Crystallization device and crystallization method

Abstract

Provided is a crystallization device that is capable of simultaneously carrying out crystallization tests of a crystallization target using a plurality of solutions having mutually different compositions, and that is excellent in terms of safety. A crystallization device according to an embodiment of the present invention comprises a stage, a plurality of containers, a first case, a second case, a heater, and an inert gas supply unit. The plurality of containers are disposed on the stage. Each of the plurality of containers is capable of accepting a solution of the crystallization target. The first case is disposed so as to overlap the plurality of containers collectively when viewed from the thickness direction of the stage. The second case is positioned inside the first case. The heater is supported by the second case. The first case has a supply port. Inert gas from the inert gas supply unit is supplied to the supply port. The second case has a discharge port. Exhaust gas containing the inert gas is discharged from the discharge port.

Description

Crystallization apparatus and crystallization method

[0001] The present invention relates to a crystallization apparatus and a crystallization method.

[0002] It has been known to evaporate an organic solvent from a solution in which a specific compound is dissolved, thereby precipitating crystals of the specific compound. Compounds to be crystallized in this manner may exhibit crystalline polymorphism, which results in different crystalline forms depending on the crystallization conditions, even if they have the same chemical composition. Different crystalline forms can result in different properties even for crystals of the same compound. Therefore, it is expected that crystalline polymorphism can be controlled to produce crystals of a compound with properties appropriate for the intended use. As an example of such crystalline polymorphism control, a purification method has been proposed in which a solution of a compound is irradiated with infrared light having a specific infrared wavelength from an infrared emission device, thereby evaporating the organic solvent and precipitating a compound having a specific crystalline form (see Patent Document 1).

[0003] Japanese Patent Application Laid-Open No. 2022-125073

[0004] In recent years, the search for compounds that exhibit crystalline polymorphism has progressed, and there is a need to find crystallization conditions that can control the crystalline polymorphism of such compounds. The crystalline form of a compound can be affected not only by the composition of the solution used for crystallization (e.g., solute concentration, type of organic solvent) but also by environmental conditions (e.g., temperature, humidity, wind direction). Therefore, even if compound crystallization is repeated with different solution compositions, it is difficult to find crystallization conditions that exhibit excellent reproducibility due to changes in environmental conditions. Therefore, to reduce the influence of environmental conditions, it has been considered to prepare multiple solutions with different compositions and simultaneously conduct crystallization tests of compounds using these solutions. However, when multiple solutions are used simultaneously to crystallize a compound, the amount of organic solvent that evaporates during crystallization increases. As a result, the organic solvent concentration increases around heaters such as infrared emitters, and there is a risk of the organic solvent igniting in a gaseous state due to the heat of the heater. The main object of the present invention is to provide a crystallization apparatus that can simultaneously conduct crystallization tests of a crystallization target using multiple solutions with different compositions and that is highly safe.

[0005] [1] A crystallization apparatus according to an embodiment of the present invention includes a stage, a plurality of containers, a first case, a second case, a heater, and an inert gas supply unit. The plurality of containers are arranged on the stage. Each of the plurality of containers is capable of receiving a solution containing a solute of a crystallization target and an organic solvent. The first case is arranged so as to overlap the plurality of containers collectively when viewed in the thickness direction of the stage. The second case is located inside the first case. The heater is supported by the second case. The inert gas supply unit is configured to supply inert gas into the first case. The first case has a supply port. The inert gas from the inert gas supply unit is supplied to the supply port. The second case has an exhaust port. Exhaust gas containing the inert gas is exhausted from the exhaust port. [2] In the crystallization apparatus described in [1] above, the first case, the second case, and the heater may form a moving unit that is movable relative to the stage. The moving unit is movable between a closed position and an open position. When the moving unit is in the closed position, the first case collectively covers the multiple containers together with the stage. When the moving unit is in the open position, the first case is located away from the stage. [3] The crystallization apparatus described in [2] above may further include a flow rate adjuster and a control unit. The flow rate adjuster is capable of adjusting the flow rate of the exhaust gas discharged from the outlet. The control unit is capable of controlling the flow rate adjuster so that the flow rate of the exhaust gas is equal to or less than a predetermined value. [4] The crystallization apparatus described in [2] above may further include an HC measuring device and a control unit. The HC measuring device is capable of measuring the hydrocarbon concentration in the exhaust gas discharged from the outlet. The control unit is capable of controlling the movement of the moving unit between the closed position and the open position based on the measurement result of the HC measuring device. [5] The crystallization apparatus described in [4] above may further include an oxygen measuring device. The oxygen measuring device is capable of measuring the oxygen concentration in the exhaust gas. The control unit is capable of controlling the activation of the heater based on the measurement result of the oxygen measuring device. [6] The crystallization apparatus described in any one of [1] to [5] above may further include a partition plate.The partition plate is located between the heater and the multiple containers. The partition plate separates a first space in which the heater is disposed from a second space in which the multiple containers are disposed. [7] In the crystallization apparatus described in any of [1] to [6] above, the first case may include a first upper wall and a first side wall. The first upper wall is located on the opposite side of the second case from the stage. The first side wall extends from the peripheral edge of the first upper wall toward the stage. The crystallization apparatus may further include a heat shield. The heat shield is located between the first side wall and the heater. [8] In the crystallization apparatus described in any of [1] to [7] above, the inert gas may be nitrogen, carbon dioxide, water vapor, argon, or a mixture thereof. [9] In the crystallization apparatus described in any of [1] to [8] above, the stage may include a Peltier element. The Peltier element can adjust the temperature of the stage.

[10] In the crystallization apparatus described in any one of [1] to [9] above, the heater may be a selective radiation plate capable of emitting infrared light with a controlled wavelength.

[11] A crystallization method according to another aspect of the present invention uses the crystallization apparatus described in any one of [1] to

[10] above. In this crystallization method, the heater is driven while the inert gas is supplied into the first case through the supply port.

[0006] According to an embodiment of the present invention, a crystallization apparatus that can simultaneously perform crystallization tests on a crystallization target using a plurality of solutions with different compositions and that is highly safe can be realized.

[0007] Fig. 1 is a schematic plan view of a crystallization apparatus according to one embodiment of the present invention. Fig. 2 is a cross-sectional view of the crystallization apparatus taken along line II-II' in Fig. 1, showing a state in which a moving unit provided in the crystallization apparatus is positioned in a closed position. Fig. 3 is a cross-sectional view of the crystallization apparatus taken along line II-II' in Fig. 1, showing a state in which a moving unit provided in the crystallization apparatus is positioned in an open position. Fig. 4 is a schematic perspective view of the moving unit in Fig. 1. Fig. 5 is a schematic structural diagram of the crystallization apparatus in Fig. 1. Fig. 6 is a schematic structural diagram of a selective radiation plate provided in the crystallization apparatus in Fig. 1.

[0008] Hereinafter, embodiments of the present invention will be described with reference to the drawings, but the present invention is not limited to these embodiments. In addition, in order to clarify the description, the drawings may show the width, thickness, shape, etc. of each part more schematically than in the embodiment, but these are merely examples and do not limit the interpretation of the present invention.

[0009] A. Overview of Crystallization Apparatus Figure 1 is a schematic plan view of a crystallization apparatus according to one embodiment of the present invention, and Figure 2 is a cross-sectional view of the crystallization apparatus taken along line II-II' of Figure 1. For convenience, in Figure 1, the stage and the first case are indicated by solid lines, the container, the second case, and the heater are indicated by dotted lines, and other components are omitted.

[0010] The illustrated crystallization apparatus 100 is configured to precipitate crystals of a crystallization target by evaporating an organic solvent from a solution in which a crystallization target as a solute is dissolved in the organic solvent (hereinafter referred to as a solution of the crystallization target). In one embodiment, the crystallization apparatus 100 uses a plurality of solutions of the crystallization target having different compositions. The solution of the crystallization target contains a solute of the crystallization target and an organic solvent. The crystallization target preferably exhibits crystalline polymorphism.

[0011] As shown in FIGS. 1 and 2 , the crystallization apparatus 100 includes a stage 1, a plurality of containers 2, a first case 3, a second case 4, a heater 5, and an inert gas supply unit 8. The stage 1 typically has a generally flat plate shape. The plurality of containers 2 are arranged on the stage 1. Each of the plurality of containers 2 is capable of receiving a solution of the crystallization target material. The first case 3 is arranged so as to overlap the plurality of containers 2 collectively when viewed in the thickness direction of the stage 1. The second case 4 is located inside the first case 3. The heater 5 is supported by the second case 4. The inert gas supply unit 8 is configured to supply an inert gas into the first case 3. The first case 3 has a supply port 3 a. The inert gas from the inert gas supply unit 8 is supplied to the supply port 3 a. The second case 4 has an exhaust port 4 a. Exhaust gas containing the inert gas is exhausted from the exhaust port 4 a. With this configuration, the first case is arranged to overlap the multiple containers collectively when viewed from the thickness direction of the stage, thereby suppressing fluctuations in environmental conditions around the multiple containers. Therefore, by injecting solutions of the crystallization target material with different compositions (e.g., solute concentration, solvent type) into separate containers and evaporating the organic solvent from the solutions using a heater, crystallization tests using the solutions with different compositions can be performed simultaneously under substantially the same environmental conditions. As a result, the obtained test results can be accurately compared and verified, making it possible to smoothly find crystallization conditions that can achieve the desired crystal form with excellent reproducibility. Furthermore, when crystallization tests are performed by injecting solutions of the crystallization target material into multiple containers, the organic solvent concentration around the heater may increase. In this regard, in one embodiment, the heater is supported by a second case located inside the first case, and the first case has a supply port and the second case has an exhaust port. Therefore, the inert gas passes through the supply port, passes around the heater, and is exhausted from the exhaust port. As a result, the inert gas concentration increases and the oxygen concentration decreases around the heater. As a result, even if the organic solvent concentration increases around the heater, the oxygen concentration is sufficiently reduced, so that the ignition of the organic solvent due to the heat of the heater can be sufficiently suppressed, thereby improving the safety of the crystallization apparatus.

[0012] 2 and 3 , in one embodiment, the first case 3, the second case 4, and the heater 5 constitute a moving unit 6 that is movable relative to the stage 1. The moving unit 6 is movable between a closed position and an open position. In the illustrated example, the moving unit 6 is movable in the thickness direction of the stage 1.

[0013] 2 , when the moving unit 6 is in the closed position, the first case 3 collectively covers the multiple containers 2 together with the stage 1. In the illustrated example, when the moving unit 6 is in the closed position, the first case 3 is in contact with the stage 1. Therefore, when the moving unit 6 is in the closed position, fluctuations in the environmental conditions around the multiple containers can be stably suppressed.

[0014] 3, the moving unit 6 moves from the closed position toward the open position, moving away from the stage 1. When the moving unit 6 is in the open position, the first case 3 is positioned away from the stage 1. Therefore, after the crystallization test is completed, the moving unit is placed in the open position, so that the container in which the crystals of the crystallization target have precipitated can be smoothly removed from the crystallization apparatus.

[0015] 4, the crystallization apparatus 100 typically further includes a moving mechanism 7. The moving mechanism 7 is configured to move the moving unit 6 between a closed position and an open position. An example of the moving mechanism 7 is an elevation cylinder. In the illustrated example, the moving mechanism 7 is connected to the first case 3.

[0016] As shown in FIG. 2 , in one embodiment, the crystallization apparatus 100 further includes a partition plate 10. The partition plate 10 is located between the heater 5 and the multiple containers 2. The partition plate 10 separates a first space S1 in which the heater 5 is disposed and a second space S2 in which the multiple containers 2 are disposed. The first space S1 typically communicates with the supply port 3a. Therefore, the inert gas supplied from the inert gas supply unit flows into the first space S1 through the supply port. As a result, the inert gas can smoothly reach the periphery of the heater disposed in the first space S1. This allows the inert gas concentration to be stably increased around the heater, thereby further reducing the oxygen concentration. With this configuration, the supply of inert gas from the inert gas supply unit can be maintained regardless of whether the transfer unit is in the open position or the closed position, thereby sufficiently reducing the oxygen concentration around the heater. Therefore, even if a gaseous organic solvent reaches the periphery of the heater, ignition of the organic solvent can be sufficiently suppressed regardless of the heater temperature.

[0017] 5, in one embodiment, the crystallization apparatus 100 further includes an exhaust section 12. The exhaust section 12 is capable of discharging exhaust gas from the moving unit 6. The exhaust gas is connected to the exhaust port 4a (see FIG. 2).

[0018] In one embodiment, the crystallization apparatus 100 further includes a flow path adjustment unit 129 and a control unit 9. The flow path adjustment unit 129 can adjust the flow rate of the exhaust gas discharged from the exhaust port 4a. In the illustrated example, the exhaust unit 12 includes the flow path adjustment unit 129. The control unit 9 can control the flow path adjustment unit 129 so that the flow rate of the exhaust gas is equal to or less than a predetermined value. When the control unit controls the flow path adjustment unit so that the flow rate of the exhaust gas is equal to or less than the predetermined value, the inert gas supplied from the supply port can be retained within the first case. This can more stably increase the inert gas concentration around the heater. Therefore, whether the moving unit is positioned in the closed position, the open position, or a position between them, the oxygen concentration around the heater can be sufficiently reduced.

[0019] In one embodiment, the crystallization apparatus 100 further includes an HC measuring device 126. The HC measuring device 126 is capable of measuring the hydrocarbon concentration (i.e., the organic solvent concentration) in the exhaust gas discharged from the exhaust port 4a. In the illustrated example, the exhaust section 12 includes the HC measuring device 126. The control unit 9 can control the movement of the moving unit 6 between the closed position and the open position based on the measurement result of the HC measuring device 126. As a result, the control unit can move the moving unit from the closed position to the open position when the hydrocarbon concentration in the exhaust gas measured by the HC measuring device becomes less than a predetermined threshold, that is, after the hydrocarbon concentration around the heater has been sufficiently reduced.

[0020] In one embodiment, the crystallization apparatus 100 further includes an oxygen measuring device 125. The oxygen measuring device 125 is capable of measuring the oxygen concentration in the exhaust gas discharged from the exhaust port 4a. In the illustrated example, the exhaust unit 12 includes the oxygen measuring device 125. The control unit 9 can control the activation of the heater 5 based on the measurement results of the oxygen measuring device 125. This allows the control unit to activate the heater when the oxygen concentration in the exhaust gas measured by the oxygen measuring device falls below a predetermined threshold, that is, after the oxygen concentration around the heater has been sufficiently reduced. This further improves the safety of the crystallization apparatus.

[0021] B. Details of the Crystallization Apparatus The following describes the details of each component of the crystallization apparatus.

[0022] B-1. Stage As shown in FIG. 2, the stage 1 can support multiple containers 2 collectively. The stage 1 can have any appropriate configuration. In one embodiment, the stage 1 is equipped with a Peltier element (not shown). The Peltier element can adjust the temperature of the stage 1. This makes it possible to appropriately adjust the temperature of the solutions in the multiple containers in a crystallization test of a crystallization target. In particular, the crystallization test can be carried out while maintaining the solutions contained in the multiple containers at a temperature between 0°C and 80°C.

[0023] In one embodiment, the stage 1 is provided with a stage cover 13. The stage cover 13 typically includes an upper plate 131 and a side plate 132. The upper plate 131 is disposed at a distance from the stage 1 in the thickness direction of the stage 1. In the illustrated example, the upper plate 131 is disposed substantially parallel to the stage 1. The upper plate 131 has a plurality of positioning holes 13a. The positioning holes 13a correspond to a plurality of containers 2. A container 2 is disposed in each of the positioning holes 13a. This allows the container to be positioned on the stage. An inert gas (typically nitrogen) may be supplied to the space between the upper plate 131 and the stage 1. This prevents condensation from forming on the container or the stage even when the solution contained in the container is cooled to room temperature (23°C) or below using a Peltier element. The side plate 132 extends from the peripheral edge of the upper plate 131 toward the stage 1 and is fixed to the stage 1.

[0024] B-2. Container The container 2 has any appropriate structure capable of containing a solution of the crystallization target. The container 2 is typically a glass petri dish.

[0025] The container 2 contains a solution of the crystallization target. The crystallization target as the solute is not particularly limited. The organic solvent is not particularly limited as long as it can dissolve the solute. Examples of organic solvents include alcohol-based solvents such as methanol, ethanol, 1-propanol, 2-propanol (isopropanol (IPA)), 1-butanol, 2-butanol, isobutanol, and tert-butanol; nitrile-based solvents such as acetonitrile and propionitrile; ether-based solvents such as diethyl ether and tetrahydrofuran; ketone-based solvents such as acetone and methyl ethyl ketone; halogen-based solvents such as dichloromethane and chloroform; ester-based solvents such as ethyl acetate and methyl acetate; aliphatic hydrocarbon-based solvents such as pentane, hexane, heptane, octane, and cyclohexane; aromatic hydrocarbon-based solvents such as benzene, toluene, and xylene; and mixed solvents of alcohol-based solvents and water. The organic solvents may be used alone or in combination. The concentration of the crystallization target in the solution is, for example, 1 to 1,000 mg / mL.

[0026] The multiple containers 2 typically contain solutions with different compositions. In one embodiment, solutions with different concentrations of the crystallization target material and containing the same organic solvent are contained in separate containers 2. In another embodiment, solutions with different organic solvents and the same concentration of the crystallization target material are contained in separate containers 2. Note that a crystallization test may be carried out by containing solutions with the same composition in all of the multiple containers 2.

[0027] B-3. ​​First Case A cross section of the first case 3 cut in the thickness direction of the stage 1 typically has a substantially U-shape that opens toward the stage 1. The first case 3 includes a first upper wall 31 and a first side wall 32.

[0028] The first upper wall 31 is located on the opposite side of the second case 4 from the stage 1. In the illustrated example, the first upper wall 31 is disposed substantially parallel to the stage 1. The first upper wall 31 has any appropriate shape. Examples of the shape of the first upper wall 31 as viewed in the thickness direction include a rectangle, a pentagon, a polygon having hexagons or more sides, and a circle. As shown in FIG. 1 , in one embodiment, the first upper wall 31 has a rectangle as viewed in the thickness direction. As shown in FIG. 2 , the first upper wall 31 typically has the above-mentioned supply port 3 a. The supply port 3 a is disposed at any appropriate position on the first upper wall 31. In the illustrated example, the above-mentioned movement mechanism 7 is connected to the surface (top surface) of the first upper wall 31 opposite the second case 4 (see FIG. 4 ).

[0029] The first side wall 32 extends from the peripheral edge of the lower surface of the first upper wall 31 toward the stage 1. In the illustrated example, the thickness direction of the first side wall 32 is perpendicular to the thickness direction of the first upper wall 31.

[0030] The first upper wall 31 and the first side wall 32 are typically integrally configured as a first case body. The first case body may be made of any appropriate material. Examples of materials for the first case body include metal materials such as stainless steel, plated steel plate, and aluminum. Stainless steel is preferred as the material for the first case body.

[0031] In one embodiment, the first case 3 further includes a contact portion 33. The contact portion 33 is typically fixed to the end (free end) of the first side wall 32 opposite the first upper wall 31. In the illustrated example, the contact portion 33 is attached to the inner surface of the free end of the first side wall 32. The contact portion 33 extends in the thickness direction of the stage 1. One end of the contact portion 33 protrudes from the free end edge of the first side wall 32 toward the stage 1. The contact portion 33 contacts the stage 1 when the moving unit 6 is in the closed position. The contact portion 33 is typically made of an elastic material. Therefore, damage to the stage can be prevented when the moving unit moves from the open position to the closed position. Examples of elastic materials include heat-resistant rubbers such as silicone rubber and fluorine-based rubber. When the moving unit 6 is in the open position, the contact portion 33 is spaced apart from the stage 1 (see FIG. 3 ).

[0032] In one embodiment, the first case 3 supports the above-described partition plate 10. The partition plate 10 is typically supported by the first side wall 32. In the illustrated example, the partition plate 10 is located on the opposite side of the contact portion 33 from the stage 1. The partition plate 10 is disposed approximately parallel to the stage 1.

[0033] In one embodiment, the partition plate 10 includes a metal plate 101 and an insulating layer 102. The metal plate 101 is made of any appropriate metal material. Examples of the metal material include aluminum, plated steel, and stainless steel. Among the metal materials, aluminum is preferred. The insulating layer 102 is provided on the surface (underside) of the metal plate 101 opposite the heater 5. During crystallization of the crystallization target, the metal plate may be heated by the heater. Therefore, if a user's hand comes into contact with the metal plate when removing the container, the user may be burned. In this regard, in one embodiment, the partition plate includes an insulating layer, which reduces the possibility of the user being burned when removing the container. The insulating layer 102 may be provided on the entire underside of the metal plate 101 or only on a portion of the underside of the metal plate 101. In the illustrated example, the insulating layer 102 is provided on the entire underside of the metal plate 101. The insulating layer 102 is typically made of an insulating material. The heat insulating material may be, for example, the heat-resistant rubber described above.

[0034] In one embodiment, when the moving unit 6 is in the closed position, the first upper wall 31, the first side wall 32, and the partition plate 10 define the first space S1, and the partition plate 10, the contact portion 33, and the stage 1 define the second space S2. The partition plate 10 typically has a plurality of openings 10a. Each of the plurality of openings 10a communicates with the first space S1 and the second space S2. The plurality of openings 10a correspond to a plurality of containers 2. Each of the plurality of openings 10a is arranged to overlap with a container 2 when viewed from the thickness direction of the stage 1. Therefore, even if the crystallization apparatus includes a partition plate, the organic solvent of the solution contained in the container can be appropriately evaporated by the heater.

[0035] 1, in one embodiment, the crystallization apparatus 100 includes a second case 4. In the illustrated example, one second case 4 is disposed inside one first case 3. The second case 4 is disposed so as to overlap the plurality of containers 2 collectively when viewed from the thickness direction of the stage 1.

[0036] 2 , a cross section of the second case 4 cut in the thickness direction of the stage 1 typically has a substantially U-shape that opens toward the stage 1. The second case 4 includes a second upper wall 41 and a second side wall 42.

[0037] The second upper wall 41 is disposed at a distance from the first upper wall 31 in the thickness direction of the first upper wall 31. In the illustrated example, the second upper wall 41 is disposed substantially parallel to the first upper wall 31. The second upper wall 41 has any appropriate shape. For example, the shape of the second upper wall 41 as viewed in the thickness direction is a rectangle. In one embodiment, the second upper wall 41 has the above-mentioned discharge opening 4a. The discharge opening 4a is disposed at any appropriate position on the second upper wall 41.

[0038] The second side wall 42 extends from the peripheral edge of the lower surface of the second upper wall 41 toward the stage 1. In the illustrated example, the thickness direction of the second side wall 42 is perpendicular to the thickness direction of the second upper wall 41. The second side wall 42 is disposed at a distance from the first side wall 32 in the thickness direction of the first side wall 32. The second side wall 42 is disposed approximately parallel to the first side wall 32. The space between the first side wall 32 and the second side wall 42 communicates with the supply port 3 a and can function as a flow path for the inert gas supplied from the inert gas supply unit 8.

[0039] The second upper wall 41 and the second side wall 42 are typically integrally configured as a second case body. The second case body may be made of any appropriate material. Examples of materials for the second case body include metal materials such as stainless steel, plated steel plate, and aluminum. Stainless steel is a preferred material for the second case body.

[0040] In one embodiment, the second case 4 is connected to the first case 3 via a connecting portion 61. This fixes the second case 4 to the first case 3. The connecting portion 61 is located inside the first case 3. In the illustrated example, the connecting portion 61 connects the first upper wall 31 of the first case 3 and the second upper wall 41 of the second case 4.

[0041] In one embodiment, the second case 4 supports a heat shield 11. The heat shield 11 is located between the first side wall 32 and the heater 5. This can prevent the first side wall of the first case from being heated by the heater.

[0042] The heat shield 11 is typically supported by the second side wall 42. In the illustrated example, the heat shield 11 is fixed to the end of the second side wall 42 opposite the second upper wall 41. The heat shield 11 extends in the same direction as the second side wall 42. The heat shield 11 is disposed at a distance from the first side wall 32 in the thickness direction of the first side wall 32. The heat shield 11 is disposed approximately parallel to the first side wall 32. The space between the first side wall 32 and the heat shield 11 can function as a flow path for the inert gas supplied from the inert gas supply unit 8. In one embodiment, the end (free end) of the heat shield 11 opposite the second side wall 42 is positioned at a small distance from the partition plate 10 when the moving unit 6 is in the closed position. The distance between the free end of the heat shield 11 and the partition plate 10 is, for example, 5 mm to 20 mm.

[0043] The heat shield 11 is made of any appropriate material. Examples of materials for the heat shield include the metal materials described above, preferably plated steel plates, and more preferably gold-plated steel plates. As described in detail below, the heater may be configured as a selective radiation plate capable of emitting infrared rays. In this case, if the heat shield is made of a metal material, it can function as a reflector capable of reflecting infrared rays. Therefore, it can reflect infrared rays emitted from the infrared heater toward the solution contained in the container and can prevent infrared rays from being irradiated onto the first side wall.

[0044] B-5. Heater The heater 5 is supported by the second case 4. Typically, multiple heaters 5 are supported by one second case 4. That is, as shown in FIG. 1 , the crystallization apparatus 100 includes multiple heaters 5. Typically, the number of heaters 5 arranged in one first case 3 is the same as the number of containers 2 that overlap with the first case 3 when viewed from the thickness direction of the stage 1. The number of heaters 5 arranged in one first case 3 is, for example, 1 to 18, preferably 2 to 8, and more preferably 6.

[0045] 2 , in one embodiment, the heater 5 is supported by the second case 4 via a support portion 62. The support portion 62 is located inside the second case 4. The support portion 62 includes a support plate 621 and a shaft 622.

[0046] The support plate 621 is disposed between the second upper wall 41 and the container 2. In the illustrated example, the support plate 621 is disposed substantially parallel to the second upper wall 41. The peripheral edge of the support plate 621 is positioned with a small gap between it and the second side wall 42. A heater 5 is fixed to the lower surface of the support plate 621.

[0047] The shaft 622 typically connects the support plate 621 and the second upper wall 41. In this way, the support plate 621 is fixed to the second upper wall 41 via the shaft 622.

[0048] The support portion 62 may further include a rectifying plate 623. The rectifying plate 623 is located between the support plate 621 and the second upper wall 41. The rectifying plate 623 is located at a distance from the second upper wall 41. The rectifying plate 623 faces the exhaust port 4a. This allows the exhaust gas to be rectified and smoothly discharged from the exhaust port. In the illustrated example, the rectifying plate 623 is disposed approximately parallel to the second upper wall 41. An end of the rectifying plate 623 is located at a small distance from the second side wall 42. The rectifying plate 623 is fixed to the shaft 622.

[0049] The support portion 62 may be made of any suitable material, such as the material of the first case described above.

[0050] In one embodiment, the heater 5 is a selective radiation plate 51 capable of emitting infrared rays. When the heater is a selective radiation plate, the crystal shape of the precipitated crystallization object can be precisely controlled. The selective radiation plate 51 can emit infrared rays with a controlled wavelength, more specifically, infrared rays with a controlled wavelength at which the normal emissivity is maximized (hereinafter referred to as the peak wavelength).

[0051] In one embodiment, the selective radiation plate 51 is capable of emitting infrared rays having a maximum peak with a normal emissivity of 0.80 or greater. The maximum peak can be determined, for example, from an infrared emissivity curve obtained by plotting the wavelength of infrared rays versus normal emissivity. The peak wavelength of the maximum peak is, for example, within a range of 2.0 μm to 10 μm, and for example, within a range of 3.0 μm to 7.0 μm. The normal emissivity of the maximum peak is preferably 0.85 or greater, more preferably 0.90 or greater. On the other hand, the upper limit of the normal emissivity of the maximum peak is typically 1.0. The normal emissivity of infrared rays is calculated, for example, by applying Kirchhoff's law with transmittance set to 0. The normal reflectivity is measured, for example, using a Fourier transform infrared spectrometer (FT-IR) equipped with an integrating sphere: (Normal emissivity) = 1 - (Normal reflectivity) (1) The half-width of the maximum peak is, for example, 1.5 μm or less, and preferably 1.0 μm or less. On the other hand, the lower limit of the half width of the maximum peak is typically 0 μm.

[0052] As shown in FIG. 6 , the selective radiation plate 51 includes a dielectric layer 52, a plurality of first conductors 53, a second conductor 54, a support substrate 55, and a heating unit 57. The plurality of first conductors 53 are disposed on the dielectric layer 52. The plurality of first conductors 53 are arranged at intervals to form a periodic structure. The second conductor 54 is disposed on the opposite side of the dielectric layer 52 from the first conductors 53. The plurality of first conductors 53, the dielectric layer 52, and the second conductors 54 form a metamaterial structure 58. The metamaterial structure 58 is typically configured to generate a resonance phenomenon due to magnetic polaritons. When this resonance phenomenon occurs, a strong electromagnetic field confinement effect can occur within the dielectric layer 52 between the plurality of first conductors 53 and the second conductors 54. As a result, portions of the dielectric layer 52 sandwiched between the first conductors 53 and the second conductors 54 function as infrared radiation sources. Then, infrared rays with controlled peak wavelength are emitted from a portion of the surface of the dielectric layer 52 where the multiple first conductor portions 53 are not provided (hereinafter referred to as the radiation surface 51a), around the multiple first conductor portions 53.

[0053] B-5-1. Dielectric Layer The dielectric layer 52 is disposed between a plurality of first conductor sections 53 and second conductor sections 54. In the illustrated example, the dielectric layer 52 is in contact with each of the first conductor sections 53 and the second conductor sections 54. The material constituting the dielectric layer 52 may be any suitable inorganic oxide capable of forming a metamaterial structure. Examples of inorganic oxides include silica (SiO ２ ), alumina (Al ２ O ３ ), and preferably alumina. The inorganic oxides can be used alone or in combination. The thickness of the dielectric layer 52 is, for example, 30 nm to 300 nm, and preferably 150 nm to 210 nm.

[0054] B-5-2. Multiple First Conductors The multiple first conductors 53 are arranged at equal intervals on the dielectric layer 52 to form a periodic structure. More specifically, rows of multiple first conductors 53 arranged at equal intervals in the first plane direction of the dielectric layer 52 are arranged in parallel at equal intervals in the second plane direction perpendicular to the first plane direction.

[0055] Each of the first conductors 53 may have a single-layer structure or a multilayer structure in which multiple metal films are stacked. The first conductors 53 are made of any appropriate metal material. Examples of metal materials that may be used for the first conductors 53 include chromium (Cr), nickel (Ni), titanium (Ti), gold (Au), silver (Ag), copper (Cu), ruthenium (Ru), palladium (Pd), iron (Fe), aluminum (Al), and alloys thereof.

[0056] In the planar direction (first planar direction or second planar direction) of the dielectric layer, the period of the periodic structure formed by the plurality of first conductors 53 is, for example, 500 nm to 8000 nm, and preferably 1000 nm to 4000 nm. The thickness of the first conductors 53 is, for example, 30 nm to 200 nm, and preferably 50 nm to 100 nm.

[0057] B-5-3. Second Conductor Portion The second conductor portion 54 is typically provided on the surface of the dielectric layer 52 opposite to the first conductor portion 53. The second conductor portion 54 may be provided over the entire surface of the dielectric layer 52 opposite to the first conductor portion 53, or may be provided over only a portion of that surface. In the illustrated example, the second conductor portion 54 is provided in a layer form over the entire surface of the dielectric layer 52 opposite to the first conductor portion 53.

[0058] The second conductor 54 may have a single-layer structure or a laminated structure in which multiple metal films are stacked. The second conductor 54 is made of any appropriate metal material. Examples of metal materials that make up the second conductor 54 include the same metal materials that make up the first conductor 53. The thickness of the second conductor 54 is, for example, 30 nm to 500 nm, and preferably 50 nm to 300 nm.

[0059] B-5-4. Support Substrate The support substrate 55 is disposed on the opposite side of the second conductor portion 54 from the dielectric layer 52. The support substrate 55 can provide excellent mechanical strength to the selective radiation plate 51. Examples of materials that can be used to form the support substrate 55 include materials with excellent heat resistance. Specific examples include sapphire, silicon (Si), and quartz. The support substrate 55 may have a single-layer structure, or a layered structure in which multiple substrates are stacked. The thickness of the support substrate 55 is, for example, 100 μm to 1000 μm, or, for example, 50 μm to 700 μm.

[0060] B-5-5. Heating Unit The heating unit 57 can heat the metamaterial structure 58. In the metamaterial structure 58, the above-mentioned resonance phenomenon can occur due to heating by the heating unit 57. This allows the selective radiation plate to stably radiate the above-mentioned infrared rays. In the illustrated example, the heating unit 57 is in contact with the support substrate 55. Therefore, the heating unit can efficiently heat the metamaterial structure via the support substrate. The heating temperature of the heating unit 57 is, for example, 200°C to 800°C, preferably 400°C to 600°C. Any appropriate heat generating unit can be used as the heating unit 57. The heating unit 57 is typically configured as a planar heater. For example, a ceramic heater, preferably an AlN heater, can be used as the heating unit 57.

[0061] In one embodiment, a metal thin film 56 is provided on the surface of the heating unit 57 opposite the support substrate 55. This can achieve radiant heat insulation of the heating unit, allowing the power applied to the heating unit to be reduced. As a result, overheating of the selective radiation plate can be suppressed. The metal thin film 56 is typically a sputtered film. Examples of materials for the metal thin film 56 include the same metal materials as those constituting the first conductor 53, and gold (Au) is preferred. The thickness of the metal thin film 56 is, for example, 30 μm to 200 μm, and preferably 30 μm to 50 μm.

[0062] As shown in Fig. 5, the inert gas supply unit 8 is capable of supplying an inert gas into the first case 3. Examples of the inert gas include nitrogen, carbon dioxide, water vapor, argon, and a mixture thereof. Of the inert gases, nitrogen is preferred.

[0063] The inert gas supply unit 8 includes a supply line 81 and a storage tank 82. The supply line 81 is typically a pipe through which the inert gas can pass. An upstream end of the supply line 81 in the direction of passage of the inert gas is connected to the storage tank 82. A downstream end of the supply line 81 in the direction of passage of the inert gas is connected to the first upper wall 31 of the first case 3 so as to communicate with the supply port 3a (see FIG. 2 ). In the illustrated example, a valve 83 is provided in the supply line 81. The valve 83 is capable of opening and closing the supply line 81. The valve 83 may be capable of adjusting the opening degree of the supply line 81. This makes it possible to adjust the flow rate of the inert gas passing through the supply line. The storage tank 82 is typically capable of storing the inert gas described above. The storage tank 82 may have any appropriate configuration.

[0064] B-7. Exhaust Unit The exhaust unit 12 is capable of discharging exhaust gas from the second case 4. In one embodiment, the exhaust unit 12 includes an exhaust line 121 and an exhaust fan 122. The exhaust line 121 is typically a pipe through which exhaust gas can pass. The upstream end of the exhaust line 121 in the direction of passage of the exhaust gas is connected to the second upper wall 41 of the second case 4 so as to communicate with the exhaust port 4a (see FIG. 2). The downstream end of the exhaust line 121 in the direction of passage of the exhaust gas is connected to the exhaust fan 122. The exhaust fan 122 is typically capable of sending out exhaust gas. The exhaust fan 122 has any appropriate configuration. The exhaust gas sent out from the exhaust fan 122 is released into the atmosphere after, for example, purifying the evaporated organic solvent in a purification device (not shown).

[0065] In one embodiment, the exhaust unit 12 further includes the above-described flow path adjustment unit 129. In the illustrated example, the flow path adjustment unit 129 is provided in the exhaust line 121. The flow path adjustment unit 129 may have any appropriate configuration. An example of the flow path adjustment unit 129 is a valve that can adjust the opening of the exhaust line 121. This can adjust the flow rate of exhaust gas passing through the exhaust line.

[0066] In one embodiment, the exhaust unit 12 further includes a first branch line 123 and the above-described oxygen measuring device 125. The first branch line 123 is typically a pipe through which exhaust gas can pass. In the illustrated example, the upstream end of the first branch line 123 in the direction of passage of the exhaust gas is connected to a portion of the exhaust line 121 between the exhaust fan 122 and the flow path adjusting unit 129. The downstream end of the first branch line 123 in the direction of passage of the exhaust gas is connected to the oxygen measuring device 125. A valve 127 is provided in the first branch line 123. The valve 127 is capable of opening and closing the first branch line 123. The oxygen measuring device 125 has any appropriate configuration capable of measuring the oxygen concentration in the exhaust gas.

[0067] In one embodiment, the exhaust unit 12 further includes a second branch line 124 and the above-described HC measuring device 126. The second branch line 124 is typically a pipe through which exhaust gas can pass. In the illustrated example, the upstream end of the second branch line 124 in the direction of passage of the exhaust gas is connected to a portion of the exhaust line 121 between the exhaust fan 122 and the flow path adjusting unit 129. The downstream end of the second branch line 124 in the direction of passage of the exhaust gas is connected to the HC measuring device 126. In the illustrated example, a valve 128 is provided in the second branch line 124. The valve 128 is capable of opening and closing the second branch line 124. The HC measuring device 126 has any appropriate configuration capable of measuring the hydrocarbon concentration (i.e., the organic solvent concentration) in the exhaust gas.

[0068] B-8. Control Unit In the illustrated example, the control unit 9 is communicatively connected to each of the heater 5, the movement mechanism 7, the flow path adjustment unit 129, the oxygen measuring device 125, and the HC measuring device 126. The control unit 9 includes, for example, a central processing unit (CPU), a ROM, and a RAM. The control unit 9 may be electrically connected to each of the valves 83, 127, and 128.

[0069] C. Crystallization Method Next, one embodiment of a method for crystallizing a crystallization target using the crystallization apparatus 100 will be described with reference to Figures 2 to 5. The dimensions of the first case 3 in Figure 4 are 200 mm x 200 mm x 200 mm. As shown in Figure 3, first, a solution of the crystallization target is poured into multiple containers 2 placed on the stage 1 (pouring step). At this time, the moving unit 6 is positioned in the open position.

[0070] Next, with the moving unit 6 in the open position, inert gas is supplied into the first case 3 to replace the air inside the first case 3 with inert gas (replacement process). In one embodiment, the flow path adjustment unit 129 (see FIG. 5 ) is opened, and inert gas is supplied from the inert gas supply unit 8 to the first case 3. In the replacement process, the flow rate of the inert gas passing through the supply port 3a is, for example, 10 L / min to 30 L / min, preferably 20 L / min. In the illustrated example, the inert gas supplied to the first case 3 passes between the first side wall 32 and the second side wall 42, and between the first side wall 32 and the heat shield 11, in that order, toward the partition plate 10. Next, upon reaching the partition plate 10, the inert gas makes a U-turn and passes between the free end of the heat shield 11 and the partition plate 10. The inert gas then passes around the heater 5, passes through the gap between the end of the straightening plate 623 and the second side wall 42, and is discharged from the exhaust port 4a. The exhaust gas discharged from the exhaust port 4a typically contains an inert gas and air. In the replacement step, the flow rate of the exhaust gas passing through the exhaust port 4a is, for example, 10 L / min to 25 L / min, and preferably 16 L / min to 18 L / min.

[0071] Next, the heater 5 is activated while supplying inert gas into the first case 3 through the supply port 3a (activation step). As shown in Fig. 5 , in one embodiment, in the activation step, first, the valve 127 is opened and exhaust gas from the second case 4 is supplied to the oxygen measuring device 125. The oxygen measuring device 125 measures the oxygen concentration in the supplied exhaust gas and transmits the measurement result to the control unit 9. When the oxygen concentration in the exhaust gas received from the oxygen measuring device 125 is below a predetermined threshold (e.g., less than 5% by volume), the control unit 9 transmits an activation signal to the heater 5 to activate the heater 5. Thereafter, the valve 127 is changed from the open state to the closed state.

[0072] As shown in FIG. 3 , in one embodiment, when the heater 5 is driven (including startup), the flow rate of the inert gas passing through the supply port 3a is maintained within the above range, while the flow rate of the exhaust gas passing through the exhaust port 4a is reduced. This allows the inert gas to remain in the first case, stably reducing the oxygen concentration around the heater. In particular, when the crystallization apparatus is equipped with a partition plate, the oxygen concentration around the heater can be reduced to less than 5% by volume. In the illustrated example, the flow rate of the exhaust gas is adjusted by the flow path adjustment unit 129 (see FIG. 5 ). In this case, the flow rate of the exhaust gas passing through the exhaust port 4a is smaller than the flow rate of the inert gas passing through the supply port 3a. The difference between the flow rate of the inert gas and the flow rate of the exhaust gas (inert gas flow rate - exhaust gas flow rate) is, for example, 1 L / min or more, preferably 2 L / min or more. The flow rate of the exhaust gas passing through the exhaust port 4a is, for example, 20 L / min or less, preferably 18 L / min or less. Such a reduction in the flow rate of the exhaust gas can further reduce the oxygen concentration around the heater.

[0073] 2, the moving unit 6 is moved from the open position to the closed position (moving step). In one embodiment, the control unit 9 sends a movement signal for the moving unit 6 to the moving mechanism 7. This causes the moving mechanism 7 to move the moving unit 6 from the open position to the closed position.

[0074] Next, with the moving unit 6 in the closed position, the heater 5 evaporates the organic solvent from the solution contained in the container 2, thereby crystallizing the object to be crystallized (crystallization step). Note that, in the crystallization step, the supply of the inert gas and the discharge of the exhaust gas are maintained as described above. In the crystallization step, since the organic solvent evaporates from the solution, the exhaust gas typically further contains the organic solvent in a gaseous state.

[0075] As shown in FIG. 5 , in one embodiment, during the crystallization process, the valve 128 is opened and exhaust gas is supplied to the HC measuring device 126. The HC measuring device 126 measures the hydrocarbon concentration in the supplied exhaust gas and transmits the measurement result to the control unit 9. When the hydrocarbon concentration in the exhaust gas received from the HC measuring device 126 is below a predetermined threshold, for example, below 25% LEL (lower explosive limit), the control unit 9 determines that crystallization of the crystallization target is complete and transmits a movement signal for the moving unit 6 to the moving mechanism 7, causing the moving unit 6 to move from the closed position to the open position. The valve 128 is then changed from the open state to the closed state. This allows the multiple containers 2 in which crystals of the crystallization target have precipitated to be smoothly removed.

[0076] Furthermore, the crystallization apparatus 100 is typically capable of continuously performing the above-described crystallization method. When continuously performing the crystallization method, the multiple containers 2 containing precipitated crystals are replaced with multiple containers 2 containing new solution, with the moving unit 6 positioned in the open position. In this case, when replacing the containers, the heater is kept in an operating state, and the supply of inert gas and the discharge of exhaust gas are maintained as described above. This allows the oxygen concentration around the heater to be sufficiently reduced even when the moving unit is positioned in the open position. Therefore, the crystallization method can be performed continuously without cooling the heater when replacing the containers. As a result, the time required to crystallize the crystallization target can be shortened while ensuring sufficient safety.

[0077] The crystallization apparatus according to the embodiment of the present invention can be suitably used, for example, to search for compounds that exhibit crystalline polymorphism and to search for crystallization conditions for the compounds.

[0078] REFERENCE SIGNS LIST 1 stage 2 container 3 first case 3a supply port 4 second case 4a exhaust port 5 heater 6 moving unit 8 inert gas supply section 9 control section 10 partition plate 11 heat shield plate 12 exhaust section 125 oxygen measuring device 126 HC measuring device 129 flow path adjusting section

Claims

1. A crystallization apparatus comprising: a stage; a plurality of containers arranged on the stage, the plurality of containers being capable of receiving a solution containing a solute of a material to be crystallized and an organic solvent; a first case arranged to overlap the plurality of containers collectively when viewed in the thickness direction of the stage; a second case located inside the first case; a heater supported by the second case; and an inert gas supply unit configured to supply an inert gas into the first case, wherein the first case has a supply port through which inert gas is supplied from the inert gas supply unit, and the second case has an exhaust port through which exhaust gas containing the inert gas is discharged.

2. The crystallization apparatus of claim 1, wherein the first case, the second case and the heater form a moving unit that is movable relative to the stage, and the moving unit is movable between a closed position in which the first case, together with the stage, collectively covers the multiple containers, and an open position in which the first case is positioned away from the stage.

3. The crystallization apparatus of claim 2, further comprising: a flow rate adjusting unit capable of adjusting the flow rate of the exhaust gas discharged from the exhaust port; and a control unit capable of controlling the flow rate adjusting unit so that the flow rate of the exhaust gas is equal to or lower than a predetermined value.

4. The crystallization apparatus described in claim 2, further comprising: an HC measuring device capable of measuring the hydrocarbon concentration in the exhaust gas discharged from the exhaust port; and a control unit capable of controlling the movement of the moving unit between the closed position and the open position based on the measurement results of the HC measuring device.

5. The crystallization apparatus according to claim 4, further comprising an oxygen measuring device capable of measuring the oxygen concentration in the exhaust gas, and the control unit is capable of controlling the start-up of the heater based on the measurement results of the oxygen measuring device.

6. The crystallization apparatus of claim 1, further comprising a partition plate positioned between the heater and the plurality of containers, the partition plate separating a first space in which the heater is disposed from a second space in which the plurality of containers are disposed.

7. The crystallization apparatus of claim 1, wherein the first case comprises a first upper wall located on the opposite side of the second case from the stage, and a first side wall extending from a peripheral portion of the first upper wall toward the stage, and the crystallization apparatus further comprises a heat shield located between the first side wall and the heater.

8. The crystallization apparatus according to claim 1, wherein the inert gas is nitrogen, carbon dioxide, water vapor, argon, or a mixture thereof.

9. The crystallization apparatus of claim 1, wherein the stage is equipped with a Peltier element capable of adjusting the temperature of the stage.

10. The crystallization apparatus according to claim 1, wherein said heater is a selective radiation plate capable of emitting infrared rays with a controlled wavelength.

11. A method for crystallizing an object to be crystallized using a crystallization apparatus as defined in any one of claims 1 to 10, comprising driving the heater while supplying the inert gas into the first case through the supply port.

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