed in space, unlike mechanical force conduction which requires a physical object as a medium, magnetic field conduction does not require a physical object as a medium, and is not easily blocked by general substances. Moreover, the magnetic field can be generated by electric current, so the Tongshou intelligent control circuit module 500 of the present invention controls the current size and direction of the electromagnetic module 300, thereby producing different change modes. These change modes can be adjusted by the intelligent control circuit module 500 to control the strength and polarity of the magnetic field generated by the electromagnetic module 300. At present, the intelligent chip represented by the Arduino UNO chip can be used to personalize the output of the electrical signal through a computer, and the output mode of the Arduino UNO chip can be remotely controlled in real time through the Bluetooth function of a general mobile device.

[0111] The electromagnetic module 300 is provided with an electromagnet 310L1 and a variable resistance potentiometer 320R1, the electromagnet 310L1 and the variable resistance potentiometer 320R1 are electrically connected to the intelligent control circuit module 500, the electromagnet 310L1 is electrically connected to the variable resistance potentiometer 320R1, the electromagnet 310L1 abuts against the magnetic conductive part 230, and the magnetic conductive part 230 is electromagnetically connected to the electromagnet 310L1.

[0112] The intelligent control circuit module 500 is provided with a relay module 510K1, a control chip 520U1, a Bluetooth chip 530U2, a DC power supply BT1, a coupling capacitor C1, a coupling capacitor C2, a coupling capacitor C3 and an LED1. The RXD end of the Bluetooth chip 530U2 is connected to the D1 / TX end of the control chip 520U1, the TXD end of the Bluetooth chip 530U2 is connected to the D0 / RX end of the control chip 520U1, the GND end of the Bluetooth chip 530U2 is grounded, the VCC end of the Bluetooth chip 530U2 is connected to the VCC end of the relay module 510K1, the D8 end of the control chip 520U1 is connected to the IN end of the relay module 510K1, the GND end of the control chip 520U1 is grounded, and the 5V end of the control chip 520U1 is connected to The VCC end of the relay module 510K1 is connected, the positive electrode of the coupling capacitor C1, the positive electrode of the coupling capacitor C2, the positive electrode of the coupling capacitor C3 and the positive electrode of the LED1 are all connected to the VCC end of the relay module 510K1, the negative electrode of the coupling capacitor C1, the negative electrode of the coupling capacitor C2, the negative electrode of the coupling capacitor C3 and the negative electrode of the LED1 are all grounded, the GND end of the relay module 510K1 is grounded, the COM end of the relay module 510K1 is connected to the negative electrode of the DC power supply BT1, the NO end of the relay module 510K1 is connected to a fixed end and an adjustment end of the variable resistance potentiometer 320R1, the other fixed end of the variable resistance potentiometer 320R1 is connected to one side of the electromagnet 310L1, and the other end of the electromagnet 310L1 is connected to the positive electrode of the DC power supply BT1.

[0113] The control chip 520U1 of the present invention is a single-chip microcomputer such as an Arduino UNO R3 chip, an Arduino UNO R2 chip, an Arduino NANO chip, an Arduino MEGA chip or an Arduino Leonardo chip, the relay module 510K1 is a Relay Module V4.0, the Bluetooth chip 530U2 is a HC-06, HC-05 or a PCBA board with a Bluetooth transmission function, the capacitance values ​​of the coupling capacitors C1, C2 and C3 are all 4.7 microfarads, and the voltage value of the DC power supply BT1 is 12V. The variable resistance potentiometer 320R1 is a mechanical or digitally controlled potentiometer, and the maximum resistance value of the variable resistance potentiometer 320R1 is 10 ohms to 5000 ohms. The maximum suction force of the electromagnet 310L1 is 5Kg to 500Kg, and the shape of the electromagnet 310L1 is a round or square electromagnet 310L1.

[0114] The specific model of the Bluetooth chip 530U2 in this embodiment is HC-06, and the specific model of the control chip 520U1 is Arduino UNO R3 chip. The electromagnet 310L1 is a circular electromagnet 310L1 with a maximum suction force of 60kg. The variable resistance potentiometer 320R1 is a mechanical variable resistance potentiometer 320 with a maximum resistance of 600 ohms.

[0115] The function of the Bluetooth chip 530U2 of the present invention is to connect with a mobile device, so that the mechanical loading state of the instrument in the incubator can be adjusted by wireless remote control instructions through the mobile device, and the wireless remote control instructions are sent to the control chip 520U1, and the function of the control chip 520U1 is to adjust the output working electrical signal according to the wireless remote control instructions, and transmit the output working electrical signal to the relay module 510K1. The function of the relay module 510K1 is to adjust the current size of the working circuit of the electromagnet 310L1 by controlling the resistance value of the variable resistance potentiometer 320R1. The relay module 510K1 can also control the on and off of the current, thereby controlling the size of the electromagnetic field.

[0116] Compared with Example 1, the magnetically controlled cell dynamic mechanical stimulation culture device of this embodiment also has the following beneficial effects:

[0117] (1) The present invention uses Arduino UNO chip as the control chip 520 of the intelligent control circuit module 500, and outputs the working electrical signal through the control chip 520. In addition, the Arduino UNO chip, as a programming platform, can set different programs according to actual needs to meet personalized needs. In the prior art, the way to obtain current changes (electronic signals) is mainly through a signal generator, which is large in size and high in cost, and cannot be programmed independently, which is not conducive to the miniaturization, simplification and functional personalization of the instrument. Therefore, the intelligent control circuit module 500 of the present invention has the advantages of low cost, small size, simplicity and the ability to set personalized programs.

[0118] (2) The cell dynamic mechanical stimulation culture device of the present invention also introduces Bluetooth technology, and the operator can use any mobile device that supports Bluetooth function to wirelessly remotely adjust the mechanical loading state in the cell dynamic mechanical stimulation culture device, so that the operation is simple and effective, and meets the actual needs of cytological experiments. However, most existing biomechanical stimulation cell culture devices do not support similar remote control functions.

[0119] (3) The present invention can be controlled by the intelligent control circuit module 500, thereby imitating the dynamic and sudden physiological processes such as natural skeletal muscle, myocardium, smooth muscle generating muscle force, bone or cartilage cells bearing compressive stress, and nerve cells generating action potentials. In addition, it can also control the electromagnetic module 300 to generate a variety of tensile or compressive load application modes, such as linear function change mode, sinusoidal function change mode and exponential function change mode.

[0120] Example 3.

[0121] A magnetically controlled cell dynamic mechanical stimulation culture device, such as Fig.15 As shown, other features are the same as those of Example 2, and also have the following characteristics: a microscope component 400 for observing the force-bearing portion 223 is also provided, and the microscope component 400 is provided below the culture chamber 210 and corresponds to the position of the stretching groove 2112.

[0122] The microscope assembly 400 of this embodiment is specifically provided with a lifting platform and a digital microscope, wherein the digital microscope is fixedly mounted on the lifting platform, and the field of view of the digital microscope is located in the area of ​​the stretching groove 2112. The maximum magnification of the digital microscope is 300 to 1000 times.

[0123] Compared with the first embodiment, the present embodiment is further provided with a microscope component 400 so as to observe and record the state of the force-bearing portion 223 in real time.

[0124] Example 4.

[0125] A magnetically controlled cell dynamic mechanical stimulation culture device, the other features of which are the same as those of Example 1, except that: the force-bearing part 223 of this example is a 3D-printed bionic tissue, specifically a polyester bionic cartilage scaffold.

[0126] The polyester bionic cartilage scaffold of the present invention is a polyester bionic cartilage scaffold produced by 3D printing.

[0127] The operation method of using mouse C2C12 myoblasts digested with pancreatic enzyme for 10 generations as the specific force-bearing part 223 is as follows: centrifuge mouse C2C12 myoblasts digested with pancreatic enzyme for 10 generations, resuspend the whole culture, dilute to 70% cell seeding density with methacrylated gelatin solution that has been filtered and sterilized, drip 1000 microliters on the polyester bionic cartilage scaffold, irradiate with 405nm ultraviolet lamp for 15 seconds, and the methacrylated gelatin undergoes photocrosslinking and changes from liquid to hydrogel. The cell seeding of the polyester bionic cartilage scaffold is completed. Continue to add 50ml to 60ml of the whole culture solution, install the buoyancy dish 2121 and the positioning iron block 2122 under sterile operation, and cover the culture chamber 210 lid. After the magnetic conductive part 230 is embedded in the placement groove 2114, the cell culture chamber 210 is placed in the incubator as a whole, and left to stand for 12 hours at 37°C and 5% CO2 to allow the cells to complete adhesion. When the mouse C2C12 myoblasts within 10 generations are digested with trypsin as the force-bearing part 223, the electromagnetic module 300 of the present invention makes the tensile strain of the force-bearing part 223 be between 10% and 30%.

[0128] It should be noted that the cells inoculated in the polyester bionic cartilage scaffold of this embodiment can also be MC3T3 osteoblasts within 10 generations of pancreatic digestion. When MC3T3 osteoblasts within 10 generations of pancreatic digestion are used as inoculated cells, the electromagnetic module 300 of the present invention makes the compressive strain of the force-bearing part 223 between -10% and -30%.

[0129] The force-bearing portion 223 of this embodiment is a polyester bionic cartilage scaffold, which simulates the dynamic mechanics of natural skeletal muscle.

[0130] Example 5.

[0131] A magnetically controlled cell dynamic mechanical stimulation method is performed using any one of the magnetically controlled cell dynamic mechanical stimulation culture devices described in Examples 1 to 4.

[0132] Compared with the prior art, the magnetically controlled cell dynamic mechanical stimulation method has the following beneficial effects: (1) It adopts a technical solution of applying biomechanical loads by magnetic field. Since the distribution of the magnetic field is not blocked by the culture chamber, the stretching power source and the culture chamber can be completely separated, which reduces the probability of bacterial contamination in the culture chamber and is also beneficial to the modular partition management and operation of the instrument as a whole. (2) The magnetic field for applying biomechanical loads in the present invention is generated by an electromagnetic module. Therefore, by controlling the current size and direction of the electromagnetic module, the strength, polarity and change mode of the magnetic field can be instantly controlled, so that the mechanical control is more convenient and effective. (3) The biomechanical load applied by the present invention can better meet the requirements of bionics. (4) The biomechanical load applied by the present invention can ensure a strain application range of -30% to 100%.

[0133] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solution of the present invention can be modified or replaced by equivalents without departing from the essence and scope of the technical solution of the present invention.

Claims

1. A magnetically controlled cell dynamic mechanical stimulation culture device, characterized in that: A main body outer frame, a cell culture module and an electromagnetic module for generating a magnetic field for the cell culture module are provided, the cell culture module and the electromagnetic module are respectively assembled on the main body outer frame, and the cell culture module is electromagnetically connected to the electromagnetic module; The cell culture module is provided with a culture chamber and a strain component which generates strain under the control of the magnetic force of the electromagnetic module, the culture chamber is assembled on the outer frame of the main body, the strain component is detachably assembled inside the culture chamber, the strain component is electromagnetically connected to the electromagnetic module, and the electromagnetic module is located outside the culture chamber; The strain assembly is provided with a stator, a magnetic mover and a force-bearing part for inoculating cells, one side of the force-bearing part is fixedly connected to the stator, the other side of the force-bearing part is fixedly connected to the magnetic mover, and the stator and the magnetic mover are arranged opposite to each other, the stator is fixedly assembled inside the culture chamber, and the magnetic mover moves inside the culture chamber; The cell culture module is further configured to suspend the magnetic actuator on the buoyancy portion and the cover of the culture chamber, the buoyancy portion floats on the surface of the culture liquid contained in the culture chamber, the strain assembly is detachably assembled inside the culture chamber, and the cover is buckled on the upper bottom surface of the culture chamber; The buoyancy part is provided with a buoyancy dish and a positioning iron block, the buoyancy dish floats inside the culture chamber, the positioning iron block is placed at the center of the buoyancy dish, and the positioning iron block is magnetically connected to the magnetic mover; The culture bin is provided with a fixed groove, a stretching groove and a liquid exchange groove, which are all located on the inner surface of the culture bin, and the stretching groove and the liquid exchange groove are respectively connected to the fixed groove, the stator is detachably embedded in the fixed groove, and the magnetic mover moves in the stretching groove; The sum of the lengths of the stretching groove and the fixing groove is defined as A, and the length of the strain component in the original state is defined as B, and there exists 1cm≤1.5B≤A≤3B; The culture chamber is also provided with a magnetic conductive part and a placement groove for conducting the magnetic field of the electromagnetic module to the stretching groove. The magnetic conductive part is embedded in the culture chamber, and the position of the magnetic conductive part corresponds to the stretching groove. The magnetic conductive part abuts against the side of the electromagnetic module, and the magnetic conductive part is electromagnetically connected to the electromagnetic module. The placement groove is located on the outer surface of the culture chamber, the electromagnetic module is located on the outer side of the placement groove, and the magnetic conductive part is assembled in the placement groove.

2. The magnetically controlled cell dynamic mechanical stimulation culture device according to claim 1, characterized in that: The stator is a stator with a hollow structure, and one side of the force-bearing part is fixedly embedded in the hollow structure of the stator; The magnetic mover is a magnetic mover with a hollow structure, and the other side of the force-bearing part is fixedly embedded in the hollow structure of the magnetic mover.

3. The magnetically controlled cell dynamic mechanical stimulation culture device according to claim 1, characterized in that: An intelligent control circuit module is also provided for controlling the size of the electromagnetic field through Bluetooth. The intelligent control circuit module is electrically connected to the electromagnetic module, and the intelligent control circuit module can be detachably assembled on the outer frame of the main body; The electromagnetic module is provided with an electromagnet L1 and a variable resistance potentiometer R1, which are electrically connected to the intelligent control circuit module, the electromagnet L1 is electrically connected to the variable resistance potentiometer R1, the electromagnet L1 abuts against the magnetic conductive part, and the magnetic conductive part is electromagnetically connected to the electromagnet L1.

4. The magnetically controlled cell dynamic mechanical stimulation culture device according to claim 3, characterized in that: The intelligent control circuit module is provided with a relay module K1, a control chip U1, a Bluetooth chip U2, a DC power supply BT1, a coupling capacitor C1, a coupling capacitor C2, a coupling capacitor C3 and an LED1. The RXD end of the Bluetooth chip U2 is connected to the D1 / TX end of the control chip U1, the TXD end of the Bluetooth chip U2 is connected to the D0 / RX end of the control chip U1, the GND end of the Bluetooth chip U2 is grounded, the VCC end of the Bluetooth chip U2 is connected to the VCC end of the relay module K1, the D8 end of the control chip U1 is connected to the IN end of the relay module K1, the GND end of the control chip U1 is grounded, the 5V end of the control chip U1 is connected to the The positive electrode of the coupling capacitor C1, the positive electrode of the coupling capacitor C2, the positive electrode of the coupling capacitor C3 and the positive electrode of the LED1 are all connected to the VCC end of the relay module K1, the negative electrode of the coupling capacitor C1, the negative electrode of the coupling capacitor C2, the negative electrode of the coupling capacitor C3 and the negative electrode of the LED1 are all grounded, the GND end of the relay module K1 is grounded, the COM end of the relay module K1 is connected to the negative electrode of the DC power supply BT1, the NO end of the relay module K1 is connected to a fixed end and an adjustment end of the variable resistance potentiometer R1, the other fixed end of the variable resistance potentiometer R1 is connected to one side of the electromagnet L1, and the other end of the electromagnet L1 is connected to the positive electrode of the DC power supply BT1.

5. The magnetically controlled cell dynamic mechanical stimulation culture device according to claim 4, characterized in that: The model of the control chip U1 is Arduino UNO R3 chip, Arduino UNO R2 chip, Arduino NANO chip, Arduino MEGA chip or Arduino Leonardo chip, the model of the relay module K1 is Relay Module V4.0, the model of the Bluetooth chip U2 is HC-06, HC-05 or a PCBA board with Bluetooth transmission function, the capacitance values ​​of the coupling capacitors C1, C2 and C3 are all 4.7 microfarads, the voltage value of the DC power supply BT1 is 12V, the variable resistance potentiometer R1 is a mechanical or digitally controlled potentiometer, and the maximum resistance value of the variable resistance potentiometer R1 is 10 ohms to 5000 ohms, the maximum suction force of the electromagnet L1 is 5 kg to 500 kg, and the shape of the electromagnet L1 is a round or square electromagnet L1; The magnetic actuator is a neodymium iron boron magnet; The stator is a silica gel stator; The force-bearing part is an elastic membrane or a 3D-printed bionic tissue; The culture chamber is a glass culture chamber, an acrylic culture chamber, a photosensitive resin culture chamber or a transparent silica gel culture chamber.

6. The magnetically controlled cell dynamic mechanical stimulation culture device according to claim 5, characterized in that: A microscope component for observing cells in the force-bearing part and a positioning and embedding instrument for embedding the force-bearing part into the stator and the magnetic mover are also provided. The microscope component is arranged below the culture chamber and corresponds to the position of the stretching groove, and the positioning and embedding instrument is an independent structure.

7. A magnetically controlled cell dynamic mechanical stimulation method, characterized in that: The method is carried out using the magnetically controlled cell dynamic mechanical stimulation culture device as described in any one of claims 1 to 6.

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