Magnetic separation device, magnetic separation method, and liquid separation system

Abstract

Provided are a magnetic separation device, magnetic separation method and liquid separation system with which it is possible to suitably perform liquid-liquid separation on a magnetic fluid and a non-magnetic fluid.　The present invention provides a magnetic separation device comprising a liquid separation tank and a magnetic field generation unit. The liquid separation tank is configured to accommodate a liquid containing a magnetic fluid and a non-magnetic fluid. The magnetic field generation unit is configured to apply a magnetic field to the liquid, thereby attracting the magnetic fluid in the liquid and separating the magnetic fluid from the non-magnetic fluid.

Description

Magnetic separation device, magnetic separation method, and liquid separation system

[0001] The present invention relates to a magnetic separation device, a magnetic separation method, and a liquid separation system capable of separating a magnetic fluid and a non-magnetic fluid.

[0002] Patent Document 1 discloses a filtration separation device for magnetic particles that switches the on / off of magnetic force by sliding a ring-shaped magnet. Further, Patent Document 2 discloses a cleaning method for magnetic substances that switches the on / off of magnetic force by sliding a rod-shaped magnet.

[0003] Japanese Patent Application Laid-Open No. 2023-017207, Japanese Patent Application Laid-Open No. 2013-151713

[0004] Regarding solid-liquid separation technology for recovering solids from liquids by magnetic force, various developments have been made as in the above-mentioned Patent Documents 1 and 2. However, for technology for suitably liquid-liquid separating a magnetic fluid and a non-magnetic fluid, little development has been made conventionally.

[0005] The present invention has been made in view of such circumstances, and provides a magnetic separation device, a magnetic separation method, and a liquid separation system capable of suitably liquid-liquid separating a magnetic fluid and a non-magnetic fluid.

[0006] The present invention provides the following: [1] A magnetic separation device comprising a liquid separator tank and a magnetic field generating unit, wherein the liquid separator tank is configured to contain a liquid containing a magnetic fluid and a non-magnetic fluid, and the magnetic field generating unit is configured to attract the magnetic fluid in the liquid and separate it from the non-magnetic fluid by applying a magnetic field to the liquid. [2] The magnetic separation device according to [1], wherein the magnetic field generating unit is configured to attract the magnetic fluid near the circumferential surface of the liquid separator tank by applying a magnetic field to the liquid, while forming a separated state in which the non-magnetic fluid remains in the central part of the liquid separator tank. [3] The magnetic separation device according to [2], wherein the magnetic field generating unit comprises a plurality of magnets arranged along the circumferential surface of the liquid separator tank, wherein the plurality of magnets each have an N pole and a S pole arranged opposite each other in the radial direction of the liquid separator tank, and the N poles and S poles are arranged alternately in the direction along the circumferential surface. [4] A magnetic separation device according to [2] or [3], further comprising a stirring device, wherein the stirring device is configured to mix the separated magnetic fluid and the non-magnetic fluid by stirring. [5] A magnetic separation device according to any one of [2] to [4], further comprising a heating unit, wherein the magnetic field generating unit is arranged along the inner surface inside the separatory tank, and the heating unit is arranged along the outer surface outside the separatory tank, and is configured to heat the liquid inside the separatory tank. [6] A magnetic separation method using a magnetic separation device, wherein the magnetic separation device comprises a separatory tank and a magnetic field generating unit, and includes a stirring step of stirring and mixing a liquid containing a magnetic fluid and a non-magnetic fluid introduced into the separatory tank, and a separation step of attracting the magnetic fluid in the liquid and separating it from the non-magnetic fluid by applying a magnetic field to the liquid with the magnetic field generating unit. A magnetic separation method according to [7] and [6], further comprising a draining step of introducing a new non-magnetic fluid into the separatory tank while discharging the non-magnetic fluid from the central part.[8] A magnetic separation method according to [6] or [7], wherein the stirring step includes a step of mixing the magnetic fluid and the non-magnetic fluid against magnetic force by stirring at a rotational speed of a predetermined number of rotations or more while the magnetic field generating unit applies a magnetic field to the liquid, and a step of separating the magnetic fluid and the non-magnetic fluid by magnetic force by stirring at a rotational speed of less than the predetermined number of rotations. [9] A liquid separation system comprising a magnetic separation device and a liquid supply unit, wherein the magnetic separation device comprises a liquid separation tank and a magnetic field generating unit, the liquid separation tank is configured to contain a liquid containing a magnetic fluid and a non-magnetic fluid, the liquid supply unit is configured to supply to the liquid separation tank one of a non-polar solvent or a polar solvent as a magnetic fluid and the other as a non-magnetic fluid, and the magnetic field generating unit is configured to attract the magnetic fluid in the liquid and separate it from the non-magnetic fluid by applying a magnetic field to the liquid.

[10] A magnetic separation device according to [1], further comprising a stirring device, wherein the stirring device is configured to stir the liquid contained in the separatory tank, and the magnetic field generating unit is attached to the stirring device and is configured to apply a magnetic field to the liquid to attract the magnetic fluid near the stirring device, thereby forming a separation state in which the magnetic fluid is separated from the non-magnetic fluid.

[11] A magnetic separation device comprising a separatory tank and a magnetic field generating unit, wherein the separatory tank is configured to contain a liquid containing a magnetic fluid and a non-magnetic fluid, and the magnetic field generating unit is configured to apply a magnetic field to the liquid to attract the magnetic fluid near the circumferential surface of the separatory tank, while forming a separation state in which the non-magnetic fluid remains in the center of the separatory tank.

[12] A magnetic separation method using a magnetic separation device, wherein the magnetic separation device comprises a liquid separator tank and a magnetic field generating unit, and includes: a stirring step of stirring and mixing a liquid containing a magnetic fluid and a non-magnetic fluid introduced into the liquid separator tank; and a separation step of applying a magnetic field to the liquid with the magnetic field generating unit so that the magnetic fluid is attracted to the vicinity of the circumferential surface of the liquid separator tank, while the non-magnetic fluid remains in the center of the liquid separator tank, forming a separated state.

[13] A liquid separation system comprising a magnetic separation device and a liquid supply unit, wherein the magnetic separation device comprises a liquid separation tank and a magnetic field generating unit, the liquid separation tank is configured to contain a liquid containing a magnetic fluid and a non-magnetic fluid, the liquid supply unit is configured to supply the liquid separation tank with one of a non-polar solvent or a polar solvent as the magnetic fluid and the other as the non-magnetic fluid, and the magnetic field generating unit is configured to apply a magnetic field to the liquid so that the magnetic fluid is attracted to the vicinity of the circumferential surface of the liquid separation tank, while the non-magnetic fluid remains in the central part of the liquid separation tank, thereby forming a separated state.

[14] A magnetic separation device comprising a liquid separator, an agitator, and a magnetic field generating unit, wherein the liquid separator is configured to contain a liquid containing a magnetic fluid and a non-magnetic fluid, the agitator is configured to agitate the liquid contained in the liquid separator, and the magnetic field generating unit is attached to the agitator and configured to apply a magnetic field to the liquid to attract the magnetic fluid near the agitator, thereby forming a separation state in which the magnetic fluid is separated from the non-magnetic fluid.

[15] A magnetic separation method using a magnetic separation device, wherein the magnetic separation device comprises a liquid separator, an agitator, and a magnetic field generating unit, and includes an agitation step of agitating and mixing a liquid containing a magnetic fluid and a non-magnetic fluid introduced into the liquid separator, and a separation step of applying a magnetic field to the liquid with the magnetic field generating unit to attract the magnetic fluid near the agitator, thereby forming a separation state in which the magnetic fluid is separated from the non-magnetic fluid.

[16] A liquid separation system comprising a magnetic separator and a liquid supply unit, wherein the magnetic separator comprises a liquid separator tank, a stirring device, and a magnetic field generating unit, the liquid separator tank is configured to contain a liquid containing a magnetic fluid and a non-magnetic fluid, the stirring device is configured to stir the liquid contained in the liquid separator tank, the liquid supply unit is configured to supply the liquid separator tank with one of a non-polar solvent or a polar solvent as the magnetic fluid and the other as the non-magnetic fluid, and the magnetic field generating unit is attached to the stirring device and is configured to apply a magnetic field to the liquid to attract the magnetic fluid near the stirring device, thereby forming a separation state in which the magnetic fluid is separated from the non-magnetic fluid.

[0007] In the magnetic separation apparatus of the present invention, the magnetic field of the magnetic field generating unit attracts the magnetic fluid to the circumferential surface of the separatory tank or to the vicinity of the stirring device, while allowing only the non-magnetic fluid to be appropriately discharged from the separatory tank. Therefore, it is possible to suitably separate the magnetic fluid and the non-magnetic fluid in the separatory tank.

[0008] Figure 1 is a diagram showing the schematic configuration of a liquid separation system 1 according to the first embodiment of the present invention. Figure 2 is a perspective view showing the schematic configuration of the magnetic separation device 2 of Figure 1. Figure 3A is a schematic diagram showing the magnetic field lines generated by the magnetic field generating unit 22 of the magnetic separation device 2, and Figure 3B is a schematic diagram showing the state in which the magnetic fluid 4A and the non-magnetic fluid 4B have been separated by the magnetic field generating unit 22. Figure 4A shows the state in which the magnetic fluid and the non-magnetic fluid have been stirred and mixed by the stirring member 27B in the liquid separation tank 21 of the magnetic separation device 2, and Figure 4B shows the state in which the magnetic fluid 4A and the non-magnetic fluid 4B have been separated in the liquid separation tank 21. Figure 5 is a flowchart showing a magnetic separation method using the magnetic separation device 2. Figure 6A is a perspective view showing the schematic configuration of the magnetic field generating unit 5 according to the second embodiment of the present invention, and Figure 6B is a perspective view showing the schematic configuration of the magnet holder 5A of the magnetic field generating unit 5. Figure 7 is a perspective view showing the schematic configuration of the magnetic separation device 2A according to the second embodiment. Figure 8A schematically shows the magnetic field lines generated by the magnetic field generating unit 5 of the magnetic separation device 2A, and Figure 8B schematically shows the state in which the magnetic fluid 4A and the non-magnetic fluid 4B are separated by the magnetic field generating unit 5. Figure 9A is a perspective view showing the schematic configuration of the magnetic field generating unit 8 of a modified example of the second embodiment, and Figure 9B schematically shows the magnetic field lines generated by the magnetic field generating unit 8. Figure 10A schematically shows the state in which the magnetic fluid 4A and the non-magnetic fluid 4B are separated by the magnetic field generating unit 8, and Figure 10B schematically shows the state of the magnetic fluid 4A in the vicinity of the disk-type magnets 8A to 8C. Figure 11A is a perspective view showing the schematic configuration of the stirring device 40 used in the third embodiment, Figure 11B is a plan view showing the schematic configuration of the stirring device 40, and Figure 11C is a side view showing the schematic configuration of the stirring device 40. Figure 12A shows the state in which the magnetic fluid 4A and the non-magnetic fluid 4B are separated by the magnetic field of the stirring device 40, and Figure 12B shows the state in which the disk turbine blades (disk 42 and blade 43) are arranged in three stages. Figure 13A schematically shows the magnetic field lines generated by the magnets 45A and 45B of the disk 42 and blade 43, Figure 13B schematically shows the magnetic field lines generated by the magnet 45A of the disk 42, and Figure 13C schematically shows the magnetic field lines generated by the magnet 45B of the blade 43.Figure 14 shows a modified example using both a stirring device 40 and a magnetic field generating unit 22. Figure 15A shows a schematic of magnetic nanoparticles, Figure 15B shows the magnetic nanoparticles dispersed in cyclohexane, and Figure 15C shows the state in which the magnetic fluidized cyclohexane and acetonitrile have separated. Figure 16A shows the interface state at a magnetic nanoparticle concentration of 5.0 mg / mL, Figure 16B shows the interface state at a magnetic nanoparticle concentration of 3.0 mg / mL, Figure 16C shows the interface state at a magnetic nanoparticle concentration of 2.0 mg / mL, Figure 16D shows the interface state at a magnetic nanoparticle concentration of 1.0 mg / mL, Figure 16E shows the interface state at a magnetic nanoparticle concentration of 0.5 mg / mL, and Figure 16F shows the interface state at a magnetic nanoparticle concentration of 0.1 mg / mL.

[0009] 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 constitutes an independent invention.

[0010] <First Embodiment> As shown in Figure 1, the liquid separation system 1 comprises a magnetic separation device 2 capable of separating magnetic fluid and non-magnetic fluid, and liquid supply units 3A and 3B capable of supplying liquid to the magnetic separation device 2.

[0011] <Magnetic Separation Device 2> The magnetic separation device 2 comprises a liquid separator tank 21, a drainage unit 20, a magnetic field generating unit 22, liquid introduction units 23A and 23B, a stirring device 27, and a control unit 28.

[0012] The separatory tank 21 has a bottom surface and a circumferential surface that rises from the peripheral edge of the bottom surface. The separatory tank 21 can be made of, for example, glass. In this embodiment, the separatory tank 21 has a circular shape in plan view, but is not limited to this.

[0013] The separatory tank 21 is configured to contain a liquid containing a magnetic fluid and a non-magnetic fluid that are immiscible with each other. In this embodiment, the separatory tank 21 is configured to contain a first solvent (magnetic fluid) which is a non-polar solvent that is immiscible with each other, and a second solvent (non-magnetic fluid) which is a polar solvent. Furthermore, when a chemical reaction is carried out in the separatory tank 21, the separatory tank 21 also functions as a reaction tank. In this embodiment, the first solvent supplied to the separatory tank 21 is cyclohexane and the second solvent is acetonitrile, but the combination is not limited to this.

[0014] The drainage section 20 is configured to discharge the non-magnetic fluid from the central part of the separatory tank 21. The drainage section 20 includes a discharge port 21A and an automatic valve 24C. The discharge port 21A is located in the center of the bottom surface of the separatory tank 21. The automatic valve 24C is positioned between the discharge port 21A and the pipeline 25 and is configured to selectively discharge liquid from the discharge port 21A of the separatory tank 21. The ends of the pipeline 25 are connected to the first receiving tank 26A and the second receiving tank 26B via automatic valves 24A and 24B, respectively.

[0015] Considering the need to suitably separate the magnetic fluid and the non-magnetic fluid using the magnetic field generating unit 22, it is preferable that the bottom surface of the separatory tank 21 has a flat shape. Furthermore, it is preferable to use a flush valve or the like as the automatic valve 24C described above so that there is no liquid accumulation at the bottom surface of the separatory tank 21 and the liquid can be easily discharged.

[0016] The first receiving tank 26A is configured to receive the first solvent recovered by the liquid-liquid extraction operation in the liquid-liquid extraction tank 21. The second receiving tank 26B is configured to receive the second solvent recovered by the liquid-liquid extraction operation in the liquid-liquid extraction tank 21.

[0017] The stirring device 27 comprises a drive unit 27A including a motor and a stirring member 27B. The stirring member 27B is connected to the drive unit 27A via a rotating shaft and is rotationally driven by the drive unit 27A. As the stirring member 27B, for example, a ball turbine (registered trademark) manufactured by M-Revo Japan Co., Ltd. can be suitably used, but is not limited thereto. The liquid in the separatory tank 21 is mixed by stirring with the stirring member 27B. The control unit 28 is configured to comprehensively control the operation of each part of the magnetic separation device 2.

[0018] The magnetic field generating unit 22 is configured to apply a magnetic field to the liquid in the separatory tank 21, thereby attracting the magnetic fluid to the vicinity of the separatory tank 21 while creating a separated state in which the non-magnetic fluid remains in the center of the separatory tank 21. Details of the magnetic field generating unit 22 will be described later. The liquid introduction units 23A and 23B are, for example, cylindrical pipe members and are configured to allow the introduction of liquid from the liquid supply units 3A and 3B into the separatory tank 21.

[0019] <Liquid supply units 3A, 3B> Liquid supply unit 3A includes a first solvent tank 31A, a pump 32A, and a magnetic imparting unit 33A, while liquid supply unit 3B includes a second solvent tank 31B, a pump 32B, and a magnetic imparting unit 33B.

[0020] The first solvent tank 31A is configured to store the first solvent supplied to the separatory tank 21. Examples of the first solvent stored in the first solvent tank 31A include, in addition to the cyclohexane mentioned above, nonpolar solvents such as N,N-dimethylformamide, tetrahydrofuran, toluene, dichloromethane, chloroform, cyclopentyl methyl ether, ethyl acetate, and N-methylpyrrolidone.

[0021] The second solvent tank 31B is configured to store the second solvent supplied to the separatory tank 21. Examples of the second solvent stored in the second solvent tank 31B include polar solvents such as methanol, ethanol, propanol, acetone, and water, in addition to the acetonitrile mentioned above. The solvents in the first solvent tank 31A and the second solvent tank 31B are sent toward the separatory tank 21 by pumps 32A and 32B, respectively. Although pumps 32A and 32B are used here, if gravity transfer is possible, such as when the first solvent tank 31A and the second solvent tank 31B are positioned higher than the separatory tank 21, it is not necessary to use pumps 32A and 32B.

[0022] The magnetic imparting unit 33A is configured to impart magnetism to the first solvent and turn it into a magnetofluid by supplying magnetic nanoparticles that are dispersible in the liquid first solvent. The magnetic nanoparticles used in the magnetic imparting unit 33A are preferably surface-modified to exhibit hydrophobicity. Similarly, the magnetic imparting unit 33B is configured to impart magnetism to the second solvent and turn it into a magnetofluid by supplying magnetic nanoparticles that are dispersible in the liquid second solvent. The magnetic nanoparticles used in the magnetic imparting unit 33B are preferably surface-modified to exhibit hydrophilicity.

[0023] <Magnetic Imparting Units 33A, 33B> As described above, the magnetic imparting unit 33A is configured to turn the first solvent into a magnetic fluid, and the magnetic imparting unit 33B is configured to turn the second solvent into a magnetic fluid. In this embodiment, magnetic nanoparticles are supplied to the first solvent by the magnetic imparting unit 33A before it is supplied to the separatory tank 21. Suitable materials for the magnetic nanoparticles include iron oxide, iron, cobalt, nickel, etc. Furthermore, the magnetic nanoparticles supplied to the first solvent have their surfaces modified with a surface modifier to improve their dispersibility in the first solvent. Since the first solvent is a nonpolar solvent, the surfaces of the magnetic nanoparticles are modified to exhibit hydrophobicity.

[0024] The magnetic nanoparticles used in this embodiment are modified with a surface modifier consisting of a compound having a phosphonic acid group, isocyanate group, carboxyl group, alcohol group, or thiol group. Compounds having a phosphonic acid group, isocyanate group, carboxyl group, alcohol group, or thiol group have been confirmed to exhibit strong adsorption to iron oxide surfaces. Furthermore, these compounds are expected to exhibit strong adsorption not only to iron oxide but also to surfaces such as iron, cobalt, and nickel. The important properties of the surface modifier are that it adheres strongly to the magnetic nanoparticles and does not peel off, and even if it does peel off, it does not become a factor that inhibits chemical reactions.

[0025] Phosphonic acid groups, isocyanate groups, or carboxyl groups, when bonded to organic substances of a certain length (e.g., alkyl or alkenyl groups with approximately 10 to 24 carbon atoms), can act as surface modifiers exhibiting an aggregation-inhibiting effect in nonpolar solvents, using steric hindrance as a repulsive force. On the other hand, for a surface modifier to obtain an aggregation-inhibiting effect in polar solvents, it is preferable to use the Coulomb force generated by charging the surface of magnetic nanoparticles as the repulsive force. Alternatively, the magnetic nanoparticles may be given the function of dispersibility in water by using polyethylene glycol (PEG) or the like.

[0026] The magnetic imparting unit 33A includes, for example, an ultrasonic generator (not shown) and is configured to apply ultrasonic waves to the first solvent in order to suitably disperse the magnetic nanoparticles supplied to the first solvent in the first solvent. The basic configuration of the magnetic imparting unit 33B is the same as that of the magnetic imparting unit 33A. In the case where the first solvent is made into a magnetic fluid as in this embodiment, the magnetic imparting unit 33B is an optional component and therefore does not need to be provided.

[0027] As described above, the liquids are supplied from the liquid supply units 3A and 3B to the magnetic separation device 2 in a state where either the first solvent or the second solvent is a magnetic fluid and the other is a non-magnetic fluid.

[0028] <Magnetic Field Generating Unit 22> As shown in Figure 2, in the magnetic separation device 2, the magnetic field generating unit 22 is arranged along the circumferential surface of the separatory tank 21. In this embodiment, the magnetic field generating unit 22 has a ring shape facing the outer circumferential surface of the separatory tank 21. The magnetic field generating unit 22 exerts a magnetic field widely within the separatory tank 21, thereby attracting the magnetic fluid in the separatory tank 21 toward the circumferential surface of the separatory tank 21. The magnetic field generating unit 22 is configured to be separable into a first magnetic field generating piece 22A and a second magnetic field generating piece 22B. Therefore, by appropriately moving the first magnetic field generating piece 22A and the second magnetic field generating piece 22B closer to or further away from the outer circumferential surface of the separatory tank 21, it is possible to switch the magnetic force applied to the liquid in the separatory tank 21 on or off and control its strength.

[0029] Figure 3A schematically shows the magnetic field lines generated by the magnetic field generating unit 22. For convenience, only the magnetic field lines that enter the interior of the separatory tank 21 (magnetic field lines that affect the behavior of the magnetic fluid) are shown here, and the magnetic field lines outside the separatory tank 21 are not shown. The magnetic field generating unit 22 is equipped with eight neodymium magnets 29 arranged at approximately equal intervals along the outer surface of the separatory tank 21. The neodymium magnets 29 are arranged so that the south poles and north poles are aligned in the radial direction of the separatory tank 21, and the south poles and north poles alternately face inward. That is, in the circumferential direction of the separatory tank 21, the neodymium magnets 29 are arranged with alternating south and north poles. By arranging the neodymium magnets 29 in this way, a magnetic field strength (magnetic flux density: approximately 300 to 400 millitesla) that is suitable for inducing magnetic fluid (magnetic particle concentration: approximately 2 to 10 mg / ml) can be realized in the peripheral area of ​​the separatory tank 21. As a result, as shown in Figure 3B, the magnetic fluid 4A in the liquid is attracted to the vicinity of the inner surface of the separatory tank 21, forming a donut shape. Meanwhile, the non-magnetic fluid 4B in the liquid moves to the center of the separatory tank 21 and becomes surrounded by the magnetic fluid 4A.

[0030] The applicant experimented with various arrangements of the south and north poles of the neodymium magnets 29, but found that the arrangement in which the south and north poles are aligned radially in the separatory tank 21 and alternately face inward was the most effective in terms of widely distributing the magnetic field within the separatory tank 21. In this embodiment, eight neodymium magnets 29 are used, but the type and number of magnets are not limited thereto. It is preferable to use six or more magnets in order to separate the magnetic fluid 4A into a neat donut shape. However, it is possible to further reduce the number of magnets if the magnetic fluid 4A and the non-magnetic fluid 4B are suitably separated. Also, if a sufficiently strong magnetic field can be achieved, the magnetic field may be generated selectively by electrical control.

[0031] <Switching between two-phase mixing and two-phase separation by turning the stirring device 27 on and off> Figure 4A shows the state in which the magnetic fluid and non-magnetic fluid in the separatory tank 21 are mixed by stirring. The stirring member 27B is configured to rotate at any rotational speed in the range of approximately 0 to 1200 revolutions per minute. When the stirring member 27B is rotating at a rotational speed of approximately 800 to 1200 revolutions per minute, the magnetic fluid 4A and the non-magnetic fluid 4B are stirred and mixed against the magnetic force. On the other hand, when the stirring member 27B is rotating slowly at a rotational speed of less than 800 revolutions per minute or is stopped, the magnetic fluid 4A and the non-magnetic fluid 4B are separated, as shown in Figure 4B. In this way, by controlling the rotational speed or on / off control of the stirring member 27B, it is possible to selectively separate the magnetic fluid 4A and the non-magnetic fluid 4B, thus eliminating the need for on / off control of the magnetic force. Furthermore, in this system, there may be three or more fluid supply units, and three or more fluids may be stirred in the liquid separator tank.

[0032] <Magnetic Separation Method> A magnetic separation method using the magnetic separation apparatus 2 will be explained with reference to Figure 5. First, an introduction step is performed in which a liquid containing a magnetic fluid and a non-magnetic fluid that do not mix with each other is introduced into the separatory tank 21 (S1). For example, the magnetic fluid may be used as the reaction liquid phase for carrying out the desired chemical reaction, and the non-magnetic fluid may be used as the raw material liquid phase as a carrier for the raw materials.

[0033] Next, a stirring step is performed in which the magnetic fluid and non-magnetic fluid introduced into the separatory tank 21 are stirred and mixed (S2). In this step, it is preferable that the magnetic fluid and non-magnetic fluid be thoroughly stirred and mixed in order to carry out the desired chemical reaction favorably. Furthermore, if a magnetic field has already been applied to the liquid in the separatory tank 21, it is preferable to stir thoroughly at a rotational speed of 1000 revolutions per minute or more.

[0034] Next, the magnetic field generating unit 22 applies a magnetic field to the liquid in the separatory tank 21, causing the magnetic fluid to be attracted to the vicinity of the separatory tank 21, while a separation process is performed (S3) in which the non-magnetic fluid remains in the center of the separatory tank 21. This separation of the magnetic and non-magnetic fluids makes it easier to discharge only the non-magnetic fluid from the discharge port 21A in the center of the bottom of the separatory tank 21.

[0035] Subsequently, a draining process is performed in which new non-magnetic fluid is introduced into the separatory tank 21 while the non-magnetic fluid in the central part of the separatory tank 21 is discharged (S4). If the discharged non-magnetic fluid contains, for example, impurities generated by a chemical reaction, it becomes possible to replace the non-magnetic fluid containing the impurities with fresh non-magnetic fluid. In this embodiment, after the separation and standing of the liquid phase of the magnetic fluid (cyclohexane phase) and the liquid phase of the non-magnetic fluid (acetonitrile phase), fresh acetonitrile is introduced from above while or after the acetonitrile containing the impurities is discharged from the discharge port 21A. In order to prevent loss due to the dissolution of cyclohexane into the acetonitrile side, it is preferable to introduce acetonitrile saturated with a small amount of cyclohexane (in a volume ratio of about 10 to 1) when introducing new acetonitrile.

[0036] Subsequently, if the desired processing is completed, such as the removal of impurities from the magnetic fluid, the process ends there. If further processing such as stirring and mixing is required, the process returns to the stirring step in S2 (S2).

[0037] <Second Embodiment> Figures 6A and 6B show the configuration of the magnetic field generating unit 5 in the second embodiment of the present invention. The magnetic field generating unit 22 in the first embodiment is located outside the separatory tank 21, which has the advantage of making it easy to control the on / off state of the magnetic force. However, it has the disadvantage of making it difficult to place a simple heating unit (such as a jacket heater or ribbon heater) on the outer surface of the separatory tank 21. For this reason, in the magnetic separation device 2 of the first embodiment, when it was necessary to heat the liquid in the separatory tank 21, it was necessary to perform heating using microwaves or the like.

[0038] Therefore, in the second embodiment, a magnetic field generating unit 5 that can be placed inside the liquid separator 21 is employed. The magnetic field generating unit 5 is equipped with eight magnet holders 5A to 5H that can house neodymium magnets 29 inside. The magnet holders 5A to 5H are each positioned at locations corresponding to the vertices of a regular octagon in a plan view, and adjacent holders are connected to each other by connecting members 50. Each of the magnet holders 5A to 5H has a bottomed cylindrical shape with a square cross-section, and a cap 6 can be attached to the opening. When the cap 6 is attached, the inside of the magnet holders 5A to 5H is sealed watertight. The cap 6 preferably has a tapered shape at the top so that liquid does not accumulate at the top. Here, the top has a square pyramidal shape. In this embodiment, the magnet holders 5A to 5H, the connecting members 50, and the cap 6 are made of non-magnetic stainless steel (e.g., austenitic SUS304). The materials of the magnet holders 5A to 5H, the connecting member 50, and the cap 6 are not limited to these, and other materials such as glass can be used as long as they have chemical resistance that prevents them from dissolving in the solvent in the separatory tank 21 and are not magnetic.

[0039] Here, multiple neodymium magnets 29 are placed in each of the magnet holders 5A to 5H, but a single magnet of a size that fits within the internal space of the magnet holders 5A to 5H may also be placed. Similar to the first embodiment, it is preferable that the neodymium magnets 29 are arranged so that the south poles and north poles are aligned in the radial direction of the separatory tank 21, and that the south poles and north poles alternately face inward.

[0040] Figure 7 is a perspective view showing the schematic configuration of a magnetic separation device 2A employing a magnetic field generating unit 5. As shown in the figure, the magnetic field generating unit 5 is placed on the bottom surface of the separatory tank 21. The magnet holders 5A to 5H of the magnetic field generating unit 5 are arranged along the inner circumferential surface inside the separatory tank 21. On the other hand, a ribbon heater 7 is arranged along the outer circumferential surface outside the separatory tank 21. In Figure 7, for ease of illustration, the ribbon heater 7 is shown with a dashed line. The ribbon heater 7 is configured to heat the liquid in the separatory tank 21 to about 50 to 100°C. Here, the ribbon heater 7 corresponds to the heating unit of the present invention. In place of the ribbon heater 7, other simpler heating units such as jacket heaters may be used.

[0041] Figure 8A schematically shows the magnetic field lines generated by the magnetic field generating unit 5. Since the magnetic field generating unit 5 is located inside the separatory tank 21, it is possible to reliably apply a magnetic field to the central part of the separatory tank 21. Even if the diameter of the separatory tank 21 is increased, it is possible to apply a magnetic field to the separatory tank 21 by increasing the number of magnets placed inside the separatory tank 21. In addition, since it is possible to install a ribbon heater 7 or the like along the outer surface of the separatory tank 21 without causing physical interference with the magnetic field generating unit 5, the design for heating the liquid in the separatory tank 21 becomes easier.

[0042] <Modification of the Second Embodiment> The magnetic field generating unit 5, which can be placed inside the liquid separatory tank 21 as described above, can be replaced with a magnetic field generating unit 8, for example, as shown in Figures 9 and 10. As shown in Figure 9A, the magnetic field generating unit 8 is configured to have three disk-shaped magnets 8A to 8C arranged at a predetermined interval in the height direction. Here, the disk-shaped magnets 8A to 8C are connected by connecting members 80. In addition, a leg portion 81 is connected to the lower surface of the lowest disk-shaped magnet 8C, and a space is also formed between the lower surface of the disk-shaped magnet 8C and the bottom surface of the liquid separatory tank 21.

[0043] The three disk-shaped magnets 8A to 8C are each annular (ring-shaped) in a plan view, with S poles and N poles arranged in the height direction (vertical direction), and the S poles and N poles are alternately arranged along the circumferential direction. For example, in the disk-shaped magnets 8A to 8C, the lower surface becomes the N pole where the S pole is arranged on the upper surface. On the upper surface side and the lower surface side, a six-pole configuration is adopted in which the S poles and N poles are alternately arranged at approximately 60-degree intervals along the circumferential direction. However, the number and arrangement of the S poles and N poles are not limited to this, and the number of magnets laminated in the height direction is not limited to three either.

[0044] Regarding the locations where the S poles are arranged on the upper surface of the disk-shaped magnet 8A, the S poles are also arranged at the corresponding locations on the upper surface of the disk-shaped magnet 8B below it, and the S poles are further arranged at the corresponding locations on the upper surface of the disk-shaped magnet 8C below that. Therefore, in the disk-shaped magnets 8A to 8C, different polarities are arranged on the mutually facing surfaces.

[0045] FIG. 9B schematically shows the magnetic field lines generated by the magnetic field generation unit 8. In the disk-shaped magnets 8A to 8C, magnetic field lines directed from the N pole to the S pole are generated along the inner circumferential surface and the outer circumferential surface, respectively. For this reason, as shown in FIGS. 10A and 10B, the magnetic fluid 4A in the liquid is attracted to the vicinity of the upper surface, lower surface, inner circumferential surface, and outer circumferential surface of the disk-shaped magnets 8A to 8C and forms a doughnut shape. On the other hand, the non-magnetic fluid 4B in the liquid moves to the central portion of the liquid separation tank 21 and is surrounded by the magnetic fluid 4A. At this time, the non-magnetic fluid 4B may also exist in other locations where there is no magnetic fluid 4A, such as between the disk-shaped magnet 8A and the disk-shaped magnet 8B, between the disk-shaped magnet 8B and the disk-shaped magnet 8C, and further outside the vicinity of the outer circumferential surface of the disk-shaped magnets 8A to 8C. Thus, even when the magnetic field generation unit 8 is arranged inside the liquid separation tank 21, it is possible to suitably separate the magnetic fluid and the non-magnetic fluid. The disk-shaped magnets 8A to 8C may be configured by arranging a plurality of arc-shaped magnets in a ring-shaped holder, or a single ring-shaped magnet may be used.

[0046] <Operation of the liquid separation system 1> Subsequently, an example will be described in which cyclohexane magnetically fluidized in the liquid separation tank 21 is introduced using the above-described liquid separation system 1 to carry out a chemical reaction, and by-products (such as contaminants) generated in the chemical reaction are removed using acetonitrile. Cyclohexane and acetonitrile do not mix with each other and form two phases. Also, cyclohexane and acetonitrile form an emulsion, and it takes time to separate the emulsion into two phases. Compounds with high hydrophobicity are selectively dissolved in cyclohexane. On the other hand, compounds with high polarity are selectively dissolved in acetonitrile.

[0047] First, cyclohexane in the first solvent tank 31A is sent to the magnetization imparting section 33A. Subsequently, in the magnetization imparting section 33A, magnetic nanoparticles (e.g., iron oxide Fe ３ O ４ ) surface-modified with a surface modifier having a phosphonic acid group (e.g., saturated alkylphosphonic acid having 14 carbon atoms) are supplied into cyclohexane. Then, ultrasonic waves are applied, and the magnetic nanoparticles are uniformly dispersed in cyclohexane. When the magnetic nanoparticles are uniformly dispersed, cyclohexane becomes magnetically fluidized. Note that the surface-modified magnetic nanoparticles and cyclohexane may be respectively supplied to the liquid separation tank, and the magnetic nanoparticles may be dispersed in cyclohexane by stirring.

[0048] The magnetically fluidized cyclohexane is sent to the liquid separation tank 21. Since cyclohexane is a nonpolar solvent, a chemical reaction using a hydrophobic substance as the target substance can be suitably carried out in cyclohexane. Examples of the chemical reaction include synthesis reactions such as liquid-phase peptide (amino acid) synthesis, nucleic acid (nucleotide) synthesis, peptide nucleic acid synthesis, and low-molecular compound synthesis. As will be described later, the usefulness of the liquid separation operation according to the liquid separation system 1 in liquid-phase peptide synthesis has been confirmed. The liquid separation operation according to the liquid separation system 1 is not limited to this, and it is considered applicable to chemical reactions with low molecules, nucleic acid synthesis with medium molecules, and generally to the liquid separation operation of two immiscible liquids that are emulsified in the field of fine chemicals and the like.

[0049] After the desired chemical reaction proceeds in the separatory tank 21, the acetonitrile in the second solvent tank 31B is sent to the separatory tank 21. The mixture of cyclohexane and acetonitrile is thoroughly stirred by the stirring member 27B at a rotation speed of 1000 revolutions per minute or more, and then the stirring device 27 is stopped. Subsequently, the magnetic force of the magnetic field generating unit 22 separates the cyclohexane and acetonitrile in the separatory tank 21, as shown in Figures 3B and 8B.

[0050] Even when cyclohexane and acetonitrile form an emulsion in the separatory tank 21, the magnetic force allows the cyclohexane and acetonitrile to separate effectively. In this state, by opening automatic valves 24B and 24C, acetonitrile containing impurities can be recovered from the discharge port 21A at the bottom of the separatory tank 21 into the second receiving tank 26B. At this time, it is preferable to supply the separatory tank 21 with the same amount of fresh acetonitrile as the discharged acetonitrile. Furthermore, it is even more preferable that the newly introduced acetonitrile contains cyclohexane by volume of about 10%.

[0051] In this way, it becomes possible to suitably perform a liquid-liquid extraction operation with the main product present in cyclohexane and the by-products present in acetonitrile, which are immiscible with each other. This makes it possible to quickly remove impurities while retaining the desired main product in the liquid-liquid extraction tank 21. Since the mixing state and separation state of the two liquid phases can be switched by turning the stirrer on and off, it becomes possible to carry out the synthesis process of the main product and the separation process of impurities as a series of automated processes.

[0052] Phosphonic acids and carboxylic acids (especially phosphonic acids) are expected to have a strong adsorption force to iron oxide. Therefore, by using these acids, magnetic nanoparticles of surface-modified iron oxide can be stably obtained. Since such magnetic nanoparticles are easily dispersed in a desired solvent using ultrasound or the like, a magnetic fluid exhibiting good dispersibility can be obtained. For this reason, they are readily suitable as dispersants for converting a desired solvent into a magnetic fluid.

[0053] <Third Embodiment> Figures 11A to 11C show the configuration of the stirring device 40 according to the third embodiment of the present invention. In the first embodiment, the magnetic field generating unit 22 was located outside the liquid separator tank 21, but in this embodiment, the stirring device 40 has the same function as the magnetic field generating unit 22. In the third embodiment as well, the basic configuration of the magnetic separation device 2 is the same as in the first embodiment.

[0054] Figure 11A shows the basic configuration of the agitator 40. The agitator 40 employs, for example, a so-called disk turbine blade type structure. The agitator 40 comprises a rotating shaft 41, a disk 42, and a plurality of blades 43. The rotating shaft 41 is connected to a drive unit 27A (not shown), as in the first embodiment. The disk 42 is a thin, circular plate with a circular hole in the center through which the rotating shaft 41 is inserted. The disk 42 is attached to the rotating shaft 41 via a mounting fixture 44. The blades 43 are thin, rectangular plates and are attached to the disk 42 so that their main surfaces are perpendicular to each other. Multiple blades 43 are attached radially from the center of the disk 42. Each blade 43 is arranged to extend radially from the disk 42. Preferably, the blades 43 are arranged at equal intervals along the circumferential direction of the disk 42. In this embodiment, six blades 43 are provided, but the number of blades 43 may be less than or more than six.

[0055] Magnets 45A and 45B are attached to the disk 42 and the blade 43, respectively. In this embodiment, six magnets 45A are provided on one main surface of the disk 42. Six magnets 45A are also provided at corresponding positions on the opposite main surface of the disk 42. Therefore, a total of 12 magnets 45A are attached to the disk 42. On the other hand, two magnets 45B are provided on one main surface of the blade 43. Two magnets 45B are also provided at corresponding positions on the opposite main surface of the blade 43. Therefore, four magnets 45B are attached to one blade 43, and a total of 24 magnets 45B are attached to the six blades 43. However, the mounting positions and number of magnets 45A and magnets 45B are not limited to those shown herein.

[0056] The stirring device 40 is configured to stir the liquid contained in the separatory tank 21. In this embodiment, magnets 45A and 45B, which are attached to predetermined positions on the stirring device 40, correspond to the magnetic field generating unit of the present invention. As shown in Figure 12A, magnets 45A and 45B attract the magnetic fluid 4A to the vicinity of the stirring device 40 by applying a magnetic field to the liquid contained in the separatory tank 21. On the other hand, the non-magnetic fluid 4B near the stirring device 40 is pushed away from the stirring device 40 by the magnetic fluid 4A. As a result, a separation state is formed in which the magnetic fluid 4A near the stirring device 40 is separated from the non-magnetic fluid 4B.

[0057] Figure 12A shows an example where only one stage of disk turbine blades (disk 42 and blade 43) is arranged, but as shown in Figure 12B, multiple stages of disk turbine blades (disk 42 and blade 43) may be arranged. Alternatively, only disks 42 may be installed in some of the multiple stages. By adopting such a configuration, even when the volume of liquid increases due to the increased capacity of the separatory tank 21, it becomes possible to suitably apply a magnetic field to the liquid contained in the separatory tank 21.

[0058] Figures 13A and 13B schematically show the magnetic field lines generated by magnets 45A and 45B. Neodymium magnets are preferable for magnets 45A and 45B, as in the first embodiment. In this embodiment, since non-magnetic materials (e.g., austenitic SUS304) are used for the disk 42 and blade 43, magnets 45A and 45B are placed on both sides of the disk 42 and blade 43, respectively, and attached by being sandwiched from both sides using magnetic force. However, if magnetic materials (e.g., ferrite SUS430) are used for the disk 42 and blade 43, magnets 45A and 45B can be attached to one main surface of the disk 42 and blade 43 by magnetic force.

[0059] The magnets 45A are arranged at approximately equal intervals along the circumferential direction on the main surface of the disk 42, with alternating south and north poles. Two magnets 45B are attached to the main surface of the blade 43, with one exposed surface being the south pole and the other exposed surface being the north pole. By arranging the magnets 45A and 45B in this manner, a magnetic field strength (magnetic flux density: approximately 300 to 400 millitesla) suitable for attracting magnetic fluid (magnetic particle concentration: approximately 2 to 10 mg / ml) can be realized in the space near the stirring device 40.

[0060] <Magnetic Separation Method> In the magnetic separation method using the stirring device 40, the following stirring and separation steps can be performed. In the stirring step, the liquid containing the magnetic fluid 4A and the non-magnetic fluid 4B introduced into the separatory tank 21 is mixed by stirring. In the separation step, magnets 45A and 45B apply a magnetic field to the liquid in the separatory tank 21, causing the magnetic fluid 4A to be attracted to the vicinity of the stirring device 40, and a separated state is formed in which the magnetic fluid 4A is separated from the non-magnetic fluid 4B.

[0061] In the configuration of the third embodiment, the magnetic fluid 4A is held by the stirring device 40, and only the non-magnetic fluid 4B can be discharged by opening the discharge port 21A at the bottom of the separatory tank 21. Since the magnetic field generator is built into the stirring device 40, there is no need to provide a magnetic field generator on the outside of the separatory tank 21, making it easy to place a simple heating unit (such as a jacket heater or ribbon heater) on the outer surface of the separatory tank 21. Also, similar to the second embodiment, the mixing state and separation state of the two liquid phases can be switched by turning the stirring device 40 on and off, so it becomes possible to carry out the synthesis process of the main product and the separation process of impurities as a series of automated processes.

[0062] Furthermore, the disk turbine blade structure used in the stirring device 40 has a significant advantage in that it allows magnets 45A and 45B to be positioned over a wide range of height and radial locations in the separatory tank 21. However, the stirring device 40 is not limited to a disk turbine blade structure; it may also be a paddle blade structure, an anchor blade structure, a propeller blade structure, etc.

[0063] <Modification of the Third Embodiment> In principle, if the stirring device 40 is present, it is not necessary to provide the magnetic field generating unit 22 outside the separatory tank 21. However, as shown in Figure 14, the stirring device 40 and the magnetic field generating unit 22 may be used together. With such a configuration, it becomes possible to hold the magnetic fluid 4A more firmly. The stirring device 40 can also be used together with the magnetic field generating unit 5 of the second embodiment, provided that no physical interference occurs.

[0064] <Other Embodiments> The stirring speed and magnetic flux density shown in the embodiments described above are based on the assumption of a separatory tank 21 with an inner diameter of Φ100 mm (empty cylinder volume of approximately 1 L, liquid volume of 400 ml). Therefore, if the size of the separatory tank 21, the liquid volume, the concentration of magnetic nanoparticles, and other conditions differ significantly, it is preferable to set appropriate stirring speeds and magnetic flux densities as needed.

[0065] In the embodiments described above, an example was explained in which magnetic nanoparticles are modified with a surface modifier having a phosphonic acid group, but the surface modifier is not limited to this. Similar dispersibility improvement effects can be expected by using compounds having an isocyanate group or a carboxyl group, which have a proven track record as dispersants for suitably dispersing magnetic nanoparticles, as surface modifiers.

[0066] As a surface modifier, phosphonic acids other than saturated alkylphosphonic acids with 14 carbon atoms can be used. For example, alkylphosphonic acids or alkenylphosphonic acids with different numbers of carbon atoms can be used. In this case, it is preferable that the alkylphosphonic acid or alkenylphosphonic acid has 10 or more carbon atoms, and it is even more preferable that the alkylphosphonic acid or alkenylphosphonic acid has 14 or more carbon atoms. The upper limit for the number of carbon atoms of the alkylphosphonic acid or alkenylphosphonic acid is preferably around 24, and even more preferably 18. If good dispersibility cannot be obtained at room temperature, the dispersibility may be improved by heating as appropriate.

[0067] 1. Dispersibility of Magnetic Nanoparticles The specific magnetic fluid applicable to the above-described liquid-liquid separatory system 1 will be explained. Surface modification of iron oxide nanoparticles with saturated alkylphosphonic acids and oleylphosphonic acids having 10, 14, and 18 carbon atoms was attempted. It was confirmed that iron oxide nanoparticles modified with saturated alkylphosphonic acids and oleylphosphonic acids having 14 carbon atoms were highly dispersed in cyclohexane. Figures 15A and 15B show the modification of iron oxide nanoparticles with oleylphosphonic acid iron oxide nanoparticles. Furthermore, when a magnetic force of 200 millitesla was applied to the cyclohexane containing dispersed iron oxide nanoparticles using a neodymium magnet, the dispersed magnetic nanoparticles maintained their dispersibility without being attracted magnetically. As shown in Figure 15C, it was confirmed that when the magnet was moved, the cyclohexane moved in the intended direction as a magnetic fluid. In Figure 15C, a clear interface is shown at the boundary between the cyclohexane on the left and the acetonitrile on the right. This suggests that cyclohexane containing dispersed magnetic nanoparticles exhibits extremely excellent properties in magnetic separation from acetonitrile. Even if an emulsion forms between cyclohexane and acetonitrile, bringing a magnet close will separate the cyclohexane and acetonitrile from each other within a few seconds.

[0068] Figures 16A to 16F show the phase separation after magnetic phase separation when using a saturated alkylphosphonic acid with 14 carbon atoms. The mass concentration of iron oxide nanoparticles modified with this alkylphosphonic acid in cyclohexane is indicated at the top of each figure. Since saturated alkylphosphonic acid with 14 carbon atoms is a commercially available product and is considered useful for future scale-up, the concentration dependence of iron oxide nanoparticles modified with this phosphonic acid was investigated. As shown in Figures 16A to 16F, even at concentrations of magnetic nanoparticles below 1.0 mg / mL, a clear interface was observed between the magnetic fluidized cyclohexane and acetonitrile, indicating that it can adequately perform the intended function.

[0069] The separated acetonitrile phase was almost colorless and transparent, indicating that the cyclohexane phase containing iron oxide nanoparticles was firmly retained in the separatory tank. However, at a concentration of 0.5 mg / mL, the cyclohexane phase's magnetism was somewhat insufficient, resulting in a somewhat weaker response to the magnet.

[0070] 2. Apparatus used in the example The example used was the second embodiment of the present invention. Specifically, a flat-bottomed cylindrical glass container with an inner diameter of 100φ (empty cylinder volume of approximately 1L) was used as the reaction vessel, and a manual flush valve was installed at the liquid discharge port in the center of the bottom. Six neodymium magnets 29 measuring 10mm x 5mm x 20mm were attached to each of the bottomed square prism magnet holders 5A to 5H made of SUS304 with an inner dimension of 11mm. The eight magnet holders 5A to 5H were assembled as shown in Figure 6A, and the magnet orientation was set as shown in Figure 8A, and then set inside the reaction vessel as shown in Figure 7. An electronically controlled stirrer (Eurostar 20 Digital) with a maximum rotation speed of 2,000 rpm was used as the stirring device 27, and an Emrevo ball turbine (outer diameter 24φ, made of SUS304) was used as the stirring member 27B.

[0071] 3. Verification Objectives of the Example In this example, liquid-phase peptide synthesis was performed using the TAG-assisted Liquid-Phase Peptide Synthesis method with a hydrophobic liquid-phase peptide synthesis support (TAG). First, a hydrophobic TAG was prepared as a starting material by attaching leucine (Leu) with an Fmoc (9-fluorenylmethoxycarbonyl) protecting group as the first amino acid, in an external container (introduction of amino acids to TAG). Magnetic nanoparticles were dispersed in cyclohexane in an external container, and after transferring this to the reaction vessel, the hydrophobic TAG with the first amino acid attached was added and dissolved. From this state, the objective was to verify whether the deprotection reaction of the Fmoc protecting group, the peptide elongation reaction, and the removal of impurities after each reaction were achieved as expected in this apparatus. In the peptide elongation reaction, good mixing of the two liquids was obtained simply by increasing the rotation speed of the stirrer without removing the magnet from the apparatus. The progress of the reaction was also tracked and confirmed by thin-layer chromatography (TLC) analysis. Since peptide synthesis is a repetition of the cycle of <deprotection reaction of the Fmoc protecting group>, <subsequent separation operation>, <peptide elongation reaction>, and <subsequent separation operation>, in this example only one cycle was confirmed, and the bonding of two amino acid residues was limited.

[0072] 4. Operating conditions in the examples: Solvents and solvent amounts used: Acetonitrile was used as the polar solvent and cyclohexane as the nonpolar solvent, with each volume being 100 mL. Magnetic nanoparticles and particle concentration used: Iron oxide nanoparticles of about 10 nm modified with a saturated alkylphosphonic acid with 14 carbon atoms were used. The particle concentration was 1.0 mg / mL (cyclohexane). Hydrophobic TAG and concentration used: A hydrophobic TAG represented by the following chemical formula was used. The TAG concentration was 0.025 mmol / mL (cyclohexane). First amino acid: Leucine with an Fmoc protecting group (Leu) was used. Second amino acid used: Phenylalanine with an Fmoc protecting group (Phe) was used. Reaction vessel heater: A ribbon heater was used.

[0073] 5. Implementation Status (1) Dispersion of magnetic nanoparticles 100 mg of magnetic nanoparticles were weighed out and added to a flask containing 100 mL of cyclohexane, and the mixture was stirred with ultrasound. The dispersion operation was completed after confirming that the magnetic nanoparticles were well dispersed without being attracted to the magnet or agglomerating and settling.

[0074] (2) Introduction of amino acids into TAG The chemical reaction equation for the introduction of amino acids into TAG is as follows: A 300 mL round-bottom flask was used as the reaction vessel. 2.50 mmol of TAG (molecular weight = 913.7), i.e., 2.28 g of TAG, was added to 50 mL of toluene and heated until the TAG dissolved.

[0075] Next, leucine with an Fmoc protecting group, N,N'-diisopropylcarbodiimide (DIPCI), and 4-dimethylaminopyridine (DMAP) were added and stirred for 1 hour. The amounts used were as follows: • Leucine with an Fmoc protecting group (molecular weight = 353.3): 1.1 equivalents, 2.75 mmol (971.6 mg) • DIPCI (density 0.82 g / mL, molecular weight = 126.2): ​​1.6 equivalents, 4.0 mmol (504.8 mg, 615.6 μL) • DMAP (molecular weight = 122.17): 0.2 equivalents, 0.5 mmol (61.1 mg)

[0076] After stirring for 1 hour, the reaction was monitored by TLC to confirm that the reaction had proceeded. Then, 300 mL of acetonitrile (molecular weight = 41.05, density 0.786 g / mL) was added, the solvent was removed, and the white precipitate was collected by suction filtration.

[0077] (3) Deprotection reaction of Fmoc protecting group The chemical equation for the Fmoc deprotection reaction is as follows: Here, a 1L container for demonstration purposes was used as the reaction vessel. First, cyclohexane and acetonitrile in which magnetic nanoparticles were dispersed in (1) were poured into the reaction vessel, and then leucine with a TAG-modified Fmoc protecting group in (2) was added and stirred to dissolve.

[0078] The mixture was heated to 50°C using a ribbon heater, and then 4.0 equivalents, or 10.0 mmol (1.52 g, 1.49 mL), of 1,8-diazabicyclo[5.4.0]-7-undecene (DBU) (molecular weight = 152.24, density 1.02 g / mL) were added, and the mixture was stirred for 5 minutes. In this case, the magnet was not removed from inside the reaction vessel during the reaction, and the reaction was carried out with a magnetic field applied. The rotation speed of the stirrer was gradually increased, and the mixing of the liquid in the reaction vessel was visually confirmed to be good, and the stirring state was maintained at 1,200 rpm. After 5 minutes, a sample was taken during stirring, and the reaction state was tracked and visually confirmed by TLC, confirming that the deprotection reaction had proceeded completely.

[0079] (4) Separation operation After the completion of (3) above, the rotation speed of the stirrer was gradually reduced and stopped. The cyclohexane phase, which had been fluidized by magnetic nanoparticles, was attracted to the area around the magnet holder installed in the reaction vessel and collected in a donut shape within the vessel. The acetonitrile phase, on the other hand, collected in the area corresponding to the hole of the donut, and the two liquids were separated without forming any emulsion. After confirming this state, the acetonitrile phase was drained from the flush valve at the bottom of the vessel. At this time, the cyclohexane phase remained held in place by magnetic force and was not discharged together with the acetonitrile. The discharge of acetonitrile was stopped when it was close to the point where cyclohexane would start to flow out together with it.

[0080] (5) Washing procedure Following the above (4), 100 mL of acetonitrile / cyclohexane (10:1 (V / V)) solution was added from the top of the reaction vessel to remove impurities (washing). During washing, the mixture was stirred at 1200 rpm for 1 minute, then the stirring was stopped, and the acetonitrile was drained in the same manner as in (4) above. This procedure was repeated a total of two times to complete the washing procedure.

[0081] (6) Peptide synthesis (elongation reaction) The chemical equation for the peptide elongation reaction is as follows: Following step (5), the solution in the reaction vessel was heated to 50°C, and then phenylalanine with an Fmoc protecting group, (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphate (COMU), and N,N-diisopropylethylamine (DIPEA) were added, and the mixture was stirred at 1,200 rpm for 20 minutes. The amounts used were as follows: - Phenylalanine with Fmoc protecting group (molecular weight = 387.4): 2.0 equivalents, 5.0 mmol (1.94 g) - COMU (molecular weight = 428.3): 2.0 equivalents, 5.0 mmol (2.14 g) - DIPEA (molecular weight = 129.24, density 0.76 g / mL): 4.0 equivalents, 10.0 mmol (1.29 g, 1.7 mL) Here, COMU is a coupling agent that can simultaneously activate the carboxylic acid and convert it to an active ester using a coupling aid.

[0082] Subsequently, the reaction was tracked by TLC and confirmed to have progressed, but the reaction was insufficient after 20 minutes. Upon checking again after 30 minutes, it was confirmed that the reaction had progressed completely. (7) Separation procedure: Equivalent to (4) and omitted (8) Washing procedure: Equivalent to (5) and omitted

[0083] 1: Liquid separation system, 2: Magnetic separation device, 2A: Magnetic separation device, 3A: Liquid supply unit, 3B: Liquid supply unit, 4A: Magnetic fluid, 4B: Non-magnetic fluid, 5: Magnetic field generation unit, 5A: Magnet holder, 5B: Magnet holder, 5C: Magnet holder, 5D: Magnet holder, 5E: Magnet holder, 5F: Magnet holder, 5G: Magnet holder, 5H: Magnet holder, 6: Cap, 7: Ribbon heater, 8: Magnetic field generation unit, 20: Drainage unit, 21: Liquid separation tank, 21A: Discharge port, 22: Magnetic field generation unit, 22A: First magnetic field generating piece, 22B: Second magnetic field generating piece, 23A: Liquid guide 23B: Liquid introduction section, 24A: Automatic valve, 24B: Automatic valve, 24C: Automatic valve, 25: Pipeline, 26A: First receiving tank, 26B: Second receiving tank, 27: Agitator, 27A: Drive unit, 27B: Agitator, 28: Control unit, 29: Neodymium magnet, 31A: First solvent tank, 31B: Second solvent tank, 32A: Pump, 32B: Pump, 33A: Magnetic imparting unit, 33B: Magnetic imparting unit, 40: Agitator, 41: Rotating shaft, 42: Disc, 43: Blade, 44: Mounting fixture, 45A: Magnet, 45B: Magnet, 50: Connecting member, 80: Connecting member

Claims

1. A magnetic separation device comprising a liquid separator tank and a magnetic field generating unit, wherein the liquid separator tank is configured to contain a liquid containing a magnetic fluid and a non-magnetic fluid, and the magnetic field generating unit is configured to attract the magnetic fluid in the liquid and separate it from the non-magnetic fluid by applying a magnetic field to the liquid.

2. A magnetic separation device according to claim 1, wherein the magnetic field generating unit is configured such that, by applying a magnetic field to the liquid, the magnetic fluid is attracted to the vicinity of the circumferential surface of the separatory tank, while the non-magnetic fluid remains in the central part of the separatory tank, thus forming a separated state.

3. A magnetic separation device according to claim 2, wherein the magnetic field generating unit comprises a plurality of magnets arranged along the circumferential surface of the separatory tank, and each of the plurality of magnets has an N pole and a S pole arranged opposite each other in the radial direction of the separatory tank, and the N poles and S poles are arranged alternately in the direction along the circumferential surface.

4. A magnetic separation apparatus according to claim 2 or claim 3, further comprising a stirring device, wherein the stirring device is configured to mix the separated magnetic fluid and the non-magnetic fluid by stirring them.

5. A magnetic separation apparatus according to claim 2 or claim 3, further comprising a heating unit, wherein the magnetic field generating unit is arranged along the inner circumferential surface inside the liquid separator tank, and the heating unit is arranged along the outer circumferential surface outside the liquid separator tank, and is configured to heat the liquid inside the liquid separator tank.

6. A magnetic separation method using a magnetic separation device, wherein the magnetic separation device comprises a liquid separator tank and a magnetic field generating unit, and includes a stirring step of stirring and mixing a liquid containing a magnetic fluid and a non-magnetic fluid introduced into the liquid separator tank, and a separation step of attracting the magnetic fluid in the liquid and separating it from the non-magnetic fluid by applying a magnetic field to the liquid with the magnetic field generating unit.

7. A magnetic separation method according to claim 6, further comprising a draining step of introducing a new non-magnetic fluid into the separatory tank while discharging the non-magnetic fluid from the central portion.

8. A magnetic separation method according to claim 6 or claim 7, wherein the stirring step includes: stirring at a rotational speed of a predetermined number of rotations or higher while the magnetic field generating unit applies a magnetic field to the liquid, thereby mixing the magnetic fluid and the non-magnetic fluid against magnetic force; and stirring at a rotational speed of less than the predetermined number of rotations, thereby separating the magnetic fluid and the non-magnetic fluid by magnetic force.

9. A liquid-separating system comprising a magnetic separation device and a liquid supply unit, wherein the magnetic separation device comprises a liquid-separating tank and a magnetic field generating unit, the liquid-separating tank is configured to contain a liquid containing a magnetic fluid and a non-magnetic fluid, the liquid supply unit is configured to supply the liquid-separating tank with one of a non-polar solvent or a polar solvent as the magnetic fluid and the other as the non-magnetic fluid, and the magnetic field generating unit is configured to attract the magnetic fluid in the liquid and separate it from the non-magnetic fluid by applying a magnetic field to the liquid.

10. A magnetic separation apparatus according to claim 1, further comprising a stirring device, wherein the stirring device is configured to stir the liquid contained in the liquid separator tank, and the magnetic field generating unit is attached to the stirring device and is configured to apply a magnetic field to the liquid to attract the magnetic fluid near the stirring device, thereby forming a separation state in which the magnetic fluid is separated from the non-magnetic fluid.

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