CN114470851A - Bionic system and method for in-vitro regulation and control of inorganic salt crystallization - Google Patents
Bionic system and method for in-vitro regulation and control of inorganic salt crystallization Download PDFInfo
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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- B01D9/00—Crystallisation
- B01D9/0063—Control or regulation
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/84—Systems specially adapted for particular applications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N25/00—Investigating or analyzing materials by the use of thermal means
- G01N25/14—Investigating or analyzing materials by the use of thermal means by using distillation, extraction, sublimation, condensation, freezing, or crystallisation
- G01N25/147—Investigating or analyzing materials by the use of thermal means by using distillation, extraction, sublimation, condensation, freezing, or crystallisation by cristallisation
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/84—Systems specially adapted for particular applications
- G01N2021/8411—Application to online plant, process monitoring
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/84—Systems specially adapted for particular applications
- G01N2021/8477—Investigating crystals, e.g. liquid crystals
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Abstract
The invention belongs to the technical field of crystallization, and particularly relates to a bionic system and a method for in-vitro regulation and control of inorganic salt crystallization. The bionic system for in-vitro regulation and control of inorganic salt crystallization mainly comprises a constant temperature module I, an ultraviolet sterilization module II, an inorganic salt crystallization module III and a real-time monitoring module IV. The invention simulates the body fluid composition, the human body temperature, the pH, the body fluid flow rate, the inorganic salt crystallization microenvironment and concentration and the like, and realizes the simulation of the inorganic salt crystallization process in the physiological environment. Crystals with a morphology similar to that of the inorganic salts in vivo can be obtained and the crystallization mechanism of the inorganic salts in vivo is revealed. In addition, the crystal growth behavior can be regulated and controlled through the functionalization of the flat membrane. The crystallization system has low cost, is easy to build and control, has low requirements on the surrounding environment, is suitable for regulation and control and mechanism exploration of the inorganic salt crystallization process in different physiological environments, and has important significance on the research of pathological crystallization diseases.
Description
Technical Field
The invention belongs to the technical field of crystallization, and particularly relates to a bionic system and a method for in-vitro regulation and control of inorganic salt crystallization.
Background
Pathological crystallization is a common and frequent disease, mainly including urolithiasis, vascular calcification, kidney stone and crystal arthritis, and the pathogenesis of the pathological crystallization is related to a plurality of factors such as heredity, sex, age, living and eating habits, abnormal metabolism of organisms and the like. In recent years, the incidence of the diseases is rising and the diseases tend to be younger around the world, which seriously threatens the health of human beings and becomes one of the research hotspots in the medical field. At present, the treatment of pathological crystallization diseases at home and abroad mainly takes medicine and surgical removal as main treatment, and can cause great damage to human bodies. In fact, the pathological changes of the crystal are all caused by the fact that inorganic salts (such as calcium oxalate, calcium phosphate and sodium urate) reach supersaturation at a certain part of the human body and crystallize. Therefore, more and more students explore the cause of pathological crystalline diseases from the crystallography perspective, and try to find a method capable of effectively inhibiting/decomposing crystal growth and deposition, thereby providing a new idea for the treatment of the pathological crystalline diseases.
At present, the research on in-vivo inorganic salt crystallization in the field of crystallography mainly takes in-vitro static experiments, and neglects the physiological environment and the circulating flow of body fluid during crystal crystallization, so that the cognition on the in-vivo inorganic salt crystallization mechanism is lacked. Meanwhile, the concentration of the solute used in the experimental process is very high and far exceeds the physiological concentration, so that the experimental result has larger deviation from the real condition, and the method has no guiding significance for treating diseases. Therefore, the crystal growth research is carried out under the physiological environment that inorganic salt crystals can be reduced as far as possible, the growth state, the process and the rule of the crystals are observed, the related in-vivo crystallization mechanism is revealed, and an effective inhibition/decomposition method is found, so that the method has important significance for treating pathological crystallization diseases. But the related bionic system and research method which have universality and can accurately regulate and control the in-vivo inorganic salt crystallization are not reported in documents and related patents.
Disclosure of Invention
The invention designs a bionic system and a method for regulating and controlling inorganic salt crystallization in vitro, which realize the accurate regulation and control of crystal crystallization behavior by highly reducing the physiological environment of inorganic salt crystallization in vivo and based on the regulation and control of a flat membrane system, and have important application significance for the exploration and treatment of pathological crystallization diseases.
The technical scheme of the invention is as follows:
the invention provides a bionic system for in vitro regulation and control of inorganic salt crystallization, which comprises a constant temperature module I, an ultraviolet sterilization module II, an inorganic salt crystallization module III and a real-time monitoring module IV; the high-power camera 11 in the ultraviolet sterilization module II, the inorganic salt crystallization module III and the real-time monitoring module IV is positioned in the constant temperature module I, and the user computer 10 in the real-time monitoring module IV is positioned outside the constant temperature module I;
the ultraviolet sterilization module II is positioned at the top in the constant temperature module I and comprises an ultraviolet lamp, so that the internal environment of the constant temperature module I is in a sterile environment;
the inorganic salt crystallization module III comprises a flat membrane 1, a membrane module 2, a peristaltic pump 3, a pH agent 4, an ion selective electrode 5, a crystallization liquid tank 6, a simulated body liquid tank 7, a thermometer 8 and a flowmeter 9;
a flat membrane 1 is arranged in the middle of the membrane component 2; the liquid outlet pipes of the crystallization liquid tank 6 and the simulated body liquid tank 7 pass through the peristaltic pump 3, the thermometer 8 and the flowmeter 9 and then are introduced into the inlet end of the membrane component 2, and the outlet end of the membrane component 2 is respectively introduced into the crystallization liquid tank 6 and the simulated body liquid tank 7; the pH agent 4 is respectively placed in a crystallization liquid tank 6 and a simulated body liquid tank 7, so that the stability of the pH of the solution in the experimental process is ensured; an ion selective electrode 5 is arranged in the crystallization liquid tank 6, and the change of the inorganic salt ion concentration in the crystallization liquid tank 6 is monitored in real time;
the real-time monitoring module IV comprises a user computer 10 and a high power camera 11, the user computer 10 and the high power camera 11 are connected by a data line, and the high power camera 11 observes the crystal crystallization process and the growth state of the crystal in the crystal liquid tank 6 in real time;
the flat membrane 1 consists of an active layer and a supporting layer, wherein the active layer is one of PEG, PEGDA, PEGDMA, EGDMA, PVA, PAM, PEI, CA and EGDMA-HEMA; the support layer is one of PVDF, PP, PAN, PSF and PES; the thickness of the active layer is 0.1-2000 μm, and the aperture is 0.4-1 nm; the tensile strength of the active layer is 0.8-25 MPa; the surface of the active layer is hydrophilic and electronegative; the aperture of the supporting layer is 0.05-10 μm;
selecting a membrane component 2 with proper size, shape and material according to the in-vivo crystallization environment, so that the membrane component is suitable for the crystallization of target inorganic salt, the in-vivo crystallization environment of the inorganic salt is better simulated, and the real-time observation of the crystallization process and the stable circulation of a crystallization solution and simulated body fluid are facilitated; the membrane component 2 is in the shape of one of kidney, knee joint, ankle joint, finger joint and metatarsophalangeal joint, the size is determined according to the real size of each part, the material is one of glass, organic glass, resin, organic silicon and polyvinyl chloride, but the membrane component can not react with a target crystal; the plastic mode is 3D printing, model etching, rapid forming or machining.
Selecting a membrane material according to the physiological environment of inorganic salt crystals in a body, and preparing a flat membrane matched with the size and the shape of the membrane component; the material has good stability and mechanical property, has mass transfer function, and can effectively simulate the in-vivo inorganic salt crystallization environment for a long time.
The active layer of the flat membrane 1 is modified by carboxyl to inhibit the crystal crystallization, for example, one of EGDMA-HEMA-MAA, EGDMA-HEMA-AA, EGDMA-AA or EGDMA-MAA, so as to regulate and control the crystal crystallization behavior.
The components are connected by transparent hoses, and the materials are polyurethane, silica gel, polyvinyl chloride or fluororubber; has good toughness and wear resistance to ensure long-term operation of the experiment.
The membrane module 2 is transparent and visible as a whole and is used for observing the crystallization process in real time.
A method for regulating inorganic salt crystallization in vitro, comprising the following steps:
step one, assembling a flat membrane 1 and a membrane component 2; the flat membrane 1 is ensured to be flat and free from folds and defects, and meanwhile, the whole membrane component 2 has sealing performance;
step two, respectively preparing the crystallization liquid and the simulated body liquid in the crystallization liquid tank 6 and the simulated body liquid tank 7;
setting the temperature of the environment where the inorganic salt crystallization module III is located through the constant temperature module I, maintaining the temperature at a set value, and monitoring the temperature in real time through the thermometer 8;
setting the flow rates of the liquid in the crystal liquid tank 6 and the liquid in the simulated body liquid tank 7 through the peristaltic pump 3, and monitoring the flow rates through the flowmeter 9;
fifthly, the internal environment of the constant temperature module I is in a sterile environment through the ultraviolet sterilization module II;
and step six, adjusting the angle, the magnification factor and the brightness of the high-power camera 11 through a real-time monitoring module IV, and monitoring the crystal crystallization process in real time through a user computer 10.
The crystal liquid tank 6 in the second step is a body fluid containing target crystal inorganic salt, and the concentration of the target crystal substance is 0.1-1000 mM.
In the third step, the temperature setting range of the constant temperature module I is 0-60 ℃.
The flow rate range of the peristaltic pump 3 is 0-6000 mu L.min-1。
The power of the ultraviolet lamp is 5-30W.
The bionic system or the bionic method is provided for simulating the crystallization process of inorganic salt in vivo and regulating the crystallization behavior of the inorganic salt.
The invention has the beneficial effects that: the invention utilizes the advantages of easy functionalization (surface structure, electric charge, hydrophilicity and hydrophobicity), multiple selection types, strong plasticity, good biocompatibility and the like of the flat membrane, combines the membrane crystallization technology, and adopts devices such as a thermostat, a peristaltic pump, an ultraviolet lamp, an online observation high power camera and the like to highly reproduce the crystallization microenvironment in the inorganic salt body. The invention aims to reproduce the crystallization environment of inorganic salt in pathological crystallization, obtain crystals with similar form with inorganic salt in vivo and reveal the crystallization mechanism of inorganic salt in vivo. In addition, the precise regulation and control of inorganic salt crystallization behavior is realized through the functionalization of the flat membrane, and the method is of great importance for the research of in vivo crystal growth inhibition/decomposition methods and the treatment of pathological crystallization diseases. In the invention, the crystallization system is easy to build and control, has low requirement on the surrounding environment, has wide application range, can be observed in real time, and can realize the research on the crystallization mechanism and process of inorganic salt in different physiological environments.
Drawings
FIG. 1 is a biomimetic system for in vitro regulation of inorganic salt crystallization.
In the figure: i, a constant temperature module; II, an ultraviolet sterilization module; III inorganic salt crystallization module; IV, a real-time monitoring module; 1, flat membrane; 2, a membrane module; 3, a peristaltic pump; 4, a pH agent; 5 an ion-selective electrode; 6, a crystallization liquid tank; 7 analog body liquid tank; 8, a thermometer; 9 a flow meter; a user computer 10 and a high power camera 11.
FIG. 2 is a scanning electron micrograph of sodium urate crystals prepared by the biomimetic system of the present invention.
In the figure: (a) sodium urate crystal prepared by EGDMA-HEMA flat membrane; (b) sodium urate crystal prepared from EGDMA-HEMA-AA flat membrane; (c) and the EGDMA-AA flat membrane is used for preparing sodium urate crystals.
Figure 3 is a digital photograph of sodium urate crystals prepared by different flat sheet membranes under the same experimental conditions and for the same time.
In the figure: (a) sodium urate crystal prepared by EGDMA-HEMA flat membrane; (b) sodium urate crystal prepared from EGDMA-HEMA-AA flat membrane; (c) and sodium urate crystals prepared from EGDMA-AA flat membrane.
Detailed Description
The following further describes a specific embodiment of the present invention with reference to the drawings and technical solutions.
Example 1
(1) Designing and preparing a membrane component 2 similar to the structure of a human knee joint;
(2) preparing a nontoxic EGDMA-HEMA flat membrane 1 with good biocompatibility and similar mechanical property with hyaline cartilage, wherein the molar ratio is 3:5, and cutting the membrane into a size and a shape matched with the membrane component 2;
(3) assembling the membrane component 2 with an EGDMA-HEMA flat membrane 1;
(4) preparing 2 bottles of 100mL simulated body fluid with sodium ion concentration of 140mM and pH of 7.4, wherein 1.5mM uric acid is added into one bottle of the simulated body fluid to be used as a crystal liquid;
(5) setting the temperature of the environment where the inorganic salt crystallization module III is located, maintaining the temperature at 20 ℃ by using the constant temperature module I, and monitoring the temperature in real time by using a thermometer 8;
(6) the liquid outlet pipes of the crystallization liquid tank 6 and the analog body liquid tank 7 pass through the peristaltic pump 3, the thermometer 8 and the flowmeter 9 through the polyvinyl chloride transparent hose and then are introduced into the inlet end of the membrane component 2, the outlet end of the membrane component 2 is respectively introduced into the crystallization liquid tank 6 and the analog body liquid tank 7, and the flow rate is regulated to 2500 mu L/min through the peristaltic pump-1So that the stable circulation system is formed;
(7) sterilizing an inorganic salt crystallization environment through an ultraviolet sterilization module II, wherein the power of an ultraviolet lamp is 5W;
(8) the crystallization state and process of the sodium urate in the crystallization liquid tank 6 are observed in real time by using a user computer 10 and a high power camera 11 which are provided with cameras.
The formation and growth process of sodium urate on the surface of transparent cartilage of knee joint of human body is explored through the system, and fibrous sodium urate crystal with similar appearance to that of tophus of human body is obtained, as shown in (a) in fig. 2, and the crystallization mechanism of sodium urate in vivo is revealed.
Example 2
(1) Designing and preparing a membrane component 2 similar to the structure of a human knee joint;
(2) preparing a nontoxic EGDMA-HEMA-AA flat membrane 1 with good biocompatibility and similar mechanical property with hyaline cartilage, wherein the molar ratio is 2:5:3, and cutting the membrane into a size and a shape matched with the membrane component 2;
(3) assembling the membrane component 2 and the EGDMA-HEMA-AA flat membrane 1 together;
(4) preparing 2 bottles of 100mL simulated body fluid with sodium ion concentration of 140mM and pH of 7.4, wherein 1.5mM uric acid is added into one bottle of the simulated body fluid to be used as a crystal liquid;
(5) setting the temperature of the environment where the inorganic salt crystallization module III is located, maintaining the temperature at 20 ℃ by using the constant temperature module I, and monitoring the temperature in real time by using a thermometer 8;
(6) the liquid outlet pipes of the crystal liquid tank 6 and the analog liquid tank 7 pass through the peristaltic pump 3, the thermometer 8 and the flowmeter 9 and then are introduced into the membrane component 2 through the polyvinyl chloride transparent hoseThe outlet end of the membrane component 2 is respectively communicated into a crystal liquid tank 6 and a simulated body liquid tank 7; and the flow rate is adjusted to 2500 mu L/min by a peristaltic pump-1So that the stable circulation system is formed;
(7) sterilizing the inorganic salt crystallization environment by an ultraviolet sterilization module II, wherein the power of an ultraviolet lamp is 5W;
(8) the crystallization state and process of the sodium urate in the crystallization liquid tank 6 are observed in real time by a user computer 10 and a high power camera 11 which are provided with digital camera software.
Through the modification of the flat membrane 1, the crystallization of sodium urate crystals is effectively inhibited, as shown in (b) in fig. 3, and the method has important significance for the treatment and the defense of gout.
Example 3
(1) Designing and preparing a membrane component 2 similar to the structure of a human knee joint;
(2) preparing a nontoxic EGDMA-AA flat membrane 1 with good biocompatibility and similar mechanical property with hyaline cartilage, wherein the molar ratio is 3:5, and cutting the membrane into a size and a shape matched with the membrane component 2;
(3) assembling the membrane component 2 and the EGDMA-AA flat membrane 1 together;
(4) preparing 2 bottles of 100mL simulated body fluid with sodium ion concentration of 140mM and pH of 7.4, wherein 1.5mM uric acid is added into one bottle of the simulated body fluid to be used as a crystal liquid;
(5) setting the temperature of the environment where the inorganic salt crystallization module III is located, maintaining the temperature at 20 ℃ by using the constant temperature module I, and monitoring the temperature in real time by using a thermometer 8;
(6) passing through a polyvinyl chloride transparent hose, liquid outlet pipes of a crystallization liquid tank 6 and a simulated body liquid tank 7 through a peristaltic pump 3, a thermometer 8 and a flowmeter 9, then introducing into an inlet end of a membrane component 2, introducing an outlet end of the membrane component 2 into the crystallization liquid tank 6 and the simulated body liquid tank 7 respectively, and adjusting the flow rate to 2500 muL/min through the peristaltic pump-1So that the stable circulation system is formed;
(7) sterilizing the inorganic salt crystallization environment by an ultraviolet sterilization module II, wherein the power of an ultraviolet lamp is 5W;
(8) the crystallization state and process of the sodium urate in the crystallization liquid tank 6 are observed in real time by a user computer 10 and a high power camera 11 which are provided with digital camera software.
The crystallization of sodium urate crystals is effectively inhibited by modifying the flat membrane, as shown in (c) in fig. 3, which is of great significance for treating gout.
The yields of sodium urate crystals obtained after 1-week operation of examples 1-3 were compared, and when different flat sheet membranes EGDMA-HEMA, EGDMA-HEMA-AA and EGDMA-AA were used, the latter two membranes showed significant inhibition effects on nucleation and growth of sodium urate crystals, and sodium urate crystals with similar appearance to that of tophus of human body were obtained.
Although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that changes may be made in the embodiments and/or equivalents thereof without departing from the spirit and scope of the invention. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (9)
1. A bionic system for in vitro regulation and control of inorganic salt crystallization is characterized by comprising a constant temperature module (I), an ultraviolet sterilization module (II), an inorganic salt crystallization module (III) and a real-time monitoring module (IV); the high-power camera (11) in the ultraviolet sterilization module (II), the inorganic salt crystallization module (III) and the real-time monitoring module (IV) are positioned in the constant temperature module (I), and the user computer (10) in the real-time monitoring module (IV) is positioned outside the constant temperature module (I);
the ultraviolet sterilization module (II) is positioned at the top in the constant temperature module (I) and comprises an ultraviolet lamp, so that the internal environment of the constant temperature module (I) is in a sterile environment;
the inorganic salt crystallization module (III) comprises a flat membrane (1), a membrane module (2), a peristaltic pump (3), a pH agent (4), an ion selective electrode (5), a crystallization liquid tank (6), a simulated body liquid tank (7), a thermometer (8) and a flowmeter (9);
a flat membrane (1) is arranged in the middle of the membrane component (2); liquid outlet pipes of the crystal liquid tank (6) and the simulated body liquid tank (7) pass through the peristaltic pump (3), the thermometer (8) and the flowmeter (9) and then are introduced into an inlet end of the membrane component (2), and outlet ends of the membrane component (2) are respectively introduced into the crystal liquid tank (6) and the simulated body liquid tank (7); the pH agent (4) is respectively placed in the crystallization liquid tank (6) and the simulated body liquid tank (7) to ensure the stability of the pH of the solution in the experimental process; an ion selection electrode (5) is arranged in the crystallization liquid tank (6), and the change of the concentration of inorganic salt ions in the crystallization liquid tank (6) is monitored in real time;
the real-time monitoring module (IV) comprises a user computer (10) and a high power camera (11), the user computer (10) and the high power camera (11) are connected by a data line, and the high power camera (11) observes the crystal crystallization process and the growth state in the crystal liquid tank (6) in real time;
the flat membrane (1) consists of an active layer and a support layer, wherein the active layer is one of PEG, PEGDA, PEGDMA, EGDMA, PVA, PAM, PEI, CA and EGDMA-HEMA; the support layer is one of PVDF, PP, PAN, PSF and PES; the thickness of the active layer is 0.1-2000 μm, and the aperture is 0.4-1 nm; the tensile strength of the active layer is 0.8-25 MPa; the surface of the active layer is hydrophilic and electronegative; the aperture of the supporting layer is 0.05-10 μm;
the membrane component (2) is in one shape of kidney, knee joint, ankle joint, finger joint and metatarsophalangeal joint, the size is determined according to the real size of each part, and the material is one of glass, organic glass, resin, organic silicon and polyvinyl chloride; the plastic mode is 3D printing, model etching, rapid forming or machining.
2. The biomimetic system for in-vitro regulation and control of inorganic salt crystallization according to claim 1, characterized in that the active layer of the flat membrane (1) is subjected to carboxyl modification to realize inhibition of crystal crystallization.
3. The bionic system for regulating and controlling crystallization of inorganic salt in vitro as claimed in claim 1 or 2, wherein each component connection adopts a transparent hose made of polyurethane, silica gel, polyvinyl chloride or fluororubber.
4. The bionic system for in vitro regulation and control of inorganic salt crystallization according to claim 3, wherein the membrane module (2) is transparent and visible as a whole and is used for real-time observation of the crystallization process.
5. A method for regulating and controlling inorganic salt crystallization in vitro is characterized by comprising the following steps:
step one, assembling a flat membrane (1) and a membrane component (2); the flat membrane (1) is ensured to be flat and free from folds and defects, and meanwhile, the whole membrane component (2) has sealing property;
step two, respectively preparing a crystallization liquid and a simulation body liquid in a crystallization liquid tank (6) and a simulation body liquid tank (7);
setting the temperature of the environment where the inorganic salt crystallization module (III) is located through the constant temperature module (I), maintaining the temperature at a set value, and monitoring the temperature in real time through the thermometer (8);
setting the flow rates of the liquid in the crystal liquid tank (6) and the liquid in the simulated body liquid tank (7) through the peristaltic pump (3), and monitoring the flow rates through the flowmeter (9);
fifthly, the internal environment of the constant temperature module (I) is in a sterile environment through the ultraviolet sterilization module (II);
and step six, adjusting the angle, the magnification factor and the brightness of the high-power camera (11) through a real-time monitoring module (IV), and monitoring the crystal crystallization process in real time through a user computer (10).
6. The biomimetic method for in vitro regulation and control of inorganic salt crystallization according to claim 5, wherein in the second step, the crystallization liquid tank (6) is a body fluid containing the target crystallization inorganic salt, and the concentration of the target crystallization substance is 0.1-1000 mM.
7. The biomimetic method for in vitro regulation and control of inorganic salt crystallization according to claim 6, wherein in the third step, the temperature setting range of the constant temperature module (I) is 0-60 ℃.
8. The method of claim 7, wherein the crystallization of the inorganic salt is controlled in vitroThe bionic method is characterized in that the flow speed range of the peristaltic pump (3) is 0-6000 muL-min-1。
9. The biomimetic method for in vitro regulation and control of inorganic salt crystallization according to claim 8, wherein the power of the ultraviolet lamp is 5-30W.
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| CN202223452600.0U CN219455156U (en) | 2022-01-20 | 2022-12-23 | Bionic system for in-vitro regulation and control of inorganic salt crystallization |
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