Fluid, solid and biochemical process coupling calculation method based on multi-component mesh medium

Abstract

The invention discloses a fluid, solid and biochemical process coupling calculation method based on a multi-component mesh medium, which comprises the following four steps: optimizing the structure of a pump impeller to improve the efficiency by utilizing a macroscopic fluid low-resistance anti-coagulation anti-dissolution mechanical calculation method, constructing a pump lung mechanical optimization design system based on multi-component multi-field coupling calculation, and optimizing the membrane lung oxygenation efficiency. An optimal design system based on mechanical-biochemical multi-field coupling calculation is formed, and the pump lung system with the advantages of low resistance, anticoagulation and dissolution resistance is manufactured. The invention relates to the technical field of medical treatment. According to the fluid, solid and biochemical process coupling calculation method based on the multi-component mesh medium, through bionic design, a biological functional active molecule anticoagulant polysaccharide fragment and a functional anti-inflammatory active polysaccharide fragment are introduced into the inner surface of an ECMO pipeline, the anticoagulant effect and the anti-inflammatory effect of the surface of an endothelial cell are selectively exerted, and the anti-inflammatory effect of the surface of the endothelial cell is improved. A hydrophilic compound polysaccharide fragment is grafted to the surface of polyvinyl chloride to improve the biocompatibility of the polyvinyl chloride.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to a coupled calculation method for multi-component mesh medium fluid, solid, and biochemical processes. Background Art

[0002] The extracorporeal membrane oxygenation (ECMO) circulatory system primarily consists of a membrane lung, a centrifugal pump head, and tubing. These tubing connects the membrane lung to the centrifugal pump head and, via arteriovenous cannulas, to blood vessels within the body. The centrifugal pump drains the patient's venous blood outside the body. Gas exchange in an artificial lung (oxygenator) oxygenates the venous blood into arterial blood, which is then returned to the body, providing a stable circulating blood volume for patients with cardiopulmonary failure.

[0003] The invention with publication number CN 105536086 A discloses a multifunctional ECMO circulation pipeline and a method for extracorporeal membrane oxygenation using the same. The ECMO circulation pipeline includes: an arterial circulation pipeline, a venous circulation pipeline, a blood purification blood inlet catheter and a blood purification blood transfusion catheter; the arterial circulation pipeline and the venous circulation pipeline are respectively provided with a blood oxygen sensor, and the blood oxygen sensor is connected to a blood gas detection device; the blood purification blood inlet catheter and the blood purification blood transfusion catheter are respectively provided with a one-way valve near one end of the circulation pipeline.

[0004] As shown in the above invention, the existing ECMO circulation pipeline can monitor the oxygen partial pressure in the blood before and after blood oxygenation in real time, solving the problem of difficult blood collection operation on the two ends of the pipeline during ECMO treatment, which easily leads to blood or flushing fluid spraying. However, the existing ECMO circulation pipeline has poor anti-coagulation and anti-inflammatory effects, and its production is scarce and expensive, which is not conducive to daily consumption and use. Summary of the Invention

[0005] In view of the deficiencies of the existing technology, the present invention provides a coupled calculation method for fluid, solid and biochemical processes based on a multi-component mesh medium, which solves the existing problems.

[0006] To achieve the above objectives, the present invention is implemented through the following technical solutions: A method for coupling calculation of fluid, solid, and biochemical processes based on a multi-component mesh medium, comprising the following steps:

[0007] Step 1: Establish a fluid circulation model, a mathematical model of blood flow and oxygenation process;

[0008] Step 2: Combine the thrombosis model, hemolysis model, oxygenation effect model, and resistance analysis to construct a mechanical driving model of the effective oxygenation process;

[0009] Step 3: Associate the key structural and material parameters of the pump-lung system to form an optimized design system based on mechanical, biochemical and multi-field coupling calculations to manufacture a pump-lung system with low resistance, anti-coagulation and anti-solvent advantages;

[0010] Step 4: Optimize the structural design of the simulated dynamic blood pump as well as the hemolysis effect and oxygenation analysis through simulation and calculation of the flow field inside the pump.

[0011] Preferably, the fluid circulation model mainly includes a simulated blood pump, an anti-coagulation and anti-inflammatory ECMO pipeline, and a hollow fiber synthetic membrane.

[0012] Preferably, the simulated blood pump includes an impeller and a water pressure chamber. The water pressure chamber is configured as a spiral structure and is designed according to the conservation of angular momentum. The trajectory of the liquid particles flowing out of the impeller is a logarithmic spiral, and the water pressure chamber is spiral, which conforms to the flow law of the liquid particles and has high hydraulic efficiency.

[0013] Preferably, the initial geometric parameters of the impeller are estimated based on the provided target parameters, including the blood pump inlet diameter, blood pump outlet diameter, impeller inner diameter, impeller outer diameter, blade inlet angle, blade outlet angle, number of blades, blade wrap angle, and blade width.

[0014] Preferably, the anticoagulant and anti-inflammatory ECMO tube introduces biofunctional active molecule anticoagulant polysaccharide fragments and functional anti-inflammatory active polysaccharide fragments into the inner surface of the ECMO tube, selectively exerts the anticoagulant and anti-inflammatory effects on the endothelial cell surface, and grafts the hydrophilic complex polysaccharide fragments onto the polyvinyl chloride surface to improve its biocompatibility.

[0015] Preferably, the preparation of the anticoagulant and anti-inflammatory ECMO tube comprises the following steps:

[0016] 1) Based on the fragmentation pretreatment of the composite coating material, a composite coating material with high binding performance is constructed;

[0017] 2) Through a special covalent binding mode of end-point fixation, an anticoagulant active unit with a good spatial conformation is constructed;

[0018] 3) Based on composite covalent coating technology, construct vascular endothelial surface biomimetic materials;

[0019] 4) By constructing a fixed-state anticoagulant biomimetic surface with good biocompatibility, an anticoagulant and anti-inflammatory ECMO tube was obtained;

[0020] 5) Through orthogonal experimental design, the optimal coating preparation conditions for ECMO tubes were screened out and qualified anti-coagulant and anti-inflammatory ECMO tubes were prepared.

[0021] Preferably, after preparation, the anti-coagulation and anti-inflammatory ECMO tube needs to measure four coagulation indicators, namely APTT, TT, PT and FT, as well as the anti-inflammatory indicators of IL-6, IL-8, IL-10, TNF-α and C-reactive protein.

[0022] Preferably, after preparation, the anticoagulant and anti-inflammatory ECMO tube is characterized by infrared spectroscopy scanning analysis, electron microscopy, and X-ray diffraction analysis of the anticoagulant and anti-inflammatory coating modified ECMO tube. The anticoagulant and anti-inflammatory ECMO tube needs to be sterilized by C0-60 radiation before use to meet medical standards.

[0023] Preferably, the hollow fiber synthetic membrane is prepared by using a thermal / non-solvent induced composite phase separation technology.

[0024] Preferably, the preparation of the hollow fiber synthetic membrane comprises the following steps:

[0025] A) Design suitable new spinneret and other composite thermally induced phase separation process equipment;

[0026] B) using water or a mixture of water and a water-soluble cosolvent in the cooling bath;

[0027] C) controlling the concentration and temperature of the water-soluble latent solvent in the cooling bath to control the density and pore size of the surface layer formed by the non-solvent-induced phase separation method, thereby obtaining a membrane with excellent anti-leakage and separation properties;

[0028] D) preparing a series of hollow fiber microporous membranes under different process conditions by regulating thermodynamic and kinetic parameters such as casting solution composition, core solution type, extrusion temperature, air gap height, cooling temperature, and winding speed;

[0029] E) preparing a functional surface segregation modifier containing low surface energy groups (such as siloxane groups) and transfer-promoting groups (such as amino groups), and combining modification technologies such as biomimetic adhesion and surface grafting to construct an anti-coagulation coating on the membrane surface;

[0030] F) Regulating the chemical and topological structures of the hollow fiber synthetic membrane surface, optimizing the blood compatibility and anti-fouling properties of the membrane surface, and obtaining a high-performance hollow fiber synthetic membrane.

[0031] Beneficial effects

[0032] The present invention provides a coupled computational method for fluid, solid, and biochemical processes in a multi-component mesh medium. Compared with existing technologies, it has the following advantages:

[0033] 1. This method, based on the coupling calculation method of multi-component mesh medium fluid, solid, and biochemical processes, utilizes the macro-fluid low-impedance coagulation and anti-dissolution mechanical calculation method to optimize the pump impeller and other structures to improve efficiency. Based on multi-component multi-field coupling calculation, it constructs a pump-lung mechanical optimization design system, optimizes the membrane lung oxygenation efficiency, and forms an optimization design system based on mechanical-biochemical multi-field coupling calculation to manufacture a pump-lung system with the advantages of low resistance, anti-coagulation, and anti-dissolution.

[0034] 2. This calculation method based on the coupling of multi-component mesh medium fluid, solid and biochemical processes uses biomimetic design to introduce biofunctional active molecules anticoagulant polysaccharide fragments and functional anti-inflammatory active polysaccharide fragments into the inner surface of the ECMO tube, selectively exerting the anticoagulant and anti-inflammatory effects on the endothelial cell surface, and grafting hydrophilic complex polysaccharide fragments onto the polyvinyl chloride surface to improve its biocompatibility.

[0035] 3. This method, based on the coupled calculation method of multi-component mesh medium fluid, solid and biochemical processes, prepares hollow fiber microporous membranes through thermal / non-solvent-induced composite phase separation technology. Through the rational design of polymer macromolecules, functional surface segregation modifiers containing low surface energy groups (siloxane groups, etc.) and transfer-promoting groups (amino groups, etc.) are prepared. Combined with modification technologies such as bionic adhesion and surface grafting, an anti-coagulation coating is constructed on the membrane surface; the chemical and topological structure of the surface of the hollow fiber synthetic membrane is regulated, the blood compatibility and anti-fouling performance of the membrane surface are optimized, and high-performance hollow fiber synthetic membranes are obtained. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Figure 1 Schematic diagram of the method flow of the present invention;

[0037] Figure 2 This is a flow chart of the covalent composite coating technology of the present invention;

[0038] Figure 3 This is a schematic diagram of the preparation process of the covalently bonded coating of the present invention;

[0039] Figure 4 Schematic diagram of the process for preparing hollow fiber synthetic membrane by thermal / non-solvent induced composite phase separation of the present invention;

[0040] Figure 5 This is a process roadmap for preparing hollow fiber synthetic membranes by thermal / non-solvent-induced composite phase separation of the present invention. DETAILED DESCRIPTION

[0041] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0042] The present invention provides two technical solutions:

[0043] Figure 1 The first embodiment is shown: a coupled calculation method for fluid, solid, and biochemical processes based on a multi-component mesh medium, including the following steps:

[0044] Step 1: Establish a fluid circulation model and a mathematical model of blood flow and oxygenation process. The fluid circulation model mainly includes a simulated blood pump, anti-coagulation and anti-inflammatory ECMO pipeline, and hollow fiber synthetic membrane;

[0045] Step 2: Combine the thrombosis model, hemolysis model, oxygenation effect model, and resistance analysis to construct a mechanical driving model of the effective oxygenation process;

[0046] Step 3: Associate the key structural and material parameters of the pump-lung system to form an optimized design system based on mechanical, biochemical and multi-field coupling calculations to manufacture a pump-lung system with low resistance, anti-coagulation and anti-solvent advantages;

[0047] Step 4: Optimize the structural design of the simulated dynamic blood pump as well as the hemolysis effect and oxygenation analysis through simulation and calculation of the flow field inside the pump.

[0048] The simulated blood pump includes an impeller and a pressure water chamber. The pressure water chamber is arranged to have a spiral structure and is designed according to the conservation of angular momentum. The trajectory of liquid particles flowing out of the impeller is a logarithmic spiral, and the pressure water chamber is spiral. It conforms to the flow law of liquid particles and has high hydraulic efficiency. The initial geometric parameters of the impeller are estimated based on the provided target parameters, including the blood pump inlet diameter, the blood pump outlet diameter, the impeller inner diameter, the impeller outer diameter, the blade inlet angle, the blade outlet angle, the number of blades, the blade wrap angle, and the blade width.

[0049] Figure 2-3 The second embodiment is shown, which differs from the first embodiment mainly in that: the anticoagulant and anti-inflammatory ECMO tube introduces biofunctional active molecules anticoagulant polysaccharide fragments and functional anti-inflammatory active polysaccharide fragments into the inner surface of the ECMO tube, selectively exerting anticoagulant and anti-inflammatory effects on the endothelial cell surface, and grafting hydrophilic complex polysaccharide fragments onto the polyvinyl chloride surface to improve its biocompatibility;

[0050] The preparation of the anticoagulant and anti-inflammatory ECMO tube comprises the following steps:

[0051] 1) Pretreatment of the inner surface of the ECMO tube: The inner surface of the extracorporeal circulation polymer material tube is cleaned with pure water ultrasonically to construct a composite coating material with high binding performance;

[0052] 2) Modification of the inner surface of the ECMO tube with activated groups: After multiple layers of surface activation modification, the inner surface of the ECMO tube is prepared;

[0053] 3) Preparation of polysaccharide fragments with anti-inflammatory and anticoagulant activities, preparation of a standard curve using the sodium iodide starch dextrin method, determination of oxidation degree, and screening of the optimal oxidation degree;

[0054] 4) catalytically covalently cross-linking the prepared anticoagulant and anti-inflammatory polysaccharide fragments with activated groups on the inner surface of the tube to prepare an anticoagulant and anti-inflammatory ECMO tube;

[0055] 5) Through orthogonal experimental design, the optimal coating preparation conditions for ECMO tubes were screened out and qualified anti-coagulant and anti-inflammatory ECMO tubes were prepared.

[0056] The anti-coagulation and anti-inflammatory ECMO tube needs to be tested for performance after preparation:

[0057] Anticoagulant activity detection: four coagulation indicators: APTT, TT, PT and FT;

[0058] Anti-inflammatory performance testing: IL-6, IL-8, IL-10, TNF-α, C-reactive protein anti-inflammatory indicators;

[0059] Coating surface hydrophilicity test: 2L of pure water was added to the surface of the dried sample using a micro-injector. The change in contact angle over time was recorded using a dynamic contact angle meter. Five points were measured for each sample, and the average value was obtained by measuring each point 10 times. The hydrophilicity of the coating was characterized by measuring the change in the surface contact angle before and after coating. The experimental data were statistically analyzed.

[0060] Protein adsorption experiment: protein quantitative determination was performed using the conventional BCA method;

[0061] Quantification of protein on the coating surface: Protein quantitative analysis was performed using the conventional BCA method. The difference in protein before and after the reaction was calculated using UV spectrophotometry, which is the amount of protein adhered to the material surface.

[0062] Platelet adhesion test on the coating surface: Platelets were measured according to laboratory routine. The platelet count and adhesion rate were calculated based on the changes in platelet count before and after the test. Adhesion amount = PLT1*PLT2; Adhesion rate = Adhesion amount / PLT1;

[0063] Thrombosis experiment on coating surface: A 10cm*10cm coating sample to be tested was vacuum-dried and weighed for dry weight W1, then trimmed appropriately and added to a 12-well culture plate; fresh unanticoagulated whole blood was drawn and quickly added to the sample wells to immerse the material; after incubation at 37°C for 60 minutes, the coating sample was removed, rinsed three times with PBS, fixed with 3% glutaraldehyde, treated with gradient ethanol, and vacuum-dried, and the dry weight sample W2 was weighed again. The difference in dry weight of the sample before and after incubation was calculated: the thrombus adhesion rate on the sample material surface = (W2-W1) / W1.

[0064] Characterization of the Anticoagulant and Anti-Inflammatory ECMO Pipeline:

[0065] Infrared spectral scanning analysis: The pipe is fully dried, the inner surface is exposed by cutting it open, and the functional groups on the surface of the coated pipe are directly detected by infrared scanning probe. Functional group analysis is performed by infrared spectral scanning of the inner surface of the ECMO pipe before and after coating modification;

[0066] Electron Microscopy and X-ray Diffraction Analysis: The ECMO tubing was thoroughly dried, and appropriately sized samples were cut and surface-coated with gold. Scanning electron microscopy was used to observe the surface morphology before and after coating. X-ray diffraction was used for morphological analysis and coating density and uniformity analysis.

[0067] Sterilization of ECMO tubing modified with anti-coagulant and anti-inflammatory coatings: Anti-coagulant and anti-inflammatory ECMO tubing must be sterilized by C0-60 radiation before use to meet medical standards.

[0068] Coating surface stability experiment: Centrifugal pump and roller pump were used to study the shedding of active groups in the extracorporeal circulation coating pipe, and the effect of the independently developed new coating pipe on the coating surface stability under the conditions of centrifugal pump drive and roller pump drive was observed.

[0069] Figure 4-5 A third embodiment is shown, which differs from the first two embodiments mainly in that the hollow fiber synthetic membrane is prepared using a thermal / non-solvent induced composite phase separation technology, and the preparation of the hollow fiber synthetic membrane includes the following steps:

[0070] A) Design suitable new spinneret and other composite thermally induced phase separation process equipment;

[0071] B) using water or a mixture of water and a water-soluble cosolvent in the cooling bath;

[0072] C) controlling the concentration and temperature of the water-soluble latent solvent in the cooling bath to control the density and pore size of the surface layer formed by the non-solvent-induced phase separation method, thereby obtaining a membrane with excellent anti-leakage and separation properties;

[0073] D) preparing a series of hollow fiber microporous membranes under different process conditions by regulating thermodynamic and kinetic parameters such as casting solution composition, core solution type, extrusion temperature, air gap height, cooling temperature, and winding speed;

[0074] E) preparing a functional surface segregation modifier containing low surface energy groups (such as siloxane groups) and transfer-promoting groups (such as amino groups), and combining modification technologies such as biomimetic adhesion and surface grafting to construct an anti-coagulation coating on the membrane surface;

[0075] F) Regulating the chemical and topological structures of the hollow fiber synthetic membrane surface, optimizing the blood compatibility and anti-fouling properties of the membrane surface, and obtaining a high-performance hollow fiber synthetic membrane.

[0076] At the same time, the contents not described in detail in this specification belong to the existing technology known to those skilled in the art, and the model parameters of each electrical appliance are not specifically limited, and conventional equipment can be used.

[0077] It should be noted that, in this document, relational terms such as first and second, etc., are used only to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any actual relationship or order between these entities or operations. Moreover, the terms "comprises," "comprising," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that includes a list of elements includes not only those elements but also other elements not explicitly listed, or elements inherent to such process, method, article, or apparatus.

[0078] While embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions, and variations may be made to these embodiments without departing from the principles and spirit of the invention, and that the scope of the invention is defined by the appended claims and their equivalents.

Claims

1. A coupled calculation method for multi-component mesh medium fluid, solid, and biochemical processes, characterized in that: The following steps are involved: Step 1: Establish a fluid circulation model, a mathematical model of blood flow and oxygenation process; Step 2: Combine the thrombosis model, hemolysis model, oxygenation effect model, and resistance analysis to construct a mechanical driving model of the effective oxygenation process; Step 3: Associate the key structural and material parameters of the pump-lung system to form an optimized design system based on mechanical, biochemical and multi-field coupling calculations to manufacture a pump-lung system with low resistance, anti-coagulation and anti-solvent advantages; Step 4: Optimize the structural design of the simulated dynamic blood pump as well as the hemolysis effect and oxygenation analysis through simulation and calculation of the flow field inside the pump.

2. The method for coupled calculation of fluid, solid, and biochemical processes based on a multi-component mesh medium according to claim 1, characterized in that: The fluid circulation model mainly includes a simulated blood pump, an anti-coagulation and anti-inflammatory ECMO pipeline, and a hollow fiber synthetic membrane.

3. The method for coupled calculation of fluid, solid, and biochemical processes based on a multi-component mesh medium according to claim 2, characterized in that: The simulated blood pump includes an impeller and a water pressure chamber. The water pressure chamber is set to a spiral structure and is designed according to the conservation of angular momentum. The trajectory of liquid particles flowing out of the impeller is a logarithmic spiral line, and the water pressure chamber is spiral, which conforms to the flow law of liquid particles and has high hydraulic efficiency.

4. The method for coupled calculation of fluid, solid, and biochemical processes based on a multi-component mesh medium according to claim 2, characterized in that: The initial geometric parameters of the impeller are estimated based on the provided target parameters, including the blood pump inlet diameter, blood pump outlet diameter, impeller inner diameter, impeller outer diameter, blade inlet angle, blade outlet angle, number of blades, blade wrap angle, and blade width.

5. The method for coupled calculation of fluid, solid, and biochemical processes based on multi-component mesh media according to claim 2, characterized in that: The anticoagulant and anti-inflammatory ECMO tube introduces biofunctional active molecule anticoagulant polysaccharide fragments and functional anti-inflammatory active polysaccharide fragments into the inner surface of the ECMO tube, selectively exerts the anticoagulant and anti-inflammatory effects on the endothelial cell surface, and grafts the hydrophilic complex polysaccharide fragments onto the polyvinyl chloride surface to improve its biocompatibility.

6. The method for coupled calculation of fluid, solid, and biochemical processes based on multi-component mesh media according to claim 2, characterized in that: The preparation of the anticoagulant and anti-inflammatory ECMO tube comprises the following steps: 1) Based on the fragmentation pretreatment of the composite coating material, a composite coating material with high binding performance is constructed; 2) Through a special covalent binding mode of end-point fixation, an anticoagulant active unit with a good spatial conformation is constructed; 3) Based on composite covalent coating technology, construct vascular endothelial surface biomimetic materials; 4) By constructing a fixed-state anticoagulant biomimetic surface with good biocompatibility, an anticoagulant and anti-inflammatory ECMO tube was obtained; 5) Through orthogonal experimental design, the optimal coating preparation conditions for ECMO tubes were screened out and qualified anti-coagulant and anti-inflammatory ECMO tubes were prepared.

7. The method for coupled calculation of fluid, solid, and biochemical processes based on multi-component mesh media according to claim 6, characterized in that: After preparation, the anti-coagulation and anti-inflammatory ECMO tube needs to measure the four coagulation indicators of APTT, TT, PT and FT, as well as the anti-inflammatory indicators of IL-6, IL-8, IL-10, TNF-α and C-reactive protein.

8. The method for coupled calculation of fluid, solid, and biochemical processes based on multi-component mesh media according to claim 6, characterized in that: After preparation, the anticoagulant and anti-inflammatory ECMO tube is characterized by infrared spectroscopy scanning analysis, electron microscopy, and X-ray diffraction analysis of the anticoagulant and anti-inflammatory coating modified ECMO tube. Before use, the anticoagulant and anti-inflammatory ECMO tube needs to be sterilized by C0-60 radiation to meet medical standards.

9. The method for coupled calculation of fluid, solid, and biochemical processes based on multi-component mesh media according to claim 2, characterized in that: The hollow fiber synthetic membrane is prepared by adopting a thermal / non-solvent induced composite phase separation technology.

10. The method for coupled calculation of fluid, solid, and biochemical processes based on multi-component mesh media according to claim 2, characterized in that: The preparation of the hollow fiber synthetic membrane comprises the following steps: A) Design a suitable spinneret composite thermally induced phase separation process equipment; B) using water or a mixture of water and a water-soluble cosolvent in the cooling bath; C) controlling the concentration and temperature of the water-soluble latent solvent in the cooling bath to control the density and pore size of the surface layer formed by the non-solvent-induced phase separation method, thereby obtaining a membrane with excellent anti-leakage and separation properties; D) preparing a series of hollow fiber microporous membranes under different process conditions by regulating the thermodynamic and kinetic parameters of the casting solution composition, core solution type, extrusion temperature, air gap height, cooling temperature, and winding speed; E) preparing a functional surface segregation modifier containing a low surface energy group and a transfer-promoting group, and combining biomimetic adhesion and surface grafting modification technology to construct an anti-coagulation coating on the membrane surface; F) Regulating the chemical and topological structures of the hollow fiber synthetic membrane surface, optimizing the blood compatibility and anti-fouling properties of the membrane surface, and obtaining a high-performance hollow fiber synthetic membrane.

Images