Method for acquiring phase diagram data and method for creating phase diagrams

Abstract

The present invention provides a method for acquiring phase diagram data that can acquire phase diagram data including both dissolution data for dissolution curves and precipitation data for precipitation curves at high throughput, and a method for creating a phase diagram that includes a phase diagram creation step of creating a phase diagram from the phase diagram data acquired using the method for acquiring phase diagram data. [Solution] A method for acquiring phase diagram data is provided, comprising a preparation step and a data acquisition step, wherein the preparation step includes at least a first coating step, in which a non-volatile solution in which the solute is a crystalline material to be acquired for data acquisition and the solvent is a non-volatile liquid, or a volatile solution in which the solute is the crystalline material, is coated onto a substrate as droplets using an inkjet method, and the data acquisition step comprises a dissolution data acquisition step for acquiring dissolution data from a data acquisition target for dissolution data acquisition, and a precipitation data acquisition step for acquiring precipitation data from a data acquisition target.

Description

[Technical Field]

[0001] The present invention relates to a method for acquiring data for phase diagrams and a method for creating phase diagrams. [Background technology]

[0002] Phase diagrams are sometimes used in materials development utilizing crystal growth technology, such as improving the physical properties of metals and inorganic / organic semiconductors, and in the drug discovery field for initial screening of protein and small molecule drugs, and for controlling various properties. Crystal growth technology is broadly classified into dry processes and solution (wet) processes. In particular, in the development of organic semiconductors, drug discovery, and other organic materials, solution processes are usually used from the standpoint of sublimation and decomposition at low temperatures and in air, as well as cost.

[0003] Generally, phase diagrams used in crystal growth in solution processes include at least one of a dissolution curve (solubility curve) and a precipitation curve. The dissolution curve is the boundary between the dissolving phase, where crystal growth due to supersaturation is impossible, and the metastable phase, where crystal growth due to supersaturation is possible but nucleation does not occur. The precipitation curve is the boundary between the metastable phase and the precipitated phase, where crystal growth due to supersaturation is possible and nucleation can occur. By utilizing such phase diagrams to appropriately control the number of nuclei and the degree of supersaturation, it becomes possible to obtain crystals with desired qualities, sizes, shapes, etc.

[0004] Patent Document 1 discloses an example of creating a glucose isomerase crystallization phase diagram including a precipitation curve. Patent Document 2 discloses that a crystallization phase diagram including a solubility curve can be created by continuously changing the solution concentration of the biomolecule to be crystallized and the solution concentration of the crystallizing agent. [Prior art documents] [Patent Documents]

[0005] [Patent Document 1] Japanese Patent Publication No. 2022-087076 [Patent Document 2] Japanese Patent Application Laid-Open No. 2004-026528

Summary of the Invention

Problems to be Solved by the Invention

[0006] However, when using the conventional phase diagram creation method, it tends to take more than one month to obtain phase diagram data (dissolution data or precipitation data) corresponding to a single point on the phase boundary such as a dissolution curve or a precipitation curve. In particular, there is a problem that it takes a very long time to obtain a plurality of phase diagram data to complete the phase diagram.

[0007] In addition, in the conventional phase diagram creation method, a large amount of (for example, gram-scale) sample is required for a single measurement. Therefore, especially when using rare samples, it is difficult to obtain a sufficient number of phase diagram data for creating a phase diagram due to cost constraints.

[0008] The present invention has been made in view of such circumstances, and an object thereof is to provide a method for obtaining phase diagram data capable of obtaining phase diagram data including dissolution data and precipitation data with high throughput. Another object of the present invention is to provide a method for creating a phase diagram including a phase diagram creation step of creating a phase diagram from the phase diagram data obtained by using the method for obtaining the phase diagram data.

Means for Solving the Problems

[0009] As a result of intensive studies by the present inventors, it has been found that the above problems can be solved by applying an inkjet method to apply a non-volatile solution in which the solute is a crystalline material to be the data acquisition target and the solvent is a non-volatile liquid, or a volatile solution in which the solute is the crystalline material, as droplets onto a substrate, leading to the completion of the present invention.

[0010] Hereinafter, various embodiments of the present invention will be exemplified. The embodiments shown below can be combined with each other. [1] A method for acquiring phase diagram data, comprising a preparation step and a data acquisition step, wherein the preparation step comprises at least a first coating step, the first coating step comprising coating a non-volatile solution in which the solute is a crystalline material to be acquired for data acquisition and the solvent is a non-volatile liquid, or a volatile solution in which the solute is the crystalline material, as droplets on a substrate using an inkjet method, and the data acquisition step comprising a dissolution data acquisition step for acquiring dissolution data from a data acquisition target for dissolution, and a precipitation data acquisition step for acquiring precipitation data from a data acquisition target. A method for acquiring phase diagram data as described in [2][1], wherein the preparation step further includes a deposition step and a second coating step, wherein in the first coating step, the volatile solution is applied to a substrate as droplets using an inkjet method; in the deposition step, the crystalline material is deposited on the substrate by drying the droplets of the volatile solution; in the second coating step, the target for dissolution data acquisition is prepared by applying a non-volatile liquid as droplets to cover the crystalline material deposited on the substrate using an inkjet method; and in the dissolution data acquisition step, the temperature of the target for dissolution data acquisition is raised. A method for acquiring phase diagram data, comprising: acquiring dissolution data of the crystalline material by, or by adding a non-volatile liquid to the target for dissolution data acquisition using an inkjet method; and in the precipitation data acquisition step, using the target for precipitation data acquisition in which the crystalline material has been completely dissolved after the dissolution data acquisition step, acquiring precipitation data of the crystalline material by, or by lowering the temperature of the target for precipitation data acquisition, or by adding the volatile solution to the target for precipitation data acquisition using an inkjet method and further volatilizing the volatile solvent contained in the volatile solution, one or more times. A method for acquiring phase diagram data as described in [3][1], wherein in the first coating step, the non-volatile solution, in which the solvent is a non-volatile liquid, is applied to a substrate as droplets using an inkjet method to produce the precipitate data acquisition target; in the precipitate data acquisition step, precipitate data of the crystalline material is acquired by lowering the temperature of the precipitate data acquisition target, or by adding the volatile solution to the precipitate data acquisition target using an inkjet method and drying the volatile solvent contained in the volatile solution, one or more times; and in the dissolution data acquisition step, dissolution data of the crystalline material is acquired by using the dissolution data acquisition target containing the precipitate of the crystalline material obtained through the precipitate data acquisition step, by raising the temperature of the dissolution data acquisition target, or by adding a non-volatile liquid to the dissolution data acquisition target using an inkjet method. A method for acquiring phase diagram data as described in any one of [4][1] to [3], wherein the volume of each droplet of the non-volatile solution or volatile solution applied in the first coating step is 10 -6 A method for acquiring phase diagram data in volumes between μL and 1 μL. A method for acquiring phase diagram data as described in [5][1], [2], or [4], wherein the volume of each droplet of the nonvolatile liquid applied in the second coating step is 10 -6 A method for acquiring phase diagram data in volumes between μL and 1 μL. A method for acquiring phase diagram data as described in any one of [6][1] to [5], wherein in the data acquisition step, the dissolution data or the precipitation data is acquired by simultaneously analyzing a plurality of the dissolution data acquisition targets or the precipitation data acquisition targets within the same field of view using microscopic analysis. A method for acquiring phase diagram data as described in any one of [7][1] to [6], wherein the density of droplets of the volatile solution or non-volatile solution present on the substrate coated in the first step is 10 2 ~10 8 pieces / cm 2 This is a method for acquiring data for phase diagrams. A method for acquiring phase diagram data as described in any one of [8][1] to [7], wherein the nonvolatile liquid used in the first coating step, the second coating step, the dissolution data acquisition step, and / or the precipitation data acquisition step is an ionic liquid composed of cations and anions, wherein the cation comprises at least one selected from the group consisting of imidazole, pyridinium, quaternary ammonium, pyrodinium, phosnium, sulfonium, and choline, and the anion comprises at least one selected from the group consisting of halide ions, tetrafluoroborate, hexafluorophosphate, persulfuric acid, perboric acid, iodic acid, dicyanamide, bis(fluoromethylsulfonyl)amide, bis(trifluoromethylsulfonyl)amide, and trifluoromethanesulfonic acid triflate. A method for acquiring phase diagram data as described in any one of [9][1] to [8], wherein in the dissolution data acquisition step, the phase change of the crystalline material is analyzed while the dissolution data acquisition target is heated at a heating rate of 0.001 to 1°C / min. A method for acquiring phase diagram data as described in any one of

[10] [1] to [9], wherein the viscosity of the volatile solution or non-volatile solution applied in the first coating step is 0.5 to 200 mPa·s, and the surface tension of the volatile solution or non-volatile solution applied in the first coating step is 20 to 73 mN / m. A method for acquiring phase diagram data as described in any one of

[11] [1], [2], [4] to

[10] , wherein the viscosity of the nonvolatile liquid applied in the second coating step is 0.5 to 200 mPa·s, and the surface tension of the nonvolatile liquid applied in the second coating step is 20 to 73 mN / m. A method for creating a phase diagram, which includes a phase diagram creation step of creating a phase diagram from phase diagram data obtained using the method for obtaining phase diagram data described in any one of

[12] [1] to

[11] . [Brief explanation of the drawing]

[0011] [Figure 1]Figure 1 is a schematic diagram of a binary phase diagram that includes dissolution and precipitation curves, with solute concentration and temperature as constituent axes. [Figure 2] Figure 2 shows the relationship between droplet flight velocity and pulse width when dispensing droplets of an orthodichlorobenzene solution of anthracene with a concentration of 100 mM. [Figure 3] Figure 3 shows the relationship between droplet flight velocity and pulse width when dispensing droplets of an ionic liquid (1-octyl-4-methylpyridinium bis(fluorosulfonyl)amide) as a non-volatile liquid. [Figure 4] Figure 4 shows the relationship between the flight velocity and volume of a droplet of an orthodichlorobenzene solution of anthracene with a concentration of 100 mM and the applied voltage. [Figure 5] Figure 5 shows the relationship between the flight velocity and volume of a droplet and the applied voltage when an ionic liquid (1-octyl-4-methylpyridinium bis(fluorosulfonyl)amide) is dispensed as a non-volatile liquid. [Figure 6] Figure 6 shows the relationship between the dissolution temperature and the heating rate in the present invention and the conventional method. [Figure 7] Figure 7 is a binary phase diagram of an orthodichlorobenzene solution of anthracene, including a dissolution curve created by plotting dissolution data obtained by the phase diagram data acquisition method according to the present invention and by a conventional method, with the heating rate set to 0.20°C / min, and connecting each plotted point with a line segment. [Figure 8A] Figure 8A shows bright-field images at 25°C of nine dissolution data acquisition targets. [Figure 8B] Figure 8B shows crossed nicol images at 25°C for nine dissolution data acquisition targets. [Figure 9A] Figure 9A shows bright-field images of nine dissolution data subjects at 55°C. The numbers shown below each dissolution data subject represent the dissolution temperature of that subject. [Figure 9B] Figure 9B shows crossed nicol images at 55°C for nine dissolution data acquisition targets. [Modes for carrying out the invention]

[0012] Embodiments of the present invention will be described below. The various features shown in the embodiments below can be combined with each other. Furthermore, each feature can stand alone as an independent invention.

[0013] 1. Phase diagram Generally, a phase diagram refers to a representation of the relationship between the phases of a substance or system and its thermodynamic state variables in an equilibrium state, and is also called an (equilibrium) phase diagram. Different types of phase diagrams are used depending on the technical field. For example, the temperature-pressure binary phase diagram is well known to represent the three states of matter.

[0014] On the other hand, to crystallize proteins and other organic materials, a precipitating agent, which is a reagent that promotes the aggregation and precipitation of solutes, is sometimes added to the solution to accelerate crystallization. In such cases, for example, solute concentration and precipitating agent concentration are selected as constituent axes of the binary phase diagram, and dissolution curves and precipitation curves may be shown in the phase diagram as phase boundaries that distinguish the phase in which the solute is dissolved (dissolved phase), the phase in which the solute precipitates (precipitated phase), and the metastable phase between these two. In other words, in the crystallization of proteins and other organic materials, a binary phase diagram including dissolution curves and precipitation curves, which are the boundaries of each phase, is sometimes used. If a precipitating agent is not used, other parameters such as temperature can be adopted as constituent axes of the binary phase diagram instead of the precipitating agent concentration. A schematic diagram of a binary phase diagram with solute concentration and temperature as constituent axes is shown in Figure 1.

[0015] The phase diagram created by the method for acquiring phase diagram data and creating a phase diagram according to the present invention can be a binary phase diagram including a dissolution curve and a precipitation curve. Furthermore, the phase diagram created by the method for acquiring phase diagram data and creating a phase diagram according to the present invention may be a ternary phase diagram including a dissolution surface and a precipitation surface, or a multi-component phase diagram including multiple data (dissolution data and precipitation data) that constitute the phase boundary related to dissolution and precipitation.

[0016] The phase diagram created by the method for acquiring phase diagram data and creating a phase diagram according to the present invention preferably uses solute concentration and temperature as constituent axes. Such a phase diagram is particularly useful for the development of various organic materials in solution processes. When a precipitating agent is used, the phase diagram created by the method for acquiring phase diagram data and creating a phase diagram according to the present invention can also be a binary phase diagram in which the precipitating agent concentration is used as a constituent axis instead of solute concentration or temperature. Furthermore, a ternary phase diagram can also be created in which the precipitating agent concentration is used as a third axis in addition to solute concentration and temperature.

[0017] The phase diagram created by the method for acquiring phase diagram data and creating a phase diagram according to the present invention can also be an n-component phase diagram if there are n parameters (n≧4, natural number) that can be adopted as constituent axes. Although an n-component phase diagram cannot necessarily be illustrated in real space, the dissolution data and precipitation data corresponding to each point that constitutes the phase boundary related to dissolution and precipitation (for example, each point on the dissolution-precipitation curve or dissolution-precipitation surface) can be recorded as a high-dimensional tensor on any recording medium. For this reason, the n-component phase diagram can be made into an (nN)-component phase diagram (3≧n-N≧2) by fixing N parameter values ​​out of n depending on the purpose of use, thereby making it possible to illustrate and use it in real space.

[0018] 2. Data for phase diagram In the present invention, one phase diagram data is one dissolution data and / or one precipitation data. The dissolution data corresponds to a specific point on the phase boundary related to dissolution (e.g., dissolution curve), and the precipitation data corresponds to a specific point on the phase boundary related to precipitation (e.g., precipitation curve).

[0019] Specifically, if the phase diagram to be created is a binary phase diagram with solute concentration C1 and temperature T as constituent axes, then one dissolution / precipitation data point must correspond to at least the data point p on the dissolution / precipitation curve (C1). 1p ,T pIt includes. For example, when the phase diagram to be created is a ternary phase diagram with the solute concentration C1, the precipitant concentration C2, and the temperature T as the constituent axes, one dissolution data / precipitation data includes at least the data (C 1p , C 2p , T p ) corresponding to the point p on the dissolution surface / precipitation surface. Similarly, even when there are n parameters that can be adopted as the constituent axes of the phase diagram, one dissolution data / precipitation data includes the data corresponding to one point on the phase boundary related to dissolution / precipitation.

[0020] One dissolution data / precipitation data may include only the data corresponding to one point on the phase boundary related to dissolution / precipitation, or may include other data. For example, when the phase diagram to be created is a binary phase diagram with the solute concentration C1 and the temperature T as the constituent axes, one dissolution data / precipitation data can be (C 1p , T p ) corresponding to one point p on the phase boundary as described above, and can also be (C 1p , T p , X) including an additional parameter X. Here, X is not particularly limited, but can be arbitrarily set, for example, as the measurement date and time t, etc. Also, one dissolution data / precipitation data may include a plurality of additional parameters, such as (C 1p , T p , X1, X2, ···).

[0021] A phase diagram including the phase boundary related to dissolution (for example, the dissolution curve) and the phase boundary related to precipitation (for example, the precipitation curve) can be created based on a plurality of phase diagram data obtained by using the method for obtaining phase diagram data according to the present invention. The details of the method for creating the phase diagram will be described later in "4. Method for Creating Phase Diagram".

[0022] 3. Method for Obtaining Phase Diagram Data The method for obtaining phase diagram data according to the present invention includes a preparation step and a data acquisition step. The data acquisition step includes a dissolution data acquisition step and a precipitation data acquisition step.

[0023] The preparation step is a step of preparing the object to be used for dissolution data acquisition or the object to be used for precipitation data acquisition, and includes at least a first coating step, which is the first coating step. The object to be used for dissolution data acquisition and the object to be used for precipitation data acquisition are minute droplets of a solution in which the solute is a crystalline material that is the object to be used for phase diagram data acquisition.

[0024] If the first data to be acquired in the data acquisition process is dissolved data, the target for dissolution data acquisition is prepared in the preparation process. If the first data to be acquired in the data acquisition process is precipitated data, the target for precipitated data acquisition is prepared in the preparation process.

[0025] The following describes in detail each step included in the method for acquiring phase diagram data according to the present invention, divided into "when preparing the target for precipitation data acquisition in the preparation step" and "when preparing the target for dissolution data acquisition in the preparation step." While the following description focuses on acquiring binary phase diagram data with solute concentration and temperature as constituent axes, the present invention is not limited to this.

[0026] 3.1. When preparing the target for sedimentation data acquisition in the preparation process. <Preparation process> (1st coating process) When preparing the target for precipitation data acquisition in the preparation step, the first coating step involves coating the substrate with a non-volatile solution, where the solute is the crystalline material for which phase diagram data is to be acquired and the solvent is a non-volatile liquid, as droplets using an inkjet method. By using an inkjet method, minute amounts of droplets can be coated onto the substrate at high speed.

[0027] The substrate on which the droplets are applied in the first coating step can be any substrate capable of performing the phase diagram data acquisition method according to the present invention, and is not particularly limited. As will be described later, in the data acquisition step, the phase change of the dissolution data acquisition target / precipitation data acquisition target can be analyzed by, for example, an optical microscope or spectroscopic analysis requiring a light source, so it is sometimes preferable to use a transparent substrate such as a glass substrate.

[0028] The non-volatile liquid used in the phase diagram data acquisition method according to the present invention is a liquid that exhibits non-volatile properties at room temperature and atmospheric pressure and can be applied or ejected by inkjet printing. The non-volatile liquid is not particularly limited, but examples include ionic liquids, deep eutectic solvents, silicone oils, glycols, etc. Two or more non-volatile liquids can also be used by appropriately mixing them to achieve a viscosity suitable for inkjet printing, for example. By using a non-volatile liquid, it becomes unnecessary to consider the volume change due to evaporation of the droplets applied in the first coating step during the data acquisition step, so even when using minute amounts of droplets, the solute concentration in the droplets can be easily determined during the data acquisition step.

[0029] The vapor pressure of a non-volatile liquid at 25°C is preferably 1 / 100,000 or less of international standard atmospheric pressure (1013.25 hPa), more preferably 1 / 1000,000 or less, and even more preferably 1 / 100,000,000 or less. Specifically, this vapor pressure is, for example, 1 / 10,000,000, 1 / 5,000,000, 1 / 100,000, 1 / 5,000,000, 1 / 100,000 of international standard atmospheric pressure (1013.25 hPa), and may be within the range between any two of the values ​​exemplified here, or less than or equal to either of them.

[0030] In one embodiment, an ionic liquid is preferably used as the non-volatile liquid. Ionic liquids are liquids composed of cations and anions, and since a large number of chemical structures exist, they have the advantage of being able to appropriately select cations and anions depending on the solute. Examples of cations that constitute ionic liquids include imidazole, pyridinium, quaternary ammonium, pyrodinium, phosnium, sulfonium, and choline. Examples of anions that constitute ionic liquids include halide ions, tetrafluoroborate, hexafluorophosphate, persulfuric acid, perboric acid, iodic acid, dicyanamide, bis(fluoromethylsulfonyl)amide, bis(trifluoromethylsulfonyl)amide, trifluoromethanesulfonic acid triflate, etc. The cations and anions are not limited to these, and one or more of these cations and anions can be used in combination. In one embodiment, the cation of the ionic liquid preferably contains at least one selected from the group consisting of imidazole, pyridinium, quaternary ammonium, pyrodinium, phosnium, sulfonium, and choline, and the anion of the ionic liquid preferably contains at least one selected from the group consisting of halide ions, tetrafluoroborate, hexafluorophosphate, persulfuric acid, perboric acid, iodic acid, dicyanamide, bis(fluoromethylsulfonyl)amide, bis(trifluoromethylsulfonyl)amide, and trifluoromethanesulfonic acid triflate. Specific examples of ionic liquids include 1-octyl-4-methylpyridinium bis(fluorosulfonyl)amide, 1-octyl-4-methylpyridinium bis(trifluoromethylsulfonyl)amide, and 1-octyl-4-methylpyridinium bis(fluorosulfonyl)amide.

[0031] The density of droplets on the substrate is not particularly limited, but from the perspective of being able to analyze multiple droplets simultaneously in the data acquisition process, 10 2 ~10 8 pieces / cm 2 It is preferable that the droplet density is, specifically, for example, 10 2 ,10 3 ,104 ,10 5 ,10 6 ,10 7 ,10 8 pieces / cm 2 And it may be within the range of any two of the numbers exemplified here.

[0032] The volume of each droplet applied in the first coating step is 10 -6 It is preferable that the volume is between μL and less than 1 μL. Specifically, this volume is, for example, 10 -6 ,10 -5 ,10 -4 ,10 -3 ,10 -2 ,10 -1 The volume of the droplets is less than 0.99 μL or 1 μL, and may be within the range of any two of the values ​​exemplified here. By keeping the droplet volume within the above range, it becomes possible to acquire multiple phase diagram data for rare crystalline materials, as well as to arrange multiple droplets at high density on the substrate. When multiple droplets are arranged at high density on the substrate, the simultaneous analysis in the data acquisition process is excellent, making it possible to acquire phase diagram data at high throughput. Furthermore, if the droplet volume is within the above range, the time to reach a phase equilibrium state when changing the solute concentration and temperature in the data acquisition process described later is short, so the heating rate, cooling rate, and dropping rate of non-volatile liquids and volatile solutions can be increased, making it possible to acquire phase diagram data at high throughput compared to conventional methods.

[0033] The viscosity of the non-volatile solution applied in the first coating step is preferably 0.5 to 200 mPa·s. Specifically, this viscosity is, for example, 0.5, 1, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, and 200 mPa·s, and may be within the range of any two of the values ​​exemplified here. Furthermore, the surface tension of the non-volatile solution applied in the first coating step is preferably 20 to 73 mN / m. Specifically, this surface tension is, for example, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73 mN / m, and may also be within the range of any two of the values ​​exemplified here. By setting the viscosity and surface tension of the non-volatile solution within this range, coating by inkjet method becomes possible.

[0034] Inkjet coating can be performed using a commercially available inkjet printer. For example, the LaboJet-500 (manufactured by MICROJET), a piezoelectric inkjet printer, can be used, and a heated inkjet head can be used as needed. In such cases, the ejection state from the head can be adjusted by changing parameters such as the voltage, pulse width, and frequency applied to the piezoelectric element of the head, as well as the presence or absence of a heater. The first coating step is preferably performed after adjusting the ejection state from the head according to the type of solute or solvent.

[0035] The solute in the non-volatile solution is a crystalline material from which phase diagram data is to be obtained. In the first coating step, the non-volatile solution can be coated at room temperature unless any particular problems arise. However, depending on the type of solute and its combination with the solvent, the solute may not dissolve well in the non-volatile liquid at room temperature, making it difficult to prepare the non-volatile solution. In such cases, the first coating step can be carried out using a non-volatile solution in which the solute has been completely dissolved in the non-volatile liquid by conventionally known heating methods.

[0036] The solute of the non-volatile solution is not particularly limited as long as it is soluble in the non-volatile liquid, but when heating is performed in the first coating step using temperature control with an inkjet head with a heater or by conventionally known heating means, it is preferable that the solute is a solid that does not sublimate or decompose at room temperature and atmospheric pressure.

[0037] <Data acquisition process> The data acquisition process includes a dissolution data acquisition process, which acquires dissolution data from a target for dissolution data acquisition, and a precipitation data acquisition process, which acquires precipitation data from a target for precipitation data acquisition. If the target for precipitation data acquisition is prepared in the preparation process, the precipitation data acquisition process is performed first in the data acquisition process.

[0038] The data acquisition process can be carried out using, for example, a device other than an inkjet printer. In one embodiment, after performing the preparation process using an inkjet printer, the substrate having the precipitate data acquisition target on it may be moved onto the stage of an optical microscope. In another embodiment, the data acquisition process may be carried out without moving the substrate using an inkjet printer equipped with observation means such as a camera or microscope and a temperature control mechanism.

[0039] (Sedimentation data acquisition process) In the precipitation data acquisition process, precipitation data is acquired by lowering the temperature of the material to be precipitated, or by using an inkjet method to add a volatile solution, the solute of which is the material to be precipitated, to the material to be precipitated, and then drying the volatile solvent contained in the volatile solution, one or more times.

[0040] Specifically, for example, in the precipitation data acquisition process, the phase change of the precipitate data acquisition target can be analyzed while lowering its temperature. This method attempts to acquire data related to the phase boundary by fixing the concentration and changing the temperature in a phase diagram with solute concentration and temperature as constituent axes. Methods for lowering the temperature include, for example, air cooling from a state heated above room temperature, cooling using a Peltier element, liquid nitrogen, or compressor, and when lowering the temperature, heating mechanisms such as heaters or PID controllers can be used in combination as needed. Since precipitation is a slower phenomenon than dissolution, the cooling rate is preferably less than or equal to the heating rate when raising the temperature in the dissolution data acquisition process, and in some cases, it is even more preferable that it is about an order of magnitude smaller than the heating rate. By appropriately setting the cooling rate in relation to the heating rate, the reliability of the obtained precipitate data can be ensured. The heating rate when raising the temperature in the dissolution data acquisition process will be described later.

[0041] Alternatively, in the precipitation data acquisition process, instead of lowering the temperature, a volatile solution whose solute is the target of phase diagram data acquisition (crystalline material) may be added to the target of precipitation data acquisition using an inkjet method, and the volatile solvent contained in the volatile solution may be dried. This operation can be performed at least once to analyze the phase change of the target of precipitation data acquisition and acquire precipitation data. This method aims to acquire data related to the phase boundary by fixing the temperature and changing the solute concentration in a phase diagram whose constituent axes are solute concentration and temperature. By performing the above operation at least once, the solute concentration of the target of precipitation data acquisition can be increased in stages. The solute concentration at which precipitation occurs can be calculated based on the solute concentration of the added volatile solution, the volume of each droplet of volatile solution applied in one operation, and the number of operations.

[0042] Methods for analyzing the phase change of the precipitate data acquisition target include, for example, morphological observation using an optical microscope, microscopic analysis such as microspectroscopy using visible light and infrared light, and local thermal analysis, electroanalysis, and magnetic analysis performed by directly introducing thermometers or electrodes to the precipitate data acquisition target. Combined analysis using these analytical methods can also be performed. If the substrate on which the droplets are coated in the first coating step is transparent, such as a glass substrate, then, for example, the presence or absence of a phase change can be observed using an optical microscope. In this case, if the density of droplets on the substrate coated in the first coating step is 10 2 ~10 8 pieces / cm 2 This offers the advantage of being able to analyze multiple droplets simultaneously within the same field of view. In particular, when multiple droplets of different concentrations are coated onto a substrate, multiple precipitation data corresponding to different points on the precipitation curve can be acquired at once, significantly reducing the time required to complete the phase diagram. The advantage of being able to analyze multiple droplets simultaneously within the same field of view is also applicable to the dissolution data acquisition process. The number of droplets placed within the same field of view is, for example, four or more. There is no upper limit, but it is, for example, 100 or less. Specifically, the number of droplets placed within the same field of view may be, for example, 4, 9, 16, 25, 36, 49, 64, 81, or 100, and may be within the range of any two of the numbers exemplified here.

[0043] (Dissolution data acquisition process) The dissolution data acquisition process can be performed after the precipitation data acquisition process has been completed. In this case, the target for dissolution data acquisition in the dissolution data acquisition process can be the precipitate of solute (crystalline material) obtained through the precipitation data acquisition process, which is covered with a non-volatile liquid. This makes it possible to perform the precipitation data acquisition process and the dissolution data acquisition process seamlessly in a single environment, leading to further increases in throughput.

[0044] It is not mandatory to perform the dissolution data acquisition process after acquiring the precipitate data in the precipitate data acquisition process. For example, after acquiring precipitate data in the data acquisition process following the preparation process, a preparation process may be performed using a different substrate as described later in "3.2. When preparing a target for dissolution data acquisition in the preparation process" to prepare a target for dissolution data acquisition, and then dissolution data may be acquired in the data acquisition process. Alternatively, multiple environments capable of implementing the phase diagram data acquisition method according to the present invention may be prepared, and the data acquisition process may be performed independently in each environment. For example, in one environment, a target for precipitate data acquisition may be prepared in the preparation process, and only precipitate data may be acquired in the data acquisition process, while in another environment, a target for dissolution data acquisition may be prepared in the preparation process, and only dissolution data may be acquired in the data acquisition process.

[0045] In the dissolution data acquisition process, dissolution data is acquired by raising the temperature of the material to be dissolved, or by adding a non-volatile liquid to the material using an inkjet method.

[0046] Specifically, in the dissolution data acquisition process, the phase change of the material from which dissolution data is to be acquired can be analyzed while increasing its temperature. This method attempts to acquire data related to the phase boundary by fixing the concentration and changing the temperature in a phase diagram with solute concentration and temperature as constituent axes. The method for increasing the temperature is not particularly limited, and any known method can be adopted. For example, a glass heater can be used as a stand for the substrate to be placed to increase the temperature of the material from which dissolution data is to be acquired, and PID control may be performed as needed. The heating rate in this case is preferably 0.001 to 1°C / min. Specifically, the heating rate can be, for example, 0.001, 0.005, 0.01, 0.05, 0.1, 0.5, 1°C / min, and may be within the range of any two of the values ​​exemplified here. If the heating rate is too low, it will take a long time to acquire data for the phase diagram, and if the heating rate is too high, the reliability of the obtained dissolution data may be impaired. Glass heaters are generally transparent, so they are particularly suitable for use when analyzing phase changes using an optical microscope or the like that requires a light source.

[0047] Furthermore, in the dissolution data acquisition process, instead of raising the temperature, dissolution data may be acquired by analyzing the phase change of the target material by adding a non-volatile liquid using an inkjet method. This method attempts to acquire data related to the phase boundary by fixing the temperature and changing the solute concentration in a phase diagram with solute concentration and temperature as constituent axes. When the non-volatile liquid is added in multiple stages, the solute concentration of the target material can be gradually lowered. The solute concentration at which dissolution occurs can be calculated based on the solute concentration before adding the non-volatile liquid and the total amount of non-volatile liquid added.

[0048] The explanation of the non-volatile liquid used in the dissolution data acquisition process is the same as the explanation of the non-volatile liquid used as the solvent for the non-volatile solution in the first coating process. Furthermore, the explanation of the method for analyzing the phase change of the target of dissolution data acquisition is the same as the explanation of the method for analyzing the phase change of the target of precipitation data acquisition.

[0049] 3.2. When preparing the target for dissolution data acquisition in the preparation process <Preparation process> When preparing the target for dissolution data acquisition in the preparation step, the preparation step further includes a precipitation step and a second coating step.

[0050] (1st coating process) When preparing the target for dissolution data acquisition in the preparation step, the first coating step involves applying a volatile solution containing the crystalline material, which is the target for phase diagram data acquisition, as a solute onto the substrate as droplets using an inkjet method. The explanation of the first coating step is, in principle, the same as the explanation of the first coating step in "3.1. When preparing the target for precipitation data acquisition in the preparation step," except for the fact that a volatile solution is applied instead of a non-volatile solution.

[0051] The solute of the volatile solution is the crystalline material from which phase diagram data is to be obtained. The solute of the volatile solution is not particularly limited, but when it is heated and dried in the precipitation process described later, it is preferable that it is a solid that does not sublimate or decompose at room temperature and atmospheric pressure.

[0052] The solvent for the volatile solution should exhibit moderate volatility at room temperature and pressure, have a boiling point suitable for the inkjet method, and be able to dissolve the crystalline material (solute) for which phase diagram data is to be obtained. The boiling point of the solvent for the volatile solution is not particularly limited, but it is preferable that it is not too low, as a boiling point that is too low may cause concentration at the tip of the inkjet head during ejection. The boiling point of the solvent for the volatile solution is preferably 50 to 200°C, more preferably 60 to 170°C, and even more preferably 70 to 150°C. Specifically, for example, it may be within the range of 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150°C, 160, 170, 180, 190, 200°C, and may also be within the range of any two of the values ​​exemplified here. Examples of solvents for volatile solutions include, but are not limited to, organic solvents such as alcohols, ketones, alkanes, aromatics, and halides, as well as water.

[0053] (Precipitation process) Following the first coating step, a deposition step is carried out. In the deposition step, a crystalline material is deposited on the substrate by drying droplets of volatile solution coated on the substrate. In the deposition step, it is preferable to almost completely evaporate the volatile solvent contained in the droplets coated in the first coating step, and more preferably to completely evaporate it.

[0054] The method for drying droplets of volatile solutions is not particularly limited, but examples include air drying, including natural drying and forced-air drying, as well as heat drying and vacuum drying. From the viewpoint of throughput for acquiring phase diagram data, it may be preferable to precipitate crystalline material by heat drying or vacuum drying.

[0055] On the other hand, if the drying rate is too high, the solute of the volatile solution may spread and precipitate on the substrate. This may necessitate the application of a large amount of non-volatile liquid in the second coating step described later to adequately cover the precipitated solute of the volatile solution. As a result, the upper limit of droplet density on the substrate may be limited, potentially making it impossible to adequately ensure simultaneous analysis of multiple droplets. In light of this possibility, the drying rate may be deliberately reduced so that the solute of the volatile solution precipitates with the desired spread. Methods for reducing the drying rate include, for example, lowering the temperature or employing a method that uses the reverse principle of vacuum drying (specifically, for example, reducing the drying rate by supplying an inert gas from the outside to a sealed system containing a volatile solvent). The drying rate can be appropriately adjusted according to the type of solute / solvent applied in the first coating step, the method of analyzing the phase change in the data acquisition step, the desired throughput, etc.

[0056] (2nd coating process) Following the deposition process, a second coating process is carried out. The second coating process is the second coating process in the preparation process. In the second coating process, a non-volatile liquid is applied as droplets using an inkjet method to cover the solute (crystalline material) deposited on the substrate, thereby creating the target for dissolution data acquisition. The description of the second coating process is, in principle, similar to the description of the first coating process in "3.1. When creating the target for precipitation data acquisition in the preparation process," except that only the non-volatile liquid is applied to cover the deposited solute (crystalline material) and not a non-volatile solution containing the solute (crystalline material). For example, the type, viscosity, surface tension, etc. of the non-volatile liquid applied in the second coating process are the same as those described in the first coating process above.

[0057] The volume of the non-volatile liquid applied in the second coating step is preferably sufficient to cover the crystalline material precipitated in the precipitation step. Specifically, the volume of each droplet of the non-volatile liquid is preferably 10 -6 It is preferable that the volume is between μL and less than 1 μL, for example, 10 -6 ,10 -5 ,10 -4 ,10 -3 ,10 -2 ,10 -1 The volume may be less than 0.99 μL or 1 μL, and may be within the range of any two of the values ​​exemplified here. If the volume of each droplet of nonvolatile liquid is too large, the coated nonvolatile liquid may spread excessively on the substrate, potentially limiting the upper limit of droplet density. Conversely, if the volume of each droplet of nonvolatile liquid is too small, it may not be able to adequately cover the precipitated crystalline material during the deposition process.

[0058] Thus, when the preparation process includes the first coating process, the precipitation process, and the second coating process, unlike in the case of "3.1. When preparing the target for precipitation data acquisition in the preparation process," it is not necessary to prepare a non-volatile solution in which the crystalline material, which is the target for phase diagram data acquisition, is completely dissolved in a non-volatile liquid. In other words, it is possible to acquire phase diagram data corresponding to high solute concentrations without heating using an inkjet head with a heater during inkjet coating.

[0059] <Data acquisition process> The data acquisition process includes a dissolution data acquisition process, which acquires dissolution data from the target for dissolution data acquisition, and a precipitation data acquisition process, which acquires precipitation data from the target for precipitation data acquisition. If the target for dissolution data acquisition is prepared in the preparation process, the data acquisition process begins with the dissolution data acquisition process.

[0060] The data acquisition process can be carried out using, for example, a device other than an inkjet printer. In one embodiment, after performing the preparation process using an inkjet printer, the substrate on which the data to be dissolved is to be acquired may be moved to an optical microscope. Alternatively, the data acquisition process may be carried out without moving the substrate using an inkjet printer equipped with observation means such as a camera or microscope and a temperature control mechanism.

[0061] (Dissolution data acquisition process) In the dissolution data acquisition process, dissolution data of the crystalline material (the material to be dissolved) is acquired by raising the temperature of the material to be dissolved, or by adding a non-volatile liquid to the material using an inkjet method. The explanation of the dissolution data acquisition process is, in principle, similar to the explanation of the dissolution data acquisition process in "3.1. When the material to be dissolved is prepared in the preparation process," except that the material to be dissolved is obtained through the second coating process.

[0062] (Sedimentation data acquisition process) Following the dissolution data acquisition process, a precipitation data acquisition process is carried out. The target of precipitation data acquisition in the precipitation data acquisition process can be a non-volatile solution obtained through the dissolution data acquisition process, in which the crystalline material is completely dissolved in a non-volatile liquid. In this case, the dissolution data acquisition process and the precipitation data acquisition process can be carried out seamlessly, leading to higher throughput.

[0063] In the precipitation data acquisition process, the precipitate data of the crystalline material is acquired by using the precipitate data acquisition target obtained through the dissolution data acquisition process, either by lowering the temperature of the precipitate data acquisition target, or by adding a volatile solution to the precipitate data acquisition target using an inkjet method and then volatilizing the volatile solvent contained in the volatile solution, repeating this operation at least once. The explanation of the precipitation data acquisition process is, in principle, similar to the explanation of the precipitation data acquisition process in "3.1. When Preparing the Precipitation Data Acquisition Target in the Preparation Process," except that the precipitate data acquisition target uses a non-volatile solution in which the crystalline material obtained through the dissolution data acquisition process is completely dissolved in a non-volatile liquid.

[0064] It is not mandatory to perform the precipitation data acquisition step after acquiring the precipitation data in the dissolution data acquisition step. For example, after acquiring dissolution data in the data acquisition step following the preparation step, it is also possible to create a target for precipitation data acquisition by performing the preparation step as described above in "3.1. When creating a target for precipitation data acquisition in the preparation step" using a different substrate, and then acquire the precipitation data in the data acquisition step. Alternatively, multiple environments capable of implementing the phase diagram data acquisition method according to the present invention may be prepared, and the data acquisition step may be performed independently in each environment. For example, in one environment, a target for dissolution data acquisition may be created in the preparation step, and only dissolution data may be acquired in the data acquisition step, while in another environment, a target for precipitation data acquisition may be created in the preparation step, and only precipitation data may be acquired in the data acquisition step.

[0065] 4. How to create a phase diagram The method for creating a phase diagram according to the present invention includes at least a phase diagram creation step of creating a phase diagram from phase diagram data acquired using the method for acquiring phase diagram data according to the present invention. The method for creating a phase diagram according to the present invention may include other steps as needed.

[0066] (Process for creating phase diagrams) In the phase diagram creation process, phase boundaries related to dissolution and precipitation are constructed based on multiple phase diagram data. Below, the phase diagram creation process is described exemplified when data for a binary phase diagram with solute concentration C1 and temperature T as constituent axes is obtained using the phase diagram data acquisition method according to the present invention, but it is not limited to the following.

[0067] When data for a binary phase diagram with solute concentration C1 and temperature T as constituent axes is obtained using the phase diagram data acquisition method according to the present invention, the dissolution data (C) pertaining to any point p on the dissolution curve is obtained. 1p ,T p ) and precipitation data (C) related to any point q on the precipitation curve 1q ,T q Multiple dissolution and precipitation data sets exist for each of these. By plotting these multiple dissolution and precipitation data sets, for example, with C1 on the vertical axis and T on the horizontal axis, the general shapes of the dissolution and precipitation curves can be confirmed.

[0068] If necessary, the accuracy of the plotted data may be verified. For example, if there is a suspicion of an outlier among the plotted data points, the deletion or correction of such data may be considered as appropriate. Alternatively, outliers may be identified using other conventionally known methods. Furthermore, if there are multiple data points corresponding to the same point p or point q, error bars based on the standard deviation, maximum value, minimum value, etc., may be added to each point corresponding to the plotted data.

[0069] After plotting the data, dissolution and precipitation curves can be created by performing curve fitting on each point corresponding to the dissolution / precipitation data. Alternatively, the dissolution / precipitation curves can be created by connecting the points corresponding to multiple dissolution / precipitation data points with line segments. Furthermore, if a large amount of dissolution and precipitation data is obtained, the data points may be densely plotted, effectively functioning as dissolution / precipitation curves themselves. In such cases, performing curve fitting or connecting the points with line segments is not essential.

[0070] In this way, a binary phase diagram including dissolution and precipitation curves can be created in the phase diagram creation process. A ternary phase diagram including dissolution and precipitation surfaces can also be created in the same way as a binary phase diagram by performing surface fitting as necessary. Furthermore, if the dissolution and precipitation data included in the acquired phase diagram data is for an n-component phase diagram (n≧4), N parameter values ​​out of n can be fixed according to the purpose of use to create an (nN)-component phase diagram (3≧n-N≧2), which makes it possible to visualize and use it in real space.

[0071] (Other processes) The method for creating a phase diagram according to the present invention may include other steps as needed. For example, it may include steps such as labeling the regions corresponding to each phase in the phase diagram created as described above as "precipitated phase," "dissolved phase," "metastable phase," etc., or steps such as adding width to the phase boundary by connecting the upper and lower parts of the error bars at each point on the phase boundary with line segments, etc. [Examples]

[0072] The present invention will be described in more detail below with reference to examples. These examples are illustrative and do not limit the scope of the present invention.

[0073] (Adjustment of discharge state) Prior to acquiring phase diagram data, the ejection settings of the inkjet printer were adjusted. First, anthracene (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), the target of phase diagram data acquisition, was dissolved in orthodichlorobenzene (manufactured by Tokyo Chemical Industry Co., Ltd.) to prepare an anthracene-orthodichlorobenzene solution (concentration: 100 mM). The prepared anthracene-orthodichlorobenzene solution was passed through a PTFE (polytetrafluoroethylene) filter (pore size: 0.2 μm) and placed in a 1 mL vial. Then, the vial was set in a piezoelectric inkjet printer (LaboJet-500, manufactured by MICROJET) equipped with a heated inkjet head (IJHE-1000, manufactured by MICROJET). The distance between the head tip and the glass substrate was set to 1-2 mm, and the air temperature during ejection of the anthracene-orthodichlorobenzene solution was set to 25°C. The relationship between the velocity of ejected droplets and the pulse width / voltage ratio was investigated by varying the voltage (0-80V) and pulse width (40-120 seconds) applied to the head and ejecting multiple times. The same method was used to investigate the relationship between the velocity of ejected droplets and the pulse width / voltage ratio for a non-volatile ionic liquid (1-octyl-4-methylpyridinium bis(fluorosulfonyl)amide (C8PryC1 FSI), manufactured by Daiichi Kogyo Seiyaku Co., Ltd.). The pulse frequency was set to 500Hz for the anthracene orthodichlorobenzene solution and 120Hz for the ionic liquid. The head temperature was set to 30°C for the anthracene orthodichlorobenzene solution and 40°C for the ionic liquid. The ejected droplets were observed using a video camera and strobe light. The flight velocity of the ejected droplets was calculated based on the droplet position in the camera image and the strobe light delay time. The volumes of droplets of anthracene orthodichlorobenzene solution and ionic liquid were calculated by measuring the mass of each droplet after ejecting it 20,000 times to a specific point on a glass substrate, and then dividing the measured value by the density of orthodichlorobenzene (1.30 g / mL) and the density of the ionic liquid (1.27 g / mL), respectively. The relationship between the ejected droplet velocity and pulse width / voltage obtained in this way is shown in Figures 2 to 5.

[0074] Figure 2 shows the relationship between droplet velocity and pulse width when dispensing droplets of an orthodichlorobenzene solution of anthracene with a concentration of 100 mM, and Figure 3 shows the relationship between droplet velocity and pulse width when dispensing droplets of an ionic liquid (1-octyl-4-methylpyridinium bis(fluorosulfonyl)amide). From Figures 2 and 3, it can be seen that there is a maximum value in the droplet velocity-pulse width graph. Since droplet formation and the propagation of flight energy from the head are mutually exclusive, it is preferable to perform droplet dispensing using conditions near the maximum value. If the pulse width is too large, the liquid pushed out from the head may not be able to deform into a droplet, and if the pulse width is too small, the energy may not be sufficiently propagated into the liquid.

[0075] Figure 4 plots the droplet velocity and volume against the applied voltage when dispensing droplets of a 100 mM anthracene orthodichlorobenzene solution, and Figure 5 plots the droplet velocity and volume against the applied voltage when dispensing droplets of an ionic liquid (1-octyl-4-methylpyridinium bis(fluorosulfonyl)amide). From Figures 4 and 5, it can be seen that the droplet velocity is proportional to the liquid volume, and that the droplet velocity and dispensed liquid volume increase as the applied voltage increases.

[0076] Based on the results shown in Figures 2 to 5, the dispensing conditions for the anthracene orthodichlorobenzene solution and ionic liquid were determined as follows. <Dispensing conditions for anthracene orthodichlorobenzene solution> Anthracene concentration: 100 mM Applied voltage: 20V Pulse frequency: 500Hz Head temperature: 30℃ Pulse width: 75 μs Number of discharges: 20,000 <Dispensing conditions for orthodichlorobenzene solution as an ionic liquid> Applied voltage: 50V Pulse frequency: 120Hz Head temperature: 40℃ Pulse width: 75 μs Number of discharges: 20,000

[0077] (Evaluation regarding heating rate) Following the adjustment of the dispensing state, we investigated the effect of the heating rate on the reliability of the dissolution data when the temperature is increased during the dissolution data acquisition process.

[0078] First, the preparation process was carried out. In the first coating process, 51 nL of a 100 mM anthracene orthodichlorobenzene solution was applied to a glass substrate by inkjet printing under the above conditions. Subsequently, in the deposition process, the solution was air-dried for 1 minute at 25°C under atmospheric pressure to volatilize only the orthodichlorobenzene and precipitate anthracene. Following the deposition process, in the second coating process, 34 nL of ionic liquid was applied using the inkjet printing method under the above conditions to create a sample for dissolution data acquisition. In the sample for dissolution data acquisition, the anthracene concentration in the ionic liquid covering the anthracene precipitate was 150 mM.

[0079] Subsequently, the glass substrate containing the material to be dissolved was placed on a transparent glass heater stage (SS-053, manufactured by BLAST) mounted on the stage of an optical microscope, and the material was heated at a constant heating rate of 0.1 to 1.0°C / min using a PID controller. The presence or absence of phase change during heating was observed in bright-field mode using an optical digital microscope (RX-100, manufactured by HIROX) equipped with a high-resolution lens (HR-5000, manufactured by HIROX). At this time, the optical microscope lens was on the glass substrate, and observation was performed by irradiating the glass substrate with white light from below. The temperature of the droplet (dissolution temperature) at the point when the precipitate contained in the material to be dissolved completely disappeared was acquired as dissolution data. The heating time for the material to be dissolved was 270 minutes when the heating rate was 0.1°C / min, and 135 minutes when the heating rate was 0.2°C / min.

[0080] For comparison, dissolution data was obtained using a conventional method. First, 13.4 mg of anthracene powder was weighed and added to a 0.5 mL vial. Then, 0.5 mL of the above-mentioned ionic liquid was added to the vial to cover the anthracene, thereby creating a sample for dissolution data acquisition. In the sample for dissolution data acquisition, the anthracene concentration in the ionic liquid covering the anthracene precipitate was 150 mM. The vial containing the sample for dissolution data acquisition at 25°C was placed in a perforated aluminum block, and this aluminum block was placed on a temperature-controlled sample stage. The vial was heated at a constant heating rate of 0.008 to 0.2 °C / min until the temperature of the vial remained constant. The temperature of the droplet (dissolution temperature) at the point when the precipitate contained in the sample for dissolution data acquisition completely disappeared was acquired as dissolution data, along with the anthracene concentration of 150 mM. The heating time for the sample for dissolution data acquisition was 3375 minutes when the heating rate was 0.008 °C / min, and 1588 minutes when the heating rate was 0.017 °C / min.

[0081] Figure 6 shows the relationship between dissolution temperature and heating rate in the present invention and the conventional method. From Figure 6, it can be seen that in both the conventional method and the present invention (inkjet) for acquiring phase diagram data, increasing the heating rate increases the dissolution temperature. This is thought to be because the heating rate is too high, causing dissolution to occur before the phase equilibrium state is reached. In the present invention, the volume of the material for which dissolution data is to be acquired is smaller than in the conventional method, and the time to reach the phase equilibrium state is shorter, so the heating rate can be increased by more than an order of magnitude compared to the conventional method. Therefore, by using the phase diagram data acquisition method according to the present invention, phase diagram data can be acquired with higher throughput than in the conventional method.

[0082] (Acquisition of multiple dissolution data, creation of a phase diagram including dissolution curves) Furthermore, by setting the heating rate to 0.20°C / min, dissolution data was obtained using the phase diagram data acquisition method according to the present invention and the conventional method, when the anthracene concentration of the ionic liquid covering the anthracene precipitate in the equilibrium state after preparation of the target for dissolution data acquisition was set to 75 mM and 300 mM. These data were plotted together with the data at a concentration of 150 mM, and a binary phase diagram including the dissolution curve created by connecting each plotted point with a line segment is shown in Figure 7. From Figure 7, it can be seen that similar results are obtained using either the phase diagram data acquisition method according to the present invention (inkjet) or the conventional method (Conventional). Therefore, it can be seen that by using the phase diagram data acquisition method according to the present invention, dissolution data can be acquired with higher throughput and without compromising reliability compared to the conventional method.

[0083] (Demonstration of simultaneous analysis) The dissolution data acquisition target (anthracene concentration: 150 mM) was prepared using the same method as described in the "Evaluation of Heating Rate" above. Nine dissolution data acquisition targets were arranged in a 3x3 array within a 1000 μm × 1000 μm area on the glass substrate. The density of the dissolution data acquisition targets was 900 units / cm³. 2 The glass substrate was heated in the same manner as described in the "Evaluation of Heating Rate" above, and the phase changes in multiple dissolution data acquisition targets were observed using an optical microscope in bright-field mode and crossed-col mode. Optical microscope images of the dissolution data acquisition targets were obtained before heating and during (or after) heating, and the temperature at which the precipitate dissolved in each dissolution data acquisition target, and the temperature at which all precipitates dissolved in all dissolution data acquisition targets were recorded.

[0084] Figures 8A and 8B show bright-field and crossed-colour images at 25°C, respectively, while Figures 9A and 9B show bright-field and crossed-colour images at 55°C, respectively. From Figures 8A and 8B and 9A and 9B, it can be seen that the precipitates (crystals) dissolved in all samples for which dissolution data was obtained before the temperature reached 55°C. Furthermore, it can be seen that the presence or absence of precipitates covered by the ionic liquid can be easily observed, especially in crossed-colour mode.

[0085] The numbers shown below each dissolution data acquisition target in Figure 9A represent the temperature at which the precipitate dissolved in each dissolution data acquisition target, i.e., the dissolution temperature of each dissolution data acquisition target. The average dissolution temperature of the nine dissolution data acquisition targets is 52.1°C, with a standard deviation of 0.8°C.

[0086] As described above, when dissolution data acquisition targets are arranged at high density on a substrate, multiple dissolution data can be analyzed and acquired simultaneously, making it easy to achieve high throughput for acquiring phase diagram data and creating phase diagrams.

[0087] (Continuous acquisition of dissolution and precipitation data) Using 9,10-dibromoanthracene (DBAn) instead of anthracene and 1-octyl-4-methylpyridinium bis(fluorosulfonyl)amide (C8PryC1 Tf2N) instead of 1-octyl-4-methylpyridinium bis(trifluoromethylsulfonyl)amide, the first coating step, precipitation step, and second coating step were performed in the preparation step using the conditions determined in "Adjustment of Discharge State" above, to prepare the sample for dissolution data acquisition. In the first coating step, 37 nL of an orthodichlorobenzene solution of 20 mM DBAn was coated. In the second coating step, 44 nL of the ionic liquid C8PryC1 Tf2N was coated.

[0088] After preparing the sample for dissolution data acquisition, the dissolution data acquisition process and the precipitation data acquisition process were carried out consecutively. First, the dissolution data acquisition process was performed in the same manner as in the "Evaluation of Heating Rate" described above, and the dissolution temperature of 100°C at a DBAn concentration of 50 mM was acquired as dissolution data.

[0089] Following the dissolution data acquisition process, the precipitation data acquisition process was carried out. Immediately after acquiring the dissolution data, a droplet of DBAn completely dissolved in the ionic liquid at 100°C was present on the substrate. This droplet was used as the target for precipitation data acquisition. Using a transparent glass heater stage (SS-053, manufactured by BLAST) and a PID controller, the temperature was lowered from the dissolution temperature of 100°C at a rate of 1°C / min while observing whether or not there was a phase change. It was confirmed that precipitate formed in the target for precipitation data acquisition at 70°C. Therefore, the precipitation temperature of 70°C at a DBAn concentration of 20 mM was acquired as precipitation data.

[0090] For comparison, dissolution and precipitation data were obtained using a conventional method. First, 3.4 mg of DBAn was weighed and added to a 0.5 mL vial. Then, 0.5 mL of the above-mentioned ionic liquid (C8PryC1 Tf2N) was added to the vial to cover the DBAn, thereby creating a sample for dissolution data acquisition. In the sample for dissolution data acquisition, the DBAn concentration in the ionic liquid covering the DBAn precipitate was 20 mM. The vial containing the sample for dissolution data acquisition was placed in a perforated aluminum block, and this aluminum block was placed on a temperature-controlled sample stage (PH121, manufactured by MSA Factory) connected to a PID controller. The temperature was controlled at a heating rate of 0.1 °C / min to maintain a constant temperature in the vial. The temperature of the droplet (dissolution temperature) at the point when the precipitate contained in the sample for dissolution data acquisition completely disappeared was acquired as dissolution data, along with the DBAn concentration of 50 mM. The dissolution temperature at this time was 100 °C.

[0091] Following the acquisition of dissolution data, precipitation data was acquired. Immediately after acquiring the dissolution data, a liquid in which DBAn was completely dissolved in the ionic liquid was present in the vial. This liquid was used as the target for precipitation data acquisition. Using a temperature-controlled sample stage connected to a PID controller, the temperature was lowered from the dissolution temperature of 100°C at a rate of 0.1°C / min while observing whether or not there was a phase change in the target for precipitation data acquisition. It was confirmed that precipitate formed in the target at 70°C. Therefore, the precipitation temperature of 70°C at a DBAn concentration of 20 mM was acquired as precipitation data. The acquisition results of dissolution data and precipitation data using the conventional method were the same as the acquisition results of dissolution data and precipitation data obtained using the phase diagram data acquisition method according to the present invention.

[0092] In the method for acquiring phase diagram data according to the present invention described above, dissolution data and precipitation data can be seamlessly acquired in a single measurement system using a small amount of sample and a non-volatile liquid, thus enabling high-throughput acquisition of phase diagram data and creation of a phase diagram.

Claims

1. A method for acquiring data for phase diagrams, Including the preparation process and the data acquisition process, The preparation step includes at least a first coating step, In the first coating step, a non-volatile solution in which the solute is the crystalline material to be acquired for data acquisition and the solvent is a non-volatile liquid, or a volatile solution in which the solute is the crystalline material, is coated onto the substrate as droplets using an inkjet method. The data acquisition step includes a dissolution data acquisition step for acquiring dissolution data from a target for dissolution data acquisition, and a precipitation data acquisition step for acquiring precipitation data from a target for precipitation data acquisition, wherein the data acquisition step is a method for acquiring phase diagram data.

2. A method for acquiring phase diagram data according to claim 1, The preparation step further includes a precipitation step and a second coating step, In the first coating step, the volatile solution is applied to the substrate as droplets using an inkjet method. In the deposition step, the crystalline material is deposited on the substrate by drying the droplets of the volatile solution. In the second coating step, the target for dissolution data acquisition is prepared by applying a non-volatile liquid as droplets to cover the crystalline material deposited on the substrate using an inkjet method. In the dissolution data acquisition step, the dissolution data of the crystalline material is acquired by raising the temperature of the object for which dissolution data is to be acquired, or by adding a non-volatile liquid to the object for which dissolution data is to be acquired using an inkjet method. A method for acquiring phase diagram data, wherein in the precipitation data acquisition step, the crystalline material is used as the target for precipitation data acquisition after the crystalline material has been completely dissolved in the dissolution data acquisition step, and the precipitation data of the crystalline material is acquired by lowering the temperature of the target for precipitation data acquisition, or by adding the volatile solution to the target for precipitation data acquisition using an inkjet method and further volatilizing the volatile solvent contained in the volatile solution, and performing this operation once or more times.

3. A method for acquiring phase diagram data according to claim 1, In the first coating step, the non-volatile solution, in which the solvent is a non-volatile liquid, is applied to the substrate as droplets using an inkjet method to create the target for precipitation data acquisition. In the precipitation data acquisition step, the precipitation data of the crystalline material is acquired by lowering the temperature of the object from which the precipitation data is to be acquired, or by adding the volatile solution to the object from which the precipitation data is to be acquired using an inkjet method, and then drying the volatile solvent contained in the volatile solution, one or more times. A method for acquiring phase diagram data, wherein the dissolution data acquisition step involves using the target for dissolution data acquisition, which includes the precipitate of the crystalline material obtained through the precipitation data acquisition step, and acquiring dissolution data of the crystalline material by raising the temperature of the target for dissolution data acquisition, or by adding a non-volatile liquid to the target for dissolution data acquisition using an inkjet method.

4. A method for acquiring phase diagram data according to claim 1, The volume of each droplet of the non-volatile solution or volatile solution applied in the first coating step is 10 －６ A method for acquiring phase diagram data in a volume between μL and 1 μL.

5. A method for acquiring phase diagram data according to claim 2, The volume of each droplet of the non-volatile liquid applied in the second coating step is 10 －６ A method for acquiring phase diagram data in a volume between μL and 1 μL.

6. A method for acquiring phase diagram data according to claim 1, A method for acquiring phase diagram data, wherein the data acquisition step involves simultaneously analyzing multiple targets for dissolution data acquisition or precipitation data acquisition within the same field of view using microscopic analysis to acquire the dissolution data or precipitation data.

7. A method for acquiring phase diagram data according to claim 1, The density of droplets of the volatile solution or non-volatile solution present on the substrate coated in the first step is 10 ２ ~10 ８ pieces / cm ２ This is a method for acquiring data for phase diagrams.

8. A method for acquiring phase diagram data according to any one of claims 1 to 7, The non-volatile liquid used in the first coating step, the second coating step, the dissolution data acquisition step, and / or the precipitation data acquisition step is an ionic liquid composed of cations and anions. The cation comprises at least one selected from the group consisting of imidazole, pyridinium, quaternary ammonium, pyrodinium, phosnium, sulfonium, and choline. A method for acquiring phase diagram data, wherein the anion comprises at least one selected from the group consisting of halide ions, tetrafluoroborate, hexafluorophosphate, persulfate, perboric acid, iodic acid, dicyanamide, bis(fluoromethylsulfonyl)amide, bis(trifluoromethylsulfonyl)amide, and trifluoromethanesulfonic acid triflate.

9. A method for acquiring phase diagram data according to any one of claims 1 to 7, A method for acquiring phase diagram data, wherein the dissolution data acquisition step involves analyzing the phase change of the crystalline material while increasing the temperature of the object to be dissolved at a heating rate of 0.001 to 1°C / min.

10. A method for acquiring phase diagram data according to any one of claims 1 to 7, The viscosity of the volatile solution or non-volatile solution applied in the first coating step is 0.5 to 200 mPa·s. A method for acquiring phase diagram data, wherein the surface tension of the volatile solution or the non-volatile solution applied in the first coating step is 20 to 73 mN / m.

11. A method for acquiring phase diagram data according to claim 2, The viscosity of the non-volatile liquid applied in the second coating step is 0.5 to 200 mPa·s. A method for acquiring phase diagram data, wherein the surface tension of the non-volatile liquid applied in the second coating step is 20 to 73 mN / m.

12. A method for creating a phase diagram, comprising a phase diagram creation step of creating a phase diagram from phase diagram data obtained using the method for obtaining phase diagram data described in any one of claims 1 to 7.

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