CN118968870B - A model animal in vitro digestive system based on software drive and its control method - Google Patents
A model animal in vitro digestive system based on software drive and its control method Download PDFInfo
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Abstract
本发明属于模式动物体外消化系统模拟装置领域领域，公开了一种基于软体驱动的模式动物体外消化系统，包括：胃部模块，包括仿生胃和用于挤压仿生胃的胃挤压装置，所述胃挤压装置包括软体机器人和磁流变液柔性装置，磁流变液柔性装置包括磁流变液柔性囊和磁场发生器，所述磁场发生器为磁流变液柔性囊提供可变磁场，软体机器人和磁流变液柔性装置作用在仿生胃上的作用强度均可调节；补液模块，包括胃补液装置，用于对胃部模块进行补液。还提供一种基于所述的基于软体驱动的模式动物体外消化系统的控制方法，上述系统和方法可以真实有效地模拟模式动物体外消化过程。
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 includes a soft robot and a magnetorheological fluid flexible device, the magnetorheological fluid flexible device includes 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, which is used to rehydrate 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
The invention belongs to the technical field of simulation of model animal in-vitro digestion systems, and particularly relates to a model animal in-vitro digestion system based on software driving and a control method thereof.
Background
In studying the functional mechanisms of the gastrointestinal tract, drug absorption metabolism and nutrient digestion processes, related animals are mostly used as alternative studies and important references for gastrointestinal tract digestion and absorption, and their gastrointestinal anatomy and physiological structure have similarities to humans. Particularly, animals such as mice, rats, pigs and the like can represent a large class of organisms (such as mammalians) in the biological kingdom, and can reveal a life phenomenon with general rules through scientific research on the animals.
For this reason, researchers have developed a variety of in vitro digestive system models, currently there are two types of static simulation and dynamic simulation, each of which has advantages and disadvantages. The existing static simulation has a simple structure, is easy to evaluate parameters of a digestion stage, but cannot reproduce the stomach structural morphology and physiological detail characteristics of organisms. Dynamic simulation can more truly reflect the stomach structural morphology and physiological detail characteristics of an organism. The existing dynamic simulation is as the Chinese patent No. 105702146B discloses a simulated device of the gastric-duodenal digestive system of a bionic dynamic mouse, which has partial form and physiological details of the bionic gastrointestinal tract, can simulate peristaltic contraction of the gastric wall and the intestinal wall, but is limited to the organism of a rat, and has a complex structure, adopts a rigid structure to mechanically extrude to realize lack of authenticity of gastrointestinal peristalsis, and cannot simulate a complex and changeable gastrointestinal peristalsis digestion process.
CN117736840B discloses an in vitro fermentation reactor for rumen reticulum, a driving device of the in vitro fermentation reactor adopts a cross-shaped soft robot, which can flexibly knead and relax the rumen to simulate complex and severe peristaltic and muscle contraction processes of the rumen, and realize up-and-down movement, rumination and screening of food particles in the rumen. However, the bending amplitude of the cross-shaped soft robot cannot be attached to the stomach of small monogastric mode animals such as mice, and weak peristalsis of the gastrointestinal tract of the small monogastric mode animals cannot be truly simulated.
Disclosure of Invention
The invention aims to solve the technical problems and overcome the defects and shortcomings in the background art, and provides a model animal in-vitro digestion system based on software driving and a control method thereof, which can truly and effectively simulate the in-vitro digestion process of the model animal.
In order to solve the technical problems, the technical scheme provided by the invention is that the model animal in-vitro digestion system based on software driving comprises:
The stomach module comprises a bionic stomach and a stomach extrusion device for extruding the bionic stomach, the stomach extrusion device comprises a soft robot and a magnetorheological fluid flexible device, the magnetorheological fluid flexible device comprises a magnetorheological fluid flexible bag and a magnetic field generator, the magnetic field generator provides a variable magnetic field for the magnetorheological fluid flexible bag, and the action intensity of the soft robot and the magnetorheological fluid flexible device on the bionic stomach can be adjusted;
The fluid infusion module comprises a gastric fluid infusion device and is used for infusing the gastric module.
In an embodiment, the magnetorheological fluid flexible device is located at the bottom of the bionic stomach, the magnetorheological fluid flexible bag comprises a magnetorheological fluid bag cavity and magnetorheological fluid filled in the magnetorheological fluid bag cavity, and a supporting surface for being attached to the outer surface of the bionic stomach is formed on the surface of the magnetorheological fluid flexible bag.
In one embodiment, the multifunctional bionic duodenum squeezing device further comprises a duodenum module, the duodenum module comprises a bionic duodenum hose and a duodenum squeezing device, the duodenum squeezing device comprises a peristaltic pump, a cam and a fixed wheel which are matched for use, and the duodenum flexible pushing soft robot is used for pushing the duodenum, and the acting strength of the duodenum squeezing device on the bionic duodenum hose is adjustable;
The fluid infusion module also comprises a duodenal fluid infusion device for infusing the duodenal fluid.
In one embodiment, the soft robots include a stomach flexible pushing soft robot for pushing and pushing the digested sample in the bionic stomach and a flexible crushing soft robot for crushing the digested sample in the bionic stomach.
In one embodiment, the stomach flexible pushing soft robot comprises a first air vent and a first clamping jaw, wherein the first air vent is connected with an external air source, the first clamping jaw comprises a plurality of independent and communicated air bags, the position, close to the bionic stomach, of the first clamping jaw is a first non-stretchable coating, and the other positions are a first soft adhesive layer;
The intestinal flexible pushing and pressing soft robot comprises a second air vent and a second clamping jaw, wherein the second air vent is connected with an external air source, the second clamping jaw comprises a plurality of independent and communicated air bags, the position, close to a bionic duodenal hose, of the second clamping jaw is a second non-stretchable coating, and the other positions are second soft adhesive layers;
The flexible crushing soft robot comprises a third vent and a flexible air bag, wherein the third vent is connected with an external air source, a third soft rubber layer is arranged at the central position of the flexible air bag, which is close to the bionic stomach, and a third non-stretchable coating is arranged at the other positions of the flexible air bag.
In one embodiment, the device further comprises a position adjustment mechanism for adjusting the orientation of the stomach flexible pushing soft robot and the flexible crushing soft robot.
In one embodiment, the gastric fluid replacement device comprises a first syringe pump and a gastric fluid secretion tube, and the duodenal fluid replacement device comprises a second syringe pump, a bile secretion tube, a third syringe pump and a pancreatic fluid secretion tube.
In one embodiment, an auxiliary module is also included, the auxiliary module including an esophagus, a gastrointestinal connector, a sampling tube, a warming lamp, and a circulation fan.
Based on the general inventive concept, there is also provided a control method of a model animal in vitro digestive system based on software driving as described above, comprising:
Injecting simulated gastric fluid of a predetermined volume and composition into the simulated stomach through the gastric fluid infusion device;
quantitatively injecting the pretreated digestive sample into the bionic stomach through the esophagus;
the simulated gastric juice is supplemented into the simulated stomach by the gastric juice supplementing device, so that the digestive sample and the simulated gastric juice are fully mixed, and different peristaltic intensities are provided for the simulated stomach by adjusting the gastric juice extruding device.
In one embodiment, the bionic duodenal tube peristaltic device is driven by the duodenal squeezing device, and meanwhile simulated intestinal fluid is injected into the bionic duodenal tube by the duodenal fluid infusion device so as to simulate the digestion process of a digestion sample in the bionic duodenal tube, wherein in the bionic duodenal tube peristaltic, different peristaltic intensities are provided for the bionic duodenal tube by adjusting the duodenal squeezing device.
Compared with the prior art, the method has the beneficial effects that in the model animal in-vitro digestion system based on soft driving, the gastric extrusion device comprises the soft robot and the magnetorheological fluid flexible device, the soft robot and the magnetorheological fluid flexible device act on the bionic stomach together, the strength and the time of the soft robot and the magnetorheological fluid flexible device acting on the bionic stomach are adjusted, the control dimensions of contraction and relaxation of gastrointestinal tract muscles, peristalsis of stomach walls and the like are increased, the contraction and the relaxation of the gastrointestinal tract muscles and the peristalsis of the stomach walls in the real digestion process are simulated, the physical digestion process of a digestive sample is simulated, the continuous secretion of digestive fluid in the real digestion process is simulated by using the fluid supplementing module and the like, so that the chemical digestion of the digestive sample is realized, and the simulation of the process of gradually emptying the digestive sample and the like is comprehensively realized.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are required in the embodiments or the description of the prior art will be briefly described, and it is obvious that the drawings in the following description are some embodiments of the present invention, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a schematic diagram of a stomach module structure of a model animal in vitro digestive system based on software driving according to an embodiment;
FIG. 2 is a schematic diagram of a duodenal module structure based on a model animal in vitro digestive system driven by software according to an embodiment;
FIG. 3 is a schematic diagram of a magnetorheological fluid flexible apparatus based on a soft-driven model animal in vitro digestive system according to one embodiment;
FIG. 4 is a schematic view of another perspective structure of a magnetorheological fluid flexible apparatus based on a soft-driven model animal in vitro digestive system according to one embodiment;
FIG. 5 is a schematic diagram of a fluid infusion device based on a soft-body-driven model animal in vitro digestive system according to an embodiment.
The reference numerals 1 to stomach module, 11 to bionic stomach, 111 to one-way valve, 112 to pylorus valve, 12 to gastric squeezing device, 121 to stomach flexible pushing soft robot, 122 to flexible crushing soft robot, 1211 to first vent, 1212 to first clamping jaw, 1221 to third vent, 1222 to flexible balloon, 123 to position adjusting mechanism, 124 to magnetorheological fluid flexible bladder, 1241 to supporting surface, 1242 to magnetorheological fluid bladder cavity, 1243 to magnetorheological fluid, 125 to magnetic field generator, 2 to duodenum module, 21 to bionic duodenum hose, 22 to duodenum squeezing device, 221 to peristaltic pump, 222 to cam, 223 to fixed wheel, 224 to intestine flexible pushing soft robot, 2241 to second vent, 2242 to second clamping jaw, 3 to fluid supplementing module, 31 to gastric fluid supplementing device, 311 to first injection pump, 312 to gastric fluid secretion tube, 32 to duodenum fluid device, 321 to second injection pump, 322 to bile secretion tube, 323 to third injection pump, 324 to pancreatic secretion tube, 4 to esophageal gland secretion tube, 41 to esophageal gland secretion tube, 42 to esophageal bypass tube, 44 to three-way tube.
Detailed Description
The present invention will be described more fully hereinafter with reference to the accompanying drawings, in which preferred embodiments are shown, for the purpose of illustrating the invention, but the scope of the invention is not limited to the specific embodiments shown.
Unless defined otherwise, all technical and scientific terms used hereinafter have the same meaning as commonly understood by one of ordinary skill in the art. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the scope of the present invention.
Unless otherwise specifically indicated, the various raw materials, reagents, instruments, equipment and the like used in the present invention are commercially available or may be prepared by existing methods.
As shown in fig. 1-5, a model animal in-vitro digestive system based on soft driving comprises a stomach module 1, a duodenum module 2, a fluid supplementing module 3 and an auxiliary module 4. The stomach module includes a simulated stomach 11 and a gastric compression device 12. The gastric compression device 12 includes a soft robotic and magnetorheological fluid flexible device, both of which are adjustable in intensity of action on the simulated stomach 11. Still further, a duodenal module 2 is included, the duodenal module 2 comprising a biomimetic duodenal tube 21 and a duodenal compression device 22. The duodenal squeezing device 22 comprises a peristaltic pump 221, a mating cam 222 and a fixed wheel 223, and a flexible pushing soft robot 224 for the intestines. The fluid infusion module 3 comprises a gastric fluid infusion device 31 and a duodenal fluid infusion device 32 which are respectively used for conveying simulated gastric fluid, simulated bile and simulated pancreatic fluid to the simulated stomach 11 and the simulated duodenal flexible tube 21, and the auxiliary module 4 comprises an esophagus 41, an inclined three-way valve 42, a four-way pipe 43, a stomach sampling tube 44 and a heating and heat-preserving device. In one embodiment, the duodenal module and the corresponding fluid infusion template may not be provided, and only the gastric module 1 and the corresponding structure are provided. The auxiliary module 4 provides auxiliary functions, and can be selected and removed according to practical situations.
In the model animal in-vitro digestion system based on soft driving, the gastric extrusion device 12 comprises a soft robot and a magnetorheological fluid flexible device, the soft robot and the magnetorheological fluid flexible device act on the bionic stomach 11 together, the strength and time of the soft robot and the magnetorheological fluid flexible device acting on the bionic stomach 11 are adjusted, the controlled dimensions of contraction and relaxation of gastrointestinal muscles, peristalsis of gastric wall and intestinal wall and the like are increased, the simulation of contraction and relaxation of the gastrointestinal muscles, peristalsis of gastric wall and intestinal wall and the physical digestion process of a digestive sample in the real digestion process is realized, the continuous secretion of digestive fluid in the real digestion process is simulated by utilizing the fluid supplementing module 3 and the like, so that the chemical digestion of the digestive sample is realized, the simulation of the gradual emptying process of the digestive sample and the like is realized, and the bionic of the gastrointestinal structure and part of physiological detail characteristics is comprehensively realized.
Specifically, in one embodiment, the gastric compression device 12 includes a gastric flexible pushing soft robot 121, a flexible crushing soft robot 122, a position adjustment mechanism 123, a magnetorheological fluid flexible bladder 124, and a magnetic field generator 125. The stomach flexible pushing soft robot 121 is used for pushing and pushing the digestive sample in the bionic stomach 11, and the flexible breaking soft robot 122 is used for breaking the digestive sample in the bionic stomach 11. The position adjusting mechanism 123 is used for realizing the functions of adjusting the positions and angles of the stomach flexible pushing soft robot 121 and the flexible crushing soft robot 122, and adjusting the distances and angles between the stomach flexible pushing soft robot 121 and the flexible crushing soft robot 122 and the bionic stomach 11 to be proper along with the change of the model of the bionic stomach 11, so that the applied force of the stomach flexible pushing soft robot 121 and the flexible crushing soft robot 122 on the bionic stomach 11 can be better controlled.
Specifically, in one embodiment, the magnetorheological fluid flexible bladder 124 includes a magnetorheological fluid bladder cavity 1242 and a magnetorheological fluid 1243 filled within the magnetorheological fluid bladder cavity 1242. The surface of the magnetorheological fluid flexible bladder 124 is formed with a backing 1241 for engaging the outer surface of the simulated stomach 11. Preferably, the bearing surface 1241 is a reverse-molded bearing surface formed by reverse molding according to the shape of the simulated stomach 11. The surface of the magnetorheological fluid flexible bag 124 is manufactured through reverse molding and is completely attached to the outer surface of the bionic stomach 11, so that the contact area between the supporting surface 1241 and the bionic stomach 11 is maximum, the acting surface of the magnetorheological fluid flexible bag 124 on the bionic stomach 11 is maximum, and the change of the viscosity and the hardness of the magnetorheological fluid 1243 in the magnetorheological fluid flexible bag 124 can be better acted on the bionic stomach 11. Preferably, a proper amount of magnetorheological fluid 1243 is filled in the magnetorheological fluid capsule 1242, and the magnetorheological fluid 1243 is sealed in the magnetorheological fluid capsule 1242, so that no air gap is formed in the magnetorheological fluid capsule 1242 as much as possible, and the durability and the stability of the action of the magnetorheological fluid 1243 can be improved.
Specifically, in one embodiment, the magnetorheological fluid flexible bladder 124 is made of soft material, and is disposed directly under the bionic stomach 11, for fixing the spatial position of the lower half of the bionic stomach 11, and supporting the bionic stomach 11.
Specifically, in one embodiment, the magnetic field generator 125 is disposed below the magnetorheological fluid flexible bladder 124. Preferably, the top of the magnetic field generator 125 has an inner concave surface for holding the magnetorheological fluid flexible bladder 124, thereby fixing the position of the magnetorheological fluid flexible bladder 124 while limiting the morphological changes of the magnetorheological fluid flexible bladder 124 to some extent.
When the magnetic field generator 125 works, by controlling the magnetic field direction and the magnetic induction intensity, the viscosity and the hardness of the magnetorheological fluid 1243 in the magnetorheological fluid flexible bag 124 are changed according to the magnetic field direction and the magnetic induction intensity distribution, so that the technological parameters such as equivalent strain, equivalent stress and the like of the magnetorheological fluid flexible device acting on the bionic stomach 11 are adjusted, and different intensity changes of real gastric peristalsis are simulated. The magnetorheological fluid flexible device is matched with extrusion effects of the soft robot under different air pressures, and the acting force of the magnetorheological fluid flexible device and the acting force of the soft robot are used for jointly adjusting the simulated peristaltic process of the bionic stomach 11.
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 simulated stomach 11 to push the digestive sample toward the main digestive region of the simulated stomach 11. The contraction and relaxation of the flexible disruption soft robot 122 is used to drive the contraction and relaxation of the main digestive area of the simulated stomach 11 to physically squeeze the digested sample to break it into a certain size.
Specifically, the stomach flexible pushing soft robot 121 is a soft material. The number of stomach flexible pushing soft robots 121 may be one or more as desired. The stomach flexible pushing soft robot 121 includes a vent 1211 and a clamp jaw 1212. The first clamping jaw 1212 comprises a plurality of independent and communicated air bags, a first air port 1211 of the stomach flexible pushing soft robot 121 is connected with a pneumatic control system, and the contraction and the relaxation of the first clamping jaw 1212 are controlled to squeeze the bionic stomach 11 through the air pressure change in the stomach flexible pushing soft robot 121, so as to simulate the contraction and the relaxation of real stomach muscles, and peristaltically push the digestive sample in the stomach to move to the main digestive area of the bionic stomach 11. Preferably, the first clamping jaw 1212 is positioned adjacent to the simulated stomach 11 as a first non-stretchable coating and the other positions are a first soft gel layer. The first clamping jaw 1212 is generally bar-shaped. Because the clamping jaw 1212 extrudes the bionic stomach 11 through the internal air pressure change, the position close to the bionic stomach 11 is set as a non-stretchable coating, the elastic stretching of the soft adhesive layer I at other positions is utilized to deform to push and press the bionic stomach 11, the non-stretchable coating has certain rigidity, and the deformation effect of the soft adhesive layer I at other positions is combined, so that a better pushing effect is realized.
Similarly, the intestinal flexible push software robot 224 is a soft material. The number of the flexible pushing soft robots 224 for the intestines may be one or more as needed. The flexible pushing soft robot 224 for intestines includes a vent 2241 and a clamping jaw 2242. The second vent is connected with an external air source, the second clamping jaw 2242 comprises a plurality of independent and communicated air bags, the second clamping jaw 2242 is a second non-stretchable coating near the bionic duodenal hose 21, and the other positions are second soft adhesive layers. The clamping jaw 2242 is substantially strip-shaped. The bionic duodenal hose 21 is pushed and pressed by utilizing the deformation generated by the elastic stretching of the second soft adhesive layer at other positions, the non-stretchable coating has certain rigidity, and the better pushing and pressing effect is realized by combining the deformation effect of the second soft adhesive layer at other positions.
Specifically, in one embodiment, the flexible fracturing software robot 122 includes a No. three vent 1221 and a flexible bladder 1222. The flexible breaking soft robot 122 is connected with a pneumatic control system through a third vent 1221, and the contraction and the relaxation of the flexible air bag 1222 are controlled to drive the bionic stomach 11 to creep through the air pressure change of the flexible breaking soft robot 122, so as to simulate the contraction and the relaxation of the real stomach muscles and extrude the digestive sample in the stomach into a digestive sample with a certain size. Preferably, the flexible balloon 1222 is substantially spherical, with a third soft gel layer near the center of the simulated stomach 11 (the position that fits the simulated stomach 11), and a third non-stretchable coating at the other positions. The flexible air bag 1222 is approximately in a ball shape, other positions are not deformed when the air pressure is regulated, but the flexible air bag 1222 is deformed, such as bulged upwards, at the center position of the flexible air bag 1222 near the third soft rubber layer of the bionic stomach 11, and by adopting the arrangement mode, better extrusion is realized to achieve the crushing effect.
Specifically, in one embodiment, the simulated duodenal hose 21 is curved in an arc to simulate the actual internal duodenal trend. The duodenal squeezing device 22 is disposed along the biomimetic duodenal tube 21. A peristaltic pump 221 in the duodenal squeezing device 22 is fixed at the front end of the biomimetic duodenal tube 21. The duodenal tube 21 is used for receiving a digestive sample and digestive fluid mixture delivered from the gastric module 1, and is sectionally pumped to the middle and rear section of the bionic duodenal tube 21 by a peristaltic pump 221, wherein the mixture includes gastric digestive sample, simulated gastric fluid, simulated bile and simulated pancreatic fluid. The outer races of the cam 222 and the fixed sheave 223 are each wrapped with a layer of soft material. The cam 222 and the fixed wheel 223 are fixed on two sides of the bionic duodenal tube 21, and the maximum and minimum distances between the cam 222 and the fixed wheel 223 are respectively equal to the outer diameter and twice the wall thickness of the bionic duodenal tube 21, so as to squeeze the digestive sample and digestive juice mixture in the bionic duodenal tube 21 to peristaltic and convey to the rear section so as to simulate peristaltic digestion of the real duodenum.
The flexible pushing and pressing soft robot 224 for the intestines is made of soft material, and the flexible pushing and pressing soft robot 224 for the intestines is used for extruding the rear section of the bionic duodenal hose 21 to simulate peristaltic digestion of the real duodenum.
Specifically, in one embodiment, the simulated stomach 11 is a soft stomach, and is made using soft material+3D printing techniques. The simulated stomach 11 can be generally divided into a glandless region, a cardiac region, a fundus region, and a pylorus region, with different divisions depending on the model of animal being simulated. The glandless region is used for connecting the cardiac orifice and the cardiac region, and the front end of the cardiac orifice is provided with a one-way valve 111, and the one-way valve 111 is communicated with the esophagus 41. The one-way valve 111 is used to avoid backflow of the digested sample in the simulated stomach to simulate control of esophageal 41 communication with the stomach by the real gastric cardia sphincter. The cardiac region is primarily used to store food and to secrete mucous to aid in lubricating the food. The fundus area is the main digestive area of the bionic stomach 11, and is provided with a gastric fluid-supplementing port connected with a gastric fluid secretion tube 312, wherein the gastric fluid-supplementing port is used for supplementing simulated gastric fluid into the bionic stomach 11 so as to simulate the secretion of gastric fluid in the real stomach, and the gastric fluid mainly comprises gastric acid (hydrochloric acid) and digestive enzymes (such as pepsin and the like). The pylorus region is used for connecting the pylorus region and the fundus region, the pylorus valve 112 is arranged at the rear end of the pylorus region, and the pylorus valve 112 is communicated with the bionic duodenal tube 21. For sieving the digested mixture, it is ensured that only liquid and digested sample mixtures smaller than a certain size can enter the biomimetic duodenal tube 21 through the pyloric valve 112 for continued digestion to simulate a real gastric emptying process. The middle part of the fundus area of the bionic stomach 11 is communicated with a first injection pump 311 through a gastric juice secretion tube 312 for continuously pumping simulated gastric juice to simulate a real gastric juice secretion process.
Specifically, in one embodiment, gastric module 1 and duodenal module 2 are in communication sequentially through a three-way valve 42 and a four-way tube 43. One end of a feed inlet of the inclined three-way valve 42 is connected with the bionic stomach 11 through the pylorus valve 112, one end of a discharge outlet of the inclined three-way valve 42 is communicated with a feed inlet of the four-way pipe 43, the other end of the inclined three-way valve is communicated with the stomach sampling pipe 44, and the tail end of the stomach sampling pipe 44 is used for periodically receiving the mixture sample digested by the stomach module 1. The 'Zhong' shaped feeding port of the four-way pipe 43 is respectively communicated with the discharging port of the inclined three-way valve 42, the bile secretion pipe 322 and the pancreatic secretion pipe 324, the discharging port of the four-way pipe 43 is communicated with the bionic duodenal flexible pipe 21, and the free end of the bionic duodenal flexible pipe 21 is used for periodically receiving the mixture sample digested by the duodenal module 2. The three-way valve 42 is used to control the flow of the mixture after digestion by the stomach module 1, to the duodenal module 2 to continue simulated digestion, or for sampling testing. The four-way pipe 43 is used for receiving the digested mixture of the stomach module 1, mixing the simulated bile and the simulated pancreatic juice and then delivering the mixture to the duodenum module 2 for digestion, so that the inclined three-way valve 42 and the four-way pipe 43 can be any devices which can realize the functions, such as five-way valves and the like. Preferably, in one embodiment, the pre-treated digestive sample injected through the esophagus 41 may be a mixture of food or drug and the like digestive samples after being thoroughly mixed with simulated saliva and broken.
Specifically, in one embodiment, the gastric fluid replacement device 31 includes a first syringe pump 311 and a gastric fluid secretion tube 312, and the duodenal fluid replacement device includes a second syringe pump 321, a bile secretion tube 322, a third syringe pump 323, and a pancreatic fluid secretion tube 324. The first syringe pump 311, the second syringe pump 321, and the third syringe pump 323 are used to stably and uniformly inject the simulated gastric fluid, the simulated bile, and the simulated pancreatic fluid into the simulated stomach 11 and the simulated duodenal tube 21, and thus may be any devices that can achieve this function.
In one embodiment, when a digestive sample is present inside the simulated stomach 11, the first syringe pump 311 continuously pumps simulated gastric fluid into the simulated stomach 11 through the gastric fluid secretion tube 312 for simulating the real stomach to continuously secrete gastric fluid for chemical digestion of the digestive sample. When a digestive sample exists in the bionic duodenal tube 21, the second syringe pump 321 and the third syringe pump 323 can continuously pump simulated bile and simulated pancreatic juice into the bionic duodenal tube 21 through the bile secretion tube 322 and the pancreatic juice secretion tube 324, and are used for simulating the real duodenum to continuously secrete bile and pancreatic juice to digest the digestive sample.
The heating and heat preserving device is used for controlling the temperature in the experiment platform to be kept relatively constant at the target temperature.
In a specific embodiment, before the simulation experiment starts, the positions and angles of the stomach flexible pushing soft robot 121 and the flexible crushing soft robot 122 relative to the simulated stomach 11 are adjusted by the position adjusting mechanism 123 according to the simulated stomach 11 model, so that the forces exerted by the stomach flexible pushing soft robot 121 and the flexible crushing soft robot 122 are adjusted, and the stomach flexible pushing soft robot 121 and the flexible crushing soft robot 122 restore the peristaltic digestion process of the stomach of animals in different modes under different states.
In one specific embodiment, during gastric peristalsis, the simulated stomach 11 has 2 driving states, ① the pyloric valve 112 is closed, and the stomach flexible pushing soft robot 121 and the flexible crushing soft robot 122 alternately compress and relax the simulated stomach 11. ② The pylorus valve 112 opens and the flexible fracturing soft robot 122 compresses and relaxes the simulated stomach 11.
The peristaltic movement of the gastric extrusion device 12 is divided into 3 stages, namely, peristaltic movement is enhanced, normal peristaltic movement and peristaltic movement is weakened, the operation condition of simulated peristaltic movement in a period can be set according to the peristaltic movement rule of animals in different modes (the combination of peristaltic stages and times can be freely set), and peristaltic movement frequency, digestive juice secretion frequency and emptying frequency are all set according to the simulated animals in different modes.
In one embodiment, the 3 peristaltic modes may be specifically:
1. Peristaltic enhancement, maximum power operation of the magnetic field generator 125, maximum applied magnetic induction, maximum air pressure operation of the soft robot.
2. Normal peristalsis, that is, the magnetic field generator 125 operates, a certain magnetic induction intensity is applied, and the air pressure in the soft robot keeps proper size to operate.
3. Peristaltic reduction-the magnetic field generator 125 is not operated and the air pressure in the soft robot remains at the proper level.
Parameters such as peristaltic mode, peristaltic frequency, pressure applied by the first jaw 1212, second jaw 2242, and flexible bladder 1222, electromagnetic field strength, time interval for switching gastric drive conditions, frequency of compression and relaxation of the first jaw 1212, second jaw 2242, and flexible bladder 1222, rotational speed of the cam, opening interval of the sampling valve, etc. are also set during digestion.
In one embodiment, a method for controlling an in vitro digestive system of a model animal based on software driving comprises the steps of:
S110, injecting simulated gastric juice with preset volume and components into the simulated stomach through a gastric fluid supplementing device;
s120, quantitatively injecting the pretreated digestive sample into the bionic stomach through the esophagus;
S130, performing bionic peristaltic motion on the stomach through a soft robot and a magnetorheological fluid flexible device of the stomach extrusion device, extruding and releasing different parts of the bionic stomach within a set time interval, and simultaneously supplementing simulated gastric fluid into the bionic stomach by utilizing a stomach fluid supplementing device so that a digestive sample and the simulated gastric fluid are fully mixed, and providing different peristaltic intensities for the bionic stomach by adjusting the stomach extrusion device.
Specifically, the bionic stomach peristalsis is driven by a stomach extrusion device to simulate the digestion process of a digestive sample in the stomach, and the stomach extrusion device consists of a soft robot and a magnetorheological fluid flexible device which are distributed around the bionic stomach. The soft robot is independently controlled by an accurate control system and matched with a magneto-rheological fluid flexible device to simulate the peristaltic movement intensity of the stomach of a living being. The control system activates and controls the soft robots step by step according to a preset peristaltic mode and frequency, and applies pressure to all parts of the bionic stomach in sequence in cooperation with the magnetorheological fluid flexible bags with variable hardness, so that the inner wall of the bionic stomach generates orderly wave-shaped contraction.
In an embodiment, further comprising:
S140, driving the peristaltic movement of the bionic duodenal hose through the duodenal extrusion device, and simultaneously injecting simulated intestinal juice into the bionic duodenal hose by utilizing the duodenal juice supplementing device so as to simulate the digestion process of a digestion sample in the bionic duodenal hose, wherein in the peristaltic movement of the bionic duodenal hose, different peristaltic intensities are provided for the bionic duodenal hose by adjusting the duodenal extrusion device.
Wherein, different peristaltic intensities comprise peristaltic strengthening, normal peristaltic and peristaltic weakening, and the peristaltic intensity is adjusted by controlling the air pressure of the soft robot and the magnetic field intensity of the magnetorheological fluid flexible device.
Specifically, all the processes of the control method of the in-vitro digestion device comprise four stages, namely a preparation stage, a feeding process, a regular peristaltic and digestion stage and a sampling stage.
The method specifically comprises the following steps:
(1) And (3) preparing and filling digestive juice, namely filling the digestive juice into the first injection pump 311, the gastric juice secretion tube 312, the second injection pump 321, the bile secretion tube 322, the third injection pump 323 and the pancreatic juice secretion tube 324 according to the corresponding formula, and connecting one end of the gastric juice secretion tube 312 with the first injection pump 311, one end of the bile secretion tube 322 with the second injection pump 321 and one end of the pancreatic juice secretion tube 324 with the third injection pump 323.
(2) The assembly system comprises the steps of fixing a bionic stomach 11, connecting an esophagus 41, a gastric secretion pipe and a pylorus valve 112, connecting the other end of the pylorus valve 112 with an inclined three-way valve 42, connecting the inclined three-way valve 42 with a stomach sampling pipe 44 and a four-way pipe 43 respectively, keeping the valve of the stomach sampling pipe 44 closed and the four-way pipe 43 communicated, connecting the left end and the right end of the four-way pipe 43 with the other end of a bile secretion pipe 322 and the other end of a pancreatic secretion pipe 324 respectively, connecting the tail end of the four-way pipe with a bionic duodenal hose 21, and arranging a stomach flexible pushing soft robot 121 and a flexible crushing soft robot 122 to proper positions and angles.
(3) And (3) adjusting the temperature in the system, namely opening a heating and heat-preserving device in the system to ensure that the temperature in the system is stably maintained at the set temperature.
(4) The preparation of the digested sample, namely placing the digested sample in deionized water (1:1, V: V) filled with simulated saliva, and fully stirring and crushing the digested sample to simulate the chewing process of the digested sample in the oral cavity.
(5) The simulated gastric fluid is injected into the simulated stomach 11 by the injection pump 311 to simulate the gastric fluid residue in the stomach under the fasted state.
(6) Injecting a digestive sample into the bionic stomach 11, namely injecting the digestive sample prepared in the step (4) into the bionic stomach 11 through the esophagus at one time.
(7) The simulated gastric 11 and the simulated duodenal tube 21 are simulated by periodically opening and closing the pylorus valve 112, driving the simulated gastric 11 to peristaltic by the gastric extrusion device 12 to simulate the physical digestion process of the stomach, continuously injecting simulated gastric fluid into the simulated stomach by the gastric fluid supplementing device 31 to simulate the chemical digestion process of the stomach, and periodically collecting a digested sample by opening the valve of the gastric sampling tube 44, wherein when the digested sample is not sampled, the digested sample continuously flows to the four-way tube 43 through the inclined three-way valve 42, simultaneously the simulated bile and the simulated pancreatic fluid are continuously injected into the four-way tube 43 by the duodenal fluid supplementing device 32, the three are mixed to flow into the simulated duodenal tube 21, and the simulated duodenal tube 21 is driven to peristaltic by the duodenal extrusion device 22 to simulate the digestion of the duodenum, and the peristaltic operation condition (combination of the peristaltic level and the frequency of the simulated peristalsis is freely set) is set according to the peristaltic law of animals in different modes, and the peristaltic frequency, the secretion frequency of the digestive fluid and the evacuation frequency are set according to animals in different modes.
(8) Recording digestion process in time periods, namely, in the digestion process in the step (7), the digestion process is divided into a plurality of time periods, the primary gastric extrusion device 12, the duodenal extrusion device 22 and the fluid supplementing module 3 are stopped in each time period, the samples digested by the bionic stomach 11 and the bionic duodenal hose 21 are respectively collected by using a sample collecting device, the pH value, the gastric emptying rate, the storage modulus, the loss modulus, the dynamic viscosity and the apparent viscosity of the samples are respectively measured and recorded, the microstructure is observed, then the gastric extrusion device 12, the duodenal extrusion device 22 and the fluid supplementing module 3 are opened, the experiment is continued until the digested samples are completely discharged from the bionic duodenal hose 21, and the pH value, the gastric emptying rate, the storage modulus, the loss modulus, the dynamic viscosity and the apparent viscosity of the finally discharged digested samples are measured and recorded, and the microstructure is observed.
(9) And (3) cleaning all devices, namely cleaning device modules in the whole system in time by deionized water after the experiment is finished, and keeping the device modules dry and storing the device modules.
Of the many mammals, only mice (small mammals) and pigs (neutral mammals) belong to model animals, and the stomach of the animals can be divided into glandless areas, cardiac areas, gastric fundus areas and pylorus areas, so that the device can dynamically simulate gastrointestinal peristaltic digestion of the model animals.
Specific example 1:
In one embodiment, the present invention is used to simulate the gastrointestinal digestion process of a small model animal. Taking the gastrointestinal tract of an adult SD rat simulating normal health as an example, the corresponding bionic model is replaced by the gastrointestinal tract model of the bionic rat.
The stomach of the bionic rat has the dimensions of length multiplied by width multiplied by height of 40 (+ -2) multiplied by 30 (+ -2) multiplied by 20 (+ -2) mm and the volume of 9.0+/-1.0 ml. The wall thickness of the forestomach (glandular region) of the stomach of the bionic rat is 0.65 plus or minus 0.15mm, and the wall thickness of the adenoma stomach (fundus region) is 1.50 plus or minus 0.25mm.
The stomach flexible pushing soft robot 121 has the dimensions of length x width x height of 45 x 30 x 22mm and the maximum negative pressure stroke of 23mm.
The balloon diameter of the flexible crushing soft robot 122 is 30mm high by 10.5mm and the maximum travel is 13mm.
The magnetic field generator 125 activates only the centrally located 1 electromagnet.
The length of the duodenum of the bionic rat is 100+/-1 mm, the inner diameter is 3.0+/-0.1 mm, and the outer diameter is 5.0+/-0.1 mm.
The flexible pushing soft robot 224 for the intestines has dimensions of 45X 30X 22mm in length, width and height, and a maximum negative pressure stroke of 23mm.
The simulation was completed according to the following steps:
(1) Digestion solution was prepared and filled, simulated saliva was prepared with alpha-amylase (. Gtoreq.150 units/mg protein) (19.90 mg, equivalent to 2985 units of alpha-amylase per gram dry sample), naCl (0.117 mg/ml), KCl (0.149 mg/ml) and NaHCO 3 (2.1 mg/ml), pH was adjusted to 7.8 with 1M NaOH, simulated gastric fluid was prepared with pepsin (. Gtoreq.250 units/mg solids), naHCO 3 (0.315 mg/ml), naCl (8.775 mg/ml), pH was adjusted to 1.6 with 1 mol/L HCl, simulated pancreatic fluid and simulated bile were prepared with pancreas (9.46 mg/g dry sample), bile salts (28.38 mg/g dry sample) and NaHCO 3 (4.5 mg/ml), pH was adjusted to 7.5 using 1M NaOH, and the prepared digestion solution was filled into corresponding injection pump and secretion line and connected.
(2) And assembling the modules in the system.
(3) The temperature in the conditioning system was stabilized to 37 ℃.
(4) A digested sample was prepared by adding 200mg of the starch sample to 2.0 ml deionized water, cooking for 15min to gelatinize, and mixing well with 2.0 ml simulated saliva to simulate the chewing process.
(5) The gastric juice is injected into the stomach of the bionic mouse, namely 0.6ml of simulated gastric juice is injected into the stomach of the bionic mouse to simulate the residual condition of the gastric juice in a fasted state.
(6) The digested sample was injected into the stomach of the biomimetic mouse.
(7) The simulated stomach peristaltic frequency is maintained at 5.6+/-0.1 times/min, 2 weakened peristaltic movements, 5 normal peristaltic movements and 3 reinforced peristaltic movements are carried out in one simulated stomach peristaltic period, after 2 stomach peristaltic periods are operated, the pylorus valve 112 is opened, the flexible crushing soft robot 122 alternately compresses and expands, the electromagnet in the center is activated by the maximum power of the magnetic field generator 125 to harden the magneto rheological fluid flexible device to realize gastric emptying, a digestive sample and gastric fluid mixture smaller than a certain size flows into the simulated mouse simulated duodenal tube through the pylorus valve 112, flows into the simulated mouse simulated duodenal tube after being mixed with pancreatic fluid and bile, and peristaltic movements are carried out at a frequency of 15.0+/-0.1 times/min through the combination of the peristaltic pump 221, the cam 222, the fixed wheel 223 and the intestinal flexible pushing soft robot 224, and in the process, simulated gastric fluid is injected into the simulated stomach of the simulated rat at a rate of 1.2ml/h, and simulated pancreatic fluid and simulated bile are injected into the simulated rat simulated intestinal tube at a rate of 0.8 ml/h.
(8) And recording digestion process in time intervals, namely stopping the operation of the gastric extrusion device 12, the duodenal extrusion device 22 and the fluid infusion module 3 after digestion for 10, 20, 30, 60, 90, 120 and 180 minutes, respectively collecting digested samples of the bionic rat stomach and the bionic rat duodenal hose by using a sample collecting device, measuring and recording the pH of the digested samples, rapidly flushing the samples by using deionized water and the like to stop reaction, then measuring and recording the samples comprising particle size, SEM imaging, glucose concentration and the like, closing a sampling valve after the digested samples are collected, and restarting the gastric extrusion device 12, the duodenal extrusion device 22 and the fluid infusion module 3 to continue the digestion process until the digested samples are completely discharged from the bionic rat stomach and the bionic rat duodenal hose, and measuring and recording the pH, the particle size, SEM imaging, the glucose concentration and the like of the finally discharged digested samples.
(9) The entire device was cleaned.
The experimental results show that the particle size, the particle surface, the glucose concentration and the like of the digested starch sample in the stomach are consistent with the in vivo experimental results after the starch sample is digested for different times, and no significant difference (P > 0.05) exists. Compared with the in vitro experimental results, the in vivo living mouse experiment shows that the pH value is gradually reduced to about 2.73 after the rise along with the increase of the digestion time. As the in vitro digestion proceeds, the particle size of the starch digested sample also gradually decreases, the proportion of starch particles of larger particle size (d >1.0 mm) gradually decreases from an initial 14% to 3%, while the proportion of starch particles of smaller particle size (d <0.65 mm) gradually increases from an initial 58% to 82%. In the initial stage of in vitro digestion, a large amount of small fragments appear on the surface of the compact starch particles, the tissue structure is loose, which indicates enzymolysis, and along with the progress of the digestion process, the small fragments on the surface and the inside of the particles are gradually replaced by holes with different sizes and take on irregular honeycomb shapes. The glucose concentration rose rapidly to 9. 9 mg/mL in the first 60 min of the in vitro digestion process, and finally reached 9.5 mg/mL after 180 min of the in vitro digestion experiment.
Specific example 2:
The present invention was used to simulate the gastrointestinal digestion process in medium-sized model animals. Taking the gastrointestinal tract of a normal and healthy adult Goldland pig as an example, the corresponding bionic model is replaced by a gastrointestinal tract model of a bionic pig.
The size length, width and height of the stomach of the bionic pig are 270 (+ -2) times 200 (+ -2) times 150 (+ -2) mm, and the volume is 8.0+/-0.2L. The wall thickness of the cardiac region of the stomach of the bionic pig is 3.0 plus or minus 0.2mm, and the wall thickness of the fundus region of the stomach is 4.0 plus or minus 0.2mm.
The stomach flexible pushing soft robot 121 has the dimensions of 145×45×40mm length×width×height, and the maximum negative pressure stroke is 80mm. The upper part of the gastric cardia region of the bionic pig is provided with 3 stomach flexible pushing soft robots 121, the total 4 stomach flexible pushing soft robots 121 are arranged in parallel, the interval is 7.0+/-1.0 mm, and 1 group of flexible pushing soft robot arrays are formed. The positions of the flexible crushing soft robots are also provided with 1 group of flexible pushing soft robot arrays.
The magnetic field generator 125 activates all 5 electromagnets.
The length of the duodenum of the bionic pig is 800+/-2 mm, the inner diameter is 30.0+/-0.1 mm, and the outer diameter is 33.0+/-0.1 mm.
The flexible pushing soft robot 224 for the intestines has dimensions of length x width x height of 62.5 x 40 x 35mm and a maximum negative pressure stroke of 40mm. 2 sets of cams, fixed wheels and a flexible pushing soft robot 224 for the intestines are additionally arranged.
The simulation experiment was completed according to the following steps:
(1) Digestive juice is prepared and filled, wherein simulated gastric juice is prepared by pepsin (with enzyme activity 30000 U/g)、NaCl（1.295 g/ml）、KCl（0.125 g/ml）、NaH2PO4（3.0 g/ml）、C6H7KO2（0.5 g/ml）, pH is regulated to 2.0 by 2 mol/L HCl, simulated intestinal juice is prepared by pancreatin and bile salt 、Na2HPO4（3.995 g/ml）、NaH2PO4（2.92 g/ml）、C6H7KO2（0.6325 g/ml）, and pH is regulated to 7.15 by 1M NaOH.
(2) And assembling the modules in the system.
(3) The temperature in the conditioning system was stabilized to 39 ℃.
(4) And (3) preparing a digestion sample, namely crushing the feed raw material to be detected, sieving with a 40-mesh sieve, and fully and uniformly mixing for later use.
(5) And (3) injecting gastric juice into the stomach of the bionic pig, namely injecting 100ml of simulated gastric juice into the stomach of the bionic pig to simulate the gastric juice residue condition in a fasted state.
(6) Injecting a digestive sample into the bionic pig stomach.
(7) The simulated stomach and simulated pig's simulated duodenum hose digestion process is referred to the normal healthy Golay pig's internal peristaltic process, the simulated stomach peristaltic frequency is set to be kept at 3.0+ -0.1 times/min, 1 weakened peristaltic, 5 normal peristaltic and 4 reinforced peristaltic are performed in one simulated stomach peristaltic cycle, after 4 stomach peristaltic cycles are operated, the pylorus valve 112 is opened, the flexible crushing soft robot 122 group above the fundus area is alternately compressed and relaxed, at the same time, the magnetic field generator 125 activates all electromagnets with maximum power to harden the magnetorheological fluid flexible device to realize gastric emptying, the digestive sample and gastric fluid mixture smaller than a certain size flows into the simulated pig's simulated duodenum hose through the pylorus valve, flows into the simulated pig's simulated duodenum hose after being mixed with pancreatic fluid and bile, and peristaltic is performed at a rate of 11.0+ -0.1 times/min by the combination of the peristaltic pump 221, the cam 222, the fixed wheel 223 and the flexible pushing robot 224, during which simulated gastric fluid is injected into the simulated stomach and simulated pig at a rate of 120ml/h, and simulated pancreas fluid is injected into the simulated pig at a simulated pancreas fluid rate of 1000ml/h and simulated duodenum hose of the simulated pig and a simulated duodenum hose of 1000ml/h, respectively.
(8) And (3) recording digestion process in a time-division manner, wherein in the digestion process, the operation of the gastric extrusion device 12, the duodenal extrusion device 22 and the fluid infusion module 3 is stopped every 1 hour, the samples digested by the simulated pig stomach and the simulated pig simulated duodenal hose are respectively collected by using a sample collecting device, the pH is measured and recorded, the reaction is stopped by using deionized water and the like for rapid flushing, then the digestibility of other nutrient substances including dry substance digestibility, crude protein digestibility and the like is measured and recorded, after the digestion samples are collected, a sampling valve is closed, the gastric extrusion device 12, the duodenal extrusion device 22 and the fluid infusion module 3 are started again to continue the digestion process until the digestion samples are completely discharged from the simulated pig stomach and the simulated pig simulated duodenal hose, and the pH, the dry substance digestibility, the crude protein digestibility and other nutrient substance digestibility of the finally discharged digestion samples are measured and recorded.
(9) The entire device was cleaned.
The experimental results show that after the digestion of the feed raw material is finished, the dry matter digestibility, the crude fat digestibility, the other nutrient digestibility and the like of the gastric digestion sample are consistent with the in vivo experimental results, and no significant difference (P > 0.05) exists.
The dry matter digestibility of corn, rapeseed meal and soybean meal subjected to the in vitro digestion process was 50.23±0.26%, 24.09±0.37% and 40.65±0.28%, respectively, whereas the dry matter digestibility of corn, rapeseed meal and soybean meal in the in vivo experiments was 56.92±1.14%, 31.87±1.63% and 47.19±1.00%, 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%, whereas the crude protein digestibility of corn, rapeseed meal and soybean meal in the in vivo experiments was 52.30 ±2.32%, 39.47±2.16% and 53.53±1.89%, the organic digestibility of corn, rapeseed meal and soybean meal was 53.12±0.26%, 26.91±0.53±0.56% and the organic digestibility of corn, rapeseed meal and soybean meal in the in vivo experiments was 56.77±1.26±1.58% and 49.17±1.17% respectively. According to the experimental data, the in-vitro digestion process simulated by the in-vitro digestion system of the model animal based on the software driving is very close to the actual digestion process of a living body, and the experimental result of the model animal based on the software driving has better parallelism.
Specific example 3:
The present invention was used to simulate the gastric digestion process in medium-sized model animals. Taking the stomach of a normal and healthy adult Goldland pig as an example, the stomach model of a bionic pig is replaced with a corresponding bionic model.
The simulation experiment was completed according to the following steps:
(1) Preparing digestive juice, and packaging, wherein pepsin (with enzyme activity 30000 U/g)、NaCl（1.295 g/ml）、KCl（0.125 g/ml）、NaH2PO4（3.0 g/ml）、C6H7KO2（0.5 g/ml）, pH is adjusted to 2.0 with 2 mol/L HCl;
(2) And assembling the modules in the system.
(3) The temperature in the conditioning system was stabilized to 39 ℃.
(4) And (3) preparing a digestion sample, namely crushing the feed raw material to be detected, sieving with a 40-mesh sieve, and fully and uniformly mixing for later use.
(5) And (3) injecting gastric juice into the stomach of the bionic pig, namely injecting 100ml of simulated gastric juice into the stomach of the bionic pig to simulate the gastric juice residue condition in a fasted state.
(6) Injecting a digestive sample into the bionic pig stomach.
(7) The digestion process of the stomach of the simulated live pig is simulated, the simulated gastric peristalsis frequency is kept at 3.0+/-0.1 times per minute by referring to the gastric peristalsis process in the body of a normal healthy Goldland pig, 1 weakened peristalsis, 5 times of normal peristalsis and 4 times of reinforced peristalsis are carried out in one simulated gastric peristalsis period, after 4 gastric peristalsis periods are operated, the pylorus valve 112 is opened, the flexible crushing soft robot 122 group above the fundus area is alternately compressed and relaxed, meanwhile, the magnetic field generator 125 activates all electromagnets at maximum power to harden the magnetorheological fluid flexible device to realize gastric emptying, and digestive sample and gastric fluid mixture smaller than a certain size flow to the sample collecting device through the pylorus valve, and in the process, the simulated gastric fluid is injected into the stomach of the simulated live pig at the speed of 120 ml/h.
(8) And (3) recording the digestion process in a time-division manner, wherein in the digestion process, the operation of the gastric extrusion device 12 and the gastric fluid infusion device 31 is stopped every 1 hour, a sample after the digestion of the simulated pig stomach is collected by using a sample collecting device, the pH of the sample is measured and recorded, the sample is quickly washed by deionized water and the like to stop the reaction, then the digestibility of other nutrient substances including dry substance digestibility, crude protein digestibility and the like is measured and recorded, after the digestion sample is collected, a sampling valve is closed, the gastric extrusion device 12 and the gastric fluid infusion device 31 are started again to continue the digestion process until the digestion sample is completely discharged from the simulated pig stomach, and the pH, the dry substance digestibility, the crude protein digestibility and the other nutrient substance digestibility of the finally discharged digestion sample are measured and recorded.
(9) The entire device was cleaned.
The experimental results show that after the digestion of the feed raw material is finished, the dry matter digestibility, the crude fat digestibility, the other nutrient digestibility and the like of the gastric digestion sample are consistent with the in vivo experimental results, and no significant difference (P > 0.05) exists. The dry matter digestibility of corn, rapeseed meal and soybean meal in the in vitro gastric digestion process is respectively 12.37+/-0.29%, 7.49+/-0.41% and 14.28+/-0.33%, while the dry matter digestibility of corn, rapeseed meal and soybean meal in the in vivo experiments is respectively 19.03+/-1.24%, 14.93+/-1.72% and 23.35+/-1.07%, the crude protein digestibility of corn, rapeseed meal and soybean meal is respectively 10.49+/-0.38%, 9.53+/-0.61% and 14.78+/-0.82%, while the crude protein digestibility of corn, rapeseed meal and soybean meal in the in vivo experiments is respectively 16.24+/-2.25%, 11.56+/-2.21% and 18.49+/-1.86%, the organic matter digestibility of corn, rapeseed meal and soybean meal is respectively 17.52+/-0.29%, 8.86+/-0.38% and 16.92+/-0.53%, and the organic matter digestibility of corn, rapeseed meal and soybean meal in the in vivo experiments is respectively 21.65+/-1.36.36% and 14.74.57%. According to the experimental data, the in-vitro digestion process simulated by the in-vitro digestion system of the model animal based on the software driving is very close to the actual digestion process of a living body, and the experimental result of the model animal based on the software driving has better parallelism.
According to the embodiment, in the model animal in-vitro digestive system based on soft driving and the control method thereof, the gastric extrusion device comprises a soft robot and a magnetorheological fluid flexible device, the soft robot and the magnetorheological fluid flexible device act on the bionic stomach together, the strength and the time of the soft robot and the magnetorheological fluid flexible device acting on the bionic stomach are adjusted, the dimensions of control such as contraction and relaxation of gastrointestinal muscles, peristalsis of gastric wall intestinal wall and the like are increased, the contraction and the relaxation of the gastrointestinal muscles, the peristalsis of gastric wall intestinal wall and the physical digestion process of a digestive sample in the real digestion process are simulated, and the bionic of the gastrointestinal structure and part of physiological detail characteristics is comprehensively realized. In particular to the magnetic induction intensity change so as to change the viscosity and hardness of magnetorheological fluid in a soft bag and increase the dimension of driving control of gastric peristalsis. Meanwhile, the technological parameters such as equivalent strain, equivalent stress and the like in the soft extrusion process can be regulated and controlled through the hardness of the magnetorheological fluid flexible device. Furthermore, the software material and 3D printing technology can simulate the structural characteristics of folds in the stomach, and can more truly embody the stomach structure. The continuous secretion of digestive juice in the real digestion process is simulated by utilizing a liquid supplementing module and the like to realize chemical digestion of the digestive sample, and the simulation of the gradual emptying process of the digestive sample and the like comprehensively realizes the bionic of gastrointestinal tract structure and part of physiological detail characteristics. The application simulates the gastrointestinal tract digestion process of model animals with different sexes, growth stages and health states by changing some control parameters such as the direction, the size and the frequency of the application force of the extrusion device, the secretion rate of digestive juice, the evacuation rate of stomach and duodenum and the like, thereby providing wider applicability and further optimizing the research of in vitro bionic dynamic digestion. Sampling is carried out through a sampling tube valve, products in different digestion stages are conveniently compared and analyzed, and the operation flow of the experimental process is optimized.
Claims (8)
1. A model animal in vitro digestive system based on software driving, comprising:
The stomach module comprises a bionic stomach and a stomach extrusion device for extruding the bionic stomach, the stomach extrusion device comprises a soft robot and a magnetorheological fluid flexible device, the magnetorheological fluid flexible device comprises a magnetorheological fluid flexible bag and a magnetic field generator, the magnetic field generator is used for providing a variable magnetic field for the magnetorheological fluid flexible bag, the magnetorheological fluid flexible device is positioned at the bottom of the bionic stomach, the magnetorheological fluid flexible bag comprises a magnetorheological fluid bag cavity and magnetorheological fluid filled in the magnetorheological fluid bag cavity, the surface of the magnetorheological fluid flexible bag is provided with a supporting surface for being attached to the outer surface of the bionic stomach, and the acting strength of the soft robot and the magnetorheological fluid flexible device on the bionic stomach can be adjusted;
The fluid infusion module comprises a gastric fluid infusion device and is used for infusing the gastric module.
2. The model animal in-vitro digestive system based on soft drive according to claim 1, further comprising a duodenal module, wherein the duodenal module comprises a bionic duodenal hose and a duodenal squeezing device, the duodenal squeezing device comprises a peristaltic pump, a cam and a fixed wheel which are matched for use and a soft pushing intestinal robot, and the action intensity of the duodenal squeezing device on the bionic duodenal hose is adjustable;
The fluid infusion module also comprises a duodenal fluid infusion device for infusing the duodenal fluid.
3. The external digestive system of model animals based on soft drive of claim 2, wherein the stomach soft pushing soft robot comprises a first air vent and a first clamping jaw, the first air vent is connected with an external air source, the first clamping jaw comprises a plurality of independent and communicated air bags, the position of the first clamping jaw close to the bionic stomach is a first non-stretchable coating, and the other positions are a first soft adhesive layer;
The intestinal flexible pushing and pressing soft robot comprises a second air vent and a second clamping jaw, wherein the second air vent is connected with an external air source, the second clamping jaw comprises a plurality of independent and communicated air bags, the position, close to a bionic duodenal hose, of the second clamping jaw is a second non-stretchable coating, and the other positions are second soft adhesive layers;
The flexible crushing soft robot comprises a third vent and a flexible air bag, wherein the third vent is connected with an external air source, a third soft rubber layer is arranged at the central position of the flexible air bag, which is close to the bionic stomach, and a third non-stretchable coating is arranged at the other positions of the flexible air bag.
4. The soft drive based model animal in vitro digestive system of claim 1, further comprising a position adjustment mechanism for adjusting the orientation of the stomach flexible pushing soft robot and the flexible crushing soft robot.
5. The software-driven model animal in vitro digestive system of claim 2, wherein the gastric fluid replacement device comprises a first syringe pump and a gastric fluid secretion tube, and the duodenal fluid replacement device comprises a second syringe pump, a bile secretion tube, a third syringe pump, and a pancreatic fluid secretion tube.
6. The soft-drive based model animal in vitro digestive system of claim 1, further comprising an auxiliary module comprising an esophagus, a gastrointestinal connector, a sampling tube, a warming lamp, and a circulation fan.
7. A method of controlling a model animal in vitro digestive system based on software driving according to any one of claims 1 to 6, comprising:
Injecting simulated gastric fluid of a predetermined volume and composition into the simulated stomach through the gastric fluid infusion device;
quantitatively injecting the pretreated digestive sample into the bionic stomach through the esophagus;
the simulated gastric juice is supplemented into the simulated stomach by the gastric juice supplementing device, so that the digestive sample and the simulated gastric juice are fully mixed, and different peristaltic intensities are provided for the simulated stomach by adjusting the gastric juice extruding device.
8. The method according to claim 7, further comprising driving the peristaltic motion of the bionic duodenal tube by the duodenal squeezing device, and simultaneously injecting simulated intestinal fluid into the bionic duodenal tube by the duodenal fluid infusion device to simulate the digestion process of the digestion sample in the bionic duodenal tube, wherein the simulated duodenal tube peristaltic motion provides different peristaltic intensities for the bionic duodenal tube by adjusting the duodenal squeezing device.
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