A permeable membrane with a surface grown cof layer and methods of making and using the same

Abstract

The application belongs to the field of membrane materials, and particularly relates to a surface-grown COF layer permeable membrane and a preparation method and application thereof. Aldehyde monomers are introduced into a casting solution for blending, a porous base membrane with aldehyde groups on the surface is obtained through a phase inversion method, and then the aldehyde-grouped porous base membrane is placed into an acidic reaction solution containing aldehyde monomers and sufficient amine monomers containing guanidine groups to obtain a porous permeable membrane with a surface-grown polyamino COF. The porous base guarantees good gas permeability, and the thin and dense layer on the surface also ensures that the membrane can not leak liquid for a long time. In addition, the enrichment of the surface amino groups also promotes the affinity of the material to carbon dioxide, which is beneficial to gas exchange in ECMO application. In addition, the surface-grown COF layer also improves the anti-protein adhesion performance of the porous base membrane.

Description

Technical Field

[0001] This invention belongs to the field of membrane materials, specifically relating to a permeable membrane with a COF layer grown on its surface, its preparation method, and its application. Background Technology

[0002] Extracorporeal membrane oxygenation (ECMO) works by drawing venous blood from the patient, oxygenating it through a membrane oxygenator, removing carbon dioxide, and then returning it to the patient's body. This extracorporeal life support is used to treat conditions such as acute respiratory failure, cardiogenic or septic shock, poisoning from ingestion, and thyroid poisoning. ECMO is often called a patient's "last straw" because it can replace normal lung function in emergency situations. The most crucial component of ECMO is the membrane oxygenator (MO). As an intermediate medium that comes into contact with both blood and external oxygen, the MO's blood compatibility, gas permeability, and ability to prevent plasma permeation are extremely important.

[0003] Currently, three materials have been successfully industrialized: PDMS, PP, and PMP. Polydimethylsiloxane (PDMS), as a first-generation membrane oxygenator material, possesses excellent gas permeability, with an oxygen permeability coefficient of 600 Barrer, far exceeding that of ethyl cellulose (20 Barrer) and polyethylene (1-8 Barrer). However, its low mechanical strength necessitates a thickness exceeding 100 micrometers, directly leading to a decrease in gas exchange efficiency. Compared to dense PDMS, porous polypropylene (PP) membranes offer lower gas transport resistance, better blood compatibility, and are non-toxic, thus being chosen as the second-generation oxygenator membrane material. However, its porous structure, beneficial for gas transport, also poses a risk of plasma leakage, affecting gas exchange rates and potentially causing complex immune responses such as thrombosis, thus hindering long-term support for extracorporeal circulation. The third-generation membrane material, polymethylpentene (PMP), successfully solved the blood leakage problem and exhibits good gas permeability. However, besides the technical bottleneck of complex membrane formation, poor blood compatibility remains a significant limitation to its long-term operation. Therefore, a modification strategy is needed that can balance gas permeability and blood leakage resistance while ensuring good blood compatibility of the membrane oxygenator, thus meeting the requirements for ECMO use.

[0004] Covalent organic frameworks (COFs) are a novel type of porous crystalline material. Due to their tunable structure and unique chemical groups, COFs can possess low density, large specific surface area, controllable pore size, and the ability to introduce specific functional sites, making them highly promising and offering significant opportunities in the field of membrane separation. Current research on COF membranes covers gas separation membranes, liquid phase separation membranes, proton exchange membranes in fuel cells, and more. Although the application of COF membranes in ECMO (electrode mechanical oxygenation) has not been widely reported, their properties warrant further exploration of their application potential in this field. Currently reported porous COFs have pore sizes ranging from 0.5 to 4.7 nanometers; the small pore structure can effectively provide more efficient and abundant gas transport channels in the event of blood leakage.

[0005] Polyethersulfone (PES) possesses excellent mechanical properties and good blood compatibility, making it widely used in biomaterials. Previous research has also explored its application as a membrane oxygenator in ECMO (extracorporeal membrane oxygenation). However, its inherent resistance to protein adhesion is poor. During long-term use in membrane oxygenators, the accumulation of proteins in the blood on the membrane can affect gas exchange or cause immune responses such as thrombosis. Furthermore, the membrane formation method significantly impacts the material structure. Thermally induced phase separation (TIPS) yields dense PES membranes, which helps prevent blood leakage but also hinders gas exchange. Non-solvent-induced phase separation (NIPS) can produce asymmetric PES membranes with high porosity, which is beneficial for gas exchange, but it is difficult to simultaneously balance its ability to prevent plasma leakage. Summary of the Invention

[0006] To address the aforementioned issues, this invention utilizes a small-pore structured COF to modify PES through a unique surface growth method, successfully overcoming the shortcomings of PES in ECMO applications. Furthermore, this invention anticipates that this COF surface growth method can be applied to other permeation membranes suitable for ECMO, such as PDMS, PP, and PMP membranes.

[0007] Specifically, in one aspect, the present invention provides a method for preparing a permeable membrane with a COF layer grown on its surface, comprising the following steps:

[0008] (1) The permeation membrane material and aldehyde monomer are blended and then formed into a membrane to obtain an aldehyde-based permeation membrane;

[0009] (2) The obtained aldehyde-modified permeation membrane is immersed in an aqueous solution containing aldehyde monomers, amine monomers containing guanidine groups and acid catalysts, and a permeation membrane with a COF layer grown on the surface is obtained by the Schiff base reaction of aldehyde group and amino group.

[0010] Furthermore, the permeation membrane material includes polydimethylsiloxane, polypropylene, polymethylpentene, or polyethersulfone.

[0011] Further, the aldehyde monomer includes trialdehyde phloroglucinol, 2,4-dihydroxy-1,3,5-pyromellitic pyroxenaldehyde, 2-hydroxy-1,3,5-phenyltricarboxaldehyde, pyromellitic pyroxenaldehyde, terephthalaldehyde, 2,5-dihydroxyterephthalaldehyde, 2-hydroxybenzene-1,4-dicarboxaldehyde, 4,6-dialdehyde phloroglucinol, 2,4-dicarboxymethyl phloroglucinol, 2,4-dihydroxyterephthalaldehyde, 2-hydroxyterephthalaldehyde, 2,6-dicarboxymethyl-4-methylphenol, or 4-hydroxyterephthalaldehyde. Even further, the aldehyde monomer is 2,5-dihydroxyterephthalaldehyde.

[0012] Furthermore, the aldehyde monomers in steps (1) and (2) can be the same or different aldehyde monomers. Even further, the aldehyde monomers in steps (1) and (2) are the same aldehyde monomers.

[0013] Further, the guanidine-containing amine monomer is triaminoguanidine hydrochloride or 1,3-diaminoguanidine hydrochloride. Even further, the guanidine-containing amine monomer is triaminoguanidine hydrochloride.

[0014] Further, the acid catalyst includes hydrochloric acid, sulfuric acid, nitric acid, acetic acid, p-toluenesulfonic acid, scandium trifluoromethanesulfonate, or trifluoroformic acid. Even further, the acid catalyst is acetic acid with a concentration of 3-6M.

[0015] Further, the film formation after blending in step (1) includes forming a film using any method suitable for the formation of a permeation membrane material, such as co-dissolving the permeation membrane material and the aldehyde monomer in an organic solvent and preparing an aldehyde-based permeation membrane by phase conversion membrane method.

[0016] Furthermore, the organic solvent includes one or more of N,N-dimethylformamide, N,N-dimethylacetamide, dichloromethane, dimethyl sulfoxide, and N-methylpyrrolidone.

[0017] Furthermore, the phase conversion membrane method uses a non-solvent-induced phase separation method to form a membrane.

[0018] Furthermore, the phase conversion membrane method includes the following steps:

[0019] S1: The permeation membrane material and aldehyde monomer are co-dissolved in an organic solvent, and the casting solution is obtained after degassing;

[0020] S2: Cast the casting solution of S1 onto the substrate, and then immerse the substrate coated with the casting solution in the antisolvent coagulation solution until a film is formed. After solvent removal and drying, the aldehyde-based permeable membrane is obtained.

[0021] Furthermore, the substrate includes glass, metal plate, or release paper, etc.

[0022] Furthermore, the antisolvent coagulation solution can be pure water, ethanol, or a mixture thereof.

[0023] Furthermore, the film-forming temperature is 20-40℃.

[0024] Furthermore, the solvent removal includes immersing the formed film in an antisolvent coagulation solution for a sufficient time to remove the solvent.

[0025] Furthermore, the Schiff base reaction includes a reaction at 10-100°C for 1-30 days.

[0026] Furthermore, the ratio of the total molar amount of the aldehyde monomers to the molar amount of the amine monomers containing guanidine groups is 1:0.8-1.2.

[0027] In other respects, the present invention provides a permeable membrane with a surface-grown COF layer, which is prepared by the preparation method described herein.

[0028] In other respects, the present invention also provides the use of permeable membranes with surface-grown COF layers as prepared or described herein in extracorporeal membrane oxygenation.

[0029] Furthermore, the permeation membrane with a surface-grown COF layer prepared or described herein can be used as an ECMO membrane.

[0030] In addition, the permeable membrane with a surface-grown COF layer prepared or described herein can also be used as an antifouling membrane, a separation membrane, etc.

[0031] Beneficial effects of the present invention

[0032] This invention first blends aldehyde monomers with a polymer matrix to prepare a membrane with monomers embedded in the matrix. Then, the aldehyde-modified porous substrate membrane is grown in situ in an acidic reaction solution containing aldehyde monomers and a sufficient amount of amine monomers containing guanidine groups to obtain a porous permeable membrane with a surface-grown polyamine COF layer. The porous substrate ensures good gas permeability, while the thin, dense surface layer ensures that the membrane remains leak-proof for extended periods. The enrichment of surface amino groups also promotes the material's affinity for carbon dioxide, which is beneficial for gas exchange in ECMO applications. Furthermore, the surface-grown COF layer improves the anti-protein adhesion properties of the porous substrate membrane. Attached Figure Description

[0033] Figure 1 The following data are shown: (A) Infrared spectrum; (B) Thermogravimetric curve; (C) X-ray photoelectron spectrum; (D) C1s spectrum of the three membrane materials in the examples and comparative examples.

[0034] Figure 2 Scanning electron microscope images of the surface (A) and cross-section (B) of the three membrane materials in the examples and comparative examples are shown.

[0035] Figure 3 The following are shown: (A) the dissolution of PES-NH2 in DMAc; (B) the dissolution of PES-COF in DMAc; (C) the infrared characterization of the undissolved surface layer of the PES-COF substrate after dissolution in DMAc; and (D) X-ray diffraction.

[0036] Figure 4 The results show (A) the static water contact angles of the four membrane materials; (B) the fluorescence of the four materials after FITC-BSA incubation observed by laser confocal microscopy; and (C) the adhesion of BSA was assessed by statistically analyzing the fluorescence intensity of the four materials using Image-J.

[0037] Figure 5 The results of blood compatibility assessments for the three membrane materials in the examples and comparative examples are shown.

[0038] Figure 6 The results show the clotting time and fibrin content in the blood of the three materials in the examples and comparative examples after incubation, as well as the blood sample control group.

[0039] Figure 7 The results of CO2 and O2 gas permeation tests for the three membrane materials in the examples and comparative examples are shown.

[0040] Figure 8 The results of gas exchange performance tests on four membrane materials using the ECMO simulation system are shown.

[0041] Figure 9 The results of the test comparison of O2 and CO2 exchange performance of PES-COF and PES-CHO membranes are shown.

[0042] Figure 10 The results of long-term humidity tests on PES-COF are shown.

[0043] Figure 11 A schematic diagram of the application of the PES-COF of the present invention in ECMO is shown. Detailed Implementation

[0044] This invention uses PES as an example to modify PES using a small-pore COF structure. First, the monomer 2,5-dihydroxyterephthalaldehyde (Dha) is introduced into a casting solution for blending. A porous substrate membrane PES-CHO with aldehyde groups on the surface is obtained through phase inversion. Then, the aldehyde-modified PES-CHO is grown in situ in an acidic reaction solution containing Dha and sufficient triaminoguanidine hydrochloride (TAG·HCl) to obtain a PES-COF membrane with a multi-amino COF surface. The porous substrate ensures good gas permeability, while the thin, dense surface layer ensures the membrane remains leak-proof for extended periods. Furthermore, the enrichment of surface amino groups promotes the material's affinity for carbon dioxide, which is beneficial for gas exchange in ECMO applications. After characterizing the material's structure and surface properties, we tested its anti-adhesion performance against BSA protein using laser confocal microscopy and a BCA kit. In addition, gas permeability tests, blood tests, and ECMO simulation tests verified the material's performance in practical application scenarios. This study further explores the application potential of COF structures in the ECMO field.

[0045] The present invention will be further illustrated below with reference to specific embodiments, but these embodiments do not limit the invention in any way. The polyethersulfone (PES, Ultrason E6020P) used in the embodiments was provided by BASF Chemical Company, Germany. 2,5-Dihydroxyterephthalaldehyde (Dha) and triaminoguanidine hydrochloride (TAG·HCl) were purchased from Adamas. Unless otherwise specified, other reagents, methods, and equipment used in this invention are conventional reagents, methods, and equipment in this technical field.

[0046] Example 1: Preparation of polyethersulfone with COF layer grown on surface

[0047] Polyethersulfone (5 g, 25 wt%) and 2,5-dihydroxyterephthalaldehyde (33.2 mg, 0.2 mmol) were stirred and dissolved in N,N-dimethylacetamide (DMAc, 15 g). After degassing in a vacuum oven, the solution was cast onto a clean glass slide using a spin coater. The glass slide coated with the casting solution was immersed in pure water, and the PES-CHO membrane was obtained through liquid-liquid phase inversion. The resulting membrane was immersed in pure water for one week, then dried and stored for further use.

[0048] Triaminoguanidine hydrochloride (42 mg, 0.3 mmol) and 2,5-dihydroxyterephthalaldehyde (16.6 mg, 0.1 mmol) were dissolved together in 40 mL of 3M acetic acid solution and sonicated for 20 minutes. The resulting PES-CHO was then immersed in the solution and reacted at room temperature for 7 days. The triaminoguanidine hydrochloride monomer was introduced onto the membrane surface via a Schiff base reaction to form a COF-like structure on the membrane surface, thus obtaining the polyethersulfone material PES-COF with a COF layer grown on the surface.

[0049] Comparative Example 1:

[0050] Polyethersulfone (25 wt%) and 2,5-dihydroxyterephthalaldehyde (0.2 mmol) were stirred and dissolved in N,N-dimethylacetamide (DMAc). After degassing in a vacuum oven, the solution was cast onto a clean glass slide using a spin coater. The glass slide coated with the casting solution was immersed in pure water, and the PES-CHO membrane was obtained through liquid-liquid phase inversion. The resulting membrane was immersed in pure water for one week, then dried and stored for further use.

[0051] Triaminoguanidine hydrochloride (0.2 mmol) was dissolved in 3M acetic acid solution and sonicated for 20 minutes. The resulting PES-CHO was then immersed in the solution and reacted at room temperature for 7 days. The triaminoguanidine hydrochloride monomer was introduced onto the membrane surface via Schiff base reaction to obtain the material PES-NH2.

[0052] Test Example 1: Characterization of Membrane Materials

[0053] The chemical structures of the different films in the examples and comparative examples were characterized using an ATR-FTIR (NICOLET iS50) spectrometer, with a test range of 400 to 2000 cm⁻¹. -1 The elemental composition and chemical state of the membrane surface were characterized using XPS (ESCALAB 250XI, Thermo Fisher Scientific) and EDS (OctaneElect Super, EDAX). The surface and cross-sectional morphology of the membrane were observed using scanning electron microscopy (Thermo Fisher Scientific). The thermal stability of the membrane was determined by thermogravimetric analysis (TGA, Mettler Toledo, Switzerland). Furthermore, the hydrophilicity of the membrane surface was characterized by water contact angle (Theta Lite, Biolin Scientific, Sweden), and the surface roughness was tested by AFM (Icon, Bruker). The results are presented below.

[0054] First, the surface functional groups of the three film materials were characterized using Fourier transform infrared absorption spectroscopy (FTIR), such as... Figure 1 A. It can be observed at 1640cm -1 The carbonyl peak in PES-CHO was introduced due to the blending of Dha, while the carbonyl peak in PES-NH2 disappeared. This is because excess triaminoguanidine hydrochloride (TAG·HCl) was added during the post-treatment reaction of PES-CHO, and the Schiff base reaction consumed the aldehyde groups on the membrane surface. However, in the preparation of PES-COF material, both 2,5-dihydroxyterephthalaldehyde (Dha) and triaminoguanidine hydrochloride were added during the reaction; therefore, the COF-like structure formed on the surface still contains unreacted carbonyl groups. The temperature-mass changes of the three membrane materials were also characterized using thermogravimetric analysis (TGA), such as... Figure 1B. It can be seen that PES-CHO has the highest weight loss rate, while PES-COF has the lowest. This is because the specific gravity of PES decreases after modification, and the introduction of new substances on the material surface is less prone to degradation reactions at high temperatures. Furthermore, elemental analysis of the material surface was performed using X-ray photoelectron spectroscopy (XPS). Figure 1 As shown in Table C and Table 1, the surface nitrogen content of PES-NH2 and PES-COF increases due to the introduction of TAG·HCl, with PES-COF exhibiting the highest nitrogen content at 5.90%. Furthermore, Figure 1 D shows the detailed C1s spectra of the three membranes. The C1s core-level spectra have four peaks at binding energies of 284.8 eV, 285.7 eV, 287.9 ​​eV, and 292.0 eV, corresponding to CC, CN(CO), C=O, and CS, respectively. The analysis confirms the successful introduction of triaminoguanidine hydrochloride and COF-like structures, respectively.

[0055] Table 1: XPS elemental content analysis of the three membrane materials in the examples and comparative examples

[0056]

[0057] Test Example 2: Surface Properties of Membrane Materials

[0058] To investigate the structural changes on the surface of the membrane material before and after modification, we observed the surface and cross-sectional structure of the material using scanning electron microscopy (SEM). Figure 2 As shown in Figure A, we can see that no pore structure is observable on the surfaces of the three films, and the surfaces of the materials before and after modification are relatively smooth. Figure 2 As shown in Figure B, after the film was fractured using liquid nitrogen, the cross-sectional structure revealed that the introduction of 2,5-dihydroxyterephthalaldehyde (2,5-dihydroxyterephthalaldehyde) into the casting solution increased the porosity to some extent during the phase transition, resulting in a thinner PES-CHO skin layer. In contrast, the modified PES-NH2 and PES-COF both exhibited a dense layer approximately 1.2 micrometers thick. This is attributed to the introduction of TAG·HCl and COF-like structures, respectively, which resulted in the growth of a continuous coating on the surface.

[0059] PES-NH2 and PES-COF were dissolved in DMAc. The PES substrate dissolved rapidly, while the surface coating remained insoluble in DMAc. Because the surface reaction of synthesized PES-NH2 mainly involves a Schiff base reaction between the Dha embedded in the substrate and TAG·HCl in the solution, the structure is not entirely intact. Therefore, after the PES substrate completely dissolves in DMAc, the strength is low, and the coating fragments and disintegrates in the solvent. Figure 3As shown in Figure A, the surface reaction for synthesizing PES-COF involves the reaction of Dha embedded in the substrate with TAG·HCl, while simultaneously, the Dha in the solution reacts with the free TAG·HCl already fixed on the surface, forming a COF-like coating on the surface. This coating is continuous and stable, and the surface layer remains stable and intact after the PES substrate dissolves in DMAc. Figure 3 As shown in B.

[0060] The COF-like coating obtained by dissolving PES-COF was characterized after being naturally dried at room temperature. Infrared spectroscopy revealed (…). Figure 3 C), at 3450cm -1 The stretching vibration peak of the -NH-(-OH) group is present at 1650 cm⁻¹. -1 The presence of stretching vibration peaks of -C=N- groups further confirms the surface structure. The crystallinity of the material was then verified using XPS, as shown below. Figure 3 D, no crystallization peak was observed. This is because the location of Dha buried in the substrate PES is restricted, which affects the subsequent structure and prevents orderly crystallization.

[0061] Test Example 3: Stain Resistance Test

[0062] Protein fouling is the most critical aspect of membrane fouling, therefore, the anti-protein adhesion performance of materials is a crucial factor. Anti-protein adhesion is characterized by four molecular-level features: the presence of polar functional groups, the presence of hydrogen bond acceptor groups, the absence of hydrogen bond donor groups, and the absence of net charge. Pure polyethersulfone (PES) materials exhibit weak antifouling ability and rapid protein adhesion. To investigate the antifouling performance of the materials in this study, three materials were compared with PES. First, the surface hydrophilicity of the four membrane materials was tested. Increased surface polarity improved the hydrophilicity of the materials, such as... Figure 4 A. With further reaction, the hydrophilicity gradually increased, and the water contact angle decreased from 86° for PES-CHO to 78° for PES-NH2 and 74° for PES-COF. Next, the anti-protein adhesion properties of the materials were tested. After co-incubating the materials with FITC-BSA in the dark for 3 hours, the free fluorescently labeled proteins were washed away with PBS buffer. Observation using laser confocal microscopy and statistical analysis of fluorescence intensity revealed that, compared with pure polyethersulfone membranes, all three membrane materials in this study exhibited very good anti-protein adhesion properties. This is due to the introduction of polar groups such as hydroxyl, aldehyde, and amide structures. Among them, the carbonyl and amide structures are hydrogen bond acceptor groups, which are more favorable for anti-protein adhesion. This, to a certain extent, contributes to improving the antibacterial properties and blood compatibility of the materials. Figure 4 (B and 4C).

[0063] Test Example 4: Blood Compatibility Assessment

[0064] As the medium for the exchange of gases between the blood and the external environment in an artificial lung, the membrane material must have good blood compatibility. Here, we conducted blood compatibility tests on these three membrane materials. First, we co-incubated the materials and red blood cells in a shaker at 37 degrees Celsius. After three hours, we centrifuged the EP tube containing the materials and red blood cells. Figure 5 B shows that the supernatant in the EP tubes of all three material samples was transparent, and no significant hemoglobin release was observed after co-incubation with red blood cells. Furthermore, by measuring the absorbance of the supernatant to calculate the hemolysis rate, we can see that the hemolysis rate of all materials was less than 1%. Figure 5 A) This is significantly lower than the ISO standard (5%). Next, the red blood cells and platelets adhering to the material surface were fixed with 2.5 wt% glutaraldehyde for 24 hours, then subjected to gradient dehydration with ethanol, dried at room temperature, and observed using a scanning electron microscope. Figure 5 C. It can be observed that the erythrocytes on the PES-COF surface are regular, centrally concave discs; the erythrocytes on the PES-NH2 surface are also disc-shaped, but with irregular edges; while the erythrocytes on the PES-CHO surface are all deformed, appearing as spikes. Observation of platelet adhesion revealed that platelets on the PES-COF surface were partially deformed but not significantly activated, while platelets on the PES-CHO and PES-NH2 surfaces were significantly activated, exhibiting pseudopodia and agglomerating onto the material surface. The effects of several membranes on blood cells were tested using a complete blood count, such as... Figure 5 As shown in Figures D and 5E, the number of red blood cells (RBCs), white blood cells (WBCs), and platelets (PLTs) in the blood after co-incubation with PES-COF was not significantly different from that in the control group. Hemoglobin concentration (HGB) and hematocrit (HCT) were also unaffected by the materials. However, the blood cell parameters of the other two materials differed to varying degrees from those of the control group. Furthermore, blood flow cytometry results also showed that the blood cell counts after PES-COF treatment were consistent with those in the control group. Figure 5 F).

[0065] In addition, to investigate the effects of the three materials on the coagulation system, we measured the coagulation time (APTT), PT, TT, Fbg, and fibrin concentration of plasma treated with the three membrane materials and compared them with the control group. Figure 6 As shown, none of the three materials promoted coagulation, which is beneficial for the use of blood contact materials. Therefore, the blood compatibility characterization results indicate that the prepared PES-COF membrane has good blood compatibility and is superior to the other two membranes.

[0066] Test Example 5: CO2 and O2 Gas Permeation Test

[0067] To evaluate the gas permeability of the membranes before and after modification, we systematically analyzed the gas permeability of three membranes using the differential pressure method. For example... Figure 7 As shown in Figure A, compared with the original PES and PES-CHO membranes, the carbon dioxide and oxygen permeabilities of PES-NH2 and PES-COF were slightly reduced, but this did not have a substantial impact. The oxygen and carbon dioxide permeabilities (Barrer values) of PES-COF reached 83.4 and 219.0, respectively. Furthermore, with modification, the CO2 / O2 selectivity of PES-COF increased to 2.6. The increased thickness of the dense layer after modification did not significantly affect the material's carbon dioxide permeability, which is beneficial for the ECMO system. Figure 7 B).

[0068] Test Example 6: Gas Permeation Performance in ECMO Simulated Circulation System

[0069] In the clinical application of ECMO, membrane materials are used as an intermediate medium that simultaneously contacts blood and oxygen, promoting blood oxygenation and carbon dioxide removal. Therefore, they need to possess good gas exchange capacity and liquid barrier properties. We therefore built our own ECMO simulation system and tested several membrane materials (such as...). Figure 8 A). The membrane is fixed between two chambers. Saturated carbon dioxide water is added to the flask and maintained at 37 degrees Celsius. The solution is circulated in the upper chamber by a pump, and the concentrations of carbon dioxide and oxygen in the solution are measured using relevant instruments. One end of the lower chamber is connected to an oxygen cylinder to control the oxygen flow rate, while the other end allows for the measurement of ambient humidity using relevant instruments.

[0070] We used this simulated circulation device to test the gas exchange performance of four membrane materials. The experimental results showed that, for example... Figure 8 Compared to PES-CHO, the modified PES-NH2 and PES-COF both promoted the passage of oxygen and carbon dioxide. After 30 minutes, the carbon dioxide content in the solution decreased to 51.2%, 43.4%, and 44.4% of the original levels, respectively, while the liquid phase oxygen concentration increased from 0.76 ppm to 4.48, 5.76, and 4.83 ppm, respectively. The change in carbon dioxide concentration in the gas phase also showed a significantly faster rate of increase for PES-NH2 and PES-COF. It can be seen that in the ECMO simulation system, the gas permeability performance of PES-NH2 and PES-COF is significantly superior to that in a simple gas phase environment. This may be because, under unpressurized conditions, the polarity of the material surface plays a greater role in promoting gas permeation than the increased thickness of the dense surface layer.

[0071] Although PES-NH2 exhibited the best gas exchange performance in the ECMO simulation system, PES-COF was deemed the optimal candidate for artificial lungs based on comprehensive blood compatibility assessment, and its gas permeability surpassed that of most studied polymer membranes. Therefore, to evaluate actual oxygenation and carbon dioxide removal performance, the saturated carbon dioxide water in the upper chamber was replaced with pig blood. The O2 and CO2 exchange performance of the membrane was assessed using a blood gas analyzer while maintaining an ambient temperature of 37°C and a blood-to-gas ratio of 1:2.5. Figure 9 As shown in the results, PES-COF achieved blood oxygen saturation (95%) faster than PES-CHO, and its CO2 elimination rate was also faster, with O2 and CO2 gas fluxes of 103.70 ml / (min·m). 2 ) and 755.95 ml / (min·m 2 The surface area of ​​an ECMO membrane lung is typically 1–3 m². 2 This meets the gas exchange efficiency (250 ml / min) required for clinical ECMO use. Furthermore, the PES-COF surface showed no significant changes after blood circulation.

[0072] Besides gas permeability, plasma leakage is another critical issue with membrane oxygenators (MEAs). During ECMO cycles, plasma may leak through the membrane pores, leading to decreased gas exchange efficiency and inevitably requiring MEA replacement. Therefore, we conducted a long-term humidity test on the PES-COF, monitoring humidity and temperature changes in the lower chamber over a continuous 120-hour cycle. Figure 10 As shown, relative humidity and temperature fluctuated slightly but did not change significantly, which verifies the excellent liquid permeation resistance of the PES-COF membrane. These data confirm that PES-COF possesses excellent performance and can be applied to ECMO systems.

[0073] In summary, this invention utilizes an in-situ growth strategy to introduce a relatively dense COF layer onto the surface of PES to prepare a membrane lung material for ECMO. We introduced Dha monomer into a polyethersulfone casting solution to prepare an aldehyde-modified polyethersulfone membrane, and then introduced a COF layer through a co-reaction of Dha and TAG·HCl with the aldehyde-modified polyethersulfone membrane. Benefiting from the affinity of nitrogen-rich amide groups and unreacted amino groups for carbon dioxide on the surface, the modified membrane exhibits significantly enhanced carbon dioxide selectivity. Furthermore, compared to the original PES membrane, the modified membrane not only shows enhanced resistance to protein adhesion but also improved blood compatibility. Moreover, ECMO simulation tests demonstrate that the modified membrane exhibits excellent gas exchange performance and leak resistance. The surface modification method in this study is effective, easily industrialized, and applicable to hollow fiber membranes, which have great application potential.

[0074] It should be noted that while the preferred embodiments of the present invention are given in the specification and accompanying drawings, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. These embodiments are not intended to impose additional limitations on the content of the present invention; their purpose is to provide a more thorough and comprehensive understanding of the disclosure of the present invention. Furthermore, the above-described technical features can be combined with each other to form various embodiments not listed above, all of which are considered to be within the scope of the present invention specification. Moreover, those skilled in the art can make improvements or modifications based on the above description, and all such improvements and modifications should fall within the protection scope of the appended claims.

Claims

1. A method for producing a permeation membrane of a surface-grown COF layer, characterized by, Includes the following steps: (1) The permeation membrane material and aldehyde monomer are blended and then formed into a membrane to obtain an aldehyde-based permeation membrane; (2) The obtained aldehyde-modified permeation membrane is immersed in an aqueous solution containing aldehyde monomers, amine monomers containing guanidine groups and acid catalysts, and a permeation membrane with a COF layer grown on the surface is obtained by the Schiff base reaction of aldehyde group and amino group. The membrane formation after blending in step (1) includes dissolving the permeable membrane material and the aldehyde monomer in an organic solvent and preparing a permeable membrane with the aldehyde monomer embedded in the matrix by a phase conversion membrane method. The aldehyde monomers include trialdehyde phloroglucinol, 2,4-dihydroxy-1,3,5-pyromellitic pyroxenaldehyde, 2-hydroxy-1,3,5-pyromellitic pyroxenaldehyde, pyromellitic pyroxenaldehyde, 2,5-dihydroxy-terephthalaldehyde, 2-hydroxybenzene-1,4-dicarboxaldehyde, 4,6-dialdehyde phloroglucinol, 2,4-dicarboxyl phloroglucinol, 2,4-dihydroxy-pyromellitic pyroxenaldehyde, 2-hydroxy-pyromellitic pyroxenaldehyde, 2,6-dicarboxyl-4-methylphenol, or 4-hydroxy-pyromellitic pyroxenaldehyde; The aldehyde monomers in steps (1) and (2) may be the same or different aldehyde monomers; The amine monomer containing the guanidine group is triaminoguanidine hydrochloride or 1,3-diaminoguanidine hydrochloride.

2. The preparation method according to claim 1, characterized in that, The permeation membrane material includes polydimethylsiloxane, polypropylene, polymethylpentene, or polyethersulfone.

3. The preparation method according to claim 1, characterized in that, The acid catalysts include hydrochloric acid, sulfuric acid, nitric acid, acetic acid, p-toluenesulfonic acid, scandium trifluoromethanesulfonate, or trifluoroformic acid.

4. The preparation method according to claim 1, characterized in that, The organic solvent includes one or more of N,N-dimethylformamide, N,N-dimethylacetamide, dichloromethane, dimethyl sulfoxide, and N-methylpyrrolidone.

5. The preparation method according to claim 1, characterized in that, The phase conversion membrane method uses a non-solvent-induced phase separation method to form a membrane.

6. The preparation method according to claim 5, characterized in that, The phase conversion membrane method includes the following steps: S1: The permeation membrane material and aldehyde monomer are co-dissolved in an organic solvent, and the casting solution is obtained after degassing; S2: Cast the casting solution of S1 onto the substrate, and then immerse the substrate coated with the casting solution in an antisolvent coagulation bath until a film is formed. After solvent removal and drying, the aldehyde-based permeable membrane is obtained.

7. The preparation method according to claim 1, characterized in that, The Schiff base reaction includes a reaction at 10-100°C for 1-30 days.

8. The preparation method according to claim 1, characterized in that, The ratio of the total molar amount of the aldehyde monomers to the molar amount of the amine monomers containing guanidine groups is 1:0.8-1.

2.

9. A permeable membrane with a COF layer grown on its surface, which is prepared by the preparation method according to any one of claims 1-8.

10. The use of a permeable membrane with a surface-grown COF layer prepared by the method described in claim 9 or any one of claims 1-8 in the preparation of a membrane oxygenator for extracorporeal membrane oxygenation.

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