CN110607552B - Method for preparing monocrystal or amorphous substance by using aqueous solution - Google Patents
Method for preparing monocrystal or amorphous substance by using aqueous solution Download PDFInfo
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- CN110607552B CN110607552B CN201911039677.5A CN201911039677A CN110607552B CN 110607552 B CN110607552 B CN 110607552B CN 201911039677 A CN201911039677 A CN 201911039677A CN 110607552 B CN110607552 B CN 110607552B
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- single crystal
- freezing
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- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 4
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- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
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- 229940079593 drug Drugs 0.000 description 1
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- 238000002003 electron diffraction Methods 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- NVVZQXQBYZPMLJ-UHFFFAOYSA-N formaldehyde;naphthalene-1-sulfonic acid Chemical compound O=C.C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 NVVZQXQBYZPMLJ-UHFFFAOYSA-N 0.000 description 1
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- OCXSDHJRMYFTMA-KMFBOIRUSA-M nafcillin sodium monohydrate Chemical compound O.[Na+].C1=CC=CC2=C(C(=O)N[C@@H]3C(N4[C@H](C(C)(C)S[C@@H]43)C([O-])=O)=O)C(OCC)=CC=C21 OCXSDHJRMYFTMA-KMFBOIRUSA-M 0.000 description 1
- 229960004387 nafcillin sodium monohydrate Drugs 0.000 description 1
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- 125000000561 purinyl group Chemical class N1=C(N=C2N=CNC2=C1)* 0.000 description 1
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- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 1
- 230000026267 regulation of growth Effects 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 229940043267 rhodamine b Drugs 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C30—CRYSTAL GROWTH
- C30B—SINGLE-CRYSTAL GROWTH; UNIDIRECTIONAL SOLIDIFICATION OF EUTECTIC MATERIAL OR UNIDIRECTIONAL DEMIXING OF EUTECTOID MATERIAL; REFINING BY ZONE-MELTING OF MATERIAL; PRODUCTION OF A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; SINGLE CRYSTALS OR HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; AFTER-TREATMENT OF SINGLE CRYSTALS OR A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; APPARATUS THEREFOR
- C30B7/00—Single-crystal growth from solutions using solvents which are liquid at normal temperature, e.g. aqueous solutions
- C30B7/08—Single-crystal growth from solutions using solvents which are liquid at normal temperature, e.g. aqueous solutions by cooling of the solution
Abstract
The invention relates to the field of single crystal preparation, in particular to a method for preparing single crystals or amorphous substances by using aqueous solution, which is applicable to the preparation and culture of any water-soluble molecular single crystals or amorphous substances. The method comprises the following steps: (a 1) preparing an aqueous solution of a substance to be crystallized; (a2) Freezing, optionally ripening, the aqueous solution of the substance to be crystallised of step (a 1) to produce a single crystal or amorphous-ice mixed system containing the substance to be crystallised; optionally, (a 3) separating the single crystal or amorphous form of the substance to be crystallized of step (a 2) from the ice mixture to obtain the single crystal or amorphous form of the substance to be crystallized. Aiming at the defects that the nucleation and aggregation speed of molecules are difficult to control in the process of culturing single crystals or amorphous substances by the traditional method, the method provided by the invention firstly provides a method for rapidly and effectively preparing the single crystals or amorphous substances of solute molecules by freezing an aqueous solution to induce the nucleation and crystallization of the solute molecules.
Description
The present application claims 2018112792527, entitled "method for preparing and growing single crystals from aqueous solutions," priority of the prior application, filed on the national intellectual property office of China on 10/30 th 2018, which is incorporated herein by reference in its entirety.
Technical Field
The invention relates to the field of preparation of single crystals or amorphous substances, in particular to a method for preparing single crystals or amorphous substances by using an aqueous solution, which is applicable to preparation of any water-soluble molecular single crystals or amorphous substances.
Technical Field
Single crystals have a significant role in various modern scientific fields, such as organic molecular and protein structural analysis, photovoltaic devices, medicine, aerospace, and other fields. At present, the method of molecular crystallization is widely studied, and a solvent slow volatilization method, a cooling method, a liquid phase diffusion method, a high molecular induced crystallization and a gas phase diffusion method and the like are commonly used. However, the above method generally has the problems of poor crystal nucleation and growth controllability, difficult single crystal growth, easy generation of polycrystal and the like. Some molecules cannot even be single crystals obtained by the above method, so how to efficiently prepare perfect single crystals remains a great challenge. In addition, certain amorphous materials play an important role in the scientific field.
Disclosure of Invention
In order to solve the problems in the prior art, the present invention provides a method for preparing a single crystal or an amorphous material using an aqueous solution.
A method for preparing a single crystal or amorphous material using an aqueous solution, the method comprising the steps of:
(a1) Preparing an aqueous solution of a substance to be crystallized;
(a2) Freezing the aqueous solution of the substance to be crystallized of step (a 1);
optionally curing to obtain a single crystal or amorphous-ice mixed system containing the substance to be crystallized;
optionally, (a 3) separating the single crystal or amorphous form of the substance to be crystallized of step (a 2) from the ice mixture to obtain the single crystal or amorphous form of the substance to be crystallized.
According to the invention, in step (a 1)
The water includes, but is not limited to, ultrapure water, secondary water, deionized water.
The substance to be crystallized includes, but is not limited to, inorganic substances and/or organic substances.
The solubility of the substance to be crystallized in water is insoluble, slightly soluble, soluble or easily soluble.
In the present invention, the step (a 2) specifically includes the following steps:
cooling and freezing the aqueous solution of the substance to be crystallized in the step (a 1) into a solid mixture, and optionally curing to obtain a mixed system of single crystals or amorphous substances containing the substance to be crystallized and ice.
In the present invention, in the step (a 2), the freezing is to convert the aqueous solution of the substance to be crystallized of the step (a 1) from a liquid state to a solid state.
In the invention, the freezing method comprises one or a combination of several cooling freezing methods of cooling freezing of compression refrigeration equipment, cooling freezing of semiconductor refrigeration equipment, cooling freezing of liquid nitrogen, cooling freezing of liquid helium, cooling freezing of liquid carbon dioxide, cooling freezing of liquid oxygen, cooling freezing of liquid ethane, cooling freezing of dry ice, cooling freezing of ice and the like.
In the invention, the freezing process comprises one or a combination of a plurality of freezing processes including rapid cooling, slow cooling, step cooling, heating first and cooling later.
In the present invention, the freezing includes, but is not limited to, complete freezing, incomplete freezing.
In the present invention, the maturation maintains the aqueous solution of the substance to be crystallized in a frozen state for a period of time.
In the present invention, the aging time refers to the time required for heating or cooling to the aging temperature after the freezing process is completed, and the time for maintaining at the aging temperature.
In one embodiment, the step (a 2) is to freeze the solution of the substance to be crystallized in the step (a 1) to prepare a mixed system of a single crystal containing the substance to be crystallized and ice.
In one embodiment, the step (a 2) includes a curing step, that is, in the step (a 2), the solution of the substance to be crystallized in the step (a 1) is frozen and cured to prepare a mixed system of a single crystal or amorphous substance containing the substance to be crystallized and ice.
In one embodiment, in the step (a 2), during the curing process, the temperature is raised or lowered at a speed of 10 ℃ per minute or more to a certain temperature, and the curing time is less than 25 minutes, so as to prepare a mixed system of amorphous substance containing the substance to be crystallized and ice.
In yet another embodiment, the greater the difference between the certain temperature reached and the freezing temperature, the greater the particle size of the resulting amorphous material. The particle size of the obtained amorphous material can be controlled by adjusting the magnitude of the temperature difference.
In one embodiment, the step (a 2) is to prepare a mixed system of a single crystal containing a substance to be crystallized and ice by heating or cooling the temperature to a certain temperature at a heating or cooling rate of less than 10 ℃/min during the curing process and/or for at least 25 min.
Illustratively, during the curing process, the temperature is raised or lowered to a certain temperature at a rate of less than 10 ℃ per minute, and maintained for a period of time to prepare a mixed system of single crystals containing the substance to be crystallized and ice.
Illustratively, in the curing process, the temperature is raised to a certain temperature at any temperature raising or lowering speed, and the mixture is cured for at least 25min, so that a mixed system of single crystals containing a substance to be crystallized and ice is prepared.
Illustratively, during the curing process, the temperature is allowed to reach a certain temperature at a heating or cooling rate of less than 10 ℃ per minute, and the mixture is cured for at least 25 minutes to prepare a mixed system of the single crystal containing the substance to be crystallized and ice.
In the present invention, in step (a 3), the separation is performed by physically and/or chemically separating the single crystal from ice.
In the present invention, the physical means include, but are not limited to, one or a combination of mechanical separation and sublimation (such as vacuum sublimation).
In the present invention, the chemical means includes, but is not limited to, one or a combination of chemical reaction and electrolysis.
In the invention, the method further comprises the following steps:
(a4) Collecting the single crystal or amorphous substance obtained in the step (a 3).
In the present invention, in step (a 4), the collection includes, but is not limited to, collection with one or a combination of several of optical microscope, scanning electron microscope, dual beam electron microscope, transmission electron microscope.
The invention also provides a method for growing single crystals, which comprises the method for preparing single crystals.
In the present invention, the method of growing a single crystal further comprises the steps of:
(b1) Transferring the single crystal of the substance to be crystallized prepared above into mother liquor of the substance to be crystallized for cultivation;
(b2) Collecting the single crystal grown in step (b 1).
In the step (b 1), the transferring may be to transfer the single crystal-ice mixed system containing the substance to be crystallized of the step (a 2) into a mother liquor of the substance to be crystallized for single crystal cultivation; or directly transferring the single crystal removed from the ice in the step (a 3) into mother liquor of a substance to be crystallized for single crystal cultivation; or transferring the single crystal collected in the step (a 4) into mother liquor of the substance to be crystallized for single crystal cultivation.
In the present invention, the transfer includes, but is not limited to, one or a combination of several of optical microscope transfer, scanning electron microscope transfer, dual beam electron microscope transfer, and transmission electron microscope transfer.
In the present invention, in the step (b 1), the method of growing the single crystal includes, but is not limited to, one or a combination of several of evaporation, cooling, and diffusion.
In the present invention, in step (b 2), the collection includes, but is not limited to, collection with one or a combination of several of optical microscope, scanning electron microscope, dual beam electron microscope, transmission electron microscope.
Advantageous effects
(1) Aiming at the defects that the molecular supply, aggregation, nucleation speed are difficult to control and the like in the process of preparing single crystals or amorphous substances by the traditional method, the invention provides a method for controlling nucleation and crystallization of solute molecules induced by freezing of aqueous solution for the first time. Crystallization of dissolved solute molecules is achieved during water crystallization, and single crystals or amorphous forms of solute molecules are rapidly and efficiently prepared by regulating the freezing of an aqueous solution, and optionally the maturation process. Meanwhile, the problem that the molecules are difficult to crystallize in the traditional single crystal preparation and culture process is solved, the problem that some substances are difficult to form amorphous substances, particularly high-purity amorphous substances, can be solved, and the method has universality.
(2) In the research process, compared with the traditional evaporation method or cooling crystallization method, the method adopts the ice recrystallization method, the regulation range of the concentration of the solution is larger, and the preparation of single crystals or amorphous substances can be realized from very low concentration to supersaturated concentration. The acquisition of single crystals or amorphous substances under extremely low solution concentration is realized for the first time; the problems that the monocrystal formation is difficult to control, polycrystal and/or twin crystal are easy to form and the like due to the fact that aggregation of solute molecules is too fast under high concentration are also solved; in addition, the present invention has the feature of obtaining a single crystal or amorphous substance of a substance to be crystallized in a short time (several minutes to several hours).
(3) The solution freezing is a technical key point in the invention. The freezing process refers to freezing the aqueous solution in any manner, and the freezing time, freezing temperature gradient, freezing method, freezing process, and the like are not particularly limited. Experiments prove that the essence of preparing solute single crystals or amorphous substances by freezing aqueous solution is that in the freezing process, water molecules form ice crystals, meanwhile, solute molecules are released and aggregated at the ice crystal interface, and the release and aggregation rate of the solute molecules are further regulated and controlled by controlling the water freezing process and the recrystallization of the ice crystals, so that the nucleation and growth regulation of the solute molecules are effectively realized, and the single crystals or amorphous substances of target molecules are obtained.
(4) The curing process of the invention is to keep the frozen aqueous solution in a solid state for a certain time, the temperature is not limited, but the heating or cooling speed needs to be controlled. Experiments prove that the curing process is optionally used as a complementary means to the freezing process, and can optimize the regulation and control of the ice crystal recrystallization process, so that the release rate of solute molecules in the ice crystal and the aggregation rate of the solute molecules to the ice crystal interface are regulated and controlled, and the growth of amorphous matters and the nucleation and growth of single crystals after the solution is frozen are further optimized. Moreover, the curing process is free from excessive limitation on temperature, and the frozen system is not required to be continuously frozen, but single crystals or amorphous substances with the particle size ranging from nanometer to micrometer can be obtained through the curing process, so that the optimal preparation of the single crystals or amorphous substances can be realized at a more economical temperature with higher efficiency, and the reduction of energy consumption is facilitated, so that the cost is greatly saved. Compared with the traditional method, the method realizes the optimal regulation and control on the recrystallization of the ice crystal by regulating and controlling the temperature rising or reducing rate in the curing process, can further regulate and control the aggregation speed of solute molecules in the ice crystal to the ice crystal interface, further effectively obtain monocrystal or amorphous matters of the solute molecules, has the advantages of saving energy, improving efficiency and the like, and is more beneficial to large-scale industrial production.
(5) The preparation method of the monocrystal or amorphous substance and the further culture method provided by the invention have wide application range, are applicable to the existing inorganic substance and organic substance, and can be used for obtaining the monocrystal or amorphous substance of the substance which is difficult to crystallize in the traditional method. And the experimental method is simple and has strong operability. The method is not only applicable to basic research in laboratories, but also meets the requirements of industrial production.
Drawings
FIG. 1 is a scanning electron micrograph of a copper sulfate single crystal prepared in examples 1,2 and 3.
FIG. 2 is a scanning electron micrograph of a glutamic acid single crystal prepared in examples 4,7,8 and 9.
FIG. 3 is a scanning electron micrograph of a single crystal of benzylpenicillin prepared in examples 5 and 6.
FIG. 4 is a scanning electron micrograph of a glycine single crystal prepared in example 10.
FIG. 5 is a scanning electron micrograph of a raffinose single crystal prepared in examples 11 and 12.
FIG. 6 is a scanning electron micrograph of a glutathione single crystal prepared in example 13.
FIG. 7 is a scanning electron micrograph of the erythromycin single crystal prepared in example 14.
FIG. 8 is a scanning electron micrograph of a trehalose monocrystal prepared in examples 15 and 16.
FIG. 9 is a scanning electron micrograph of a single crystal tartaric acid prepared in examples 17 and 18.
FIG. 10 shows vitamin B prepared in example 19 3 Scanning electron microscope photograph of single crystal.
FIG. 11 is a scanning electron micrograph of a single crystal of lysozyme prepared in example 20, the lysozyme being derived from egg.
FIG. 12 is a scanning electron micrograph of an alanine single crystal produced in example 21.
FIG. 13 is a scanning electron micrograph of a sodium chloride single crystal prepared in example 22.
FIG. 14 is a scanning electron micrograph of chloramphenicol single crystals prepared in examples 23,24, and 25.
FIG. 15 is a scanning electron micrograph of a penicillin G sodium salt single crystal prepared in examples 26 and 27.
FIG. 16 is a scanning electron micrograph of a single crystal of carbenicillin disodium salt prepared in example 28.
FIG. 17 is a scanning electron micrograph of nafcillin sodium monohydrate single crystal prepared in example 29.
FIG. 18 shows ginsenoside Rh prepared in examples 30 and 31 2 Scanning electron microscope photograph of single crystal.
FIG. 19 shows ginsenoside Rb prepared in examples 32 and 33 2 Scanning electron microscope photograph of single crystal.
FIG. 20 is a scanning electron micrograph of a single crystal of ginsenoside Rd prepared in examples 34 and 35.
FIG. 21 is a drawing of gibberellin A prepared in example 36 1 Scanning electron microscope photograph of single crystal.
FIG. 22 is a drawing of gibberellin A prepared in example 37 5 Scanning electron microscope photograph of single crystal.
FIG. 23 is a scanning electron micrograph and chemical formula of AIE35 single crystal prepared in example 38.
FIG. 24 is a scanning electron micrograph of rhodamine B single crystal prepared in example 39.
FIG. 25 is a scanning electron micrograph of an L-carnosine single crystal prepared in examples 40,41 and 42.
FIG. 26 is a scanning electron micrograph of a single crystal of N-glycylglycine prepared in example 43.
FIG. 27 is a scanning electron micrograph of the aminopeptidase single crystal produced in example 44.
FIG. 28 shows the results of examples 45 and 46 [ Cu (NH) 3 ) 4 ]SO 4 Scanning electron microscope photograph of single crystal.
FIG. 29 is a K prepared in example 47 4 [Fe(CN) 6 ]Scanning electron microscope photograph of single crystal.
FIG. 30 is a sample of [ Co (NH) 3 ) 5 Cl]Cl 2 Scanning electron microscope photograph of single crystal.
FIG. 31 is a C prepared in example 49 6 H 9 NaO 7 Scanning electron microscope pictures and chemical structural formulas of the single crystal.
FIG. 32 is a scanning electron micrograph of a single crystal of malic acid prepared in example 50.
FIG. 33 is a scanning electron micrograph of the sodium hydrogen phosphate single crystal produced in example 51.
FIG. 34 is a scanning electron micrograph of a sodium sulfite single crystal prepared in example 52.
FIG. 35 is a scanning electron micrograph of the sodium benzoate single crystal prepared in example 53.
FIG. 36 is a scanning electron micrograph of a single crystal of p-toluenesulfonic acid prepared in example 54.
FIG. 37 is a schematic diagram of the principle of the invention for forming single crystals.
FIG. 38 is a diagram showing a process of forming a single crystal of AIE35 according to the present invention.
FIG. 39 is a diagram showing a process of forming a single crystal of p-toluenesulfonic acid according to the present invention.
Detailed Description
In the present invention, "optionally" means with or without subsequent steps.
[ method for producing Single Crystal or amorphous Material ]
As described above, the present invention provides a method for preparing a single crystal or amorphous substance using an aqueous solution, the method comprising the steps of:
(a1) Preparing an aqueous solution of a substance to be crystallized;
(a2) Freezing, optionally curing, the aqueous solution of the substance to be crystallized from step (a 1) to prepare a single crystal or amorphous-ice mixed system containing the substance to be crystallized; optionally, the composition may be used in combination with,
(a3) Separating the single crystal or amorphous substance of the substance to be crystallized from the mixed system of the single crystal or amorphous substance and ice containing the substance to be crystallized in the step (a 2).
[ method for producing Single Crystal ]
As described above, the present invention provides a method of preparing a single crystal, the method comprising the steps of:
(a1) Preparing an aqueous solution of a substance to be crystallized;
(a2) Freezing, optionally curing, the aqueous solution of the substance to be crystallized from step (a 1) to produce a mixed system of single crystals and ice containing the substance to be crystallized;
(a3) Separating the mixed system of the monocrystal of the substance to be crystallized in the step (a 2) and ice to prepare the monocrystal of the substance to be crystallized;
wherein the heating or cooling rate in the curing process is less than 10 ℃/min, and/or the curing time in the curing process is at least 25min.
Illustratively, in the curing process, the temperature is raised or lowered to a certain temperature at a speed of less than 10 ℃/min, and the temperature is maintained for a period of time, so that a mixed system of the monocrystal containing the substance to be crystallized and the ice is obtained.
Illustratively, in the curing process, the temperature is raised or lowered at any speed to a certain temperature, and the mixture is cured for at least 25min, so that a mixed system of single crystals containing the substance to be crystallized and ice is obtained.
Illustratively, in the curing process, the temperature is raised to a certain temperature at a heating or cooling rate of less than 10 ℃/min, and the mixture is cured for at least 25min, so that a mixed system of the monocrystal and the ice containing the substance to be crystallized is obtained.
Illustratively, the certain temperature reached is, for example, equal to or less than 0 ℃, and also, for example, equal to or less than-5 ℃; in particular, it may be-10 ℃, -15 ℃, -18 ℃, -20 ℃, -24 ℃, -25 ℃, -30 ℃, -72 ℃, -80 ℃, -90 ℃, -100 ℃ or liquid nitrogen temperature, etc.
As mentioned above, the heating or cooling rate is less than 10 ℃/min, for example, may be less than 9 ℃/min, further for example, less than or equal to 5 ℃/min; depending on the substance to be crystallized. It will be understood that if the rate is 0℃per minute, curing is performed while maintaining the same temperature as the freezing temperature.
As described above, the aging time is at least 25min, and may be, for example, 30min, 40min, 50min, 55min, 60min, 90min, 100min, 120min, 150min, 200min, 300min, 500min or more, etc.; depending on the substance to be crystallized.
[ method for producing amorphous substance ]
As previously described, the present invention provides a method of preparing an amorphous material, the method comprising the steps of:
(a1) Preparing an aqueous solution of a substance to be crystallized;
(a2) Freezing and curing the aqueous solution of the substance to be crystallized in the step (a 1) to prepare an amorphous and ice mixed system containing the substance to be crystallized; optionally, the composition may be used in combination with,
(a3) Separating amorphous material to be crystallized from the mixed system in the step (a 2);
wherein the heating or cooling rate in the curing process is more than or equal to 10 ℃/min, and the curing time in the curing process is less than 25min.
Illustratively, in the curing process of the step (a 2), the temperature is cured for less than 25 minutes at a temperature rising or reducing speed of more than or equal to 10 ℃/min, so as to obtain the mixed system of the amorphous substance containing the substance to be crystallized and the ice.
In one embodiment, the greater the difference between the certain temperature reached and the freezing temperature, the greater the particle size of the resulting amorphous material. The particle size of the obtained amorphous material can be controlled by adjusting the temperature. Illustratively, the certain temperature reached is, for example, equal to or less than 0 ℃, and also, for example, equal to or less than-5 ℃; in particular, -5 ℃, -7 ℃, -8 ℃, -10 ℃, -12 ℃, -20 ℃, -45 ℃, etc. Preferably, the temperature is raised from the liquid nitrogen temperature to the above temperature at a temperature rise rate of 10 ℃/min or more.
As described above, the heating or cooling rate is 10 ℃/min or more, for example 15 ℃/min, 16 ℃/min, 17 ℃/min, 18 ℃/min, 19 ℃/min, 20 ℃/min, 21 ℃/min, 22 ℃/min, 23 ℃/min, 24 ℃/min, 25 ℃/min, 26 ℃/min, 27 ℃/min, 28 ℃/min, 29 ℃/min, 30 ℃/min or more; the aging time is less than 25min, for example, 25min, 23min, 22min, 21min, 20min, 19min, 18min, 17min, 16min, or the like; depending on the substance to be crystallized.
[ embodiment of the above method ]
According to an embodiment of the present invention, in step (a 1), the preparation of the aqueous solution of the substance to be crystallized may be carried out by means of operations known to those skilled in the art, such as by standard solution preparation methods.
According to an embodiment of the present invention, the substance to be crystallized includes, but is not limited to, an inorganic substance and/or an organic substance. The quasi-crystalline material includes, but is not limited to, inorganic and organic materials. The inorganic substance is selected from, for example, metal salts or nonmetal salts; the organic substance is an organic molecule soluble in water, for example selected from the group consisting of aromatic compounds, non-aromatic heterocyclic compounds, amino acids, saccharides, polypeptides, proteins, drugs, water-soluble metal-organic complexes, and the like. For example, the inorganic substance is selected from, for example, copper sulfate, sodium chloride, quaternary ammonium salts, and the like; the aromatic compound is selected from, for example, phenol, p-toluenesulfonic acid, naphthalene sulfonate formaldehyde condensate, etc., and the non-aromatic hybrid compound is selected from, for example, purine compounds; such as water-soluble biporphyrin metal complexes and the like.
According to an embodiment of the present invention, the substance to be crystallized has a certain solubility in water; it will be appreciated by those skilled in the art that the solubility of the substance to be crystallized in water may be arbitrary, that is, the substance to be crystallized may be dissolved in water, and the amount thereof to be dissolved in water is not particularly limited; it will be appreciated that the solubility of the substance to be crystallised in water may be readily soluble, slightly soluble or poorly soluble, for example.
According to an embodiment of the present invention, preferably, the amount of the substance to be crystallized dissolved in water is 1×10 or more -7 g/100g, for example, 0.001g/100g or more, such as 0.01g/100g or more, such as 0.1g/100g or more, such as 1g/100g or more, such as 10g/100g or more.
According to an embodiment of the present invention, the concentration of the aqueous solution of the substance to be crystallized is not particularly limited, that is, the substance to be crystallized can be dissolved in water; the substance to be crystallized may be an unsaturated solution or a saturated solution or a supersaturated solution in water, as known to those skilled in the art; of course, the concentration of the aqueous solution of the substance to be crystallized has great influence on the aggregation rate of the substance to be crystallized, and when the concentration is low, the aggregation rate of the substance to be crystallized is low, and the time required for obtaining single crystals or amorphous substances is correspondingly increased; at higher concentrations, the rate of aggregation of the substance to be crystallized is faster and the time required to obtain a single crystal or amorphous is correspondingly reduced. Therefore, the preparation time of single crystals or amorphous matters is regulated and controlled through the solution concentration by reasonably selecting the concentration; of course, the time for preparing the single crystal or amorphous form is not only dependent on the concentration of the solution, but is also closely related to the curing process (e.g., curing temperature, curing time).
According to an embodiment of the present invention, the concentration of the aqueous solution of the substance to be crystallized is 1×10 or more -7 g/100g, for example, 0.001g/100g or more, such as 0.01g/100g or more, such as 0.1g/100g or more, such as 1g/100g or more, such as 10g/100g or more. The upper limit of the concentration of the aqueous solution of the substance to be crystallized is not particularly limited, and may be a supersaturated solution or a saturated solution of the substance to be crystallized in water.
Preferably, the water of the substance to be crystallizedThe concentration of the solution was 1X 10 -7 g/100g to 1g/100g.
According to the invention, said step (a 2) comprises in particular the steps of:
cooling and freezing the aqueous solution of the substance to be crystallized in the step (a 1) into solid, and optionally curing to obtain a mixed system of monocrystal or amorphous substance containing the substance to be crystallized and ice.
According to embodiments of the present invention, the inventors have unexpectedly found that the aqueous solution freezes to a solid during freezing, whereas the quasi-crystalline substance dissolved in the aqueous solution achieves concentration aggregation at the ice interface, thereby making it possible to form single crystals or amorphous substances. In addition, when the frozen aqueous solution of the substance to be crystallized is further subjected to the freezing process and optionally the further aging process, the grain size of a certain amount of ice is gradually increased, the substance to be crystallized is gradually released from the disappeared solid solvent, and thus the substance to be crystallized is continuously aggregated at the interface of ice to form a single crystal or an amorphous substance and is continuously grown or the formed single crystal or amorphous substance is continuously grown, and finally a single crystal of the substance to be crystallized having a grain size of several tens nm to several hundreds nm can be obtained, as shown in fig. 36. Illustratively, the aggregate luminescent material is not capable of being excited to emit light at any wavelength when in the free molecular state, but the molecule is excited to fluoresce when in the aggregate state; to demonstrate that ice crystals aggregate solute molecules at their interface during freezing, or optionally further ripening, we have selected an aggregate luminescent material (AIE 35) to verify this process. During the experiment, the aqueous AIE35 solution was frozen to a solid by either means, and the ice formed a separate polycrystalline system, as shown in fig. 37, at the interface between any two contacting ice crystals, AIE35 formed aggregates and crystallized. As can be seen from FIG. 38 a, fluorescence enhancement at the interface suggests that AIE35 molecules can aggregate at the interface and gradually transition from amorphous material to AIE35 nano-single crystals. And as can be seen from fig. 38 b, the aggregates formed at the interface undergo a transition from an amorphous state to a single crystal, and the volume of the single crystal thereof gradually increases. Wherein fig. 38 is a transmission electron microscope and electron diffraction characterization result.
In order to further prove the principle of monocrystal formation, the method adopts p-toluenesulfonic acid molecules, adopts a transmission electron microscope to attenuate total reflection infrared at a low temperature in situ, and observes the aggregation of the p-toluenesulfonic acid in the freezing and curing processes of water and forms the monocrystal and the continuous growth process of the monocrystal. The detection result shows that the freezing process forms a p-toluenesulfonic acid monocrystal which grows gradually when being cured, and the characteristic peak of the p-toluenesulfonic acid is 1035cm -1 The generation and blue shift of (the stretching vibration of sulfonate) also strongly demonstrates that as curing proceeds, the p-toluenesulfonic acid molecules accumulate continuously so that the single crystal formed grows continuously (see fig. 39).
According to an embodiment of the present invention, in step (a 2), the freezing includes, but is not limited to, complete freezing, not complete freezing. As will be appreciated by those skilled in the art, by completely frozen is meant that the aqueous solution of the substance to be crystallized of step (a 1) is completely frozen into a solid; the incomplete freezing means that the aqueous solution of the substance to be crystallized in the step (a 1) is partially frozen into a solid and partially is also in a liquid state.
In step (a 2), according to an embodiment of the present invention, it will be understood by those skilled in the art that the freezing may be by freezing an aqueous solution of a substance to be crystallized having any volume and shape into a solid in any one or several cooling processes by any one or several cooling methods. That is, the freezing is to freeze the aqueous solution of the substance to be crystallized in the step (a 1) into a solid or a solid-liquid mixed state. Compared with the traditional evaporation method and cooling crystallization method, the freezing crystallization method has a larger regulating and controlling range for the concentration of the aqueous solution of the substance to be crystallized, and the time required for obtaining the crystal of the substance to be crystallized is greatly shortened.
According to the embodiment of the present invention, the freezing time, freezing temperature gradient, freezing method, freezing process, and the like are not particularly limited, and any volume and shape of the aqueous solution of the substance to be crystallized may be frozen in a solid or solid-liquid mixed state. Of course, the concentration of the aqueous solution of the substance to be crystallized can be reasonably selected in consideration of the freezing process, so as to control the diffusion rate of water molecules and molecules of the substance to be crystallized, thereby influencing the crystallization process. For example, if the concentration of the aqueous solution of the substance to be crystallized is high, the freezing time selected at this time can be appropriately shortened, and the freezing temperature can be appropriately lowered; the purpose of this is to prevent the crystallization of the substance to be crystallized in the higher concentration solution from forming a polycrystal with difficulty in control; if the concentration of the aqueous solution of the substance to be crystallized is low, the freezing time selected at the moment can be properly prolonged, and the freezing temperature can be properly increased; the purpose of such an operation is to achieve efficient aggregation of molecules of the substance to be crystallized, thereby forming an amorphous substance or a single crystal.
According to the embodiment of the invention, the freezing method is an operation mode known to a person skilled in the art, such as cooling and freezing operation by using any refrigeration device or cooling and freezing by using any low-temperature substance; illustratively, the freezing method includes, but is not limited to, one or more of compression refrigeration equipment de-chilling, semiconductor refrigeration equipment de-chilling, liquid nitrogen de-chilling, liquid helium de-chilling, liquid carbon dioxide de-chilling, liquid oxygen de-chilling, liquid ethane de-chilling, dry ice de-chilling, etc.
The operation pressure of the freezing is not limited as well, and may be freezing under normal pressure or freezing treatment under high pressure or low pressure.
According to embodiments of the present invention, the freezing process is a manner of operation known to those skilled in the art, such as by any process that freezes an aqueous solution of a substance to be crystallized from a liquid state to a solid state, illustratively including, but not limited to, one or a combination of freezing processes of rapid cooling, slow cooling, stepwise cooling, first heating and then cooling, and the like.
According to an embodiment of the present invention, the volume and shape of the aqueous solution of the substance to be crystallized are not particularly limited; the volume and shape of the solid frozen from the aqueous solution of the substance to be crystallized are not particularly limited as long as the solid or a solid-liquid mixture can be obtained by freezing the solid; it will be appreciated by those skilled in the art that the freezing may be by freezing an aqueous solution of the substance to be crystallized in its entirety in any volume, or by freezing a film formed of an aqueous solution of the substance to be crystallized in any volume, or by freezing droplets formed of an aqueous solution of the substance to be crystallized in any volume.
According to embodiments of the present invention, the crystallization process may optionally be performed with maturation, which may be used to form single crystals of a system in which the freezing process does not form single crystals, to control the rate of single crystal growth, and to control the size of the single crystals; can also be used to further optimize the control of the growth rate of the single crystal and the control of the single crystal size of the system in which the freezing process forms the single crystal. The curing process is not limited by temperature, so that the energy consumption and the cost generated by the low temperature required in the freezing process can be reduced, and the method is convenient for industrial production.
According to an embodiment of the present invention, an aqueous solution of a substance to be crystallized frozen into a solid is subjected to a ripening treatment; the curing temperature, curing time and curing process in the curing process are not particularly limited, but the aqueous solution of the to-be-crystallized substance frozen into a solid in the curing process is required to be kept in a solid state, namely the aqueous solution of the to-be-crystallized substance is kept in a frozen state in the curing process; curing the solid, for example, by the same method as the freezing treatment, or by another method; the curing treatment aims to realize the regulation and control of the aggregation of the substance to be crystallized and the growth speed of the nano particles, so as to prepare the monocrystal or amorphous substance of the substance to be crystallized. As will be appreciated by those skilled in the art, the maturation temperature should be below a temperature at which the aqueous solution of the frozen pseudocrystalline material will re-melt (i.e., T Melting ) Preferably, the curing temperature is lower than T Melting At 5 ℃ or higher, more preferably lower than T Melting At a temperature of 10 ℃ or above.
According to an embodiment of the present invention, the ripening is a process in which an aqueous solution of the substance to be crystallized is left in a frozen state for a while. The frozen state may be either completely frozen or not completely frozen, and may be selected according to operations known to those skilled in the art.
According to the embodiment of the invention, the curing process adopts a rapid heating (or cooling) or slow heating (or cooling) mode, for example, the heating or cooling rate of the curing process is more than or equal to 10 ℃/min, and the heating or cooling rate in the range can lead solute molecules to be quickly released from a solid mixture and generate disordered aggregation, so that the preparation of amorphous matters is ensured by limiting the curing time.
Illustratively, the rate of heating or cooling during the aging process is less than 10 ℃/min, which range of heating or cooling causes slow release of solute molecules from the solid mixture to produce ordered aggregation, and single crystals can be prepared.
According to the embodiment of the invention, the curing temperature (i.e. the certain temperature reached) controls the size of ice particles and the aggregation speed of the substance to be crystallized, i.e. the larger the difference between the curing temperature and the freezing temperature is, the larger the size of the ice particles is, the faster the aggregation speed of the substance to be crystallized is, and the shorter the time required for forming the monocrystal or the amorphous substance is, so that the particle size of the monocrystal or the amorphous substance of the substance to be crystallized is also larger; the smaller the difference between the curing temperature and the freezing temperature, the smaller the ice particle size, the slower the aggregation speed of the substance to be crystallized, the longer the time required for forming the monocrystal or the amorphous substance, and the smaller the particle size of the monocrystal or the amorphous substance of the substance to be crystallized. That is, the larger the difference between the aging temperature and the freezing temperature, the larger the particle size of the single crystal or amorphous substance of the substance to be crystallized is.
The curing time is not particularly limited according to the embodiment of the present invention, and may be performed by operations known to those skilled in the art, and as can be seen from the above description of the mechanism of the method of the present application, the curing process may be understood as nucleation and growth of an amorphous material or formation and growth of a single crystal, and a proper extension of the curing time may be performed, so that a single crystal or amorphous material with a complete particle size and morphology may be obtained, but it should be noted that since the nature of adjusting the curing time is to regulate the concentration of the aggregation of the crystallization-like material, too long curing may cause the concentration of aggregation to be too high, which may be disadvantageous to form the amorphous material or the single crystal. Illustratively, the time of maturation is greater than 1 picosecond, preferably the time of maturation is from 1 to 1000 minutes, and still more preferably the time of maturation is from 10 to 300 minutes.
Illustratively, the curing time is less than 25 minutes, and the preparation of the amorphous material can be achieved by regulating the rate of temperature rise or temperature reduction with the curing process. When the aging time is 25 minutes or longer, the concentration of the aggregation of the substance to be crystallized can be further controlled, for example, a single crystal can be produced. However, the aging time must not be too long, and the aging time may be too long to further change the obtained single crystal into a polycrystalline structure.
According to the embodiment of the invention, the curing process can be realized by adopting any refrigeration device or adopting any low temperature, so that the water solution of the substance to be crystallized is kept in a frozen state; for example, using a compression refrigeration device, a semiconductor refrigeration device, or using one or a combination of several methods of liquid nitrogen, liquid helium, liquid carbon dioxide, liquid oxygen, liquid ethane, dry ice, etc.
According to an embodiment of the present invention, in step (a 3), the separation of the ice may be performed by physically and/or chemically separating the ice. After the freezing or optionally further ripening has been completed, a single crystal or amorphous material has been prepared, which is present at the ice interface and which needs to be separated by a suitable method; or ice removal.
According to embodiments of the present invention, the physical means include, but are not limited to, one or a combination of mechanical separation, sublimation (e.g., vacuum sublimation). The sublimation can be performed, for example, by freeze-drying; the vacuum sublimation can be performed, for example, by freeze-drying under vacuum.
According to embodiments of the present invention, the chemical means includes, but is not limited to, one or a combination of chemical reactions, electrolysis.
According to the invention, the method further comprises the steps of:
(a4) Collecting the single crystal or amorphous substance obtained in the step (a 3).
According to an embodiment of the present invention, in step (a 4), the collecting includes, but is not limited to, collecting with one or a combination of several of optical microscopy, scanning electron microscopy, dual beam electron microscopy, transmission electron microscopy.
[ method of growing Single Crystal ]
As described above, the present invention also provides a method of growing a single crystal, the method including the above method of producing a single crystal.
According to an embodiment of the present invention, the method of growing a single crystal further comprises the steps of:
(b1) Transferring the single crystal of the substance to be crystallized prepared above into mother liquor of the substance to be crystallized for cultivation;
(b2) Collecting the single crystal of step (b 1).
According to embodiments of the present invention, the transfer is any method known to those skilled in the art capable of transferring single crystals, including, but not limited to, one or a combination of several of optical microscope transfer, scanning electron microscope transfer, dual beam electron microscope transfer, transmission electron microscope transfer.
According to an embodiment of the invention, the mother liquor is a mother liquor system which is known to the person skilled in the art to be adapted to the single crystal to be grown.
The present invention will be described in further detail with reference to the following specific embodiments, but it should not be construed that the scope of the present invention is limited to the specific examples. Various substitutions and alterations are also possible without departing from the spirit of the invention, and all such modifications are intended to be within the scope of the invention.
The aging time described in the following examples means the time required for heating up or cooling down to the aging temperature after the freezing process is completed, and the time for maintaining at the aging temperature; the maintaining time refers to the time maintained at the curing temperature.
Example 1
Preparing copper sulfate solution with concentration of 500 mu M by using ultrapure water, taking 100ml of the solution into a beaker by using a dosage cylinder, slowly cooling to complete freezing in a refrigerator with the temperature of-24 ℃, finally curing for 30min in a refrigerator with the temperature of-15 ℃, and then freeze-drying the sample to complete sublimating solid ice to obtain the monocrystal. And finally, selecting a single crystal with better quality from a beaker, transferring the single crystal to a saturated copper sulfate aqueous solution, and placing the solution in a constant temperature and constant humidity environment with the temperature of 25 ℃ and the relative humidity of 40% for a period of time to grow copper sulfate crystals with larger volume, wherein the detection result is shown in figure 1. As can be seen from fig. 1, the obtained crystal is a single crystal.
Example 2
Preparing copper sulfate solution with concentration of 10mM by using ultrapure water, taking 30 mu L of the solution by using a syringe, spreading the solution on a silicon wafer, slowly cooling to complete freezing in a refrigerator with the temperature of-24 ℃, finally, placing the solution in a refrigerator with the temperature of-18 ℃ for curing for 40min, and then quenching to remove ice to obtain the monocrystal. And finally, selecting a single crystal with better quality from the silicon wafer, transferring the single crystal to a saturated copper sulfate aqueous solution, and placing the single crystal in a constant temperature and constant humidity environment with the temperature of 25 ℃ and the relative humidity of 40% for a period of time to grow copper sulfate crystals with larger volume.
Example 3
Preparing copper sulfate solution with concentration of 6mM by using ultrapure water, taking 15 mu L of the solution by using a pipette, dripping the solution to a silicon wafer with the temperature of-90 ℃, controlling the temperature of the silicon wafer by a cold and hot table, then raising the temperature to-25 ℃ at the temperature raising rate of 15 ℃/min, and maintaining the temperature for 40min. And freeze-drying the sample to sublimate the solid ice completely, then selecting a single crystal with better quality from the silicon wafer, transferring the single crystal to a saturated copper sulfate aqueous solution, and placing the single crystal in a constant temperature and constant humidity environment with the temperature of 25 ℃ and the relative humidity of 40% for a period of time to grow copper sulfate crystals with larger volume.
Example 4
Preparing a glutamic acid solution with the concentration of 50mM by using ultrapure water, taking 100ml of the solution into a beaker by using a dosage cylinder, slowly cooling to complete freezing in a refrigerator with the temperature of-24 ℃, finally curing for 15min in a refrigerator with the temperature of-20 ℃, and then freeze-drying the sample to complete sublimating solid ice, thereby obtaining the monocrystal. And finally, selecting a single crystal with better quality from a beaker, transferring the single crystal to a saturated glutamic acid aqueous solution, and placing the single crystal in a constant temperature and constant humidity environment with the temperature of 25 ℃ and the relative humidity of 40% for a period of time to grow glutamic acid crystals with larger volume, wherein the detection result is shown in figure 2. As can be seen from fig. 2, the obtained crystal is a single crystal.
Example 5
Preparing benzyl penicillin solution with concentration of 1M by using ultrapure water, taking 100ml of the solution into a beaker by using a dosage cylinder, slowly cooling to complete freezing in a refrigerator with the temperature of-24 ℃, finally curing for 30min in a refrigerator with the temperature of-15 ℃, and then freeze-drying the sample to completely sublimate solid ice to obtain the monocrystal. And finally, selecting a single crystal with better quality from a beaker, transferring the single crystal to a saturated benzyl penicillin aqueous solution, and placing the solution in a constant temperature and constant humidity environment with the temperature of 25 ℃ and the relative humidity of 40% for a period of time to grow benzyl penicillin crystals with larger volumes, wherein the detection result is shown in figure 3. As can be seen from fig. 3, the obtained crystal is a single crystal.
Example 6
The benzyl penicillin solution with the concentration of 10mM is prepared by using ultrapure water, 15 mu L of the solution is taken by a liquid-transfering gun, the solution is dripped on a silicon wafer with the temperature of-90 ℃, the temperature of the silicon wafer is controlled by a cold and hot table, and then the temperature is raised to-25 ℃ at the heating rate of 5 ℃/min, and the temperature is maintained for 60 minutes. And freeze-drying the sample to sublimate the solid ice completely, then selecting a single crystal with better quality from the silicon wafer, transferring the single crystal to a saturated benzyl penicillin solution, and placing the solution in a constant temperature and constant humidity environment with the temperature of 25 ℃ and the relative humidity of 40% for a period of time to grow benzyl penicillin crystals with larger volume.
Examples 7 to 55
The procedure is as in example 1, with the following differences:
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the embodiments of the present invention have been described above. However, the present invention is not limited to the above embodiment. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (19)
1. A method for producing a single crystal or an amorphous substance using an aqueous solution, which is different from a conventional evaporation method and a cooling crystallization method, by using solution freezing to induce crystallization of a substance to be crystallized or formation of an amorphous substance,
the method utilizes solution freezing to induce crystallization of the substance to be crystallized or form amorphous substance,
the method for producing a single crystal of a substance to be crystallized includes the steps of:
(a1) Preparing an aqueous solution of a substance to be crystallized, wherein the aqueous solution of the substance to be crystallized consists of the substance to be crystallized and water;
(a2) Freezing and curing the aqueous solution of the substance to be crystallized in the step (a 1) to prepare a mixed system of single crystal or amorphous substance containing the substance to be crystallized and ice, wherein the heating or cooling rate in the curing process is less than 10 ℃/min, and/or the curing time in the curing process is at least 25min; the maturation temperature should be below a temperature at which the frozen aqueous solution of the substance to be crystallized will re-melt; optionally, the composition may be used in combination with,
(a3) Separating the single crystal of the substance to be crystallized from the mixed system of the single crystal containing the substance to be crystallized and the frozen solution of the step (a 2);
the method for preparing the amorphous substance of the substance to be crystallized comprises the following steps:
(a1) Preparing an aqueous solution of a substance to be crystallized, wherein the aqueous solution of the substance to be crystallized consists of the substance to be crystallized and water;
(a 2') freezing and curing the aqueous solution of the substance to be crystallized in the step (a 1) to prepare a mixed system of amorphous-frozen solution containing the substance to be crystallized; wherein the heating or cooling rate in the curing process is more than or equal to 10 ℃/min, and the curing time in the curing process is less than 25min; the maturation temperature should be below a temperature at which the frozen aqueous solution of the substance to be crystallized will re-melt; optionally, the composition may be used in combination with,
(a 3 ') separating the amorphous form of the substance to be crystallized from the mixed system of the amorphous form containing the substance to be crystallized and ice of the step (a 2');
the freezing is to convert the aqueous solution of the substance to be crystallized of step (a 1) from a liquid state to a solid state; the curing maintains the water solution of the substance to be crystallized in a frozen state for a period of time; in the freezing process, water is frozen into a solid state, and at the same time, the substance to be crystallized is released and aggregated at the interface of the solvent in the solid state, and the release and aggregation rate of the substance to be crystallized is further regulated and controlled through regulating and controlling the solvent crystallization process and the recrystallization process of the crystallized solvent, so that single crystals or amorphous substances are formed.
2. The method according to claim 1, wherein the temperature is allowed to reach a certain temperature at a heating or cooling rate of less than 10 ℃/min during the aging process, and the aging is performed for at least 25min, thereby obtaining a mixed system of the single crystal containing the substance to be crystallized and ice.
3. The method of claim 1, wherein the water comprises ultrapure water, secondary water, deionized water.
4. The method according to claim 1, wherein in step (a 1), the substance to be crystallized comprises an inorganic substance and/or an organic substance.
5. The method of claim 1, wherein the solubility of the substance to be crystallized in water is insoluble, slightly soluble, soluble or readily soluble.
6. The method according to claim 1, wherein in step (a 2) or step (a 2'), the freezing is a process of converting the aqueous solution of the substance to be crystallized of step (a 1) from a liquid state to a solid state by an arbitrary freezing process using an arbitrary freezing method.
7. The method of claim 6, wherein the freezing method comprises using one or more of a compression refrigeration device chill, a semiconductor refrigeration device chill, a liquid nitrogen chill, a liquid helium chill, a liquid carbon dioxide chill, a liquid oxygen chill, a liquid ethane chill, a dry ice chill, and an ice chill.
8. The method of claim 6, wherein the freezing process comprises one or a combination of freezing processes of rapid cooling, slow cooling, stepwise cooling, first warming and then cooling.
9. The method of claim 6, wherein the freezing comprises complete freezing, incomplete freezing.
10. The method of claim 1, wherein in step (a 3), the separation is performed by separating the single crystal from ice in any manner.
11. The method of claim 10, wherein the arbitrary means comprises physical means and/or chemical means.
12. The method of claim 11, wherein the physical means comprises one or a combination of mechanical separation, sublimation, dissolution, and adsorption.
13. The method of claim 11, wherein the chemical means comprises one or a combination of chemical reactions and electrolysis.
14. The method according to claim 1, characterized in that the method further comprises the steps of: (a 4) collecting the single crystal prepared in the step (a 3);
in step (a 4), the collecting includes collecting with one or a combination of several of optical microscope, scanning electron microscope, dual beam electron microscope, and transmission electron microscope.
15. A method of growing a single crystal, characterized in that the method comprises the method of producing a single crystal according to any one of claims 1 to 14;
the method further comprises the steps of:
(b1) Transferring a single crystal of a substance to be crystallized prepared by the method for producing a single crystal according to any one of claims 1 to 14 into a mother liquor of the substance to be crystallized for cultivation; optionally, the composition may be used in combination with,
(b2) Collecting the single crystal grown in step (b 1).
16. The method according to claim 15, wherein in the step (b 1), the transfer is a single crystal culture in which the mixed system of the single crystal containing the substance to be crystallized and ice of the step (a 2) is transferred to a mother liquor of the substance to be crystallized; or directly transferring the single crystal removed from the ice in the step (a 3) into mother liquor of a substance to be crystallized for single crystal cultivation; or transferring the single crystal collected in the step (a 4) into mother liquor of the substance to be crystallized for single crystal cultivation.
17. The method of claim 16, wherein said transferring comprises one or a combination of several of optical microscope removal, scanning electron microscope removal, dual beam electron microscope removal, transmission electron microscope removal.
18. The method according to claim 16, wherein in the step (b 1), the method of growing the single crystal comprises one or a combination of several of an evaporation method, a cooling method, and a diffusion method.
19. The method of claim 16, wherein in step (b 2), the collecting comprises employing one or a combination of several of optical microscopy, scanning electron microscopy, dual beam electron microscopy, transmission electron microscopy.
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