Fine particle production device and fine particle production method

Abstract

To provide a fine particle production device and a fine particle production method that enable efficient production of fine particles in a desired size.SOLUTION: A fine particle production device 1A includes: an inlet section 2 for introducing a solution S that includes a target T; an outlet section 3 for discharging the solution S; a flow channel 4 for circulating the solution S from the inlet section 2 to the outlet section 3; a capturing section 5 for trapping particles P exceeding a specific size in the target T within the solution S along the flow channel 4, while permitting the particles P within the specific size to pass toward the outlet section 3; and a light source section 6 for outputting laser light L for crushing the target T directed at the capturing section 5.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present disclosure relates to a particle manufacturing apparatus and a particle manufacturing method. [Background technology]

[0002] Currently, the pharmaceutical industry invests hundreds of billions to over 1 trillion yen in new drug development, but the probability of a new drug being approved after going through non-clinical and clinical trials, i.e., the probability of successful development, remains at approximately 0.004% or less. The difficulty of new drug development is due to the fact that more than 70% of candidate compounds are poorly water-soluble.

[0003] In addition, for pharmaceuticals already on the market, reducing side effects caused by poor water solubility is an issue. For example, paclitaxel, known as an anticancer drug, is a drug that preferentially attacks cancer cells, which divide more frequently than normal cells, by inhibiting cell division, and is widely used in cancer treatment. However, its solubility in water is very low, less than 10 μg / mL. For this reason, when administering paclitaxel to patients, solvents such as ethanol and polyoxyethylene castor oil are used to improve solubility, but attention must be paid to the occurrence of hypersensitivity reactions caused by the use of solvents.

[0004] From the viewpoint of improving the water solubility of drugs, a method of microparticulating a target and increasing the surface area of ​​a material has been attracting attention. Methods that have been widely put to practical use as a method for producing microparticles include the ball mill method and the high-pressure homogenization method, but these methods have problems such as low recovery efficiency of the generated microparticles and contamination with impurities. In recent years, a laser irradiation method that uses laser light to microparticulate a target has been attracting attention as a method that can overcome these problems. For example, in the method of generating nanoparticles described in Patent Document 1, a target placed in a liquid is irradiated with ultrashort pulse light with a high repetition rate, and nano-level microparticles are generated by laser ablation. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] JP2014-129608A Summary of the Invention [Problem to be solved by the invention]

[0006] However, in the method of Patent Document 1, the target placed in the container needs to be replaced at a certain timing, and the generation of the microparticles cannot be performed continuously, so it is considered difficult to improve the production efficiency of the microparticles. In addition, since the particle diameter of the microparticles generated by the irradiation of the laser light cannot be controlled, there is a problem that the size of the obtained microparticles varies.

[0007] The present disclosure has been made to solve the above-mentioned problems, and has an object to provide a particle manufacturing apparatus and a particle manufacturing method that can efficiently manufacture particle of a desired size. [Means for solving the problem]

[0008] A microparticle manufacturing apparatus according to one aspect of the present disclosure includes an inlet section into which a solution containing a target is introduced, an outlet section from which the solution is removed, a flow path for circulating the solution from the inlet section toward the outlet section, a capture section that captures particles of the target in the solution that exceed a predetermined size in the flow path and allows particles of the target that are equal to or smaller than the predetermined size to pass toward the outlet section, and a light source section that outputs laser light toward the capture section for use in crushing the target.

[0009] In this microparticle manufacturing device, a solution containing targets is circulated from an introduction section to an extraction section, and targets exceeding a predetermined size are captured by a capture section provided in the flow path. The targets captured in the capture section are then pulverized by irradiation with laser light, and particles that have become smaller than the predetermined size are passed to the extraction section and removed from the extraction section. This method allows the target to be continuously pulverized by the flow of the solution, and the size of the particles removed by the extraction section can be adjusted according to the size that can pass through the capture section. Therefore, this microparticle manufacturing device can efficiently manufacture microparticles of a desired size.

[0010] In this microparticle manufacturing apparatus, the target is captured in the capture section, so that the irradiation time with the laser light can be easily secured. Therefore, it is possible to easily crush targets that require a long irradiation time to crush. In addition, in this microparticle manufacturing apparatus, the target in the solution is crushed with the laser light, so that the temperature rise of the target due to the irradiation with the laser light can be suppressed. Even if the target captured in the capture section continues to be irradiated with the laser light, the temperature rise of the target can be suppressed by replacing the solution around the target by supplying the solution. By suppressing the temperature rise of the target, re-agglomeration of particles after crushing can be suppressed, and the efficiency of the production of microparticles can be further improved.

[0011] The trapping sections may be provided in multiple stages in the flow path so that the size of particles that can be captured by the trapping sections closer to the outlet section becomes smaller. By gradually reducing the size of particles that can be captured, fine particles of a desired size can be stably produced and excessive clogging of the trapping sections by particles can be suppressed.

[0012] The capture section may be configured such that at least a portion of the flow path gradually narrows from the inlet section to the outlet section. In this case, the flow path itself can be used as the capture section to a certain extent. This makes it possible to effectively suppress excessive changes in flow rate in the flow path and excessive clogging of the capture section by particles.

[0013] The capture section may be configured by disposing a porous member having a plurality of openings in the flow path, which makes it possible to configure the capture section with a simple structure while avoiding a complicated configuration of the flow path.

[0014] The trapping section may allow only particles with a size of 1 μm or less to pass through, which allows for the stable production of fine particles with a size of 1 μm or less.

[0015] The fluence of the laser light emitted from the light source is 0.1 J / cm 2 In this case, by setting the fluence of the laser light to a sufficient value, the target in the trapping section can be efficiently crushed.

[0016] The microparticle manufacturing apparatus may further include a scanning unit that scans the trapping unit with the laser light. In this case, by scanning the trapping unit with the laser light, the target in the trapping unit can be efficiently pulverized.

[0017] The microparticle manufacturing apparatus may further include a recovery mechanism that reverses the flow of the solution in the capture section and recovers the particles captured in the capture section. By providing such a recovery mechanism, it becomes possible to selectively recover particles of any size captured in the capture section. In addition, clogging of the capture section can be eliminated.

[0018] The microparticle production apparatus may further include a vibration applying unit that applies vibration to the flow path. In this case, applying vibration to the flow path can suitably suppress retention of particles in the flow path and clogging of the capture unit by particles.

[0019] The target may be surface-treated with a dispersion stabilizer. In this case, the aggregation of particles after pulverization by the laser light can be suppressed, and fine particles of the desired size can be stably generated. In addition, by suppressing the aggregation of particles, clogging of the trapping section by particles can be suppressed.

[0020] A microparticle manufacturing method according to one aspect of the present disclosure includes an introduction step of introducing a solution containing a target from an introduction section into a flow path, a circulation step of circulating the solution from the introduction section toward an extraction section, a capture step of capturing targets in the solution that exceed a predetermined size in a capture section of the flow path and allowing particles that are equal to or smaller than the predetermined size to pass toward the extraction section, a light irradiation step of outputting laser light used to crush the target toward the capture section, and a removal step of removing the particles that have passed through the capture section from the removal section.

[0021] In this method for producing microparticles, a solution containing targets is circulated from an introduction section to an extraction section, and targets exceeding a predetermined size are captured by a capture section provided in the flow path. The targets captured in the capture section are then pulverized by irradiation with laser light, and particles that have become smaller than the predetermined size are passed to the extraction section and taken out from the extraction section. With this method, the target can be continuously pulverized by the flow of the solution, and the size of the particles taken out at the extraction section can be adjusted according to the size that can pass through the capture section. Therefore, this method for producing microparticles can efficiently produce microparticles of a desired size.

[0022] In this method for producing microparticles, the irradiation time with the laser light can be easily secured by capturing the target in the capturing section. Therefore, it is possible to easily crush targets that require a long irradiation time to crush. In addition, in this method for producing microparticles, the target in the solution is crushed with the laser light, so that the temperature rise of the target due to the irradiation with the laser light can be suppressed. Even if the target captured in the capturing section continues to be irradiated with the laser light, the temperature rise of the target can be suppressed by replacing the solution around the target by supplying the solution. By suppressing the temperature rise of the target, re-agglomeration of the particles after crushing can be suppressed, and the efficiency of the production of microparticles can be further improved. Effect of the Invention

[0023] According to the present disclosure, microparticles of a desired size can be efficiently produced. [Brief description of the drawings]

[0024] [Figure 1] FIG. 1 is a schematic perspective view showing a fine particle manufacturing apparatus according to a first embodiment of the present disclosure. [Diagram 2] 1 is a flowchart illustrating a method for producing microparticles according to an embodiment of the present disclosure. [Diagram 3] FIG. 4 is a schematic perspective view showing a microparticle manufacturing apparatus according to a second embodiment of the present disclosure. [Figure 4] FIG. 11 is an enlarged cross-sectional view of a main portion of a microparticle manufacturing apparatus according to a third embodiment of the present disclosure. [Diagram 5] FIG. 11 is a schematic perspective view showing a fine particle manufacturing apparatus according to a fourth embodiment of the present disclosure. [Figure 6] 6(a) to 6(c) are schematic enlarged cross-sectional views showing a main part of a recovery mechanism in the fine particle producing apparatus shown in FIG. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0025] Hereinafter, preferred embodiments of a microparticle manufacturing apparatus and a microparticle manufacturing method according to one aspect of the present disclosure will be described in detail with reference to the drawings.

[0026] [First embodiment] FIG. 1 is a schematic perspective view showing a microparticle manufacturing apparatus according to a first embodiment of the present disclosure. For convenience of explanation, FIG. 1 shows a cross section of a flow path constituting the apparatus cut in the longitudinal direction. The microparticle manufacturing apparatus 1A shown in FIG. 1 is configured as an apparatus for pulverizing a target T by irradiating it with a laser beam L to manufacture microparticles of a desired size. The size of the particles is defined, for example, by the size of the particle diameter. The size of the particles is measured, for example, by observation using a scanning electron microscope, a particle size distribution measuring device using a dynamic light scattering method, or the like. In this embodiment, the microparticle manufacturing apparatus 1A is used to manufacture microparticles of a size of, for example, 1 μm or less.

[0027] An example of the target T is a drug that is poorly water-soluble. In the microparticle manufacturing device 1A, the target T, which is a drug that is poorly water-soluble, is pulverized by irradiation with laser light L and finely divided into nano-level particles. This finely divided material increases the surface area, improving the water solubility of the drug that is poorly water-soluble. The solubility of the drug that is poorly water-soluble is not particularly limited, but an example of the drug that is poorly water-soluble is one that has a solubility of 50 μg / mL or less at a temperature of 25° C. According to the Japanese Pharmacopoeia, a drug that requires a solvent amount of 100 mL or more to dissolve 1 mg is defined as "hardly soluble," a drug that requires a solvent amount of 1000 mL or more is defined as "extremely difficult to dissolve," and a drug that requires a solvent amount of 10,000 mL or more is defined as "almost insoluble."

[0028] Examples of drugs that are poorly water-soluble include paclitaxel, which is known as an anticancer drug. Other examples include commercially available drugs such as cyclosporine, tacrolimus, nifedipine, nicardipine hydrochloride, phenytoin, digitoxin, diazepam, nitrofurantoin, benoxaprofen, griseofulvin, sulfathiazole, piroxicam, carbamazepine, phenacetin, tolbutamide, theophylline, griseofulvin, chloramphenicol, camptothecin, cisplatin, daunorubicin, methotrexate, mitomycin C, docetaxel, vincristine, amphotericin B, nystatin, ibuprofen, and adrenocortical hormones such as clobetasone butyrate, and other new drug candidate compounds under development.

[0029] 1, the particle production apparatus 1A according to the first embodiment includes an introduction section 2, an extraction section 3, a flow path 4, a capture section 5, a light source section 6, and a scanning section 7. The particle production apparatus 1A also includes a temperature control section 8 and a vibration applying section 9.

[0030] The inlet section 2 is a section where the solution S containing the target T is introduced. The outlet section 3 is a section where the solution S containing the microparticulated target T is taken out. In this embodiment, the inlet section 2 and the outlet section 3 are configured in a cylindrical shape with a circular cross section, and are provided integrally with the flow path 4 as part of the flow path 4. For example, an etching method used in semiconductor processes can be used to fabricate the flow path 4 including the inlet section 2 and the outlet section 3. Here, the inlet section 2 and the outlet section 3 extend in a direction perpendicular to the flow path 4. The target T is introduced into the inlet section 2, for example, vertically downward, and the solution S containing the microparticulated target T is taken out from the outlet section 3, for example, vertically upward.

[0031] The size of the introduction part 2 is not particularly limited as long as it is a size that allows the target T to pass through, but is designed to have an inner diameter of about 10 mm, for example. The size of the discharge part 3 is not particularly limited as long as it is a size that allows the particles P after the target T is pulverized to pass through, but is designed to be the same size as the introduction part 2, for example, from the viewpoint of simplifying the configuration.

[0032] The target T is contained in the solution in the form of, for example, pellets. For example, a pellet can be used that is molded by drying a material placed in a mold made of PDMS (polydimethylsiloxane) and removing it from the mold. By using such pellets, it is possible to make the size of the target T uniform at the stage of being introduced from the introduction part 2, and by making the size of the target T uniform, it becomes easy to set the irradiation range of the laser light L. The target T is not limited to pellets, and may be a material obtained by dispersing a synthesized material in a solution, or a paste-like material obtained by removing the solution from the solution containing the synthesized material.

[0033] For example, water or an organic solvent such as ethanol can be used as the solution S. From the viewpoint of safely administering the solution containing the pulverized fine particles to the human body, it is preferable to use water.

[0034] The target T may be surface-treated with a dispersion stabilizer. The dispersion stabilizer may be contained in the target T in advance, or may be added to the solution S containing the target T. As the dispersion stabilizer, a polymer or a surfactant may be used. The polymer is preferably a substance that is highly water-soluble and easily soluble in various organic solvents. Examples of such polymers include cellulose derivatives such as hydroxypropyl methylcellulose, methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, sodium carboxymethylcellulose, and cellulose acetate phthalate, agar, gelatin, sodium alginate, polyvinylpyrrolidone, aminoalkyl methacrylate copolymer, methacrylic acid copolymer, carboxyvinyl polymer, polyvinyl alcohol, and polyethylene glycol. The surfactant is preferably low-toxic. Examples of such surfactants include sodium lauryl sulfate, cholic acid, deoxycholic acid, and polyoxyethylene sorbitan fatty acid ester.

[0035] The flow path 4 is a part that flows the solution S containing the target T from the introduction part 2 to the extraction part 3. An external pump or the like can be used for the flow of the solution S. The flow path 4 is made of a material that is transparent to the laser light L output from the light source part 6. Examples of materials that form the flow path 4 include glass. The flow path 4 is arranged horizontally so as to be perpendicular to the introduction part 2 and the extraction part 3. There is no particular limit to the flow rate of the solution S flowing through the flow path 4, but by flowing the solution S, the temperature change of the target T can be suppressed. From the viewpoint of suppressing the temperature change of the solution S around the target T, the flow rate of the solution S is set to, for example, about 1 mm / s to 100 mm / s. In the following description, the axis connecting the introduction part 2 and the extraction part 3 is the length direction of the flow path 4, the horizontal axis perpendicular to the length direction is the width direction of the flow path 4, and the vertical axis perpendicular to the length direction is the height direction of the flow path 4.

[0036] The flow path 4 has a front stage 11 located on the introduction section 2 side with the capture section 5 in between, and a rear stage 12 located on the removal section 3 side with the capture section 5 in between. The front stage 11 has a connection section 13A with the introduction section 2. In the example of FIG. 1, the length of the front stage 11 (the length from the connection section 13A to the capture section 5) and the height of the front stage 11 are both constant. The length of the front stage 11 may be sufficient for the target T, and is set to, for example, about 30 mm. The height of the front stage 11 is not particularly limited as long as it is a size that allows the target T to pass through, but is set to, for example, about 10 mm to match the inner diameter of the introduction section 2.

[0037] 1, the width of the front stage 11 gradually increases from the connection portion 13A toward the capture portion 5. Since the width of the front stage 11 gradually increases, even if a large number of targets T are contained in the solution S introduced from the introduction portion 2, the targets T can flow smoothly toward the capture portion 5 without being retained in the front stage 11. The width of the front stage 11 is at its maximum just before the capture portion 5, and the maximum width is maintained until the capture portion 5 is reached. The maximum width is set to, for example, about 20 mm.

[0038] The rear stage 12 has a connection portion 13B with the extraction portion 3. In the example of FIG. 1, the length of the rear stage 12 (the length from the capture portion 5 to the connection portion 13B) and the height of the rear stage 12 are both constant. The length of the rear stage 12 may be sufficient for the pulverized target T, and is set to, for example, about 30 mm, similar to the front stage 11. The height of the rear stage 12 is set according to the size of the pulverized target T, i.e., the size of the particles P to be extracted from the extraction portion 3. When the particles P of the desired size are nanoparticles, the height of the rear stage 12 is set to, for example, about several nm to several hundred nm.

[0039] 1, the width of the rear stage 12 gradually decreases from the capture section 5 toward the connection section 13B. By gradually decreasing the width of the rear stage 12, the particles P formed by pulverization of the target T can be efficiently collected and flowed into the extraction section 3. The width of the front stage 11 is maintained at a maximum width over a certain length from the capture section 5, and then gradually decreases toward the connection section 13B. The maximum width is set to, for example, about 20 mm, similar to the maximum width of the front stage 11.

[0040] The capture section 5 is a section that captures particles P of targets T in solution S that exceed a predetermined size in the flow path 4, and allows particles P of the predetermined size or less to pass to the extraction section 3 side. In this embodiment, the capture section 5 is configured by a step surface 14 in the height direction between the front stage 11 and the rear stage 12. The capture section 5 captures particles P of targets T in solution S that exceed the height of the rear stage 12 at the step surface 14, and allows only particles P of a size equal to or less than the height of the rear stage 12 to pass to the rear stage 12 side.

[0041] 1, as described above, the height of the front stage 11 is set to about 10 mm, whereas the height of the rear stage 12 is set to 1 μm or less. Therefore, among the targets T in the solution S, particles P having a size of 10 mm or more are captured by the capture section 5, and only the particles P that have been atomized to a size of 1 μm or less by irradiation with the laser light L pass through the capture section 5 and flow to the extraction section 3.

[0042] The light source unit 6 is a part that outputs laser light L used for crushing the target T toward the capture unit 5. The light source unit 6 outputs, for example, infrared laser light as the laser light L. From the viewpoint of ensuring the peak power required for crushing the target T and suppressing the temperature rise of the target T, the laser light L is preferably pulsed light. The output conditions of the laser light L are that it transmits through the material of the incident surface of the laser light L (the material forming the flow path 4) and has a wavelength that includes the absorption wavelength of the target T, and further has an intensity and focused size that crush the target T. Examples of such output conditions of the laser light L include an infrared region with a wavelength of 900 nm or more, a pulse width of 0.1 ns or more, a pulse energy of 1 mJ or more, and a beam area of ​​0.01 cm. 2 The fluence (energy per unit area) of the laser light L can be 0.1 J / cm or more. 2 More than this is preferable.

[0043] The scanning unit 7 is a part that scans the capturing unit 5 with the laser light L. The scanning unit 7 is configured to include mirror elements such as a galvanometer mirror, a polygon mirror, and a MEMS mirror, and scans the optical path of the laser light L from the light source unit 6 to the capturing unit 5. The scanning area R of the laser light L by the scanning unit 7 is a region in front of the step surface 14 in the front stage 11. In this embodiment, the scanning area R is a rectangular region in front of the step surface 14 in the front stage 11, where the width of the front stage 11 is the maximum.

[0044] The scanning method of the laser light L in the scanning area R is not particularly limited, but may be, for example, a method in which the laser light L is scanned in the width direction, scanned to the scanning end in the width direction, and then shifted in the length direction and scanned again in the width direction with the laser light L. Unidirectional scanning in which the scanning direction in the width direction is the same for each scan may be adopted, or bidirectional scanning in which the scanning direction in the width direction is reversed for each floor may be adopted.

[0045] The temperature control unit 8 is a part that controls the temperature of the solution S flowing through the flow path 4. The temperature control unit 8 is configured to include, for example, a temperature sensor provided in the flow path 4 and a cooling mechanism that cools the flow path 4 based on a detection signal from the temperature sensor. The temperature control unit 8 may be configured to include a temperature sensor provided in the flow path 4 and a cooling mechanism that cools the solution S before it is introduced into the introduction part 2 based on a detection signal from the temperature sensor. By controlling the temperature of the solution S, it is possible to suppress reagglomeration of the particles P after the target T is pulverized by the laser light L, and it is considered that the size of the particles P after passing through the capture part 5 can be suppressed from increasing due to reagglomeration.

[0046] The vibration imparting unit 9 is a part that imparts vibration to the flow channel 4. The vibration imparting unit 9 is composed of a vibration actuator using, for example, a piezoelectric element. The arrangement position of the vibration imparting unit 9 in the flow channel 4 is not particularly limited, but in this embodiment, the vibration imparting unit 9 is arranged on at least one of the outer wall portion between the connection portion 13A and the step surface 14 in the front stage portion 11 and the outer wall portion between the step surface 14 and the connection portion 13B in the rear stage portion 12. The vibration imparting unit 9 imparts vibration to the flow channel 4 during the period in which the solution S is circulated through the flow channel 4. The vibration imparting unit 9 can preferably suppress the retention and clogging of the particles P in the flow channel 4 by peeling off the particles P attached to the inner wall of the flow channel 4 by vibration or by making the particles P easier to flow near the center of the flow channel 4 using an acoustic focusing technique.

[0047] Next, a method for producing fine particles according to one aspect of the present disclosure will be described.

[0048] Fig. 2 is a flow chart showing a method for producing microparticles according to an embodiment of the present disclosure. As shown in Fig. 2, the method for producing microparticles according to this embodiment includes an introduction step (step S01), a circulation step (step S02), a capture step (step S03), a light irradiation step (step S04), and a removal step (step S05). The method for producing microparticles according to this embodiment is carried out using, for example, the above-mentioned microparticle production apparatus 1A.

[0049] The introduction step S01 is a step of introducing a solution S containing a target T from the introduction part 2 into the flow path 4. The solution S introduced from the introduction part 2 proceeds to the flow path 4 through the connection part 13A. Here, with the start of the introduction step S01, the temperature control of the solution S by the temperature control part 8 and the application of vibration to the flow path 4 by the vibration application part 9 are started. The circulation step S02 is a step of circulating the solution S from the introduction part 2 toward the extraction part 3. The solution S that has proceeded to the flow path 4 through the connection part 13B flows through the front stage 11 of the flow path 4 and then proceeds to the capture part 5.

[0050] The capture step S03 is a step of capturing particles P exceeding a predetermined size among targets T in solution S by capture section 5 of flow path 4, and allowing particles P equal to or smaller than the predetermined size to pass to the extraction section 3. In this embodiment, particles P exceeding the predetermined size are captured by step surface 14 of capture section 5, and only particles having a size equal to or smaller than the height of rear section 12 pass through capture section 5 and proceed to rear section 12.

[0051] The light irradiation step S04 is a step of outputting laser light L used for pulverizing the target T toward the capture section 5. The target T captured in the capture section is pulverized by irradiation with the laser light L, and the particles P that have been reduced in size to a size equal to or smaller than the height of the rear section 12 pass through the capture section 5 sequentially and proceed to the rear section 12. The removal step S05 is a step of removing the particles P that have passed through the capture section 5 from the removal section 3. Fine particles of a desired size are removed from the removal section 3 together with the solution S.

[0052] As described above, in this embodiment, the solution S containing the target T is circulated from the introduction section 2 to the discharge section 3, and the capture section 5 provided in the flow path 4 captures the targets T that exceed a predetermined size. The target T captured by the capture section 5 is then pulverized by irradiation with laser light L, and the particles P that have become smaller than the predetermined size are passed to the discharge section and taken out from the discharge section 3. According to this method, the target T can be continuously pulverized by the circulation of the solution S, and the size of the particles P taken out by the discharge section 3 can be adjusted according to the size that can pass through the capture section 5. Therefore, the microparticle production device 1A can efficiently produce microparticles of a desired size.

[0053] In the microparticle manufacturing apparatus 1A, the target T is captured by the capture unit 5, so that the irradiation time of the laser light L can be easily ensured. Therefore, it is possible to easily crush the target T that requires an irradiation time for crushing. In addition, in the microparticle manufacturing apparatus 1AA, the target T in the solution S is crushed by the laser light L, so that the temperature rise of the target T due to the irradiation of the laser light L can be suppressed. Even if the target T captured in the capture unit 5 continues to be irradiated with the laser light L, the solution S around the target T is replaced by the supply of the solution S, so that the temperature rise of the target T can be suppressed. By suppressing the temperature rise of the target T, the re-aggregation of the particles P after crushing can be suppressed, and the efficiency of the production of microparticles can be further improved.

[0054] In this embodiment, the capture unit 5 is configured to pass only particles P having a size of 1 μm or less. This allows for stable production of fine particles having a size of 1 μm or less. In this embodiment, the fluence of the laser light L output from the light source unit 6 is 0.1 J / cm 2 As described above, by setting the fluence of the laser light L to a sufficient value, the target T in the capture unit 5 can be efficiently pulverized.

[0055] In this embodiment, a scanning unit 7 is provided that scans the capturing unit 5 with laser light L. By scanning the capturing unit 5 with laser light L, the target T in the capturing unit 5 can be efficiently pulverized. In addition, in this embodiment, a vibration applying unit 9 that applies vibration to the flow path 4 is provided. By applying vibration to the flow path 4, retention of particles P in the flow path 4 (for example, adhesion of particles P to the inner wall of the flow path 4) and clogging of the capturing unit 5 with particles P can be suitably suppressed.

[0056] In this embodiment, the target T is surface-treated with a dispersion stabilizer. Such surface treatment can suppress the aggregation of the particles P after pulverization by the laser light L, and can stably generate fine particles of a desired size. By suppressing the aggregation of the particles P, clogging of the capture unit 5 by the particles P can also be suppressed.

[0057] [Second embodiment] Fig. 3 is a schematic perspective view showing a particle production apparatus according to a second embodiment of the present disclosure. As in Fig. 1, Fig. 3 shows a cross section of a flow path constituting the apparatus cut in the longitudinal direction for convenience of explanation. As shown in Fig. 3, the particle production apparatus 1B according to the second embodiment differs from the particle production apparatus 1A according to the first embodiment in that the flow path 4 has capture units 5 arranged in multiple stages.

[0058] Specifically, in the microparticle production apparatus 1B, the introduction section 2 is configured to have a rectangular cross section, and the size (inner dimension in the length direction) of the introduction section 2 gradually decreases toward the connection section 13A. The connection section 13A constitutes the first stage of the capture section 5A. The size (inner dimension in the length direction) of the connection section 13A matches the inner dimension in the length direction at the lower end of the introduction section 2, and particles P exceeding this inner dimension are captured by the capture section 5A, and only particles P having a size equal to or smaller than this inner dimension pass through the capture section 5A and proceed to the front stage 11.

[0059] As in the first embodiment, the second-stage capture section 5B is configured by a step surface 14 between the front stage 11 and the rear stage 12 of the flow path 4. The height of the rear stage 12 is smaller than the size (inner dimension in the longitudinal direction) of the connection section 13A. Therefore, of the particles P that have passed through the capture section 5A and proceeded to the front stage 11, the second-stage capture section 5B captures, at the step surface 14, particles P that have a size exceeding the height of the rear stage 12, and allows only particles P that have a size equal to or smaller than the height of the rear stage 12 to pass to the rear stage 12 side.

[0060] In this type of microparticle manufacturing apparatus 1B, as in the first embodiment, the target T can be continuously pulverized by the flow of the solution S, and the size of the particles P taken out at the take-out section 3 can be adjusted according to the size that can pass through the capture section 5. Therefore, microparticles of a desired size can be efficiently manufactured. Furthermore, in the microparticle manufacturing apparatus 1B, by gradually reducing the size of the particles P that can be captured, microparticles of a desired size can be stably produced, and excessive clogging of the particles P in the capture section 5 can be suppressed.

[0061] In the microparticle manufacturing apparatus 1B, the scanning area R of the laser light L by the scanning unit 7 includes two areas: A) an area corresponding to the connecting portion 13A (the lower end of the introduction portion 2), and B) an area in front of the step surface 14 in the front stage portion 11. When both A) and B) are used as the scanning area R of the laser light L, the target T is crushed in both the capture portion 5A and the capture portion 5B, so that the time required for crushing the target T is shortened and clogging of the particles P in the capture portions 5A and 5B can be effectively suppressed. On the other hand, when only A) is used as the scanning area R of the laser light L, the temperature rise of the solution S can be suppressed and re-aggregation of the particles P after being crushed by the laser light L can be suppressed.

[0062] [Third embodiment] Fig. 4 is an enlarged cross-sectional view of a main part of a microparticle manufacturing apparatus according to a third embodiment of the present disclosure. As shown in Fig. 4, the microparticle manufacturing apparatus 1C according to the third embodiment is different from the first embodiment in that the capture section 5 is formed by a step surface 14 between the front stage 11 and the rear stage 12 in that at least a part of the flow path 4 is gradually narrowed from the introduction section 2 toward the removal section 3. Specifically, in the microparticle manufacturing apparatus 1C, the flow path 4 is not divided into the front stage 11 and the rear stage 12, and the height of the flow path 4 is uniformly reduced from the introduction section 2 toward the removal section 3.

[0063] In this type of microparticle manufacturing apparatus 1C, as in the first embodiment, the target T can be continuously pulverized by the flow of the solution S, and the size of the particles P taken out at the take-out section 3 can be adjusted according to the size that can pass through the capture section 5. Therefore, microparticles of a desired size can be efficiently manufactured. Furthermore, in the microparticle manufacturing apparatus 1C, the flow path 4 itself can be used as the capture section 5 within a certain range. This makes it possible to effectively suppress excessive changes in the flow rate in the flow path 4 and excessive clogging of the particles P in the capture section 5.

[0064] In the microparticle manufacturing apparatus 1C, the entire flow path 4 may be gradually narrowed from the inlet 2 to the outlet 3, or only a part of the flow path 4 may be gradually narrowed from the inlet 2 to the outlet 3. In the former case, excessive changes in flow rate in the flow path 4 and excessive clogging of the particles P in the capture section 5 can be more effectively suppressed. In the latter case, the scanning area R of the laser light L can be kept within a certain range, and the target T can be efficiently pulverized.

[0065] [Fourth embodiment] Fig. 5 is a schematic perspective view showing a microparticle manufacturing apparatus according to a fourth embodiment of the present disclosure. As shown in Fig. 5, the microparticle manufacturing apparatus 1D according to the fourth embodiment has a different configuration of a flow path 4 and a capture unit 5 from those of the first embodiment. Specifically, in the microparticle manufacturing apparatus 1D, the flow path 4 is formed by a cylindrical portion having a circular cross section. The flow path 4 has a first cylindrical portion 21A extending in one direction and a second cylindrical portion 21B extending in a direction intersecting (here, perpendicular to) the first cylindrical portion 21A, and one end of the second cylindrical portion 21B is connected to a central portion of the first cylindrical portion 21A, thereby forming a T-shape in a front view.

[0066] In the example of FIG. 5, the first cylindrical portion 21A is disposed horizontally, and the second cylindrical portion 21B is disposed vertically. In addition, in the example of FIG. 5, the inner diameters of the first cylindrical portion 21A and the second cylindrical portion 21B are constant and are equal to each other. The inner diameters of the first cylindrical portion 21A and the second cylindrical portion 21B are set to, for example, 10 mm to 20 mm. The inner diameters of the first cylindrical portion 21A and the second cylindrical portion 21B may be different from each other. The inner diameter of a part of the first cylindrical portion 21A or a part of the second cylindrical portion 21B may be larger or smaller than the inner diameter of the other part.

[0067] Both ends of the first cylindrical portion 21A serve as inlet portions 2 into which a solution S containing a target T is introduced. The solution S introduced from each of the inlet portions 2, 2 at both ends of the first cylindrical portion 21A joins at a connection portion 22 between the first cylindrical portion 21A and the second cylindrical portion 21B, and proceeds to the second cylindrical portion 21B. The other end of the second cylindrical portion 21B (the end opposite to the connection portion 22) serves as an outlet portion 3 from which the solution S is taken out.

[0068] In the second cylindrical portion 21B, a porous member 23 having a plurality of openings 24 is disposed as the capture portion 5. For example, pore glass can be used as the porous member 23. The porous member 23 is fitted inside the second cylindrical portion 21B so that the extension direction of the plurality of openings 24 faces the extension direction of the second cylindrical portion 21B. In this embodiment, the porous member 23 is provided in multiple stages in the second cylindrical portion 21B so that the size of the particles that can be captured by the capture portion 5 closer to the extraction portion 3 becomes smaller. In the example of FIG. 5, the porous member 23 is provided in two stages in the second cylindrical portion 21B. In the first stage porous member 23A, the diameter of the opening is, for example, about several μm, and in the second stage porous member 23B, the diameter of the opening is, for example, about 0.1 μm.

[0069] Laser light L from the light source unit 6 is irradiated onto the flow path 4 from the connection unit 22 side, for example, parallel to the extending direction of the second cylindrical portion 21B. The scanning area R of the laser light L by the scanning unit 7 is, for example, a cross-sectional area of ​​the internal space of the second cylindrical portion 21B. In this embodiment, the entire cross-sectional area of ​​the internal space of the second cylindrical portion 21B is the scanning area R.

[0070] In this particle production apparatus 1D, as in the first embodiment, the target T can be continuously pulverized by the flow of the solution S, and the size of the particles P taken out at the take-out section 3 can be adjusted according to the size that can pass through the capture section 5. Therefore, particles of a desired size can be efficiently produced. In addition, in the particle production apparatus 1D, by arranging the porous member 23 having a plurality of openings 24 in the flow path 4, the capture section 5 can be configured with a simple structure while avoiding a complex structure of the flow path 4.

[0071] 6(a) to 6(c), the microparticle producing apparatus 1D may have a recovery mechanism 31 that reverses the flow of the solution S in the capture section 5 and recovers the particles P captured by the capture section 5. To construct the recovery mechanism 31, for example, a plurality of branch paths 32 and a plurality of on-off valves 33 are used in the second cylindrical section 21B.

[0072] 6(a) to 6(c), in the second cylindrical portion 21B, a branch passage 32A is provided between the first-stage porous member 23A and the second-stage porous member 23, and a branch passage 32B is provided between the second-stage porous member 23 and the extraction portion 3. In addition, an on-off valve 33A is provided between the connection portion 22 and the first-stage porous member 23A, an on-off valve 33B is provided between the second-stage porous member 23 and the extraction portion 3, closer to the extraction portion 3 than the branch passage 32B, an on-off valve 33C is provided in the branch passage 32A, and an on-off valve 33D is provided in the branch passage 32B.

[0073] During the period in which the target T is pulverized by irradiation with the laser light L, as shown in Fig. 6(a), the on-off valves 33C and 33D are closed, and the particles P that have passed through the first-stage porous member 23A and the second-stage porous member 23B are taken out from the take-out section 3 together with the solution S. Thereafter, when the particles P captured in the second-stage porous member 23B are to be collected, as shown in Fig. 6(b), the on-off valves 33A and 33B are closed, and the on-off valves 33C and 33D are opened. In this state, the solution S (the solution S not containing the target T) is caused to flow backward from the branch path 32B toward the branch path 32A, so that the particles P captured in the second-stage porous member 23B can be taken out from the branch path 32A.

[0074] When the particles P captured in the first-stage porous member 23A are to be collected, as shown in FIG. 6(c), the on-off valves 33B and 33D are closed, and the on-off valves 33A and 33C are opened. In this state, the solution S (the solution S not containing the target T) is caused to flow backward from the branch passage 32A toward the first cylindrical portion 21A, so that the particles P captured in the first-stage porous member 23A can be taken out from the introduction portion 2. By providing such a collection mechanism 31, it becomes possible to selectively collect particles P of any size captured in the capture portion 5. Also, clogging of the capture portion 5 can be eliminated.

[0075] [Variations] The present disclosure is not limited to the above embodiment. For example, in the above embodiment, when the target T captured by the capture unit 5 is crushed by the laser light L, the scanning unit 7 scans the laser light L on the scanning area R, but the arrangement of the scanning unit 7 may be omitted. In this case, for example, a beam shaping optical system may be used to increase the beam area of ​​the laser light L, and the entire capture unit 5 may be irradiated with the laser light L at once. In addition, the laser light L may be split into multiple light beams using a diffractive optical element, a spatial light phase modulator (LCOS-SLM), or the like, and the entire capture unit 5 may be irradiated with the laser light L at multiple points.

[0076] In the first to third embodiments, a recovery mechanism as shown in Fig. 6(a) to Fig. 6(c) may be provided. In the first to third embodiments, a sorting mechanism for sorting the size of the particles P may be provided. An example of the sorting mechanism is a micropillar. For example, by arranging a plurality of micropillars at regular intervals in the flow path 4 downstream of the capture unit 5, it is possible to control particles of different sizes to flow through different paths. By providing a plurality of outlets corresponding to the different paths, the size of the particles P can be easily sorted.

[0077] The gist of the present disclosure is as follows: [1] to

[11] . [1] A microparticle manufacturing apparatus comprising: an inlet section into which a solution containing a target is introduced; an outlet section from which the solution is extracted; a flow path for circulating the solution from the inlet section toward the outlet section; a capture section for capturing particles of the target in the solution that exceed a predetermined size in the flow path and allowing particles of the target that are equal to or smaller than the predetermined size to pass toward the outlet section; and a light source section for outputting laser light toward the capture section for use in crushing the target. [2] The microparticle manufacturing apparatus according to [1], wherein the capture sections are provided in multiple stages in the flow path so that the size of the particles that can be captured by the capture sections closer to the removal section becomes smaller. [3] The apparatus for producing microparticles described in [1], wherein the capture section is configured such that at least a portion of the flow path gradually narrows from the inlet section toward the outlet section. [4] The microparticle manufacturing apparatus according to [1], wherein the capture section is constructed by placing a porous member having a plurality of openings within the flow path. [5] The apparatus for producing fine particles according to any one of [1] to [4], wherein the capture section allows only particles having a size of 1 μm or less to pass therethrough. [6] The fluence of the laser light output from the light source unit is 0.1 J / cm 2 The above-mentioned fine particle production apparatus according to any one of [1] to [5]. [7] The apparatus for producing fine particles according to any one of [1] to [6], further comprising a scanning unit that scans the trapping unit with the laser light. [8] The apparatus for producing fine particles according to any one of [1] to [7], further comprising a recovery mechanism for backflowing the solution in the capture section and recovering the particles captured in the capture section. [9] The apparatus for producing fine particles according to any one of [1] to [8], further comprising a vibration imparting unit that imparts vibration to the flow path.

[10] The apparatus for producing fine particles according to any one of [1] to [9], wherein the target is surface-treated with a dispersion stabilizer.

[11] A method for producing microparticles, comprising: an introduction step of introducing a solution containing a target from an introduction part into a flow path; a circulation step of circulating the solution from the introduction part to an extraction part; a capture step of capturing particles of the target in the solution exceeding a predetermined size in a capture part of the flow path and allowing particles of the predetermined size or smaller to pass toward the extraction part; a light irradiation step of outputting laser light used for crushing the target toward the capture part; and a removal step of removing particles that have passed through the capture part from the removal part. [Explanation of symbols]

[0078] Reference Signs: 1A to 1D...microparticle manufacturing apparatus, 2...introduction section, 3...extraction section, 4...flow path, 5, 5A, 5B...capture section, 6...light source section, 7...scanning section, 9...vibration applying section, 14...step surface (capture section), 23 (23A, 23B)...porous member (capture section), 31...recovery mechanism, T...target, S...solution, P...particle, L...laser light.

Claims

1. an introduction section into which a solution containing a target is introduced; a take-out section from which the solution is taken out; a flow path for distributing the solution from the inlet portion to the outlet portion; a capture section that captures particles exceeding a predetermined size among the targets in the solution in the flow path and allows particles equal to or smaller than the predetermined size to pass to the removal section; a light source unit that outputs laser light used for crushing the target toward the capture unit.

2. 2. The apparatus for producing fine particles according to claim 1, wherein the trapping sections are provided in a plurality of stages in the flow path such that the size of particles that can be captured by the trapping sections becomes smaller as the trapping sections are closer to the outlet section.

3. 2. The apparatus for producing fine particles according to claim 1, wherein the capture section is configured by gradually narrowing at least a portion of the flow path from the inlet section toward the outlet section.

4. 2. The apparatus for producing fine particles according to claim 1, wherein the capture section is configured by arranging a porous member having a plurality of openings in the flow path.

5. The apparatus for producing fine particles according to claim 1 , wherein the trapping section allows only particles having a size of 1 μm or less to pass therethrough.

6. The fluence of the laser light output from the light source unit is 0.1 J / cm ２ The apparatus for producing fine particles according to claim 1 .

7. The apparatus for producing fine particles according to claim 1 , further comprising a scanning unit that scans the trapping unit with the laser light.

8. The apparatus for producing fine particles according to claim 1 , further comprising a recovery mechanism for causing the solution to flow backward in the trapping section and recovering the particles captured in the trapping section.

9. The apparatus for producing fine particles according to claim 1 , further comprising a vibration applying unit that applies vibration to the flow path.

10. 10. The apparatus for producing fine particles according to claim 1, wherein the target is surface-treated with a dispersion stabilizer.

11. an introduction step of introducing a solution containing a target into a flow channel from an introduction portion; a flowing step of flowing the solution from the introduction part to the removal part; a capture step of capturing particles exceeding a predetermined size among the targets in the solution in a capture section of the flow path and allowing particles equal to or smaller than the predetermined size to pass to the removal section; a light irradiation step of outputting a laser beam used for crushing the target toward the capture unit; and a removal step of removing the particles that have passed through the capture section from the removal section.

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