A model animal in vitro digestive system based on software drive and its control method

Abstract

The present invention belongs to the field of model animal in vitro digestive system simulation devices, and discloses a model animal in vitro digestive system based on software drive, including: a stomach module, including a bionic stomach and a stomach squeezing device for squeezing the bionic stomach, the stomach squeezing device including a soft robot and a magnetorheological fluid flexible device, the magnetorheological fluid flexible device including a magnetorheological fluid flexible capsule and a magnetic field generator, the magnetic field generator provides a variable magnetic field for the magnetorheological fluid flexible capsule, and the intensity of the action of the soft robot and the magnetorheological fluid flexible device on the bionic stomach can be adjusted; a rehydration module, including a stomach rehydration device, for rehydrating the stomach module. A control method based on the software-driven model animal in vitro digestive system is also provided, and the above system and method can truly and effectively simulate the in vitro digestion process of the model animal.

Description

Technical Field

[0001] The present invention belongs to the technical field of simulation of in vitro digestive system of model animals, and in particular relates to an in vitro digestive system of model animals based on software drive and a control method thereof. Background Art

[0002] In the study of gastrointestinal function, drug absorption and metabolism, and nutrient digestion, most animals are used as alternatives and important references for gastrointestinal digestion and absorption. Their gastrointestinal anatomy and physiological structure are similar to those of humans. In particular, model animals such as mice, rats, and pigs can represent a large class of organisms in the biological world (such as the class of mammals). Scientific research on them can reveal certain life phenomena with universal laws.

[0003] To this end, researchers have developed a variety of in vitro digestive system models, currently there are two types: static simulation and dynamic simulation, each of which has its own advantages and disadvantages. The existing static simulation structure is simple and easy to evaluate the parameters of the digestion stage, but it cannot reproduce the gastric structure morphology and physiological details of the organism. Dynamic simulation can more realistically reflect the gastric structure morphology and physiological details of the organism. Existing dynamic simulations such as Chinese invention patent CN105702146B disclose a bionic dynamic mouse gastroduodenal digestive system simulation device, which has some bionic gastrointestinal morphology and physiological details, and can simulate the peristaltic contraction of the stomach wall and intestinal wall, but is limited to rats, and its device structure is complex, and the use of rigid structure to mechanically squeeze to achieve gastrointestinal peristalsis lacks authenticity, and cannot simulate the complex and changeable gastrointestinal peristaltic digestion process.

[0004] CN117736840B discloses a rumen-reticulum in vitro fermentation reactor, whose driving device adopts a "cross-shaped" soft robot, which can realize the flexible kneading and relaxation of the rumen to simulate the complex and violent peristalsis and muscle contraction process of the rumen, and realize the up and down movement, rumination and screening of food particles in the rumen. However, the bending amplitude of the "cross-shaped" soft robot cannot fit the stomach of small single-stomach model animals such as mice, and cannot truly simulate the weak peristalsis of their gastrointestinal tract. Summary of the invention

[0005] The technical problem to be solved by the present invention is to overcome the deficiencies and defects mentioned in the above background technology and provide a software-driven in vitro digestion system for model animals and a control method thereof that can truly and effectively simulate the in vitro digestion process of model animals.

[0006] In order to solve the above technical problems, the technical solution proposed by the present invention is: a model animal in vitro digestive system based on software drive, comprising:

[0007] A stomach module, comprising a bionic stomach and a stomach squeezing device for squeezing the bionic stomach, wherein the stomach squeezing device comprises a soft robot and a magnetorheological fluid flexible device, wherein the magnetorheological fluid flexible device comprises a magnetorheological fluid flexible capsule and a magnetic field generator, wherein the magnetic field generator provides a variable magnetic field for the magnetorheological fluid flexible capsule, and the strength of the action of the soft robot and the magnetorheological fluid flexible device on the bionic stomach can be adjusted;

[0008] The fluid replenishment module includes a gastric fluid replenishment device for replenishing fluid to the gastric module.

[0009] In one embodiment, the magnetorheological fluid flexible device is located at the bottom of the bionic stomach, the magnetorheological fluid flexible bag includes a magnetorheological fluid bag cavity and magnetorheological fluid filled in the magnetorheological fluid bag cavity, and the surface of the magnetorheological fluid flexible bag is formed with a supporting surface for fitting the outer surface of the bionic stomach.

[0010] In one embodiment, it also includes a duodenum module, which includes a bionic duodenum hose and a duodenum extrusion device, wherein the duodenum extrusion device includes a peristaltic pump, a paired cam and a fixed wheel, and a flexible intestinal pushing soft robot, and the duodenum extrusion device has an adjustable strength of action on the bionic duodenum hose;

[0011] The fluid infusion module also includes a duodenal fluid infusion device for infusing fluid into the duodenum.

[0012] In one embodiment, the soft robot includes a stomach flexible pushing soft robot and a flexible crushing soft robot, wherein the stomach flexible pushing soft robot is used to squeeze and push the digestion sample in the bionic stomach, and the flexible crushing soft robot is used to crush the digestion sample in the bionic stomach.

[0013] In one embodiment, the stomach flexible pushing soft robot comprises a No. 1 vent and a No. 1 clamp; the No. 1 vent is connected to an external air source, the No. 1 clamp comprises a plurality of independent and interconnected air bags, the No. 1 clamp is provided with a No. 1 non-stretchable coating near the bionic stomach, and the other positions are provided with a No. 1 soft rubber layer;

[0014] The intestinal flexible pushing soft robot comprises a No. 2 vent and a No. 2 clamp; the No. 2 vent is connected to an external air source, the No. 2 clamp comprises a plurality of independent and interconnected air bags, the No. 2 clamp close to the bionic duodenal hose is a No. 2 non-stretchable coating, and the other positions are a No. 2 soft rubber layer;

[0015] The flexible crushing soft robot includes a No. 3 air vent and a flexible airbag, wherein the No. 3 air vent is connected to an external air source; the center position of the flexible airbag near the bionic stomach is a No. 3 soft rubber layer, and the other positions are a No. 3 non-stretchable coating.

[0016] In one embodiment, it also includes a position adjustment mechanism, which is used to adjust the positions of the stomach flexible pushing soft robot and the flexible crushing soft robot.

[0017] In one embodiment, the gastric infusion device comprises a No. 1 syringe pump and a gastric juice secretion tube, and the duodenal infusion device comprises a No. 2 syringe pump, a bile secretion tube, a No. 3 syringe pump and a pancreatic juice secretion tube.

[0018] In one embodiment, an auxiliary module is further included, and the auxiliary module includes an esophagus, a gastrointestinal connector, a sampling tube, a heating lamp, and a circulation fan.

[0019] Based on the general inventive concept, a control method for the in vitro digestive system of a model animal based on software drive as described above is also provided, comprising:

[0020] injecting simulated gastric fluid of predetermined volume and composition into the bionic stomach through a gastric rehydration device;

[0021] The pre-treated digestive sample was quantitatively injected into the bionic stomach through the esophagus;

[0022] The soft robot and magnetorheological fluid flexible device of the stomach squeezing device drive the bionic stomach to peristalsis, squeeze and release different parts of the bionic stomach at set time intervals, and use the gastric rehydration device to replenish simulated gastric fluid into the bionic stomach so that the digestive sample and the simulated gastric fluid are fully mixed; different peristaltic intensities are provided for the bionic stomach by adjusting the stomach squeezing device.

[0023] In one embodiment, it also includes: driving the peristalsis of the bionic duodenal tube by a duodenal extrusion device, and injecting simulated intestinal fluid into the bionic duodenal tube using a duodenal rehydration device to simulate the digestion process of the digestive sample in the bionic duodenal tube, wherein during the peristalsis of the bionic duodenal tube, different peristaltic intensities are provided to the bionic duodenal tube by adjusting the duodenal extrusion device.

[0024] Compared with the prior art, the beneficial effects of the present invention are as follows: in the soft-driven model animal in vitro digestion system of the present invention, the stomach squeezing device includes a soft robot and a magnetorheological fluid flexible device, and the soft robot and the magnetorheological fluid flexible device act together on the bionic stomach; by adjusting the intensity and time of the soft robot and the magnetorheological fluid flexible device acting on the bionic stomach, the control dimensions of the contraction and relaxation of the gastrointestinal muscles, the peristalsis of the stomach wall, etc. are increased, so as to simulate the contraction and relaxation of the gastrointestinal muscles, the peristalsis of the stomach wall and the physical digestion process of the digestion sample in the real digestion process, and utilize the rehydration module and the like to simulate the continuous secretion of the digestive fluid in the real digestion process to realize the chemical digestion of the digestion sample; by simulating the process of gradual emptying of the digestion sample, etc., the bionics of the stomach structure and some physiological details are fully realized. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0026] Figure 1 A schematic diagram of the structure of a stomach module of a model animal in vitro digestive system based on software drive according to one embodiment;

[0027] Figure 2 This is a schematic diagram of the structure of a duodenum module of a model animal in vitro digestive system based on software drive according to one embodiment;

[0028] Figure 3 This is a schematic diagram of the structure of a magnetorheological fluid flexible device based on a software-driven model animal in vitro digestive system according to one embodiment;

[0029] Figure 4 A schematic structural diagram of another perspective of a magnetorheological fluid flexible device based on a software-driven model animal in vitro digestive system according to an embodiment;

[0030] Figure 5 This is a schematic diagram of the structure of a fluid replenishment device for a model animal's in vitro digestive system based on software drive according to one embodiment.

[0031] Figure numerals: 1: stomach module, 11: bionic stomach, 111: one-way valve, 112: pyloric valve, 12: stomach squeezing device, 121: stomach flexible pushing soft robot, 122: flexible crushing soft robot, 1211: No. 1 vent, 1212: No. 1 clamp, 1221: No. 3 vent, 1222: flexible airbag, 123: position adjustment mechanism, 124: magnetorheological fluid flexible sac, 1241: support surface, 1242: magnetorheological fluid sac cavity, 1243: magnetorheological fluid, 125: magnetic field generator, 2: duodenum module, 21: bionic duodenum soft Tube, 22: Duodenal extrusion device, 221: Peristaltic pump, 222: Cam, 223: Fixed wheel, 224: Intestinal flexible pushing software robot, 2241: No. 2 vent, 2242: No. 2 clamp, 3: Rehydration module, 31: Gastric rehydration device, 311: No. 1 injection pump, 312: Gastric juice secretion tube, 32: Duodenal rehydration device, 321: No. 2 injection pump, 322: Bile secretion tube, 323: No. 3 injection pump, 324: Pancreatic juice secretion tube, 4: Auxiliary module, 41: Esophagus, 42: Oblique three-way valve, 43: Four-way tube, 44: Gastric sampling tube. DETAILED DESCRIPTION

[0032] In order to facilitate the understanding of the present invention, the present invention will be described more comprehensively and meticulously below in conjunction with the accompanying drawings and preferred embodiments of the present invention, but the protection scope of the present invention is not limited to the following specific embodiments.

[0033] Unless otherwise defined, all professional terms used below have the same meanings as those generally understood by those skilled in the art. The professional terms used herein are only for the purpose of describing specific embodiments and are not intended to limit the scope of protection of the present invention.

[0034] Unless otherwise specified, various raw materials, reagents, instruments and equipment used in the present invention can be purchased from the market or prepared by existing methods.

[0035] like Figure 1-5 As shown, a model animal in vitro digestion system based on soft drive includes a stomach module 1, a duodenum module 2, a rehydration module 3, and an auxiliary module 4. The stomach module includes a bionic stomach 11 and a stomach squeezing device 12. The stomach squeezing device 12 includes a soft robot and a magnetorheological fluid flexible device, and the strength of the soft robot and the magnetorheological fluid flexible device acting on the bionic stomach 11 can be adjusted. Furthermore, it also includes a duodenum module 2, and the duodenum module 2 includes a bionic duodenum hose 21 and a duodenum squeezing device 22. The duodenum squeezing device 22 includes a peristaltic pump 221, a paired cam 222 and a fixed wheel 223, and an intestinal flexible pushing soft robot 224. The rehydration module 3 includes a gastric rehydration device 31 and a duodenal rehydration device 32, which are used to deliver simulated gastric juice, simulated bile and simulated pancreatic juice to the bionic stomach 11 and the bionic duodenal hose 21 respectively; the auxiliary module 4 includes an esophagus 41, an oblique three-way valve 42, a four-way tube 43, a gastric sampling tube 44, and a heating and heat preservation device. In one embodiment, the duodenal module and the corresponding rehydration template may not be provided, and only the gastric module 1 and the corresponding structural settings are included. The auxiliary module 4 provides some auxiliary functions, which can be selected according to actual conditions.

[0036] In the above-mentioned software-driven model animal in vitro digestion system, the stomach squeezing device 12 includes a soft robot and a magnetorheological fluid flexible device, which act on the bionic stomach 11 together through the soft robot and the magnetorheological fluid flexible device; by adjusting the intensity and time of the soft robot and the magnetorheological fluid flexible device acting on the bionic stomach 11, the control dimensions of the contraction and relaxation of the gastrointestinal muscles, the peristalsis of the stomach wall and the intestinal wall are increased, so as to simulate the contraction and relaxation of the gastrointestinal muscles, the peristalsis of the stomach wall and the intestinal wall in the real digestion process, and the physical digestion process of the digestion sample; the continuous secretion of digestive fluid in the real digestion process is simulated by the rehydration module 3, etc. to realize the chemical digestion of the digestion sample; the process of simulating the gradual emptying of the digestion sample, etc., fully realizes the bionics of the gastrointestinal structure and some physiological details.

[0037] Specifically, in one embodiment, the stomach squeezing device 12 includes a stomach flexible pushing soft robot 121, a flexible crushing soft robot 122, a position adjustment mechanism 123, a magnetorheological fluid flexible capsule 124, and a magnetic field generator 125. The stomach flexible pushing soft robot 121 is used to squeeze and push the digestion sample in the bionic stomach 11, and the flexible crushing soft robot 122 is used to crush the digestion sample in the bionic stomach 11. The position adjustment mechanism 123 is used to realize the position and angle adjustment function of the stomach flexible pushing soft robot 121 and the flexible crushing soft robot 122, and adjust the stomach flexible pushing soft robot 121 and the flexible crushing soft robot 122 to a suitable distance and angle with the change of the bionic stomach 11 model, so as to better control the magnitude of the force applied by the stomach flexible pushing soft robot 121 and the flexible crushing soft robot 122 on the bionic stomach 11.

[0038] Specifically, in one embodiment, the magnetorheological fluid flexible capsule 124 includes a magnetorheological fluid capsule cavity 1242 and a magnetorheological fluid 1243 filled in the magnetorheological fluid capsule cavity 1242. The surface of the magnetorheological fluid flexible capsule 124 is formed with a supporting surface 1241 for fitting the outer surface of the bionic stomach 11. Preferably, the supporting surface 1241 is a reverse mold supporting surface formed by reverse molding according to the shape of the bionic stomach 11. The surface of the magnetorheological fluid flexible capsule 124 is made by reverse molding, and it is completely fitted with the outer surface of the bionic stomach 11, so that the contact area between the supporting surface 1241 and the bionic stomach 11 is the largest, and the magnetorheological fluid flexible capsule 124 has the largest action surface on the bionic stomach 11, which can better act on the bionic stomach 11 with the changes in viscosity and hardness of the magnetorheological fluid 1243 in the magnetorheological fluid flexible capsule 124. Preferably, the magnetorheological fluid capsule cavity 1242 is filled with a proper amount of magnetorheological fluid 1243, and the magnetorheological fluid 1243 is sealed in the magnetorheological fluid capsule cavity 1242, and the magnetorheological fluid capsule cavity 1242 is controlled to have no air gap as much as possible, thereby improving the durability and stability of the magnetorheological fluid 1243.

[0039] Specifically, in one embodiment, the magnetorheological fluid flexible bag 124 is made of soft material and is disposed directly below the bionic stomach 11 to fix the spatial position of the lower half of the bionic stomach 11 and provide support for the bionic stomach 11 .

[0040] Specifically, in one embodiment, the magnetic field generator 125 is disposed below the magnetorheological fluid flexible capsule 124. Preferably, the top of the magnetic field generator 125 has an inner concave surface for supporting the magnetorheological fluid flexible capsule 124, thereby fixing the position of the magnetorheological fluid flexible capsule 124 and limiting the morphological change of the magnetorheological fluid flexible capsule 124 to a certain extent.

[0041] When the magnetic field generator 125 is working, by controlling the direction of the magnetic field and the magnetic induction intensity, the viscosity and hardness of the magnetorheological fluid 1243 in the magnetorheological fluid flexible capsule 124 change according to the direction of the magnetic field and the distribution of the magnetic induction intensity, thereby adjusting the process parameters such as the equivalent strain and equivalent stress of the magnetorheological fluid flexible device acting on the bionic stomach 11 to simulate the different intensity changes of real gastric peristalsis. The magnetorheological fluid flexible device matches the squeezing effect of the soft robot under different air pressures, and the magnetorheological fluid flexible device and the soft robot jointly adjust the simulated peristalsis process of the bionic stomach 11.

[0042] Specifically, in one embodiment, the contraction and relaxation of the stomach flexible pushing soft robot 121 is used to drive the contraction and relaxation of the bionic stomach 11 to push the digestion sample to the main digestion area of ​​the bionic stomach 11. The contraction and relaxation of the flexible crushing soft robot 122 is used to drive the contraction and relaxation of the main digestion area of ​​the bionic stomach 11 to physically squeeze the digestion sample and crush it into a certain size.

[0043] Specifically, the stomach flexible pushing soft robot 121 is made of soft material. The number of stomach flexible pushing soft robots 121 can be set to one or more as needed. The stomach flexible pushing soft robot 121 includes a No. 1 vent 1211 and a No. 1 clamp 1212. The No. 1 clamp 1212 contains a plurality of independent and interconnected air bags. The No. 1 vent 1211 of the stomach flexible pushing soft robot 121 is connected to the pneumatic control system. The contraction and relaxation of the No. 1 clamp 1212 are controlled by the change of air pressure inside the stomach flexible pushing soft robot 121 to squeeze the bionic stomach 11, which is used to simulate the contraction and relaxation of real stomach muscles, and peristaltically propel the digested sample in the stomach to move to the main digestive area of ​​the bionic stomach 11. Preferably, the No. 1 clamp 1212 is close to the bionic stomach 11 as a No. 1 non-stretchable coating, and the other positions are a No. 1 soft rubber layer. The No. 1 clamp 1212 is roughly in the shape of a strip. Since the No. 1 clamp 1212 squeezes the bionic stomach 11 by changing the internal air pressure, the position close to the bionic stomach 11 is set as a non-stretchable coating, and the elastic stretching of the No. 1 soft rubber layer at other positions is used to produce deformation to push the bionic stomach 11. The non-stretchable coating has a certain rigidity, and combined with the deformation effect of the No. 1 soft rubber layer at other positions, a better pushing effect is achieved.

[0044] Similarly, the intestinal flexible pushing soft robot 224 is made of soft material. The number of intestinal flexible pushing soft robots 224 can be set to one or more as needed. The intestinal flexible pushing soft robot 224 includes a No. 2 vent 2241 and a No. 2 clamp 2242. The No. 2 vent is connected to an external air source, and the No. 2 clamp 2242 includes a plurality of independent and interconnected air bags. The No. 2 clamp 2242 is a No. 2 non-stretchable coating near the bionic duodenal hose 21, and the other positions are No. 2 soft rubber layers. The No. 2 clamp 2242 is roughly in the shape of a strip. The elastic stretching of the No. 2 soft rubber layer at other positions is used to produce deformation to push the bionic duodenal hose 21. The non-stretchable coating has a certain rigidity, and combined with the deformation effect of the No. 2 soft rubber layer at other positions, a better pushing effect is achieved.

[0045] Specifically, in one embodiment, the flexible crushing soft robot 122 includes a No. 3 vent 1221 and a flexible airbag 1222. The flexible crushing soft robot 122 is connected to the pneumatic control system through the No. 3 vent 1221, and the contraction and relaxation of the flexible airbag 1222 are controlled by the air pressure change of the flexible crushing soft robot 122 to drive the peristalsis of the bionic stomach 11, which is used to simulate the contraction and relaxation of real stomach muscles, and squeeze the digestion sample in the stomach into a digestion sample of a certain size. Preferably, the flexible airbag 1222 is roughly spherical, and the No. 3 soft layer is near the center of the bionic stomach 11 (the position that fits the bionic stomach 11), and the other positions are the No. 3 non-stretchable coating. The flexible airbag 1222 is roughly spherical. When the air pressure is adjusted, the other positions do not deform, but the No. 3 soft layer near the bionic stomach 11 at the center of the flexible airbag 1222 is deformed, such as bulging upwards. This setting method is used to achieve better extrusion and crushing.

[0046] Specifically, in one embodiment, the bionic duodenal hose 21 is bent into a certain arc to simulate the direction of the duodenum in a real body. The duodenal extrusion device 22 is arranged along the bionic duodenal hose 21. The peristaltic pump 221 in the duodenal extrusion device 22 is fixed to the front end of the bionic duodenal hose 21. The duodenal hose 21 is used to receive the digestion sample and digestive fluid mixture transported from the stomach module 1, and pumped to the middle and rear sections of the bionic duodenal hose 21 in sections through the peristaltic pump 221, wherein the mixture includes gastric digestion samples, simulated gastric fluid, simulated bile and simulated pancreatic fluid. The outer rings of the cam 222 and the fixed wheel 223 are both wrapped with a layer of soft material. The cam 222 and the fixed wheel 223 are fixed on both sides of the bionic duodenal hose 21. The maximum and minimum distances between the cam 222 and the fixed wheel 223 are respectively the outer diameter of the bionic duodenal hose 21 and twice the wall thickness. They are used to squeeze the digestion sample and digestive fluid mixture in the bionic duodenal hose 21 and peristaltically transport them to the rear section to simulate the peristaltic digestion of the real duodenum.

[0047] The intestinal flexible pushing soft robot 224 is made of soft material and is used to squeeze the rear section of the bionic duodenal tube 21 to simulate the peristaltic digestion of a real duodenum.

[0048] Specifically, in one embodiment, the bionic stomach 11 is a soft stomach made of soft material + 3D printing technology. The bionic stomach 11 can be roughly divided into a glandless area, a cardia area, a fundus area, and a pyloric area, which are divided differently according to the different model animals simulated. The glandless area is used to connect the cardia and the cardia area, and a one-way valve 111 is provided at the front end of the cardia, and the one-way valve 111 is connected to the esophagus 41. The one-way valve 111 is used to prevent the reflux of the digested sample in the bionic stomach to simulate the control of the cardia sphincter in the real stomach on the connection between the esophagus 41 and the stomach. The cardia area is mainly used to store food and secrete mucus to help lubricate food. The gastric fundus region is the main digestive region of the bionic stomach 11, and is provided with a gastric rehydration port, which is connected to the gastric juice secretion tube 312. The gastric rehydration port is used to replenish simulated gastric juice into the bionic stomach 11 to simulate the secretion of gastric juice in the real stomach. The gastric juice mainly contains gastric acid (hydrochloric acid) and digestive enzymes (such as pepsin, etc.). The pyloric region is used to connect the pyloric orifice and the gastric fundus region. The rear end of the pyloric orifice is provided with a pyloric valve 112, which is connected to the bionic duodenal hose 21. It is used to screen the digested mixture to ensure that only liquid and digested sample mixtures smaller than a certain size can enter the bionic duodenal hose 21 through the pyloric valve 112 to continue digestion, so as to simulate the real gastric emptying process. The middle part of the gastric fundus region of the bionic stomach 11 is connected to the No. 1 injection pump 311 through the gastric juice secretion tube 312, which is used to continuously pump simulated gastric juice to simulate the real gastric juice secretion process.

[0049] Specifically, in one embodiment, the gastric module 1 and the duodenal module 2 are sequentially connected through an inclined three-way valve 42 and a four-way pipe 43. One end of the feed port of the inclined three-way valve 42 is connected to the bionic stomach 11 through the pyloric valve 112. One end of the discharge port of the inclined three-way valve 42 is connected to the feed port of the four-way pipe 43, and the other end is connected to the gastric sampling pipe 44. The end of the gastric sampling pipe 44 is used to periodically receive the mixture sample that has been digested by the gastric module 1. The "屮"-shaped feed port of the four-way pipe 43 is respectively connected to the discharge port of the inclined three-way valve 42, the bile secretion pipe 322, and the pancreatic juice secretion pipe 324. The discharge port of the four-way pipe 43 is connected to the bionic duodenal hose 21; the free end of the bionic duodenal hose 21 is used to periodically receive the mixture sample that has been digested by the duodenal module 2. The inclined three-way valve 42 is used to control the flow direction of the mixture that has been digested by the gastric module 1, either to continue the simulated digestion in the duodenal module 2 or for sampling and inspection. The four-way pipe 43 is used to receive the mixture digested by the gastric module 1, mix the simulated bile and the simulated pancreatic juice, and then transport them to the duodenal module 2 for digestion; therefore, the inclined three-way valve 42 and the four-way pipe 43 can also be any device that can achieve this function, such as a five-way valve, etc. Preferably, in a specific embodiment, the pretreated digestion sample injected through the esophagus 41 can be a mixture of food or drug digestion samples after being fully mixed and broken with the simulated saliva.

[0050] Specifically, in one embodiment, the gastric fluid replenishing device 31 includes a first syringe pump 311 and a gastric juice secretion pipe 312; the duodenal fluid replenishing device includes a second syringe pump 321, a bile secretion pipe 322, a third syringe pump 323, and a pancreatic juice secretion pipe 324. The first syringe pump 311, the second syringe pump 321, and the third syringe pump 323 are used to inject the simulated gastric juice, the simulated bile, and the simulated pancreatic juice into the bionic stomach 11 and the bionic duodenal hose 21 stably and evenly, so they can also be any device that can achieve this function.

[0051] In a specific embodiment, when there is a digestion sample inside the bionic stomach 11, the first syringe pump 311 will continuously pump the simulated gastric juice into the bionic stomach 11 through the gastric juice secretion pipe 312, so as to simulate the continuous secretion of gastric juice by the real stomach for chemical digestion of the digestion sample. When there is a digestion sample inside the bionic duodenal hose 21, the second syringe pump 321 and the third syringe pump 323 will continuously pump the simulated bile and the simulated pancreatic juice into the bionic duodenal hose 21 through the bile secretion pipe 322 and the pancreatic juice secretion pipe 324, so as to simulate the continuous secretion of bile and pancreatic juice by the real duodenum for digestion of the digestion sample.

[0052] The heating and insulation device is used to control the temperature inside the experimental platform to remain relatively constant at the target temperature.

[0053] In a specific embodiment, before the simulation experiment begins, based on the bionic stomach 11 model, the position and angle of the stomach flexible pushing soft robot 121 and the flexible crushing soft robot 122 relative to the bionic stomach 11 are adjusted by the position adjustment mechanism 123 to adjust the force applied by the stomach flexible pushing soft robot 121 and the flexible crushing soft robot 122 so as to restore the gastric peristalsis digestion process of different model animals under different conditions.

[0054] In a specific embodiment, during the peristalsis of the stomach, the bionic stomach 11 has two driving states: ① When the pyloric valve 112 is closed, the stomach flexible pushing soft robot 121 and the flexible crushing soft robot 122 alternately compress and relax the bionic stomach 11. ② When the pyloric valve 112 is open, the flexible crushing soft robot 122 compresses and relaxes the bionic stomach 11.

[0055] The peristalsis of the gastric squeezing device 12 is divided into three levels: enhanced peristalsis, normal peristalsis and weakened peristalsis; the operation of the simulated peristalsis within a cycle can be set according to the peristaltic rules of different model animals (the combination of peristaltic levels and times can be freely set); the peristaltic frequency, digestive fluid secretion frequency, and emptying frequency are all set according to the different model animals simulated.

[0056] In one embodiment, the three peristaltic modes may be specifically:

[0057] 1. Peristalsis enhancement: The magnetic field generator 125 operates at maximum power, the applied magnetic induction intensity is maximum, and the soft robot maintains maximum air pressure.

[0058] 2. Normal peristalsis: The magnetic field generator 125 is running, applying a certain magnetic induction intensity, and the air pressure inside the soft robot is kept at an appropriate level during operation.

[0059] 3. Weakened peristalsis: The magnetic field generator 125 does not operate, and the air pressure inside the soft robot is maintained at an appropriate level during operation.

[0060] The following parameters are also set during the digestion process: peristaltic mode, peristaltic frequency, pressure applied by jaw No. 1212, jaw No. 2242 and flexible airbag 1222, electromagnetic field strength, time interval for switching of stomach drive states, frequency of compression and relaxation of jaw No. 1212, jaw No. 2242 and flexible airbag 1222, rotation speed of the cam, opening interval of the sampling valve, etc.

[0061] In one embodiment, a method for controlling an in vitro digestive system of a model animal based on software drive comprises the following steps:

[0062] S110, injecting simulated gastric fluid of a predetermined volume and composition into the bionic stomach through a gastric rehydration device;

[0063] S120, quantitatively injecting the pretreated digestion sample into the bionic stomach through the esophagus;

[0064] S130. The stomach is subjected to bionic peristalsis by means of a soft robot of a stomach squeezing device and a magnetorheological fluid flexible device. Different parts of the bionic stomach are squeezed and released at set time intervals. Simultaneously, the bionic stomach is supplemented with simulated gastric fluid by means of a gastric rehydration device so that the digestive sample is fully mixed with the simulated gastric fluid. Different peristaltic intensities are provided for the bionic stomach by adjusting the stomach squeezing device.

[0065] Specifically, the bionic stomach peristalsis is driven by a stomach squeezing device to simulate the digestion process of the digestive sample in the stomach. The stomach squeezing device consists of a soft robot and a magnetorheological fluid flexible device distributed around the bionic stomach. The soft robot is independently controlled by a precise control system and cooperates with the magnetorheological fluid flexible device to simulate the peristaltic movement intensity of the biological stomach. The control system gradually activates and controls these soft robots according to the preset peristaltic mode and frequency, and cooperates with the magnetorheological fluid flexible capsule with variable hardness to apply pressure to various parts of the bionic stomach in sequence, so that the inner wall of the bionic stomach produces orderly wavy contractions.

[0066] In one embodiment, it further comprises:

[0067] S140, driving the bionic duodenal tube to peristalsis through the duodenal extrusion device, and injecting simulated intestinal fluid into the bionic duodenal tube using the duodenal rehydration device to simulate the digestion process of the digestive sample in the bionic duodenal tube, wherein during the peristalsis of the bionic duodenal tube, the duodenal extrusion device is adjusted to provide different peristaltic intensities for the bionic duodenal tube.

[0068] Among them, different peristaltic intensities include peristalsis enhancement, normal peristalsis and peristalsis weakening. The peristaltic intensity is adjusted by controlling the air pressure of the soft robot and the magnetic field strength of the magnetorheological fluid flexible device.

[0069] Specifically, all processes of the control method of the in vitro digestion device include four stages: a preparation stage, a feeding process, a regular peristalsis and digestion stage, and a sampling stage.

[0070] The specific steps include:

[0071] (1) Preparation and filling of digestive juice: Prepare the digestive juice according to the corresponding formula, fill the No. 1 injection pump 311, the gastric juice secretion tube 312, the No. 2 injection pump 321, the bile secretion tube 322, the No. 3 injection pump 323 and the pancreatic juice secretion tube 324 with the corresponding digestive juice, and connect one end of the gastric juice secretion tube 312 to the No. 1 injection pump 311, one end of the bile secretion tube 322 to the No. 2 injection pump 321, and one end of the pancreatic juice secretion tube 324 to the No. 3 injection pump 323.

[0072] (2) Assemble the modules in the system: fix the bionic stomach 11, connect the esophagus 41, the gastric juice secretion tube and the pyloric valve 112; the other end of the pyloric valve 112 is connected to the oblique three-way valve 42, and the oblique three-way valve 42 is respectively connected to the gastric sampling tube 44 and the four-way tube 43, keep the valve of the gastric sampling tube 44 closed and the four-way tube 43 connected; the left and right ends of the four-way tube 43 are respectively connected to the other end of the bile secretion tube 322 and the other end of the pancreatic juice secretion tube 324, and the end is connected to the bionic duodenal hose 21; set the stomach flexible pushing soft robot 121 and the flexible crushing soft robot 122 to the appropriate position and angle.

[0073] (3) Adjust the temperature in the system: Turn on the heating and insulation device in the system to keep the temperature in the system stable at the set temperature.

[0074] (4) Preparation of digestion samples: Place the digestion sample in deionized water containing simulated saliva (1:1, V:V), stir and crush it thoroughly to simulate the chewing process of the digestion sample in the mouth.

[0075] (5) Injecting gastric juice into the bionic stomach 11: A certain amount of simulated gastric juice is injected into the bionic stomach 11 through the No. 1 injection pump 311 to simulate the residual gastric juice in the stomach in the fasting state.

[0076] (6) Injecting the digestion sample into the bionic stomach 11: Injecting the digestion sample prepared in step (4) into the bionic stomach 11 through the esophagus at one time.

[0077] (7) Simulating the digestion process of the bionic stomach 11 and the bionic duodenal tube 21: the pyloric valve 112 is opened and closed regularly, and the bionic stomach 11 is driven to move by the stomach squeezing device 12 to simulate the physical digestion process of the stomach. Simultaneously, the bionic stomach is continuously injected with simulated gastric juice by the gastric rehydration device 31 to simulate the chemical digestion process of the stomach. The gastric digestion sample can be regularly collected by opening the valve of the gastric sampling tube 44. When the gastric digestion sample is not sampled, the digestion sample will continue to flow to the four-way tube 43 through the inclined three-way valve 42. At the same time, the duodenal insufflation device 32 also continuously injects simulated bile and simulated pancreatic juice into the four-way tube 43, and the three are mixed and flow into the bionic duodenal hose 21, and the bionic duodenal hose 21 is driven to peristalsis by the duodenal extrusion device 22 to simulate duodenal digestion; according to the peristaltic law of different model animals, the operation status of the simulated peristalsis within a cycle is set by itself (the combination of peristaltic level and number can be freely set); the peristaltic frequency, digestive fluid secretion frequency, and emptying frequency are all set according to the different model animals simulated.

[0078] (8) Recording the digestion process in time periods: During the digestion process in step (7), the digestion process is divided into several time periods. The stomach squeezing device 12, the duodenal squeezing device 22, and the rehydration module 3 are stopped once in each time period. The samples after digestion from the bionic stomach 11 and the bionic duodenal tube 21 are collected using a sample collection device. The pH, gastric emptying rate, storage modulus, loss modulus, dynamic viscosity, and apparent viscosity thereof are measured and recorded, and the microstructure thereof is observed. Then, the stomach squeezing device 12, the duodenal squeezing device 22, and the rehydration module 3 are opened, and the experiment is continued until all the digested samples are discharged from the bionic duodenal tube 21. The pH, gastric emptying rate, storage modulus, loss modulus, dynamic viscosity, and apparent viscosity of the digested samples finally discharged are measured and recorded, and the microstructure thereof is observed.

[0079] (9) Cleaning the entire device: After the experiment, clean the device modules in the entire system with deionized water in time and keep them dry.

[0080] Currently, among many mammals, only mice (small mammals) and pigs (neutral mammals) are model animals. Their stomachs can be roughly divided into the glandless area, the cardia area, the fundus area, and the pyloric area. This device can dynamically simulate the gastrointestinal peristalsis and digestion of model animals. Specific embodiment 1:

[0082] In one specific embodiment, the present invention is used to simulate the digestive process of the gastrointestinal tract of a small model animal. Taking the gastrointestinal tract of a normal healthy adult SD rat as an example, the corresponding bionic model is replaced with a bionic rat gastrointestinal tract model.

[0083] The dimensions of the bionic rat stomach are 40(±2)×30(±2)×20(±2)mm in length×width×height, and the volume is 9.0±1.0ml. The wall thickness of the forestomach (glandless area) of the bionic rat stomach is 0.65±0.15mm, and the wall thickness of the glandular stomach (stomach fundus area) is 1.50±0.25mm.

[0084] The dimensions of the stomach flexible pushing software robot 121 are: length×width×height: 45×30×22 mm, and the maximum negative pressure stroke is 23 mm.

[0085] The airbag diameter of the flexible crushing soft robot 122 is 30 mm, the height is 10.5 mm, and the maximum stroke is 13 mm.

[0086] The magnetic field generator 125 activates only one electromagnet located in the middle.

[0087] The length of the bionic rat duodenum was 100±1mm, the inner diameter was 3.0±0.1mm, and the outer diameter was 5.0±0.1mm.

[0088] The dimensions of the intestinal flexible pushing soft robot 224 are: length×width×height: 45×30×22mm, and the maximum negative pressure stroke is 23mm.

[0089] Follow these steps to complete the simulation:

[0090] (1) Preparation and filling of digestive fluid: simulated saliva was prepared with α-amylase (≥150 units / mg protein) (19.90 mg, equivalent to 2985 units of α-amylase per gram of dry sample), NaCl (0.117 mg / ml), KCl (0.149 mg / ml) and NaHCO3 (2.1 mg / ml), and the pH was adjusted to 7.8 with 1 M NaOH; simulated gastric juice was prepared with pepsin (≥250 units / mg solid), NaHCO3 (0.315 mg / ml), and NaCl (8.775 mg / ml), and the pH was adjusted to 1.6 with 1 mol / L HCl; simulated pancreatic juice and simulated bile were prepared with pancreatin (9.46 mg / g dry sample), bile salts (28.38 mg / g dry sample) and NaHCO3 (4.5 mg / ml), and the pH was adjusted to 1.6 with 1 M Adjust the pH to 7.5 with NaOH; fill the prepared digestive fluid into the corresponding injection pump and secretion pipeline, and connect them.

[0091] (2) Assemble the modules in the system.

[0092] (3) Adjust the temperature in the system to a stable 37°C.

[0093] (4) Preparation of digestion samples: 200 mg of starch sample was added to 2.0 ml of deionized water and boiled for 15 min until gelatinized. Then, the starch sample was mixed evenly with 2.0 ml of simulated saliva to simulate the chewing process.

[0094] (5) Injection of gastric juice into the bionic mouse stomach: Inject 0.6 ml of simulated gastric juice into the bionic mouse stomach to simulate the residual gastric juice in the fasting state.

[0095] (6) Inject digestive samples into the bionic rat stomach.

[0096] (7) Simulating the digestive process of the bionic rat stomach and bionic rat bionic duodenal tube, referring to the peristaltic process in normal healthy SD rats, the simulated gastric peristalsis frequency was set to 5.6±0.1 times / min, and two weakened peristalsis, five normal peristalsis, and three enhanced peristalsis were performed in one simulated gastric peristalsis cycle. After running two gastric peristalsis cycles, the pyloric valve 112 was opened, and the flexible crushing soft robot 122 was compressed and relaxed alternately. At the same time, the magnetic field generator 125 activated the electromagnet in the center at maximum power to harden the magnetorheological fluid flexible device to achieve gastric emptying, which was less than one The digestion sample and gastric juice mixture of a fixed size flows to the bionic mouse bionic duodenal hose through the pyloric valve 112, and flows into the bionic mouse bionic duodenal hose after mixing with the pancreatic juice and bile, and is peristalticized at a frequency of 15.0±0.1 times / minute through the combination of the peristaltic pump 221, the cam 222, the fixed wheel 223 and the intestinal flexible pushing soft robot 224; during this process, the simulated gastric juice is injected into the bionic mouse stomach at a rate of 1.2ml / h, and the simulated pancreatic juice and simulated bile are injected into the bionic mouse bionic duodenal hose at a rate of 0.8ml / h and 0.3ml / h, respectively.

[0097] (8) Recording the digestion process in different time periods: During the digestion process, stop the operation of the stomach squeezing device 12, the duodenal squeezing device 22 and the rehydration module 3 after 10, 20, 30, 60, 90, 120 and 180 minutes of digestion, use the sample collection device to collect the digested samples from the bionic rat stomach and the bionic rat bionic duodenal tube, respectively, measure and record their pH, use deionized water to quickly rinse to stop the reaction, and then measure and record the particle size, SEM imaging, glucose concentration, etc. After collecting the digested samples, close the sampling valve, start the stomach squeezing device 12, the duodenal squeezing device 22 and the rehydration module 3 again to continue the digestion process until all the digested samples are discharged from the bionic rat stomach and the bionic rat bionic duodenal tube, and measure and record the pH, particle size, SEM imaging, glucose concentration, etc. of the finally discharged digested samples.

[0098] (9) Clean all equipment.

[0099] The above experimental results show that after different digestion times, the particle size, particle surface and glucose concentration of the starch samples in the stomach are consistent with the results of the in vivo experiment, and there is no significant difference (P>0.05). Compared with the results of the in vivo mouse experiment and the in vitro experiment, the pH first increased and then gradually decreased to about 2.73 with the increase of digestion time. As the in vitro digestion progressed, the particle size of the starch digestion samples also gradually decreased. The proportion of starch particles with larger particle size (d>1.0 mm) gradually decreased from the initial 14% to 3%, while the proportion of starch particles with small particle size (d<0.65 mm) gradually increased from the initial 58% to 82%. In the initial stage of in vitro digestion, a large number of small debris appeared on the surface of the dense starch particles and the tissue structure was loose, indicating enzymatic hydrolysis; as the digestion process progressed, the fine debris on the surface and inside of the particles was gradually replaced by holes of different sizes, presenting an irregular "honeycomb shape". The glucose concentration increased rapidly within the first 60 min of the in vitro digestion process, reaching 9 mg / mL; after 180 min of the in vitro digestion experiment, the glucose concentration finally reached 9.5 mg / mL. Specific embodiment 2:

[0101] The present invention is used to simulate the digestive process of the gastrointestinal tract of a medium-sized model animal. Taking the gastrointestinal tract of a normal and healthy adult Gotland pig as an example, the corresponding bionic model is replaced with a bionic pig gastrointestinal tract model.

[0102] The dimensions of the bionic pig stomach are 270 (±2) × 200 (±2) × 150 (±2) mm in length × width × height, and the volume is 8.0 ± 0.2 L. The wall thickness of the cardia region of the bionic pig stomach is 3.0 ± 0.2 mm, and the wall thickness of the fundus region is 4.0 ± 0.2 mm.

[0103] The size of the stomach flexible pushing soft robot 121 is 145×45×40mm in length×width×height, and the maximum negative pressure stroke is 80mm. Three stomach flexible pushing soft robots 121 are added above the bionic pig stomach cardia area, and a total of four stomach flexible pushing soft robots 121 are arranged in parallel with a spacing of 7.0±1.0mm, forming a group of flexible pushing soft robot arrays. A group of flexible pushing soft robot arrays is also set at the position of the flexible crushing soft robot.

[0104] The magnetic field generator 125 activates all five electromagnets.

[0105] The length of the bionic porcine duodenum is 800±2mm, the inner diameter is 30.0±0.1mm, and the outer diameter is 33.0±0.1mm.

[0106] The dimensions of the intestinal flexible pushing soft robot 224 are: 62.5×40×35 mm in length×width×height, and the maximum negative pressure stroke is 40 mm. Two sets of cams, fixed wheels and the intestinal flexible pushing soft robot 224 are added.

[0107] Follow these steps to complete the simulation:

[0108] (1) Preparation of digestive fluid and filling: simulated gastric fluid was prepared with pepsin (enzyme activity 30,000 U / g), NaCl (1.295 g / ml), KCl (0.125 g / ml), NaH2PO4 (3.0 g / ml), and C6H7KO2 (0.5 g / ml), and the pH was adjusted to 2.0 with 2 mol / L HCl; simulated intestinal fluid was prepared with pancreatin, bile salts, Na2HPO4 (3.995 g / ml), NaH2PO4 (2.92 g / ml), and C6H7KO2 (0.6325 g / ml), and the pH was adjusted to 7.15 with 1 M NaOH.

[0109] (2) Assemble the modules in the system.

[0110] (3) Adjust the temperature in the system to a stable 39°C.

[0111] (4) Preparation of digestion samples: Grind the feed materials to be tested and pass them through a 40-mesh sieve. Mix thoroughly and set aside.

[0112] (5) Injecting gastric juice into the bionic pig stomach: Inject 100 ml of simulated gastric juice into the bionic pig stomach to simulate the residual gastric juice in the fasting state.

[0113] (6) Inject digestive samples into the bionic pig stomach.

[0114] (7) The digestion process of the bionic pig stomach and the bionic pig duodenal tube was simulated. With reference to the peristaltic process in a normal healthy Gotland pig, the simulated gastric peristaltic frequency was set to be maintained at 3.0±0.1 times / minute. In one simulated gastric peristaltic cycle, 1 weakened peristalsis, 5 normal peristalsis, and 4 enhanced peristalsis were performed. After running 4 gastric peristaltic cycles, the pyloric valve 112 was opened, and the flexible crushing soft robot 122 above the gastric fundus area was compressed and relaxed alternately. At the same time, the magnetic field generator 125 activated all the electromagnets at maximum power to harden the magnetorheological fluid flexible device to achieve gastric emptying. The digestive sample and gastric juice mixture smaller than a certain size flows through the pyloric valve to the bionic pig bionic duodenal hose, mixes with pancreatic juice and bile and flows into the bionic pig bionic duodenal hose, and is peristalticized at a frequency of 11.0±0.1 times / min through the combination of peristaltic pump 221, cam 222, fixed wheel 223 and intestinal flexible pushing soft robot 224; during this process, simulated gastric juice is injected into the bionic pig stomach at a rate of 120ml / h, and simulated pancreatic juice and simulated bile are injected into the bionic pig bionic duodenal hose at rates of 1000ml / h and 100ml / h, respectively.

[0115] (8) Recording the digestion process in different time periods: During the digestion process, stop the operation of the stomach extrusion device 12, the duodenal extrusion device 22 and the rehydration module 3 every hour, use the sample collection device to collect the digested samples of the bionic pig stomach and the bionic pig bionic duodenal tube respectively, measure and record their pH, use deionized water to quickly rinse to stop the reaction, and then measure and record the digestibility of other nutrients including dry matter digestibility and crude protein digestibility. After collecting the digestion samples, close the sampling valve, start the stomach extrusion device 12, the duodenal extrusion device 22 and the rehydration module 3 again to continue the digestion process until all the digestion samples are discharged from the bionic pig stomach and the bionic pig bionic duodenal tube, and measure and record the pH, dry matter digestibility, crude protein digestibility and other nutrient digestibility of the finally discharged digestion samples.

[0116] (9) Clean all equipment.

[0117] The above experimental results show that after the digestion of feed raw materials is completed, the dry matter digestibility, crude fat digestibility, and other nutrient digestibility of the in-stomach digestion samples are consistent with the results of in vivo experiments, and there are no significant differences (P>0.05).

[0118] The dry matter digestibility of corn, rapeseed meal and soybean meal after in vitro digestion was 50.23±0.26%, 24.09±0.37% and 40.65±0.28%, respectively, while the dry matter digestibility of corn, rapeseed meal and soybean meal in in vivo experiments was 56.92±1.14%, 31.87±1.63% and 47.19±1.00%, respectively; the crude protein digestibility of corn, rapeseed meal and soybean meal was 47.39±0.38%, 36.76±0.58% and 50.93±0.77%, respectively. %, while the crude protein digestibility of corn, rapeseed meal and soybean meal in the in vivo experiment was 52.30±2.32%, 39.47±2.16% and 53.53±1.89% respectively; the organic matter digestibility of corn, rapeseed meal and soybean meal was 53.12±0.26%, 26.91±0.53% and 40.75±0.56% respectively, while the organic matter digestibility of corn, rapeseed meal and soybean meal in the in vivo experiment was 56.77±1.26%, 31.57±1.49% and 43.17±1.65% respectively. According to the above experimental data, the in vitro digestion process simulated by the in vitro digestive system of the model animal based on software drive of the present application is very close to the actual digestion process of the living body, and the experimental results of the present application have good parallelism. Specific embodiment 3:

[0120] The present invention is used to simulate the digestion process of the stomach of a medium-sized model animal. Taking the simulation of the stomach of a normal and healthy adult Gotland pig as an example, the corresponding bionic model is replaced with a bionic pig stomach model.

[0121] Follow these steps to complete the simulation:

[0122] (1) Preparation of digestive fluid and filling: simulated gastric fluid was prepared with pepsin (enzyme activity 30000 U / g), NaCl (1.295 g / ml), KCl (0.125 g / ml), NaH2PO4 (3.0 g / ml), and C6H7KO2 (0.5 g / ml), and the pH was adjusted to 2.0 with 2 mol / L HCl;

[0123] (2) Assemble the modules in the system.

[0124] (3) Adjust the temperature in the system to a stable 39°C.

[0125] (4) Preparation of digestion samples: Grind the feed materials to be tested and pass them through a 40-mesh sieve. Mix thoroughly and set aside.

[0126] (5) Injecting gastric juice into the bionic pig stomach: Inject 100 ml of simulated gastric juice into the bionic pig stomach to simulate the residual gastric juice in the fasting state.

[0127] (6) Inject digestive samples into the bionic pig stomach.

[0128] (7) The digestion process of the bionic pig stomach was simulated. With reference to the gastric peristalsis process in a normal healthy Gotland pig, the simulated gastric peristalsis frequency was set to 3.0±0.1 times / min. In one simulated gastric peristalsis cycle, one weakened peristalsis, five normal peristalsis, and four enhanced peristalsis were performed. After running four gastric peristalsis cycles, the pyloric valve 112 was opened, and the flexible crushing soft robot 122 above the gastric fundus area was compressed and relaxed alternately. At the same time, the magnetic field generator 125 activated all electromagnets at maximum power to harden the magnetorheological fluid flexible device to achieve gastric emptying. The digestion sample and gastric fluid mixture smaller than a certain size flowed through the pyloric valve to the sample collection device. During this process, the simulated gastric fluid was injected into the bionic pig stomach at a rate of 120 ml / h.

[0129] (8) Recording the digestion process in different time periods: During the digestion process, stop the operation of the stomach squeezing device 12 and the stomach rehydration device 31 every hour, collect the digested samples of the bionic pig stomach using the sample collection device, measure and record the pH, quickly rinse with deionized water to stop the reaction, and then measure and record the digestibility of other nutrients including dry matter digestibility and crude protein digestibility. After collecting the digestion samples, close the sampling valve, start the stomach squeezing device 12 and the stomach rehydration device 31 again to continue the digestion process until all the digestion samples are discharged from the bionic pig stomach, and measure and record the pH, dry matter digestibility, crude protein digestibility and other nutrient digestibility of the digestion samples finally discharged.

[0130] (9) Clean all equipment.

[0131] The above experimental results show that after the digestion of feed raw materials, the dry matter digestibility, crude fat digestibility, and other nutrient digestibility of the in-stomach digestion samples are consistent with the results of the in-vivo experiment, and there is no significant difference (P>0.05). The dry matter digestibility of corn, rapeseed meal, and soybean meal after in vitro gastric digestion was 12.37±0.29%, 7.49±0.41%, and 14.28±0.33%, respectively, while the dry matter digestibility of corn, rapeseed meal, and soybean meal in the in-vivo experiment was 19.03±1.24%, 14.93±1.72%, and 23.35±1.07%, respectively; the crude protein digestibility of corn, rapeseed meal, and soybean meal was 10.49±0.38%, 9.53±0.61%, and 14.78±0.82%, respectively. %, while the crude protein digestibility of corn, rapeseed meal and soybean meal in the in vivo experiment was 16.24±2.25%, 11.56±2.21% and 18.49±1.86% respectively; the organic matter digestibility of corn, rapeseed meal and soybean meal was 17.52±0.29%, 8.86±0.38% and 16.92±0.53% respectively, while the organic matter digestibility of corn, rapeseed meal and soybean meal in the in vivo experiment was 21.65±1.36%, 14.48±1.57% and 20.74±1.71% respectively. According to the above experimental data, the in vitro digestion process simulated by the in vitro digestive system of the model animal based on software drive of the present application is very close to the actual digestion process of the living body, and the experimental results of the present application have good parallelism.

[0132] According to the above embodiments, in the soft-driven model animal in vitro digestion system and its control method of the present application, the stomach extrusion device includes a soft robot and a magnetorheological fluid flexible device, and the soft robot and the magnetorheological fluid flexible device act on the bionic stomach together; by adjusting the intensity and time of the soft robot and the magnetorheological fluid flexible device acting on the bionic stomach, the contraction and relaxation of the gastrointestinal muscles, the peristalsis of the stomach wall and the intestinal wall are increased, and the contraction and relaxation of the gastrointestinal muscles, the peristalsis of the stomach wall and the intestinal wall in the real digestion process are simulated, and the physical digestion process of the digestion sample is realized, thereby fully realizing the bionics of the gastrointestinal structure and some physiological details. In particular, the magnetic induction intensity is changed to change the viscosity and hardness of the magnetorheological fluid in the soft pouch, and the dimension of the peristaltic drive control of the stomach is increased. At the same time, the process parameters such as equivalent strain and equivalent stress in the soft extrusion process can be regulated by the hardness of the magnetorheological fluid flexible device. Furthermore, "soft material + 3D printing technology" realizes the simulation of structural features such as wrinkles in the stomach; it can more realistically reflect the stomach structure. By using a rehydration module and other means to simulate the continuous secretion of digestive fluid in the real digestion process to achieve chemical digestion of the digestion sample; by simulating the gradual emptying of the digestion sample, etc., the bionics of the gastrointestinal structure and some physiological details are fully realized. This application simulates the gastrointestinal digestion process of model animals of different genders, growth stages, and health conditions by changing some control parameters, such as the direction, size, and frequency of the force applied by the extrusion device, the secretion rate of the digestive fluid, and the emptying rate of the stomach and duodenum, etc., providing a wider range of applicability and further optimizing the research on in vitro bionic dynamic digestion. Sampling through the sampling tube valve facilitates comparative analysis of products at different digestion stages and optimizes the operating procedures of the experimental process.

Claims

1. A model animal in vitro digestive system based on software drive, characterized in that: include: A stomach module, comprising a bionic stomach and a stomach squeezing device for squeezing the bionic stomach, wherein the stomach squeezing device comprises a soft robot and a magnetorheological fluid flexible device, wherein the magnetorheological fluid flexible device comprises a magnetorheological fluid flexible capsule and a magnetic field generator, wherein the magnetic field generator provides a variable magnetic field for the magnetorheological fluid flexible capsule, wherein the magnetorheological fluid flexible device is located at the bottom of the bionic stomach, wherein the magnetorheological fluid flexible capsule comprises a magnetorheological fluid capsule cavity and magnetorheological fluid filled in the magnetorheological fluid capsule cavity, wherein a support surface for fitting the outer surface of the bionic stomach is formed on the surface of the magnetorheological fluid flexible capsule, and the strength of the action of the soft robot and the magnetorheological fluid flexible device on the bionic stomach can be adjusted; wherein the soft robot comprises a stomach flexible pushing soft robot and a flexible crushing soft robot, wherein the stomach flexible pushing soft robot is used for squeezing and pushing digestion samples in the bionic stomach, and the flexible crushing soft robot is used for crushing digestion samples in the bionic stomach; The fluid replenishment module includes a gastric fluid replenishment device for replenishing fluid to the gastric module.

2. The software-driven in vitro digestive system for model animals according to claim 1, characterized in that: It also includes a duodenum module, which includes a bionic duodenum hose and a duodenum extrusion device, wherein the duodenum extrusion device includes a peristaltic pump, a cam and a fixed wheel used in pairs, and a flexible intestinal pushing soft robot, and the duodenum extrusion device has an adjustable strength of action on the bionic duodenum hose; The fluid infusion module also includes a duodenal fluid infusion device for infusing fluid into the duodenum.

3. The software-driven in vitro digestive system for model animals according to claim 2, characterized in that: The stomach flexible pushing soft robot comprises a No. 1 vent and a No. 1 clamp; the No. 1 vent is connected to an external air source, the No. 1 clamp comprises a plurality of independent and interconnected air bags, the No. 1 clamp is provided with a No. 1 non-stretchable coating near the bionic stomach, and the other positions are provided with a No. 1 soft rubber layer; The intestinal flexible pushing soft robot comprises a No. 2 vent and a No. 2 clamp; the No. 2 vent is connected to an external air source, the No. 2 clamp comprises a plurality of independent and interconnected air bags, the No. 2 clamp close to the bionic duodenal hose is a No. 2 non-stretchable coating, and the other positions are a No. 2 soft rubber layer; The flexible crushing soft robot includes a No. 3 air vent and a flexible airbag, wherein the No. 3 air vent is connected to an external air source; the center position of the flexible airbag near the bionic stomach is a No. 3 soft rubber layer, and the other positions are a No. 3 non-stretchable coating.

4. The software-driven in vitro digestive system for model animals according to claim 1, characterized in that: It also includes a position adjustment mechanism, which is used to adjust the positions of the stomach flexible pushing soft robot and the flexible crushing soft robot.

5. The software-driven in vitro digestive system for model animals according to claim 2, characterized in that: The gastric rehydration device comprises a No. 1 injection pump and a gastric juice secretion tube, and the duodenal rehydration device comprises a No. 2 injection pump, a bile secretion tube, a No. 3 injection pump and a pancreatic juice secretion tube.

6. The software-driven in vitro digestive system for model animals according to claim 1, characterized in that: Also included is an auxiliary module, which includes an esophagus, a gastrointestinal connection piece, a sampling tube, a heating lamp, and a circulation fan.

7. A control method for a model animal in vitro digestive system based on software drive according to any one of claims 1 to 6, characterized in that: include: injecting simulated gastric fluid of predetermined volume and composition into the bionic stomach through a gastric rehydration device; The pre-treated digestive sample was quantitatively injected into the bionic stomach through the esophagus; The soft robot and magnetorheological fluid flexible device of the stomach squeezing device drive the bionic stomach to peristalsis, squeeze and release different parts of the bionic stomach at set time intervals, and use the gastric rehydration device to replenish simulated gastric fluid into the bionic stomach so that the digestive sample and the simulated gastric fluid are fully mixed; different peristaltic intensities are provided for the bionic stomach by adjusting the stomach squeezing device.

8. The control method of the in vitro digestive system of a model animal based on software drive according to claim 7, characterized in that: Also includes: The bionic duodenal tube is driven to peristalsis by a duodenal extrusion device, and simulated intestinal fluid is injected into the bionic duodenal tube by a duodenal rehydration device to simulate the digestion process of the digestive sample in the bionic duodenal tube. During the peristalsis of the bionic duodenal tube, different peristaltic intensities are provided to the bionic duodenal tube by adjusting the duodenal extrusion device.

Images