A microfluidic-based device for visualizing the interaction of polysaccharides with milk-derived probiotic bacteria

Abstract

The application discloses a microfluidic-based polysaccharide and milk-derived probiotic interaction visualization device, and relates to the technical field of polysaccharide and milk-derived probiotic interaction.The application comprises an intestinal simulation module, an interaction tracking module, a visualization module and a database, divides an intestinal simulation cabin into simulation sub-cabins, sets inner and outer mucus layers in the simulation sub-cabins, and analyzes shear force distribution and change under different intestinal peristalsis modes, intensities and frequencies, and thickness of the inner and outer mucus layers, secretion rate of the inner mucus layer, update frequency of the outer mucus layer and peeling ratio change trend under different shear forces; intestinal simulation is performed according to the analysis results, and aminooxy-PEG-fluorescent group bifunctional crosslinking agent and sodium periodate are selected for marking, so that the effectiveness of the mucus layer simulation, the biological activity and structure of the polysaccharide and the milk-derived probiotic are ensured, and the accuracy of the polysaccharide and the milk-derived probiotic interaction process and interaction tracking in the device is improved.

Description

Technical Field

[0001] This invention relates to the field of polysaccharide-milk probiotic interaction technology, specifically to a microfluidic-based visualization device for polysaccharide-milk probiotic interaction. Background Technology

[0002] The interaction between polysaccharides and lactic probiotics is the core process of intestinal microecological regulation. This interaction is not a simple nutrient supply relationship, but involves multi-dimensional and dynamic interactions such as specific molecular recognition, metabolic coordination and signal regulation. The interaction between polysaccharides and lactic probiotics starts from the entry of polysaccharides into the intestinal microenvironment and eventually produces physiological effects.

[0003] Traditional visualization devices for polysaccharide-lactoprobiotic interactions simulate the intestinal environment using microfluidics and place a gel layer inside the intestinal simulation chamber to simulate the intestinal mucus layer. When polysaccharides and lactic probiotics interact in the intestinal simulation chamber, they are randomly chemically labeled to track the interaction process. Obviously, this kind of visualization device for polysaccharide-lactoprobiotic interactions has at least the following shortcomings: 1. Shear force is the core physical signal that regulates the entire interaction process of polysaccharides and lactic probiotics. However, traditional technology only simulates the intestinal environment and ignores the shear force brought about by intestinal peristalsis. Therefore, it cannot guarantee the consistency between the polysaccharide-lactoprobiotic interaction in the device and its actual interaction, and thus cannot guarantee the accuracy of polysaccharide-lactoprobiotic interaction tracking.

[0004] 2. The intestinal mucus layer is divided into an inner mucus layer and an outer mucus layer. The inner and outer mucus layers have different effects on the interaction between polysaccharides and lactic probiotics. Moreover, the intestinal mucus layer is the site where the interaction between polysaccharides and lactic probiotics occurs. However, traditional technology ignores this point and only uses a layer of gel to simulate the intestinal mucus layer. This cannot guarantee the effectiveness of the mucus layer simulation, nor can it guarantee the consistency between the interaction between polysaccharides and lactic probiotics in the device and their actual interaction.

[0005] 3. Traditional techniques involve random chemical labeling of polysaccharides and lactic probiotics. However, random chemical labeling may alter the bioactivity and structure of polysaccharides and lactic probiotics. The bioactivity and structure of polysaccharides and lactic probiotics cannot be guaranteed during the labeling process, which in turn affects the interaction between polysaccharides and lactic probiotics and makes it impossible to ensure the consistency between the interaction between polysaccharides and lactic probiotics in the device and their actual interaction. Summary of the Invention

[0006] To address the aforementioned technical shortcomings, the present invention aims to provide a visualization device for the interaction between polysaccharides and milk-derived probiotics based on microfluidics.

[0007] To solve the above-mentioned technical problems, the present invention adopts the following technical solution: The present invention provides a microfluidic-based visualization device for the interaction between polysaccharides and milk-derived probiotics, comprising: an intestinal simulation module, an interaction tracking module, a visualization module, and a database.

[0008] The intestinal simulation module is used to divide the intestinal simulation chamber in the visualization device, analyze the intestinal peristalsis and mucus layer of the human intestine, and simulate the intestine in the intestinal simulation chamber according to the analysis results.

[0009] The interaction tracking module is used to track the interaction process between polysaccharides and lactose-derived probiotics in the intestinal simulation chamber, and to obtain the interaction process between polysaccharides and lactose-derived probiotics.

[0010] The visualization module is used to display the interaction process between polysaccharides and lactose-based probiotics on the user terminal's screen.

[0011] The database is used to store the intestinal microenvironment, the simulated intestinal peristalsis pattern, intensity and frequency, as well as the polysaccharide distribution in the human intestinal mucus layer, and the polysaccharides and probiotics that interacted in this study.

[0012] The beneficial effects of this invention are as follows: 1. This invention provides a microfluidic-based visualization device for the interaction between polysaccharides and lactic probiotics. The intestinal simulation chamber is divided into various simulation sub-chambers. An inner mucus layer and an outer mucus layer are set in each simulation sub-chamber. The distribution and changes of shear force under different intestinal peristalsis patterns, intensities, and frequencies are analyzed, as well as the thickness of the inner and outer mucus layers, the secretion rate of the inner mucus layer, the renewal frequency of the outer mucus layer, and the trend of the peeling ratio under different shear forces. Intestinal simulation is performed based on the analysis results, and aminooxy-PEG-fluorophore bifunctional cross-linking agent and sodium periodate are selected for labeling. This ensures the effectiveness of the mucus layer simulation, the bioactivity and structure of polysaccharides and lactic probiotics, and improves the accuracy of the interaction process and interaction tracking between polysaccharides and lactic probiotics in the device.

[0013] 2. This invention obtains the intestinal microenvironment from a database and analyzes the shear force distribution and changes of each simulated sub-compartment corresponding to each intestinal part under different intestinal peristalsis patterns, intensities, and frequencies. Based on the analysis results and the intestinal microenvironment, the interaction environment of each simulated sub-compartment is simulated and controlled. An inner mucus layer and an outer mucus layer are set in each simulated sub-compartment, and the inner and outer mucus layers of each simulated sub-compartment are simulated and controlled by analyzing the mucus update information of each intestinal part under different shear forces, ensuring the effectiveness of the mucus layer simulation and improving the accuracy of the interaction process between polysaccharides and lactic probiotics in the device.

[0014] 3. This invention monitors the concentration of fluorophores and polysaccharides in polysaccharide samples, calculates the labeling degree of polysaccharide samples, and monitors the main chain structure and bioactivity of polysaccharides. Based on the monitoring data, a suitable aminooxy-PEG-fluorophore bifunctional cross-linking agent is selected to label the polysaccharides, and sodium periodate is used to label the glycocalyx on the surface of multi-source probiotics. This ensures the bioactivity and structure of polysaccharides and milk-derived probiotics, and improves the accuracy of tracking the interaction between polysaccharides and milk-derived probiotics in the device. Attached Figure Description

[0015] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0016] Figure 1 This is a schematic diagram of the system structure connection of the present invention. Detailed Implementation

[0017] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0018] Please see Figure 1 As shown, the present invention provides a microfluidic-based visualization device for the interaction between polysaccharides and milk-derived probiotics, comprising: an intestinal simulation module, an interaction tracking module, a visualization module, and a database.

[0019] The intestinal simulation module is connected to the interaction tracking module, the interaction tracking module is connected to the visualization module, and the database is connected to both the intestinal simulation module and the interaction tracking module.

[0020] The intestinal simulation module is used to divide the intestinal simulation chamber in the visualization device, analyze the intestinal peristalsis and mucus layer of the human intestine, and simulate the intestine in the intestinal simulation chamber according to the analysis results.

[0021] In one specific embodiment, the intestinal simulation module includes a partitioning unit, an environment simulation unit, and a mucus layer simulation unit.

[0022] The division unit is used to divide the intestinal simulation chamber in the visualization device into a stomach simulation chamber, a duodenum simulation chamber, a jejunum simulation chamber, an ileum simulation chamber, and a colon simulation chamber, and collectively refer to them as each simulation chamber.

[0023] It should be noted that the human intestine is divided into the stomach, duodenum, jejunum, ileum and colon. Dividing the intestinal simulation chamber according to the different parts of the human intestine is beneficial for the simulation of the intestine.

[0024] The environmental simulation unit is used to obtain the intestinal microenvironment from the database, and analyze the shear force distribution and changes of each simulated sub-compartment corresponding to each intestinal part under different intestinal peristalsis patterns, intensities and frequencies. Based on the analysis results and the intestinal microenvironment, the interaction environment of each simulated sub-compartment is simulated and controlled.

[0025] It should be noted that the gut microenvironment includes factors such as temperature, pH, and oxygen concentration within the gut.

[0026] The gut microenvironment was obtained by medical professionals through clinical trials.

[0027] It should also be noted that intestinal peristalsis patterns include propulsive peristalsis, reverse peristalsis, migratory compound movements, and sacral reciprocating movements.

[0028] It is important to know that intestinal peristalsis intensity includes mild, moderate, and severe peristalsis, and the intensity of intestinal peristalsis is set by medical staff.

[0029] In a specific embodiment, the environmental simulation unit operates as follows: A11. In a clinical trial, several experimental subjects are set up, and the intestinal peristalsis patterns, intensities, and frequencies of each experimental subject are controlled to be different. Several monitoring points are evenly set up in each part of the intestine of each experimental subject.

[0030] It should be noted that the experimental subjects were white mice.

[0031] It should also be noted that doctors used medication to control the intestinal peristalsis patterns, intensity, and frequency of the experimental subjects.

[0032] A12. For all experimental subjects, monitor the shear force at each monitoring point on each intestinal part in real time, determine whether the shear force at each monitoring point is similar, cluster the similar monitoring points to obtain each control segment of each intestinal part, and analyze the change characteristics of shear force on each control segment.

[0033] It should be noted that shear force is monitored by microparticle image velocity measurement.

[0034] It should also be noted that by comparing the shear force at each monitoring point at each time, the difference between the shear forces at each monitoring point is calculated. Monitoring points whose differences are all less than the preset difference threshold at each time are considered similar monitoring points.

[0035] The preset difference threshold is a critical value used to determine whether the monitoring points are similar, and its specific value is determined by medical staff.

[0036] A13. Based on the replication ratio between the intestinal simulation chamber and the human intestine and the control segments of each intestinal part, obtain each control segment of each simulation sub-chamber, and construct a table of intestinal peristalsis-shear force changes for each control segment in each simulation sub-chamber according to the results obtained in step A12.

[0037] It should be noted that the replica ratio of the intestinal simulator to the human intestine refers to the ratio of the length of the intestinal simulator to that of the human intestine.

[0038] It should also be noted that the characteristics of shear force variation in each control segment under different intestinal peristalsis patterns, intensities, and frequencies are stored one-to-one to form an intestinal peristalsis-shear force variation table for each control segment in each simulated sub-compartment.

[0039] A14. Integrate microenvironment control and shear force control elements in each control section of each simulation sub-compartment, and obtain the intestinal microenvironment, current intestinal peristalsis pattern, intensity and frequency from the database. Based on the intestinal microenvironment, current intestinal peristalsis pattern, intensity and frequency, and the intestinal peristalsis-shear force change table of each control section in each simulation sub-compartment, simulate and control the interaction environment of each simulation sub-compartment.

[0040] The above-mentioned analysis of the shear force variation characteristics of each control segment is specifically carried out as follows: For all control segments, the real-time shear force of each monitoring point is obtained and its average value is calculated to obtain the shear force at each time. The shear force at each time is sorted in chronological order to obtain the shear force sequence of each control segment. Based on the shear force sequence of each control segment, the shear force gradient variation characteristics of each control segment are obtained and used as the shear force variation characteristics of each control segment.

[0041] It should be noted that the shear force gradient change features are obtained through Transformer, which is an existing technology. The specific process is as follows: the shear force sequence is standardized, the encoder, decoder, input embedding layer, output embedding layer and position encoder of Transformer are constructed and trained, and after training, the processed shear force sequence is input into Transformer and the shear force gradient change features are output.

[0042] The mucus layer simulation unit is used to set up an inner mucus layer and an outer mucus layer in each simulation sub-compartment, and to simulate and control the inner mucus layer and outer mucus layer of each simulation sub-compartment by analyzing the mucus update information of each intestinal part under different shear forces.

[0043] It should be noted that the APTES-EDC / NHS covalent bonding technology is used to fix the MUC2 mucin on the surface of the glass substrate to form a dense gel layer, which is the inner mucin layer. A loose gel layer is formed above the dense layer through calcium ion-induced physical cross-linking, which is the outer mucin layer.

[0044] It should also be noted that the mucus renewal information includes the thickness of the inner and outer mucus layers under different shear forces, the secretion rate of the inner mucus layer, the renewal frequency of the outer mucus layer, and the trend of the peeling ratio.

[0045] In a specific embodiment, the mucus layer simulation unit is implemented as follows: A21, two mucus layers are set in each simulation sub-chamber, namely an inner mucus layer and an outer mucus layer.

[0046] A22. Through clinical trials, we obtained the thickness of the inner and outer mucus layers, the secretion rate of the inner mucus layer, the renewal frequency of the outer mucus layer, and the trend of the peeling ratio under different shear forces, and constructed a shear force-mucus information matching table.

[0047] It should be noted that different shear forces are stored one-to-one with the thickness of the inner and outer mucus layers, the secretion rate of the inner mucus layer, the renewal frequency of the outer mucus layer, and the trend of the peeling ratio under different shear forces, forming a shear force-mucus information matching table.

[0048] A23. Analyze the effect of calcium ion concentration on mucus information and construct a table showing the effect of calcium ion concentration.

[0049] It should be noted that the changes in different calcium ion concentrations and the trends of various mucus information in the intestinal mucus layer under different calcium ion concentrations are stored one-to-one to form a calcium ion concentration influence table.

[0050] A24. Obtain the polysaccharide distribution of the human intestinal mucus layer from the database, and simulate the polysaccharide environment of each simulated sub-compartment mucus layer according to the polysaccharide distribution of the human intestinal mucus layer using covalent bond technology.

[0051] A25. Based on the analysis results of steps A22 and A23, control the inner and outer mucus layers of each simulated sub-compartment based on step A24.

[0052] The above-mentioned clinical trial implementation process is as follows: In the clinical trial, the shear force in the intestines of several experimental subjects is controlled to be different from each other, and the thickness of the inner and outer mucus layers, the secretion rate of the inner mucus layer, the renewal frequency and the peeling ratio of the outer mucus layer are monitored in real time in each part of the intestine by embedding sensors in several experimental subjects. The thickness of the inner and outer mucus layers, the secretion rate of the inner mucus layer, the renewal frequency and the peeling ratio of the outer mucus layer are collectively referred to as the mucus information.

[0053] It should be noted that various mucus information was monitored through confocal laser microscopy, endoscopic biopsy histological analysis, endoscopic dynamic observation, and high-resolution gastrointestinal manometry.

[0054] For all the mucus information of each experimental body, the real-time monitoring values ​​are plotted on a curve. The x-axis of the curve represents time, and the y-axis represents the measured value of the mucus information. The numerical change curve of each mucus information is obtained from the plotted curve and used as the change trend of each mucus information under the corresponding shear force of each experimental body.

[0055] The above-mentioned analysis of the effect of calcium ion concentration on mucus information is carried out in the following specific process: several samples of the intestinal mucus layer of the experimental subject are obtained, and calcium ion liquid is injected into each sample, and the calcium ion concentration of the calcium ion liquid injected into each sample is different.

[0056] After injecting calcium ion liquid into each sample, the changing trends of various mucus information in the intestinal mucus layer of each sample were monitored to obtain the changing trends of various mucus information in the intestinal mucus layer under different calcium ion concentrations, which were then used as the influence of calcium ion concentration on mucus information.

[0057] The interaction tracking module is used to track the interaction process between polysaccharides and lactose-derived probiotics in the intestinal simulation chamber, and to obtain the interaction process between polysaccharides and lactose-derived probiotics.

[0058] In one specific embodiment, the interaction tracking module performs the following process: acquiring the polysaccharides and probiotics that are interacting this time.

[0059] Polysaccharides were labeled using an aminooxy-PEG-fluorophore bifunctional cross-linking agent, and the glycocalyx on the surface of multi-source probiotics was obtained. The glycocalyx on the surface of multi-source probiotics was then labeled using sodium periodate.

[0060] It should be noted that the polysaccharide analysis has a unique reducing end aldehyde group. The specific oxime reaction between the aminooxy-PEG-fluorophore bifunctional crosslinking agent and the unique reducing end aldehyde group of the polysaccharide enables precise labeling of a polysaccharide molecule with only one fluorescent tag, without destroying the main chain structure of the polysaccharide.

[0061] It should also be noted that the sodium periodate used is a low-concentration sodium periodate, and the specific concentration is determined by medical personnel. The surface of dairy probiotics is covered with a sugar coating containing a large number of vicinal diol structures. The low-concentration sodium periodate can specifically oxidize the vicinal diol to an aldehyde group, and then react with the same aminooxy-PEG-fluorophore as the polysaccharide labeling, to achieve site-specific labeling of the sugar chains on the surface of multi-source probiotics.

[0062] The labeled polysaccharides and probiotics were placed in an intestinal simulation chamber, which simulated the intestines and tracked the interaction between the polysaccharides and probiotics throughout the process.

[0063] It should be noted that the labeled polysaccharides and multi-source probiotics were tracked using confocal microscopy or light sheet microscopy.

[0064] The above-mentioned labeling of polysaccharides using aminooxy-PEG-fluorophore bifunctional cross-linking agents is specifically carried out as follows: each polysaccharide sample and each aminooxy-PEG-fluorophore bifunctional cross-linking agent are obtained, and each aminooxy-PEG-fluorophore bifunctional cross-linking agent is placed into each polysaccharide sample respectively.

[0065] It should be noted that the aminooxy-PEG-fluorophore bifunctional crosslinking agents vary depending on the PEG chain length, fluorophore type, and linker topology.

[0066] Among them, the fluorophore types include carboxyfluorescein, fluorescein isothiocyanate, carboxytetramethylrhodamine, and tetramethylrhodamine isothiocyanate.

[0067] For all polysaccharide samples, after a preset reaction time, the concentration of fluorophores and polysaccharides in the polysaccharide samples were monitored when the aminooxy-PEG-fluorophore bifunctional cross-linking agent was added. The labeling degree of the polysaccharide samples was calculated, and the main chain structure and bioactivity of the polysaccharides were monitored. Based on the monitoring and calculation results, the return value of the aminooxy-PEG-fluorophore bifunctional cross-linking agent in the polysaccharide samples was determined.

[0068] It should be noted that the preset reaction time was set by the staff based on the reaction time of the polysaccharide and the aminooxy-PEG-fluorescent bifunctional crosslinking agent.

[0069] It should also be noted that the concentrations of fluorophores and polysaccharides in polysaccharide samples were measured and monitored using a fluorescence spectrophotometer, high-performance liquid chromatography, and the phenol-sulfuric acid method, while the main chain structure and biological activity of polysaccharides were monitored using NMR and fluorescence microscopy.

[0070] It should also be noted that the labeling degree is obtained by dividing the fluorophore concentration by the polysaccharide concentration.

[0071] Specifically, when the main chain structure of the polysaccharide remains unchanged, the biological activity is greater than the preset biological activity threshold, and the labeling degree is within the preset labeling degree range, the return value of the aminooxy-PEG-fluorophore bifunctional crosslinking agent is 1; otherwise, it is 0.

[0072] It is important to know that the preset bioactivity threshold and preset labeling range are both set by staff according to actual needs.

[0073] Each aminooxy-PEG-fluorophore bifunctional cross-linking agent that returns a value of 1 is called a usable aminooxy-PEG-fluorophore bifunctional cross-linking agent. One usable aminooxy-PEG-fluorophore bifunctional cross-linking agent is randomly selected from them, and the polysaccharide is labeled using this usable aminooxy-PEG-fluorophore bifunctional cross-linking agent.

[0074] In the above, the intestinal simulation chamber simulates the intestine, and the specific process is as follows: when polysaccharides and lactose-based probiotics interact in the intestinal simulation chamber, the intestinal peristalsis pattern, intensity, and frequency of this simulation are obtained from the database. Based on the intestinal peristalsis pattern, intensity, and frequency of this simulation, as well as the intestinal peristalsis-shear force change table of each control segment in each simulation sub-chamber, the shear force of each control segment in each simulation sub-chamber is controlled in real time.

[0075] At each time point, the shear force of each control segment in each simulated sub-compartment is read and compared with the shear force-mucus information matching table to obtain the thickness of the mucus layer and outer mucus layer, the secretion rate of the inner mucus layer, the update frequency of the outer mucus layer, and the trend of the peeling ratio. The obtained results are compared with the calcium ion concentration influence table to obtain the calcium ion concentration required for the mucus layer of each control segment in each simulated sub-compartment. The current calcium ion concentration of the mucus layer in each control segment of each simulated sub-compartment is monitored. Based on the monitoring results and the calcium ion concentration required for the mucus layer of each control segment in each simulated sub-compartment, calcium ion supplementation is performed on the mucus layer of each control segment in each simulated sub-compartment. During the supplementation process, the calcium ion concentration of the mucus layer in each control segment of each simulated sub-compartment is monitored in real time. When the calcium ion concentration of the mucus layer in each control segment of each simulated sub-compartment reaches the required calcium ion concentration, calcium ion supplementation is stopped.

[0076] It should be noted that calcium ion concentration is monitored using an ion-selective electrode.

[0077] The visualization module is used to display the interaction process between polysaccharides and lactose-based probiotics on the user terminal's screen.

[0078] The database is used to store the intestinal microenvironment, the simulated intestinal peristalsis pattern, intensity and frequency, as well as the polysaccharide distribution in the human intestinal mucus layer, and the polysaccharides and probiotics that interacted in this study.

[0079] In this embodiment of the invention, the intestinal simulation chamber is divided into several simulation sub-chambers. An inner mucus layer and an outer mucus layer are set in each simulation sub-chamber. The distribution and changes of shear force under different intestinal peristalsis patterns, intensities, and frequencies are analyzed. The thickness of the inner and outer mucus layers, the secretion rate of the inner mucus layer, the renewal frequency of the outer mucus layer, and the peeling ratio are also analyzed under different shear forces. Based on the analysis results, intestinal simulation is performed. An aminooxy-PEG-fluorophore bifunctional cross-linking agent and sodium periodate are selected for labeling, ensuring the effectiveness of the mucus layer simulation, the bioactivity and structure of the polysaccharides and lactic probiotics, and improving the accuracy of the interaction process and interaction tracking between the polysaccharides and lactic probiotics in the device.

[0080] The examples described in this invention are not limited to the specific embodiments listed above. The examples are merely illustrative to facilitate understanding of the invention and do not constitute a limitation on the scope of protection of this invention. Any modifications, equivalent substitutions, etc., made within the spirit and principles of this invention should be included within the scope of protection.

[0081] The above description is merely an example and illustration of the concept of the present invention. Those skilled in the art can make various modifications or additions to the specific embodiments described or use similar methods to replace them, as long as they do not deviate from the concept of the invention or exceed the scope defined in this specification, they should all fall within the protection scope of the present invention.

Claims

1. A visualization device for the interaction between polysaccharides and milk-derived probiotics based on microfluidics, characterized in that, Includes the following modules: The intestinal simulation module is used to divide the intestinal simulation chamber in the visualization device, analyze the intestinal peristalsis and mucus layer of the human intestine, and simulate the intestine in the intestinal simulation chamber based on the analysis results; The interaction tracking module is used to track the interaction process between polysaccharides and lactose-derived probiotics in the intestinal simulation chamber, and to obtain the interaction process between polysaccharides and lactose-derived probiotics. The visualization module is used to display the interaction process between polysaccharides and lactose-based probiotics on the user terminal's screen. The database is used to store the gut microenvironment, the simulated intestinal peristalsis patterns, intensity and frequency, as well as the polysaccharide distribution in the human intestinal mucus layer, and the polysaccharides and probiotics that interacted in this study.

2. The microfluidic-based visualization device for the interaction between polysaccharides and milk-derived probiotics according to claim 1, characterized in that, The intestinal simulation module includes a partitioning unit, an environment simulation unit, and a mucus layer simulation unit; The division unit is used to divide the intestinal simulation chamber in the visualization device into a stomach simulation sub-chamber, a duodenum simulation sub-chamber, a jejunum simulation sub-chamber, an ileum simulation sub-chamber, and a colon simulation sub-chamber, and collectively refer to them as each simulation sub-chamber; The environmental simulation unit is used to obtain the intestinal microenvironment from the database, and analyze the shear force distribution and changes of each simulated sub-compartment corresponding to each intestinal part under different intestinal peristalsis patterns, intensities and frequencies. Based on the analysis results and the intestinal microenvironment, the interaction environment of each simulated sub-compartment is simulated and controlled. The mucus layer simulation unit is used to set up an inner mucus layer and an outer mucus layer in each simulation sub-compartment, and to simulate and control the inner mucus layer and outer mucus layer of each simulation sub-compartment by analyzing the mucus update information of each intestinal part under different shear forces.

3. The microfluidic-based visualization device for the interaction between polysaccharides and milk-derived probiotics according to claim 2, characterized in that, The specific process of the environmental simulation unit is as follows: A11. In clinical trials, several subjects are set up, and the intestinal peristalsis patterns, intensities and frequencies of each subject are controlled to be different. Several monitoring points are evenly set up in each part of the intestine of each subject. A12. For all experimental subjects, monitor the shear force at each monitoring point on each intestinal part in real time, and determine whether the shear force at each monitoring point is similar. Cluster the similar monitoring points to obtain each control segment of each intestinal part, and analyze the variation characteristics of shear force on each control segment. A13. Based on the replication ratio between the intestinal simulation chamber and the human intestine and the control segments of each intestinal part, obtain each control segment of each simulation sub-chamber, and construct the intestinal peristalsis-shear force change table of each control segment in each simulation sub-chamber according to the acquisition results of step A12. A14. Integrate microenvironment control and shear force control elements in each control section of each simulation sub-compartment, and obtain the intestinal microenvironment, current intestinal peristalsis pattern, intensity and frequency from the database. Based on the intestinal microenvironment, current intestinal peristalsis pattern, intensity and frequency, and the intestinal peristalsis-shear force change table of each control section in each simulation sub-compartment, simulate and control the interaction environment of each simulation sub-compartment.

4. The microfluidic-based visualization device for the interaction between polysaccharides and milk-derived probiotics according to claim 3, characterized in that, The specific process for analyzing the variation characteristics of shear force in each control segment is as follows: For all control segments, the real-time shear force at each monitoring point is obtained and its average value is calculated to obtain the shear force at each time. The shear force at each time is sorted in chronological order to obtain the shear force sequence of each control segment. Based on the shear force sequence of each control segment, the shear force gradient change characteristics of each control segment are obtained and used as the change characteristics of shear force on each control segment.

5. The microfluidic-based visualization device for the interaction between polysaccharides and milk-derived probiotics according to claim 2, characterized in that, The specific process of the mucus layer simulation unit is as follows: A21. Two layers of mucus are set in each simulation sub-chamber, namely an inner mucus layer and an outer mucus layer; A22. Through clinical trials, we obtained the thickness of the inner and outer mucus layers, the secretion rate of the inner mucus layer, the renewal frequency of the outer mucus layer, and the trend of the peeling ratio under different shear forces, and constructed a shear force-mucus information matching table. A23. Analyze the effect of calcium ion concentration on mucus information and construct a table showing the effect of calcium ion concentration. A24. Obtain the polysaccharide distribution of the human intestinal mucus layer from the database, and simulate the polysaccharide environment of each simulated sub-compartment mucus layer according to the polysaccharide distribution of the human intestinal mucus layer using covalent bond technology; A25. Based on the analysis results of steps A22 and A23, control the inner and outer mucus layers of each simulated sub-compartment based on step A24.

6. The microfluidic-based visualization device for the interaction between polysaccharides and milk-derived probiotics according to claim 5, characterized in that, The clinical trial was conducted as follows: In clinical trials, the shear forces in the intestines of several subjects were controlled to be different for each subject. Sensors were embedded in several subjects to monitor in real time the thickness of the inner and outer mucus layers, the secretion rate of the inner mucus layer, the renewal frequency and the peeling ratio of the outer mucus layer in various parts of the intestine. The thickness of the inner and outer mucus layers, the secretion rate of the inner mucus layer, the renewal frequency and the peeling ratio of the outer mucus layer are collectively referred to as the mucus information. For all the mucus information of each experimental body, the real-time monitoring values ​​are plotted on a curve. The x-axis of the curve represents time, and the y-axis represents the measured value of the mucus information. The numerical change curve of each mucus information is obtained from the plotted curve and used as the change trend of each mucus information under the corresponding shear force of each experimental body.

7. The microfluidic-based visualization device for the interaction between polysaccharides and milk-derived probiotics according to claim 5, characterized in that, The specific process for analyzing the effect of calcium ion concentration on mucus information is as follows: Several samples of the intestinal mucus layer of the experimental subjects were obtained, and calcium ion liquid was injected into each sample, with different calcium ion concentrations in the calcium ion liquid injected into each sample. After injecting calcium ion liquid into each sample, the changing trends of various mucus information in the intestinal mucus layer of each sample were monitored to obtain the changing trends of various mucus information in the intestinal mucus layer under different calcium ion concentrations, which were then used as the influence of calcium ion concentration on mucus information.

8. The microfluidic-based visualization device for the interaction between polysaccharides and milk-derived probiotics according to claim 2, characterized in that, The interaction tracking module operates as follows: Obtain the polysaccharides and multi-source probiotics involved in this interaction; Polysaccharides were labeled using an aminooxy-PEG-fluorophore bifunctional cross-linking agent, and the glycocalyx on the surface of multi-source probiotics was obtained. The glycocalyx on the surface of multi-source probiotics was then labeled using sodium periodate. The labeled polysaccharides and probiotics were placed in an intestinal simulation chamber, which simulated the intestines and tracked the interaction between the polysaccharides and probiotics throughout the process.

9. A visualization device for the interaction between polysaccharides and milk-derived probiotics based on microfluidics according to claim 8, characterized in that, The labeling of polysaccharides using an aminooxy-PEG-fluorophore bifunctional cross-linking agent is described in the following process: Each polysaccharide sample and each aminooxy-PEG-fluorophore bifunctional cross-linking agent were obtained, and each aminooxy-PEG-fluorophore bifunctional cross-linking agent was placed into each polysaccharide sample respectively. For all polysaccharide samples, after a preset reaction time, the concentration of fluorophores and polysaccharides in the polysaccharide samples were monitored when aminooxy-PEG-fluorophore bifunctional cross-linking agent was added, the labeling degree of the polysaccharide samples was calculated, and the main chain structure and bioactivity of the polysaccharides were monitored. Based on the monitoring and calculation results, the return value of aminooxy-PEG-fluorophore bifunctional cross-linking agent in the polysaccharide samples was determined. Each aminooxy-PEG-fluorophore bifunctional cross-linking agent that returns a value of 1 is called a usable aminooxy-PEG-fluorophore bifunctional cross-linking agent. One usable aminooxy-PEG-fluorophore bifunctional cross-linking agent is randomly selected from them, and the polysaccharide is labeled using this usable aminooxy-PEG-fluorophore bifunctional cross-linking agent.

10. A visualization device for the interaction between polysaccharides and milk-derived probiotics based on microfluidics according to claim 8, characterized in that, The intestinal simulation chamber simulates the intestines, and the specific process is as follows: When polysaccharides and lactose-based probiotics interact in the intestinal simulation chamber, the intestinal peristalsis pattern, intensity, and frequency of this simulation are obtained from the database. Based on the intestinal peristalsis pattern, intensity, and frequency of this simulation, as well as the intestinal peristalsis-shear force change table of each control segment in each simulation sub-chamber, the shear force of each control segment in each simulation sub-chamber is controlled in real time. At each time point, the shear force of each control segment in each simulated sub-compartment is read and compared with the shear force-mucus information matching table to obtain the thickness of the mucus layer and outer mucus layer, the secretion rate of the inner mucus layer, the update frequency of the outer mucus layer, and the trend of the peeling ratio. The obtained results are compared with the calcium ion concentration influence table to obtain the calcium ion concentration required for the mucus layer of each control segment in each simulated sub-compartment. The current calcium ion concentration of the mucus layer in each control segment of each simulated sub-compartment is monitored. Based on the monitoring results and the calcium ion concentration required for the mucus layer of each control segment in each simulated sub-compartment, calcium ion supplementation is performed on the mucus layer of each control segment in each simulated sub-compartment. During the supplementation process, the calcium ion concentration of the mucus layer in each control segment of each simulated sub-compartment is monitored in real time. When the calcium ion concentration of the mucus layer in each control segment of each simulated sub-compartment reaches the required calcium ion concentration, calcium ion supplementation is stopped.

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