A desalination process for coupling electro-dialysis with a hollow fiber membrane made of a high-salt solution of silk fibroin

Abstract

The present invention belongs to the field of purification of regenerated silk fibroin, and proposes a process for desalting silk fibroin high-salt solution by coupling hollow fiber membrane and electrodialysis, which includes a hollow fiber membrane system and an electrodialysis system. The steps include: S1 adding the silk fibroin solution to be desalted into the inner side of the membrane filaments of the hollow fiber membrane system, with pure water on the outer side of the membrane filaments of the hollow fiber membrane system, and the membrane filaments being thick pore size membrane filaments; S2 after the pure water in the hollow fiber membrane system receives salt, it forms hollow fiber membrane brine; S3 introducing the hollow fiber membrane brine into the electrodialysis system and achieving desalting in the electrodialysis membrane stack to form fresh water; S4 introducing the fresh water into the outer side of the membrane filaments of the hollow fiber membrane system, and circulating steps S1 to S4; S5 in the concentration stage, until the concentration of the silk fibroin solution reaches 2-5%. The present invention has reasonable design, the regenerated silk fibroin can be continuously filtered and produced, is suitable for industrial production, has a large processing capacity, can achieve efficient desalting and is environmentally friendly, and is suitable for large-scale promotion.

Description

Technical Field

[0001] The present invention belongs to the technical field of regenerated silk fibroin purification, and particularly relates to a desalination process for coupling a hollow fiber membrane and electrodialysis in a high-salt solution of silk fibroin. Background Art

[0002] Silk protein mainly includes sericin and silk fibroin. Regenerated silk fibroin derived from silk can be reprocessed, modified, and regulated to prepare various types of scaffold materials, which are then used in many fields such as tissue engineering, drug delivery, 3D printing, cell coating, microfluidics, and biosensors. Natural silk fibroin is insoluble in water and soluble in strong acids, strong alkalis, and some neutral salt solutions. The preparation process of regenerated silk fibroin mainly includes alkali elution degumming, high-concentration salt dissolution, ultrafiltration desalination, and freeze-drying.

[0003] To obtain high-purity soluble silk fibroin, it is usually dissolved in a high-concentration lithium bromide solution or calcium chloride solution, and then lithium bromide or calcium chloride in the silk fibroin solution is removed to obtain a regenerated silk fibroin solution. In the subsequent removal steps, in order to remove lithium bromide with a concentration as high as 80% to a bromide ion content ≤ 80 mg / g and lithium ion < 2 mg / g, methods such as dialysis bag dialysis, hollow fiber membrane ultrafiltration, electrodialysis, and diffusion dialysis are usually used. However, when these different methods are applied to the purification process of regenerated silk fibroin, there are also some practical problems. For example, in the dialysis bag dialysis process, the dialysis time is long, the water consumption is large, the processing capacity is small, and it cannot be used for large-scale industrial production; in the hollow fiber membrane desalination process, it is necessary to increase the membrane surface flow rate to prevent concentration polarization and membrane surface fouling. Silk fibroin is extremely susceptible to shear denaturation and precipitation under low-salt conditions, resulting in membrane fouling and protein yield loss; in the electrodialysis process, affected by the membrane stack flow channel structure, protein precipitation is easily formed and the flow channel is blocked, which easily leads to overloading of the electrodialysis membrane current and burning, and it is difficult to clean the flow channel after blockage, so it cannot be applied to industrial production; in the diffusion dialysis process, it is impossible to desalinate the feed liquid to a conductivity < 200 μs / cm (5% protein concentration); another example is the diffusion dialysis - electrodialysis coupling process, which uses diffusion dialysis for desalination at high salt and electrodialysis for continuous desalination at low salt, and the low-salt environment cannot avoid the precipitation of silk fibroin and the blockage of the electrodialysis flow channel. Summary of the Invention

[0004] In view of the fact that regenerated silk fibroin must go through the stages of high-salt dissolution and then desalination, and silk fibroin is extremely susceptible to shear denaturation and precipitation under low-salt conditions, the present invention proposes a desalination process for coupling a hollow fiber membrane and electrodialysis in a high-salt solution of silk fibroin, which is reasonable in design, suitable for industrial production, has a large processing capacity, and can achieve efficient desalination.

[0005] To achieve the above object, the technical solution adopted by the present invention is that a desalination process for coupling electro-dialysis of a silk fibroin high-salt solution provided by the present invention includes a hollow fiber membrane system and an electro-dialysis system. The electro-dialysis system includes an electro-dialysis membrane stack, pure water, a cathode and an anode. The electro-dialysis membrane stack includes an anion exchange homogeneous membrane and a cation exchange homogeneous membrane. The specific steps are as follows:

[0006] S1. Add the silk fibroin solution to be desalted to the inner side of the membrane filaments of the hollow fiber membrane system. The outer side of the membrane filaments of the hollow fiber membrane system is pure water. The membrane filaments are thick-pore membrane filaments with a pore diameter of 0.5 mm to 1.2 mm, which reduces the circulation resistance and reduces the severe shear of the protein by the membrane filaments;

[0007] S2. The hollow fiber membrane system forms hollow fiber membrane brine after the pure water receives salt through an internal pressure cross-flow filtration method. The hollow fiber membrane system adopts a low membrane surface flow rate and a low transmembrane pressure difference to avoid severe shear of the silk fibroin;

[0008] S3. Introduce the hollow fiber membrane brine generated in step S2 into the electro-dialysis system. The hollow fiber membrane brine does not contain silk fibroin. The hollow fiber membrane brine is desalted in the electro-dialysis membrane stack. The pure water in the electro-dialysis system receives salt to form concentrated brine, and the desalted hollow fiber membrane brine forms fresh water;

[0009] S4. Introduce the fresh water in the electro-dialysis system to the outer side of the membrane filaments of the hollow fiber membrane system, and cycle steps S1 to S4;

[0010] S5. In the concentration stage, pressurize the pressure of the hollow fiber membrane system, maintain a low membrane surface flow rate, and concentrate until the concentration of the silk fibroin solution reaches 2% to 5%.

[0011] Preferably, the low membrane surface flow rate in steps S2 and S5 is 0.05 m / s to 0.5 m / s.

[0012] Preferably, the low membrane surface flow rate in step S5 is 5% to 10% smaller than the low membrane surface flow rate in step S2.

[0013] Preferably, the transmembrane pressure difference in step S2 is <0.1 MPa, and the transmembrane pressure difference in step S5 is 0.1 MPa.

[0014] Preferably, the membrane filaments in the hollow fiber membrane system are hydrophilic membrane materials.

[0015] Preferably, the membrane filaments in the hollow fiber membrane system are ultrafiltration membranes with a molecular weight cut-off of 2 KD to 50 KD.

[0016] Preferably, the electro-dialysis uses a DC power supply to form a DC electric field and adopts a constant current and constant voltage automatic switching mode.

[0017] Compared with the prior art, the advantages and positive effects of the present invention are as follows:

[0018] 1. A desalination process for coupling a hollow fiber membrane of a silk fibroin high-salt solution with electrodialysis provided by the present invention. The treatment object of the hollow fiber membrane system is the silk fibroin solution to be desalted. The use of large-pore membrane filaments and low flow rate avoids the problem of shear precipitation of silk fibroin, which not only ensures the production quality of regenerated silk fibroin but also does not cause frequent fouling of the electrodialysis membrane stack of the electrodialysis system, and continuous filtration production can be formed. In addition, the hollow fiber membrane system adopts the method of desalination first and then concentration, and the ultrafiltration concentration time is extremely short, which neither causes shear precipitation of silk fibroin nor realizes high-fold concentration of the protein solution after desalination.

[0019] 2. A desalination process for coupling a hollow fiber membrane of a silk fibroin high-salt solution with electrodialysis provided by the present invention. The electrodialysis system coupled with the hollow fiber membrane system uses ion exchange membranes to continuously desalt the hollow fiber membrane brine, ensuring the salt concentration difference inside and outside the hollow fiber membrane, realizing continuous and rapid transfer of salt ions, effectively reducing the use of pure water on the premise of ensuring continuous filtration production of silk fibroin, and realizing the recovery of salt, reducing waste and environmental pollution.

[0020] 3. A desalination process for coupling a hollow fiber membrane of a silk fibroin high-salt solution with electrodialysis provided by the present invention is reasonably designed, and regenerated silk fibroin can be continuously filtered and produced, which is suitable for industrial production, has a large processing capacity, can realize efficient desalination, and is suitable for large-scale promotion. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for description in the embodiments will be briefly introduced below. Obviously, the drawings in the following description are some embodiments of the present invention. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative efforts.

[0022] Figure 1 It is a schematic diagram of a desalination process for coupling a hollow fiber membrane of a silk fibroin high-salt solution with electrodialysis provided for Embodiments 1 to 4;

[0023] In the above figures, 1. Hollow fiber membrane system; 2. Electrodialysis system. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0024] To more clearly understand the above objects, features, and advantages of the present invention, the present invention will be further described below in conjunction with the accompanying drawings and embodiments. It should be noted that, without conflict, the embodiments of the present application and the features in the embodiments can be combined with each other. For the convenience of narration, words such as "upper", "lower", "left", and "right" hereinafter only indicate the same directions as the upper, lower, left, and right directions of the accompanying drawings themselves, and do not limit the structure.

[0025] In the following description, many specific details are set forth in order to fully understand the present invention. However, the present invention can also be implemented in other ways different from those described herein. Therefore, the present invention is not limited by the specific embodiments disclosed in the following specification.

[0026] As Figure 1 shown, a desalination process for coupling a silk fibroin high-salt solution hollow fiber membrane with electrodialysis provided by the present invention includes a hollow fiber membrane system 1 and an electrodialysis system 2. The electrodialysis system 2 includes an electrodialysis membrane stack, pure water, a cathode, and an anode. The electrodialysis membrane stack includes an anion exchange homogeneous membrane and a cation exchange homogeneous membrane. The specific steps are as follows:

[0027] S1. Add the silk fibroin solution to be desalted to the inner side of the membrane filaments of the hollow fiber membrane system 1. The outer side of the membrane filaments of the hollow fiber membrane system 1 is pure water. The membrane filaments are thick-pore membrane filaments with a pore diameter of 0.5 mm to 1.2 mm. By using thick-pore membrane filaments, the circulation resistance can be effectively reduced, and the severe shear of the protein by the membrane filaments can be reduced.

[0028] S2. The hollow fiber membrane system 1 forms hollow fiber membrane brine after the pure water receives salt through an internal pressure cross-flow filtration method. The hollow fiber membrane system 1 adopts a low membrane surface flow rate and a low transmembrane pressure difference. The membrane surface flow rate is 0.05 m / s to 0.5 m / s, and the transmembrane pressure difference < 0.1 MPa. This can avoid severe shear of the silk fibroin.

[0029] S3. Introduce the hollow fiber membrane brine generated in step S2 into the electrodialysis system. The hollow fiber membrane brine does not contain silk fibroin. The hollow fiber membrane brine is desalted in the electrodialysis membrane stack. The pure water in the electrodialysis system 2 receives salt to form concentrated brine, and the desalted hollow fiber membrane brine forms fresh water.

[0030] S4. Introduce the fresh water in the electrodialysis system 2 to the outer side of the membrane filaments of the hollow fiber membrane system 1, and cycle steps S1 to S4.

[0031] S5. In the concentration stage, pressurize the pressure of the hollow fiber membrane system 1. The transmembrane pressure difference is 0.1 MPa, and maintain a low membrane surface flow rate until the concentration of the silk fibroin solution reaches 2 to 5%.

[0032] Example 1: A lithium bromide solution of silk fibroin with a protein concentration of 3% and a conductivity of 62 ms / cm.

[0033] The hollow fiber membrane has a molecular weight cut-off of 10 KD, an area of 0.3 ㎡. The internal circulating liquid in the hollow fiber membrane is 1 L of silk fibroin solution with a flow rate of 0.3 m / s, and the temperature is controlled at 5 - 15 °C; the initial external circulating liquid of the hollow fiber membrane is 2 L of pure water with a flow rate of 0.5 m / s. The electrodialysis membrane stack has an area of 0.15 ㎡, with a maximum voltage set at 12 V and a maximum current set at 4 A. The electrodialysis electrode water is a 3% sodium sulfate aqueous solution; concentrated water: initially 1 L of pure water, and new water is replaced when the salt concentration reaches 20%; fresh water: connected to the external circulating water of the hollow fiber membrane through a pipeline, 2 L, with a flow rate of 0.5 m / s. After continuous operation for 7 h, the silk fibroin solution has a concentration of 3% and a conductivity of 90 μs / cm, without gelation.

[0034] Example 2: A lithium bromide solution of silk fibroin with a protein concentration of 2% and a conductivity of 43.2 ms / cm.

[0035] The hollow fiber membrane has a molecular weight cut-off of 2 KD, an area of 0.3 ㎡. The internal circulating liquid in the hollow fiber membrane is 1 L of silk fibroin solution with a flow rate of 0.3 m / s, and the temperature is controlled at 10 - 20 °C; the initial external circulating liquid of the hollow fiber membrane is 2 L of pure water with a flow rate of 0.5 m / s. The electrodialysis membrane stack has an area of 0.15 ㎡, with a maximum voltage set at 12 V and a maximum current set at 4 A. The electrodialysis electrode water is a 3% sodium sulfate aqueous solution; concentrated water: initially 1 L of pure water, and new water is replaced when the salt concentration reaches 20%; fresh water: connected to the external circulating water of the hollow fiber membrane through a pipeline, 2 L, with a flow rate of 0.5 m / s. After continuous operation for 6 h, the silk fibroin solution has a concentration of 3% and a conductivity of 98 μs / cm, without gelation.

[0036] Example 3: A calcium chloride solution of silk fibroin with a protein concentration of 2% and a conductivity of 35 ms / cm. The hollow fiber membrane has a molecular weight cut-off of 10 KD, an area of 0.3 ㎡. The internal circulating liquid in the hollow fiber membrane is 1 L of silk fibroin solution with a flow rate of 0.3 m / s, and the temperature is controlled at 10 - 15 °C; the initial external circulating liquid of the hollow fiber membrane is 2 L of pure water with a flow rate of 0.5 m / s. The electrodialysis membrane stack has an area of 0.15 ㎡, with a maximum voltage set at 12 V and a maximum current set at 4 A. The electrodialysis electrode water is a 3% sodium sulfate aqueous solution (pH 3 adjusted with sulfuric acid); concentrated water: 1 L of pure water, and new water is replaced when the salt concentration reaches 15%; fresh water: connected to the external circulating water of the hollow fiber membrane through a pipeline, 2 L, with a flow rate of 0.5 m / s. After continuous operation for 5 h, the silk fibroin solution has a concentration of 2% and a conductivity of 45 μs / cm, without gelation.

[0037] Example 4: A calcium chloride solution of silk fibroin with a protein concentration of 3% and a conductivity of 45 ms / cm. The molecular weight cut-off of the hollow fiber membrane is 20 KD, and the area is 0.3 m². The internal circulating liquid in the hollow fiber membrane is 1 L of silk fibroin solution with a flow rate of 0.3 m / s, and the temperature is controlled at 5 - 10 °C; the initial external circulating liquid of the hollow fiber membrane is 2 L of pure water with a flow rate of 0.5 m / s. The electrodialysis stack is 0.15 m², with a maximum voltage of 12 V and a maximum current of 4 A set. The electrodialysis electrode water is a 3% sodium sulfate aqueous solution (pH 3 adjusted with sulfuric acid); concentrated water: 1 L of pure water, and new water is replaced when the salt concentration reaches 15%; fresh water: connected to the external circulating water of the hollow fiber membrane through a pipeline, 2 L, with a flow rate of 0.5 m / s. Continuously operate for 6 h, the concentration of the silk fibroin solution is 5%, and the conductivity is 140 μs / cm, without gelling phenomenon.

[0038] In Examples 1 - 4, the processes provided by the present invention are used to purify lithium bromide solutions and calcium chloride solutions of silk fibroin with different concentrations, effectively avoiding the gelling of silk fibroin; meanwhile, for salt solutions with a relatively large protein concentration, the continuous operation time needs to be longer, but the overall required time is within the acceptable range of industrial production.

[0039] Specifically, the hollow fiber membrane system 1 uses large-pore membrane filaments and low flow rates to avoid the problem of shear precipitation of silk fibroin, which not only ensures the production quality of regenerated silk fibroin but also does not cause frequent fouling of the electrodialysis stack of the electrodialysis system 2, enabling continuous filtration production and meeting the needs of industrial production; in addition, the hollow fiber membrane system 1 adopts the method of desalination first and then concentration, and the ultrafiltration concentration time is extremely short, which neither causes shear precipitation of silk fibroin nor realizes high-fold concentration of the protein solution after desalination. Further, the electrodialysis system 2 coupled with the hollow fiber membrane system 1 uses ion exchange membranes, namely anion exchange homogeneous membranes and cation exchange homogeneous membranes, to continuously desalt the hollow fiber membrane brine, ensuring the salt concentration difference inside and outside the hollow fiber membrane, realizing the continuous and rapid transfer of salt ions, effectively reducing the use of pure water on the premise of ensuring continuous filtration production of silk fibroin, and realizing the recovery of salt, reducing waste and environmental pollution. For the electrodialysis system 2, in Examples 1 - 4, the method of replacing new water when the salt concentration in the concentrated brine reaches 15% is adopted, which further ensures the required pure water in the system, has a relatively high water utilization rate, can effectively reduce the industrial production cost of regenerated silk fibroin, and is conducive to the industrialization of regenerated silk fibroin.

[0040] Considering the increase in the transmembrane pressure difference in step S5, in order to ensure the filtration effect on both sides of the membrane filament, the present invention adopts a membrane surface flow rate in step S5 that is 5 - 10% smaller than the membrane surface flow rate in step S2, so as to avoid the denaturation and precipitation of silk fibroin on the premise of an increasing transmembrane pressure difference.

[0041] In order to improve the processing quality of silk fibroin in the hollow fiber membrane system 1, the membrane filaments provided by the present invention adopt hydrophilic membrane materials, such as PES (polyethersulfone resin), hydrophilically modified PES, PVDF (polyvinylidene fluoride), hydrophilically modified PVDF, modified PP (polypropylene), modified PTFE (polytetrafluoroethylene), modified polysulfone, etc. In this way, the membrane filaments have high permeability, high selectivity and high chemical stability, can efficiently separate the salt solution in silk fibroin, make the transmembrane pressure difference in the operation chamber lower, and reduce the damage to silk fibroin molecules.

[0042] Furthermore, the membrane filaments in the hollow fiber membrane system 1 of the present invention are ultrafiltration membranes, which have more stable water permeability, lower transmembrane pressure difference, lower chemical cleaning frequency, can retain molecular weights from 2KD to 50KD, and can ensure the processing efficiency of regenerated silk fibroin.

[0043] In order to ensure the filtration stability of the electrodialysis system 2, the electrodialysis provided by the present invention forms a direct current electric field by using a direct current power supply and adopts a constant current and constant voltage automatic switching mode, which is realized by a power management chip. Thus, it can ensure that the electrodialysis system 2 can maintain stable filtration performance under the influence of external floating factors.

[0044] The above are only the preferred embodiments of the present invention, and are not intended to limit the present invention in other forms. Any person skilled in the art may use the disclosed technical content to make changes or modifications into equivalent embodiments with equivalent changes and apply them to other fields. However, as long as it does not depart from the technical solution content of the present invention, any simple modification, equivalent change and modification made to the above embodiments according to the technical essence of the present invention still fall within the protection scope of the technical solution of the present invention.

Claims

1. A desalination process for coupling a hollow fiber membrane of a silk fibroin high-salt solution with electrodialysis, characterized in that, It includes a hollow fiber membrane system and an electrodialysis system. The electrodialysis system includes an electrodialysis membrane stack, pure water, a cathode, and an anode. The electrodialysis membrane stack includes an anion exchange homogeneous membrane and a cation exchange homogeneous membrane. The specific steps are as follows: S1. Add the silk fibroin solution to be desalted to the inner side of the membrane filaments of the hollow fiber membrane system. The outer side of the membrane filaments of the hollow fiber membrane system is pure water. The membrane filaments are thick pore size membrane filaments with a pore size of 0.5 mm to 1.2 mm. S2. The hollow fiber membrane system forms hollow fiber membrane brine after the pure water receives salt through an internal pressure cross-flow filtration method. The hollow fiber membrane system adopts a low membrane surface flow rate and a low transmembrane pressure difference. S3. Introduce the hollow fiber membrane brine generated in step S2 into the electrodialysis system. The hollow fiber membrane brine does not contain silk fibroin. The hollow fiber membrane brine is desalted in the electrodialysis membrane stack. The pure water in the electrodialysis system receives salt to form concentrated brine, and the desalted hollow fiber membrane brine forms fresh water. S4. Introduce the fresh water in the electrodialysis system to the outer side of the membrane filaments of the hollow fiber membrane system, and cycle steps S1 to S4. S5. In the concentration stage, pressurize the pressure of the hollow fiber membrane system, maintain a low membrane surface flow rate, and concentrate until the concentration of the silk fibroin solution reaches 2% to 5%.

2. The desalination process of coupling electro-dialysis with the hollow fiber membrane in the high-salt solution of silk fibroin according to claim 1, wherein, The low membrane surface flow rate in steps S2 and S5 is 0.05 m / s to 0.5 m / s.

3. A desalination process for coupling electro-dialysis of a fibroin high-salt solution hollow fiber membrane according to claim 2, characterized in that, The low membrane surface flow rate in step S5 is 5% to 10% smaller than the low membrane surface flow rate in step S2.

4. A desalination process of coupling electro dialysis with a hollow fiber membrane in a high-salt solution of silk fibroin according to claim 3, characterized in that, The transmembrane pressure difference in step S2 < 0.1 MPa, and the transmembrane pressure difference in step S5 is 0.1 MPa.

5. A desalination process for coupling electro-dialysis with a silk fibroin high-salt solution hollow fiber membrane according to claim 1 or 4, characterized in that The membrane filaments in the hollow fiber membrane system are hydrophilic membrane materials.

6. A desalination process for coupling electro-dialysis with a silk fibroin high-salt solution hollow fiber membrane according to claim 5, characterized in that, The membrane filaments in the hollow fiber membrane system are ultrafiltration membranes with a molecular weight cut-off of 2 KD to 50 KD.

7. A desalination process for coupling electro-dialysis with a silk fibroin high-salt solution hollow fiber membrane according to claim 1 or 6, characterized in that, The electrodialysis uses a DC power supply to form a DC electric field and adopts a constant current and constant voltage automatic switching mode.

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