JP2014155915A - Apparatus and method for production of fine particle - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an apparatus and a method for production of a fine particle which enable immediate acquisition of a fine particle of a specified particle size containing desired ingredients in a sealed system.SOLUTION: A fine particle production apparatus 1 comprises: a centrifuge tube 10; a cartridge 20 which includes a storage chamber 21 for storing a liquid and is inserted into the centrifuge tube 10; a droplet tube 23 provided on a surface of the cartridge 20 inserted into the centrifuge tube 10 which surface is directed to the tip side of the centrifuge tube 10; a discharge outlet 13 for a fine particle S which is provided on the tip side of the centrifuge tube 10; and a lid 43 closing the discharge outlet 13. The cartridge 20 is rotated at a speed corresponding to a centrifugal force G, with the axis of the centrifuge tube 10 as the center, when the centrifugal force G toward the tip direction of the centrifuge tube 10 is applied to the centrifuge tube 10, with the cartridge 20 inserted into the centrifuge tube 10.

Description

  The present invention relates to a fine particle production apparatus and a fine particle production method, and more particularly to a fine particle production apparatus suitable for medical use capable of producing fine particles having a uniform particle diameter in a sealed system, and a fine particle production method.

  In the case of producing fine particles having a predetermined particle size containing a desired component, for example, the following procedure is performed. First, a component-containing solution containing a desired component and a reaction solution that reacts with the solution and cures are prepared, and the component-containing solution is supplied in a cluster form to the reaction solution. Thereby, the microparticles | fine-particles containing the desired component hardened | cured by reaction of a component containing solution and a reaction liquid are formed. Next, fine particles having a desired particle size are selectively separated from the suspension in which the fine particles are dispersed in the reaction solution. At this time, for example, the following two methods are disclosed.

  In the first method, the suspension is continuously supplied to the sedimentation tank of the vertical centrifuge and operated while allowing the suspension to overflow, and the suspension overflow rate and the number of revolutions of the sedimentation tank are accurately adjusted. As a result, fine particles having a desired particle diameter are obtained (see Patent Document 1 below).

  The second method uses a separation / recovery device having an upper container having a bottom formed by a separation membrane having holes and a lower container connected to the bottom, and a medium having a specific gravity close to that of desired particles. Inject into the container and centrifuge. As a result, particles having a small specific gravity are left in the upper container, and particles having a large specific gravity are moved to the lower container (see Patent Document 2 below).

JP 7-155509 A JP 2006-246835 A

  However, the above-described microparticle production procedure is a procedure in which only the desired microparticles are separated from the microparticles after the microparticles are formed, and there are many process procedures. For this reason, it has been difficult to apply to a site having immediacy, for example, a preparation in the form of fine particles using a tissue collected from a patient, such as a medical site, and administering this to a patient.

  In addition, it is difficult to continuously perform the step of forming fine particles and the step of separating only fine particles having a predetermined particle size from the formed fine particles in a sealed system, and it is difficult to produce fine particles in a sterile state. there were.

  Accordingly, an object of the present application is to provide a fine particle production apparatus and a production method capable of instantly obtaining fine particles having a predetermined particle size containing a desired component in a sealed system.

  The fine particle manufacturing apparatus for achieving the above object has a centrifuge tube, a storage chamber for storing a liquid therein, a cartridge inserted into the centrifuge tube, and a centrifuge tube. A surface of the cartridge in the state toward the tip of the centrifuge tube, a droplet tube provided in communication with the storage chamber, a particulate discharge port provided on the tip side of the centrifuge tube, and the drain And a lid for closing the outlet. In particular, the cartridge applies the centrifugal force toward the tip of the centrifuge tube in a state where the cartridge is inserted into the centrifuge tube, so that the centrifugal force is centered on the axis of the centrifuge tube. Rotates at the corresponding speed.

  Moreover, the manufacturing method using this microparticle manufacturing apparatus is performed as follows. First, in a state where the discharge port is closed with the lid, a reaction solution that reacts and solidifies with a component-containing solution containing a desired component is stored on the distal end side of the centrifuge tube. Further, the cartridge in which the component-containing solution is stored in the storage chamber is inserted into the centrifuge tube in which the reaction solution is stored. Thereafter, a centrifugal force directed toward the distal end of the centrifuge tube is applied to the centrifuge tube in which the reaction solution is stored and the cartridge is inserted. As a result, the component-containing solution in the storage chamber was pushed out from the droplet tube to the distal end side of the centrifuge tube, and the cartridge was rotated with respect to the axis of the centrifuge tube to be pushed out from the droplet tube. Droplets of the component-containing solution are dropped into the reaction solution to form fine particles. Next, the fine particles are separated from the reaction solution by selectively discharging the reaction solution from the centrifuge tube with respect to the fine particles.

  In the fine particle manufacturing apparatus configured as described above, a storage chamber is provided in a cartridge that rotates at a speed corresponding to the centrifugal force applied to the centrifugal tube, and a droplet tube is communicated with the cartridge, whereby a predetermined centrifugal force is obtained. As a result, the cartridge rotates at a predetermined speed. Accordingly, the droplets dropped from the droplet tube of the cartridge have a predetermined volume corresponding to the rotational speed of the cartridge. Thereby, only the fine particle of a predetermined particle diameter is formed, without performing the process of isolate | separating fine particle for every particle diameter. Therefore, by leaving only the reaction liquid while leaving the fine particles in the centrifuge tube, it is possible to obtain only the particles having a predetermined particle size in the centrifuge tube in which the fine particles are formed.

  As described above, according to the present invention, since only particles having a predetermined particle size can be obtained in a centrifuge tube in which fine particles are formed, the predetermined particle size is instantaneously set in a sealed centrifuge tube system. It is possible to obtain fine particles.

BRIEF DESCRIPTION OF THE DRAWINGS It is a figure (the 1) explaining the structure of the microparticle manufacturing apparatus of 1st Embodiment, and explaining the microparticle manufacturing method using the same. It is FIG. (2) explaining the manufacturing method of the microparticles | fine-particles in 1st Embodiment. It is FIG. (3) explaining the manufacturing method of microparticles | fine-particles in 1st Embodiment. It is FIG. (4) explaining the manufacturing method of the microparticles | fine-particles in 1st Embodiment. It is FIG. (5) explaining the manufacturing method of the microparticles | fine-particles in 1st Embodiment. It is FIG. (6) explaining the manufacturing method of the microparticles | fine-particles in 1st Embodiment. It is a figure (the 7) explaining the manufacturing method of the microparticles | fine-particles in 1st Embodiment. While showing the structure of the microparticle manufacturing apparatus of 2nd Embodiment, it is a figure (the 1) explaining the manufacturing method of microparticles | fine-particles using the same. It is FIG. (2) explaining the manufacturing method of the microparticles | fine-particles in 2nd Embodiment. It is FIG. (3) explaining the manufacturing method of the microparticles | fine-particles in 2nd Embodiment. While showing the structure of the microparticle manufacturing apparatus of 3rd Embodiment, it is a figure (the 1) explaining the manufacturing method of microparticles | fine-particles using the same. It is FIG. (2) explaining the manufacturing method of the microparticles | fine-particles in 3rd Embodiment.

  Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. Note that, in the first to third embodiments described below, the same components are denoted by the same reference numerals, and redundant descriptions are omitted.

<< Configuration of Fine Particle Manufacturing Apparatus 1 of First Embodiment >>
FIG. 1 is a configuration diagram showing a fine particle manufacturing apparatus according to the first embodiment, FIG. 1A is a plan view of a cartridge provided in the fine particle manufacturing apparatus, and FIG. 1B is an exploded view of the fine particle manufacturing apparatus. The fine particle manufacturing apparatus 1 shown in these drawings includes a centrifuge tube 10 and a cartridge 20 that is inserted into the centrifuge tube 10. The centrifuge tube 10 is provided with an opening 11 for taking in and out the cartridge 20 on the base end side, and a particle discharge port 13 on the tip side opposite to the opening 11. The openings 11 and the discharge port 13 are provided with lids 41 and 43, respectively. The cartridge 20 is provided with a storage chamber 21 for storing a liquid therein, and is characterized in that the cartridge 20 rotates around the axis of the centrifuge tube 10 while being inserted into the centrifuge tube 10.

  Hereinafter, details of each component will be described in the order of the centrifuge tube 10, the cartridge 20, and the lids 41 and 43.

<Centrifuge tube 10>
The centrifuge tube 10 is a cylindrical tube in which an opening 11 is provided with one end as a base end side, and an inner diameter is gradually narrowed with the other end as a distal end side, and a distal end with a narrow inner diameter. A discharge port 13 is provided in the part. Here, a configuration in which about 1/3 of the axial direction of the cylindrical tube shape is gradually narrowed toward the discharge port 13 side is illustrated. However, the shape of the centrifuge tube 10 is not limited to this, and a configuration in which most of the cylindrical shape is gradually narrowed toward the discharge port 13 side may be employed.

  Further, on the inner wall of the centrifuge tube 10, a fall prevention stopper 15 for preventing the cartridge 20 from dropping in the centrifuge tube 10, a movement stop stopper 17 for stopping the movement of the cartridge 20 in the centrifuge tube 10, A pin 19 for removing the lid of the cartridge 20 is provided. Next, the detail of each part which comprises the centrifuge tube 10 is demonstrated.

[Discharge port 13]
The discharge port 13 is configured as a cylindrical tube having a predetermined inner diameter, thereby being easily sealed with a lid 43 described later, and a collector for discharging liquid or taking out fine particles from the discharge port 13. It becomes the structure which is easy to join, maintaining a sealing state. The opening diameter of the discharge port 13 is sufficiently larger than the diameter of the fine particles produced by the fine particle production apparatus 1. Further, such a discharge port 13 may be provided coaxially with the axis of the centrifuge tube 10.

[Fall prevention stopper 15]
The fall prevention stopper 15 is arranged in the middle in the longitudinal direction of the centrifuge tube 10 and is provided as a protrusion that fits into a recess 20a provided on the outer wall of the cartridge 20 to be described next. The fall prevention stopper 15 is configured to be flexible, so that when the cartridge 20 is moved in the distal direction of the centrifuge tube 10 by centrifugal force, the drop prevention stopper 15 is pushed down by the outer wall of the cartridge 20 to be removed from the depression 20a. Thereby, the movement of the cartridge 20 toward the distal end of the centrifuge tube 10 is started.

  Here, as shown in FIG. 2, the state in which the cartridge 20 is inserted into the centrifuge tube 10 is a state in which the fall prevention stopper 15 of the centrifuge tube 10 is fitted in the recess 20 a of the cartridge 20. The same shall apply.

[Stopper 17 for movement stop]
The movement stopping stopper 17 is disposed closer to the distal end side of the centrifuge tube 10 than the fall prevention stopper 15. This movement stop stopper 17 does not have flexibility, and protrudes from the inner wall of the centrifuge tube 10 so as to sufficiently overlap the cartridge 20 when the centrifuge tube 10 is viewed in plan view from the direction of the opening 11. Is provided. As shown in FIG. 2, when the cartridge 20 is inserted into the centrifuge tube 10, a sufficient distance d is maintained between the cartridge 20 and the stopper 17 for stopping movement.

[Pin 19]
The pin 19 is in a position to support the lid 33 of the cartridge 20 to be described below in a state where the drop prevention stopper 15 is fitted in the recess 20a of the cartridge 20 (that is, the cartridge 20 is inserted into the centrifuge tube 10). Has been placed. The pin 19 is provided so as to protrude from the inner wall of the centrifuge tube 10 so as to sufficiently overlap the lid 33 of the cartridge 20 when the centrifuge tube 10 is viewed in plan view from the direction of the opening 11.

  The centrifuge tube 10 configured as described above includes materials for the inner wall of the discharge port 13, the fall prevention stopper 15, the movement stop stopper 17, and the pin 19, and is suitable for the fluid introduced into the centrifuge tube 10. It shall be comprised with the material which has tolerance. The fluid introduced into the centrifuge tube 10 will be described in detail in the following manufacturing method, and is as follows with reference to FIG.

  That is, the fluid introduced into the centrifuge tube 10 includes a component-containing solution L2 containing a desired component, a reaction solution L1 that solidifies by reacting with the component-containing solution L2, and a specific gravity that provides power for rotating the cartridge 20. A first fluid F1 and a second fluid F2. The component-containing solution L2 is an alginate containing, for example, platelet-rich plasma (PRP) or stem cells. As an example, the reaction liquid L1 is a calcium chloride solution. The first fluid F1 is air as an example. The second fluid F2 is castor oil as an example. Examples of materials having resistance to these fluids include metal materials such as stainless steel, glass materials, plastic materials such as fluororesin and polypropylene, and the like.

  In particular, the inner wall on the distal end side (discharge port 13 side) of the centrifuge tube 10 is preferably made of a material having low adhesion to the fine particles formed on the distal end side, together with the above-described resistance. The movement of the fine particles in the centrifuge tube 10 is facilitated, and the recovery rate of the fine particles from the centrifuge tube is ensured.

  The material of the centrifuge tube 10 is not limited as long as the inner wall is made of a material having the characteristics described above.

<Cartridge 20>
The cartridge 20 is provided with a storage chamber 21 for storing a liquid therein, and is inserted into the centrifuge tube 10. The cartridge 20 rotates about the axis of the centrifuge tube 10 in a state in which the cartridge 20 is indented by applying a centrifugal force G toward the distal end of the centrifuge tube 10. The speed at which the cartridge 20 rotates is a speed corresponding to the centrifugal force G. Such a cartridge 20 is configured as follows, for example.

  The cartridge 20 has a disk shape having an outer diameter inscribed in the centrifuge tube 10, and is separated in a state where the inside of the centrifuge tube 10 is separated into a base end side (opening 11 side) and a discharge port 13 side (tip end side). The tube 10 is invaginated.

  In addition, in a state where the cartridge 20 is inserted into the centrifuge tube 10, the centrifuge tube 10 and the cartridge 20 are kept liquid-tight and the cartridge 20 is rotatable in the centrifuge tube 10. To do.

  The outer wall of the cartridge 20 is provided with a recess 20a into which the fall prevention stopper 15 of the centrifugal tube 10 described above is recessed. On the other hand, inside the cartridge 20 are provided a storage chamber 21 that stores liquid therein, and a droplet tube 23 that communicates the storage chamber 21 with the outside of the cartridge 20. A pusher 25 is inscribed inside the storage chamber 21. The cartridge 20 also has a supply pipe 27 and a discharge pipe 29 that communicate with both sides of the disk shape. Further, a blade 31 is provided in the vicinity of the distal end side of the centrifugal tube 10 in the supply tube 27, and a lid 33 is disposed at the proximal end side of the centrifugal tube 10. Next, details of each part constituting the cartridge 20 will be described.

[Reservoir 21]
The storage chamber 21 has an opening 21a on one side of the bottom surface of the disk shape that constitutes the main body of the cartridge 20, and the disk shape is drawn out from the opening 21a to a midway depth in a constant shape. In this storage chamber 21, the opening diameter of the opening 21a is set smaller than the opening diameter of the deeper part, and the opening diameter is narrowed down over the entire circumference in the opening 21a. The cartridge 20 is inserted into the centrifuge tube 10 with the opening 21 a of the storage chamber 21 facing the proximal end of the centrifuge tube 10.

[Droplet tube 23]
The droplet tube 23 is provided in a state in which the storage chamber 21 communicates with the surface of the cartridge 20 in a state of being inserted into the centrifuge tube 10 toward the distal end of the centrifuge tube 10. The droplet tube 23 has a predetermined inner diameter. The inner diameter of the droplet tube 23 is stored in the storage chamber 21, and the droplet of the liquid (that is, the above-described component-containing solution L2) dropped through the droplet tube 23 has a predetermined volume. Suppose that The volume of the droplet is a value set so that fine particles obtained by solidifying the droplet have a predetermined diameter. The inner diameter of the droplet tube 23 is an appropriate value considering the rotational speed of the cartridge 20 in the centrifuge tube 10 and the centrifugal force applied to the liquid (that is, the component-containing solution) stored in the storage chamber 21. It is assumed that the value is designed. For example, the inner diameter of the droplet tube 23 is preferably set to a size of about 0.01 mm to 3 mm, and more preferably 0.05 mm to 0.4 mm.

  The droplet tube 23 is stored in the storage chamber 21 and has low wettability with respect to the liquid (that is, the above-described component-containing solution L2) dropped through the droplet tube 23. For example, it can be achieved by coating a material exhibiting water repellency or installing a large-diameter filter. As a result, the liquid in the storage chamber 21 is difficult to pass through the droplet tube 23 when no centrifugal force is applied.

  A plurality of such droplet tubes 23 may be arranged with respect to the storage chamber 21. In this case, the interval between the droplet tubes 23 arranged adjacent to each other is such that the droplets of the component-containing solution L2 formed through the droplet tubes 23 are not in contact with each other. It is designed to be an appropriate value in consideration of the size of the droplet.

[Presser 25]
The pusher 25 is disposed inside the storage chamber 21 and has a plate shape that is slidable in the depth direction of the storage chamber 21. Such a pusher 25 is pressed toward the distal end of the centrifuge tube 10 by applying a centrifugal force G in a state where the cartridge 20 is inserted into the centrifuge tube 10.

[Supply pipe 27]
The supply pipe 27 is provided in a state in which both sides of the disk shape of the cartridge 20 communicate with each other. Here, as an example, the supply tube 27 is configured as a groove shape opened in the outer circumferential direction of the cartridge 20, and the groove shape is blocked by the inner wall of the centrifugal tube 10 in a state where the cartridge 20 is indented into the centrifugal tube 10. A tubular shape is constructed. As a result, the supply pipe 27 communicates the distal end side and the proximal end side of the centrifugal tube 10 with the cartridge 20 indented into the centrifugal tube 10.

  Such a supply tube 27 is provided when the cartridge 20 is inserted into the centrifuge tube 10 with the pin 19 on the inner wall of the centrifuge tube 10 fitted in the groove-shaped supply tube 27. It is assumed that the drop prevention stopper 15 is provided in the recess 20a at a position where it is inserted.

  In addition, as will be described later, the supply pipe 27 passes the second fluid F2 supplied into the centrifuge tube 10 with the cartridge 20 as a bottom in a state where the cartridge 20 is indented in the centrifuge tube 10. Suppose that it is free with respect to the discharge pipe 29 demonstrated below. Being flexible with respect to the discharge pipe 29 means that the supply pipe 27 has sufficiently higher wettability with respect to the second fluid F2 than the discharge pipe 29. For example, when the second fluid F <b> 2 is oil, the inner wall of the supply pipe 27 is oleophilic and the wettability with respect to oil is better than that of the discharge pipe 29.

[Discharge pipe 29]
The discharge pipe 29 is provided in a state in which both sides of the disk shape of the cartridge 20 communicate with each other, and the distal end side and the proximal end side of the centrifugal tube 10 communicate with each other when the cartridge 20 is inserted into the centrifugal tube 10. .

  The discharge pipe 29 has low wettability with respect to the second fluid F <b> 2 (for example, castor oil) supplied to the proximal end side of the centrifuge tube 10 with respect to the cartridge 20. On the other hand, the discharge pipe 29 exhibits good wettability with respect to the first fluid F1 (for example, air) filled between the cartridge 20 and the distal end side of the centrifuge tube 10. In order to prevent the second fluid F2 from flowing into the discharge pipe 29, a one-way valve, a filter, or the like may be provided in the discharge pipe 29.

[Feather 31]
The blade 31 is provided in the vicinity of the opening of the supply pipe 27 on the surface of the cartridge 20 facing the distal end side of the centrifuge tube 10. The blade 31 receives a flow of the second fluid F2 (for example, oil) supplied from the supply pipe 27 to the distal end side of the centrifuge tube 10 and generates a propulsive force for rotating the cartridge 20. Such blades 31 may be attached to the cartridge 20 with an appropriate number, shape, and attachment angle in order to efficiently rotate the cartridge 20.

[Lid 33]
The lid 33 closes the supply pipe 27 in a state where the cartridge 20 is inserted into the centrifuge tube 10. Here, the lid 33 closes the supply pipe 27 while being supported by the pins 19 in a state where the cartridge 20 is inserted into the centrifuge tube 10. The lid 33 is lifted by the pin 19 when the cartridge 20 is pressed toward the distal end of the centrifugal tube 10 by the centrifugal force G by applying a centrifugal force G in a state where the cartridge 20 is inserted into the centrifugal tube 10. Is removed from the supply pipe 27 and the closed state of the supply pipe 27 is released.

<Lids 41 and 43>
Each of the lids 41 and 43 closes the opening 11 and the discharge port 13 of the centrifuge tube 10 while maintaining a sealed state. By attaching the lids 41 and 43 to the opening 11 and the discharge port 13, the inside of the centrifuge tube 10 is configured to be kept sealed. These lids 41 and 43 are detachable from the opening 11 and the discharge port 13 as necessary.

  Furthermore, the discharge port 13 may be configured such that a filter 43a is detachably provided in place of the lid 43. In this case, the filter 43a is provided with a plurality of holes having an opening diameter smaller than the diameter of the fine particles described above. The filter 43a can be joined to an aspirator (not shown) while maintaining a sealed state with the surroundings.

  Further, the lids 41 and 43 may be configured such that the hollow needle can be freely penetrated in a state in which a sealed state is ensured, for example. In this case, the lid 43 provided at the discharge port 13 may be configured integrally with the centrifuge tube 10 and does not necessarily need to be detachable from the discharge port 13.

<< Method for Producing Fine Particles in First Embodiment >>
Next, as a fine particle production method in the first embodiment, a fine particle production method using the fine particle production apparatus 1 described above will be described in detail with reference to FIGS.

[Figure 1]
First, as shown in FIG. 1, the discharge port 13 of the centrifuge tube 10 is closed and sealed with a lid 43, and the reaction liquid L <b> 1 is stored on the distal end side of the centrifuge tube 10. The storage amount of the reaction liquid L1 is assumed to be an amount sufficient for the formation of fine particles in which the liquid surface is at a position sufficiently lower than the stopper 17 for stopping movement. This reaction liquid L1 is a solution that reacts with a component-containing solution L2 described later and solidifies. As described above, when the component-containing solution is an alginate containing PRP or stem cells as an example, the reaction solution L1 is, for example, a calcium chloride solution.

  The reaction liquid L1 is introduced into the centrifuge tube 10 from the opened opening 11 side in a state where the cartridge 20 is taken out from the centrifuge tube 10, or the hollow needle penetrates the lid 43 of the discharge port 13. If possible, injection is performed from the outlet 13 side through a hollow needle pierced by the lid 43.

  On the other hand, the component-containing solution L2 is stored in the storage chamber 21 of the cartridge 20. At this time, the component-containing solution L2 is injected into the storage chamber 21 from the droplet tube 23 to move the pusher 25 toward the opening 21a of the storage chamber 21, and the storage chamber closed by the pusher 25. The component-containing solution L2 is stored in 21. In addition, the cartridge 20 may have an inlet that communicates with the storage chamber 21 separately from the droplet tube 23. In this case, the injection port communicates with the storage chamber 21 between the pusher 25 and the droplet tube 23, and the pusher 25 moves to the opening 21a side by injection of the component-containing solution L2 from the injection port. And

[Figure 2]
Next, as shown in FIG. 2, the cartridge 20 in which the component-containing solution L2 is stored in the storage chamber 21 is inserted into the centrifuge tube 10 in which the reaction solution L1 is stored. At this time, the cartridge 20 is inserted into the centrifuge tube 10 with the droplet tube 23 directed toward the distal end side of the centrifuge tube 10, and the pin 19 is fitted to the supply tube 27 of the cartridge 20, while the recess 20 a of the cartridge 20. The fall prevention stopper 15 is fitted to the lid 33 and the lid 33 is supported by the pin 19.

  In this state, since the component-containing solution L2 in the storage chamber 21 has low wettability with respect to the inner wall of the droplet tube 23, the component-containing solution L2 does not leak from the storage chamber 21 through the droplet tube 23. Further, between the cartridge 20 and the reaction liquid L1 in the centrifugal tube 10, the atmosphere is filled as the first fluid F1.

[Fig. 3]
Thereafter, as shown in FIG. 3, the second fluid F2 is supplied into the centrifuge tube 10 with the cartridge 20 as a bottom surface. The second fluid F2 has the following characteristics (1) to (3).

  (1) The second fluid F2 has a higher specific gravity than the first fluid F1 (here, for example, the atmosphere). (2) The second fluid F2 does not react with the reaction liquid L1 and the component-containing solution L2. (3) The second fluid F2 has good wettability with respect to the supply pipe 27, but has low wettability with respect to the discharge pipe 29, and thus does not pass through the discharge pipe 29.

  In particular, when the specific gravity of the second fluid F2 is smaller than the specific gravity of the reaction solution L1, (4) it is added to the characteristic condition that the second fluid F2 has a specific gravity smaller than that of the component-containing solution L2. On the other hand, when the specific gravity of the second fluid F2 is larger than the specific gravity of the reaction liquid L1, the second fluid F2 must dissolve and react with the reaction liquid L1 among the characteristic conditions of (2) above. It ’s fine.

  Here, as an example, when the reaction solution L1 is a calcium chloride solution, the component-containing solution L2 is an alginate containing PRP or stem cells, and the first fluid F1 is air, the above (1) to (5) are performed. Castor oil is used as the second fluid F2 to be filled.

  The supply of the second fluid F2 as described above may be performed from the opening 11 from which the lid 41 is removed. In this case, the opening 11 of the centrifuge tube 10 is closed with a lid 41 as necessary, and the inside of the centrifuge tube 10 is sealed. If the hollow needle can penetrate the lid 41, the second fluid F2 may be supplied into the centrifuge tube 10 through the hollow needle stuck in the lid 41.

[Fig. 4]
Next, as shown in FIG. 4, a centrifugal force G is applied to the centrifuge tube 10 in the direction of its distal end. In this case, a centrifugal force may be applied to the centrifuge tube 10 by using a centrifuge. Here, for example, the rotational speed in the centrifugal separator is adjusted so that a constant centrifugal force G is applied. It is assumed that the centrifugal force G applied here is large enough to perform the following operation.

  That is, the cartridge 20 in the centrifuge tube 10 is first pressed in the direction of the distal end of the centrifuge tube 10 by the centrifugal force G. At the same time, the fall prevention stopper 15 of the centrifuge tube 10 is pressed by the inner wall of the recess 20a of the cartridge 20 to exhibit flexibility. The fall restriction of is released.

  When the restriction on dropping of the cartridge 20 is released, the pin 19 on the inner wall of the centrifugal tube 10 lifts the lid 33 of the cartridge 20, and the lid 33 is removed from the supply tube 27 of the cartridge 20. The second fluid F2 flows into the distal end side, and the pin 19 is removed from the supply pipe 27, and the restriction on the rotation of the cartridge 20 is released. Thereby, the blade | wing 31 of the cartridge 20 receives the 2nd fluid F2, and rotation of the cartridge 20 is started.

  Further, in the centrifuge tube 10, the first fluid F <b> 1 that fills the front end side of the cartridge 20 flows out from the discharge pipe 29 to the proximal end side of the centrifuge tube 10 due to an increase in pressure on the front end side. Therefore, the distal end side of the centrifugal tube 10 with respect to the cartridge 20 is kept in an equilibrium state with a constant internal pressure, and the flow of the second fluid F2 through the supply tube 27 is continued.

  The second fluid F2 that has flowed from the supply pipe 27 to the distal end side of the centrifuge tube 10 has a specific gravity lighter than that of the reaction liquid L1, and thus is stored in a layer on the cartridge 20 side of the reaction liquid L1.

  Further, the pusher 25 in the storage chamber 21 is pressed toward the distal end side of the centrifugal tube 10 by the centrifugal force G, and the component-containing solution L2 in the storage chamber 21 is dropped from the droplet tube 23 communicating with the storage chamber 21. The liquid droplets C are separated by the shearing force generated by the rotation of the cartridge 20. Each droplet C continuously dropped from the droplet tube 23 has a centrifugal force G applied to the pusher 25, a rotational speed of the cartridge 20 corresponding to the centrifugal force G, an opening diameter of the droplet tube 23, and It has a predetermined volume set by the wettability of the component-containing solution L2 with respect to the inner wall of the droplet tube 23.

  Here, the droplet C of the component-containing solution L2 dropped from the droplet tube 23 has a specific gravity greater than that of the second fluid F2, and does not react with the second fluid F2. For this reason, the droplet C of the component-containing solution L2 passes through the second fluid F2 and reaches the reaction liquid L1.

  The droplet C of the component-containing solution L2 that has reached the reaction liquid L1 comes into contact with the reaction liquid L1 to form a shell s1 whose outer periphery is solidified, and fine particles S in which the component-containing solution L2 is filled in the shell s1 are formed. Is done. The diameter φ of the fine particles S is a predetermined value corresponding to the volume of the droplet C dropped from the droplet tube 23, that is, the centrifugal force G, and is larger than the inner diameter of the droplet tube 23.

  In this case, it is important that the rotation speed of the cartridge 20 is maintained at a constant speed at which the fine particles S have a predetermined diameter φ. Therefore, here, the centrifugal force G is kept constant and the rotational speed is kept at a predetermined constant speed. However, if the movement of the second fluid F2 and the component-containing solution L2 affects the rotational speed of the cartridge 20, the centrifugal force G is controlled so that the rotational speed of the cartridge 20 is kept constant. I will do it.

[Fig. 5]
Thereafter, as shown in FIG. 5, the application of the centrifugal force G is stopped in a state where a sufficient amount of fine particles S are formed. The application of the centrifugal force G may be stopped as long as a sufficient amount of fine particles S are formed. When the component-containing solution L2 in the storage chamber 21 is empty, the cartridge 20 comes into contact with the movement stop stopper 17. Alternatively, it may be performed by detecting a state in which the flow of the second fluid F2 from the supply pipe 27 stops.

[Fig. 6]
After the above, as shown in FIG. 6, the unreacted reaction liquid L1 and the second fluid F2 are discharged from the centrifuge tube 10 to separate the fine particles S from the reaction liquid L1 and the second fluid F2. For example, the reaction liquid L1 and the second fluid F2 are discharged as follows.

  First, the lid 41 is removed from the opening 11 of the centrifuge tube 10, and the second fluid F2 remaining in the storage chamber 21 of the cartridge 20 is removed. Further, if there is no need to pay attention to contamination in the centrifuge tube 10, the cartridge 20 may be taken out from the centrifuge tube 10. Thereafter, the opening 11 of the centrifuge tube 10 is again closed with a lid 41 as necessary.

  Next, the lid 43 that has sealed the discharge port 13 is replaced with a filter 43a. The filter 43a is provided with a plurality of holes having an opening diameter smaller than the diameter of the fine particles S as described above with reference to FIG. At this time, the centrifuge tube 10 may be tilted so that the discharge port 13 faces upward so that the fine particles S and the reaction liquid L1 in the centrifuge tube 10 do not leak from the discharge port 13.

  Next, for example, a syringe-type suction device 51 is joined in a sealed state to the replaced filter 43a, and the reaction solution L1 and the second fluid F2 are stored on the discharge port 13 side with the joint portion facing downward. . In this state, the reaction liquid L1 and the second fluid F2 are sucked by the aspirator 51 through the filter 43a, and the reaction liquid L1 and the second fluid F2 are selectively selected from the tip side of the centrifuge tube 10 with respect to the fine particles S. Is discharged. As a result, the microparticles S separated from the reaction liquid L1 and the second fluid F2 remain in the centrifuge tube 10.

  Note that when the suction device 51 itself has a suction filter attached to the suction tip, it is not necessary to attach the filter 43 a to the discharge port 13. In this case, a suction device equipped with a separation filter is joined in a sealed state to the discharge port 13 from which the lid 43 has been removed, and the reaction liquid L1 and the second fluid F2 are sucked through the separation filter of the suction device. Then, the reaction liquid L1 and the second fluid F2 may be selectively discharged from the centrifuge tube 10. Moreover, if the lid | cover 43 is a structure which can penetrate a hollow needle, you may attract | suck the reaction liquid L1 and the 2nd fluid F2 from the discharge port 13 through the hollow needle pierced by this lid | cover. In this case, the opening diameter of the hollow needle is smaller than the diameter of the fine particles S.

[Fig. 7]
After the above, as shown in FIG. 7, the fine particles S are taken out from the centrifuge tube 10 as necessary. At this time, the filter 43a attached to the discharge port 13 when the reaction liquid L1 and the second fluid F2 are discharged is replaced with a lid 43 through which the hollow needle can pass. Next, a hollow needle attached to a collection device 53 having a syringe-type suction function is passed through the lid 43, for example. The hollow needle has an opening diameter sufficiently larger than the diameter of the fine particles S. In this state, the fine particles S are sucked and collected in the collecting device 53 through the hollow needle. In FIG. 4 and other drawings, the size of the fine particles S is shown larger than other members for explanation.

  Here, the fine particles S can be collected even if the filter 43a is removed and a collection device having a syringe-type suction function is directly joined to the discharge port 13, and the fine particles S are sucked and collected in this collection device. good.

  Prior to the collection of the fine particles S, a procedure for collecting the fine particles S on the discharge port 13 side by performing a centrifugal treatment may be performed. Further, a procedure for cleaning the fine particles S using a cleaning liquid in the centrifuge tube 10 may be performed. The collecting device 53 may be used as a syringe for administering the fine particles S as it is.

<< Effects of First Embodiment >>
According to the fine particle production apparatus 1 and the fine particle production method of the first embodiment described above, the fine particles S having a predetermined diameter φ corresponding to the centrifugal force G are formed in the centrifuge tube 10 kept in a sealed state. This can be performed until the unreacted reaction liquid L1 and the second fluid F2 are separated. For this reason, it becomes possible to obtain fine particles having a predetermined particle diameter immediately in a sterile state.

<< Configuration of Fine Particle Manufacturing Apparatus 2 of Second Embodiment >>
FIG. 8 is a configuration diagram showing the fine particle manufacturing apparatus of the second embodiment. The particle production apparatus 2 of the second embodiment shown in this figure is different from the particle production apparatus of the first embodiment in that a separation filter 60 is provided in the centrifuge tube 10a. Thereby, the position of the discharge port 13 'is changed, and the liquid discharge port 61 is provided separately from the discharge port 13' on the distal end side of the centrifuge tube 10a. Since other configurations are the same as those in the first embodiment, the same components are denoted by the same reference numerals, and redundant description is omitted.

<Centrifuge tube 10a>
The centrifuge tube 10a is a cylindrical tube having an opening 11 with one end portion as a base end side and the other end portion as a distal end side, and the inner diameter is gradually narrowed. The movement stop stopper 17 and the pin 19 are provided in the same manner as the centrifuge tube of the first embodiment. At the distal end side of such a centrifuge tube 10a, a separation filter 60, which will be described in detail below, is provided in a state of separating the inside of the centrifuge tube 10 into a proximal end side and a distal end side. As a result, the distal end side of the centrifuge tube 10a in a state in which the cartridge 20 is inserted is divided into two chambers, that is, a particle forming chamber 10-1 on the cartridge 20 side and a drainage chamber 10-2 on the distal end side of the centrifuge tube 10a. To be separated.

  Among these, the fine particle forming chamber 10-1 is provided with a discharge port 13 'for the fine particles S. Moreover, the drainage port 61 is provided in the drainage chamber 10-2 located in the front end side of the centrifuge tube 10a.

  The discharge port 13 ′ is configured as a cylindrical tube having a predetermined inner diameter, whereby it is easily sealed with a lid 43 described later, and the suction device for taking out the fine particles S is sealed with respect to the discharge port 13 ′. It is the structure which is easy to join, maintaining. The opening diameter of the discharge port 13 ′ is sufficiently larger than the diameter of the fine particles S manufactured by the fine particle manufacturing apparatus 2. Further, such a discharge port 13 'is provided in a side peripheral portion of the centrifuge tube 10a.

  Similarly to the discharge port 13 ′, the drainage port 61 is configured as a cylindrical tube having a predetermined inner diameter, thereby being easily sealed with a lid 63 described below, and discharging liquid to the drainage port 61. The suction device for making it easy to join is maintained in a sealed state. Such a drain port 61 may be provided coaxially with the axis of the centrifuge tube 10a main body.

  The centrifuge tube 10a configured as described above is introduced into the centrifuge tube 10a, including the inner walls of the discharge port 13 'and the drain port 61, the fall prevention stopper 15, the movement stop stopper 17, and the material of the pin 19. It is the same as that of 1st Embodiment that it is comprised with the material which has tolerance with respect to the fluid to be performed.

  In particular, the particle forming chamber 10-1 of the centrifuge tube 10a is preferably made of a material having low adhesion to the particles S formed in the particle forming chamber 10-1 in addition to the above-described resistance. This facilitates the movement of the fine particles S in the fine particle formation chamber 10-1, and ensures the recovery rate of the fine particles S.

  The material of the centrifuge tube 10a is the same as that of the first embodiment in that the material of the main body is not limited as long as the inner wall is made of the material having the characteristics described above.

<Separation filter 60>
The separation filter 60 is provided perpendicular to the axis of the centrifuge tube 10a on the distal end side in the centrifuge tube 10a. The installation position of the separation filter 60 in the centrifuge tube 10a may be a position that does not hinder the formation of the fine particles S described below. For example, an interval between the separation filter 60 and the cartridge 20 that does not hinder the dropping of the droplet C supplied from the cartridge 20 to the separation filter 60 side in the formation of the particulate S described below is maintained. Suppose that you are leaning. The separation filter 60 may be disposed at the tip of the drainage port 61. In this case, the drainage chamber 10-2 is not provided on the tip side of the centrifuge tube 10a, and the particulate formation chamber 10- 1 only.

  Such a separation filter 60 may be provided in a state where the periphery is fixed to the inner peripheral wall of the centrifuge tube 10a without any gap.

  The separation filter 60 is formed with a plurality of holes having an opening diameter smaller than the diameter of the fine particles S formed in the fine particle forming chamber 10-1. These holes need not have a constant opening diameter. Moreover, the space | interval of a hole is not limited, and it is so preferable that the whole opening rate is large.

  The separation filter 60 as described above is preferably made of a material having low adhesion to the fine particles S formed in the fine particle forming chamber 10-1, and thereby the fine particles S in the fine particle forming chamber 10-1. And the recovery rate of the fine particles S is ensured.

  Further, the cartridge 20 has the same configuration as that of the first embodiment, but the surface facing the fine particle formation chamber 10-1 has low adhesion to the fine particles S formed in the fine particle formation chamber 10-1. It is preferably made of a material, which facilitates the movement of the fine particles S in the fine particle formation chamber 10-1 and ensures the recovery rate of the fine particles S.

<Lid 63>
The lid 63 closes the drain port 61 while maintaining a sealed state. By attaching the lid 63 to the drainage port 61, the inside of the centrifuge tube 10a is kept in a sealed state. The lid 63 is detachable from the drain port 61 as necessary.

  In addition, the lid 63 may be configured to allow the hollow needle to pass therethrough in a sealed state, for example. In this case, the lid 63 does not have to be detachable from the drain port 61. This is the same as the lid 43 for closing the discharge port 13 ′.

<< Method for Producing Fine Particles in Second Embodiment >>
Next, as a method for producing fine particles in the second embodiment, a method for producing fine particles using the fine particle production apparatus 2 described above will be described in detail with reference to FIGS.

[Fig. 8]
First, as shown in FIG. 8, a sufficient amount of the reaction liquid L1 is stored in the distal end side of the centrifuge tube 10a so that the separation filter 60 is sufficiently immersed. In this case, the same procedure as described with reference to FIG. 1 is performed in the description of the method for manufacturing fine particles according to the first embodiment. However, the drainage port 61 is also added as an option as an injection location of the reaction liquid L1.

  The amount of the reaction liquid L1 stored on the distal end side of the centrifuge tube 10a is a sufficient amount for the formation of fine particles because the liquid level is at a position sufficiently lower than the movement stop stopper 17 on the cartridge 20 side than the separation filter 60. Suppose that

  Further, the cartridge 20 in which the component-containing solution L2 is stored in the storage chamber 21 from the opening 11 into the centrifuge tube 10a is brought into a state of being indented.

  After the above, the second fluid F2 is supplied into the upper portion of the centrifugal tube 10a with the cartridge 20 as a bottom surface. Next, the opening 11 is closed by the lid 41 so that the inside of the centrifuge tube 10a is sealed, and a centrifugal force G toward the distal end is applied to the centrifuge tube 10a. As a result, the droplets C of the component-containing solution L2 are dropped from the storage chamber 21 to the reaction solution L1 to form the fine particles S. In this case, in the description of the fine particle manufacturing method of the first embodiment, the same procedure as that described with reference to FIGS. Thereby, fine particles S having a diameter φ corresponding to the centrifugal force G are formed.

[Fig. 9]
Next, as shown in FIG. 9, after a sufficient amount of fine particles S are formed and the application of the centrifugal force G is finished, the particles remaining in the fine particle formation chamber 10-1 and the drain chamber 10-2 are not left. By discharging the reaction liquid L1 and the second fluid F2 from the liquid discharge port 61, the fine particles S are separated from the reaction liquid L1 and the second fluid F2.

  At this time, since the opening diameter of the separation filter 60 is smaller than the diameter of the fine particles S, only the reaction liquid L1 and the second fluid F2 pass through the separation filter 60 and move to the drainage chamber 10-2. Thereby, only the reaction liquid L1 and the second fluid F2 are selectively discharged from the liquid discharge port 61 with respect to the fine particles S. In this case, for example, if the lid 63 of the drainage port 61 is configured to allow the hollow needle to penetrate, the reaction solution is discharged from the drainage port 61 using the suction device 51 via the hollow needle pierced by the lid 63. L1 and the second fluid F2 are sucked and drained. Alternatively, the lid 63 may be removed and the suction device 51 may be directly joined to the drainage port 61 to suck and drain the reaction liquid L1 and the second fluid F2.

  Prior to the discharge of the reaction liquid L1 and the second fluid F2 as described above, the lid 41 is removed from the opening 11 of the centrifuge tube 10a, and the second fluid F2 remaining in the storage chamber 21 of the cartridge 20 is removed. Alternatively, the procedure of taking out the cartridge 20 from the centrifuge tube 10 may be performed as in the first embodiment.

[FIG. 10]
After that, as shown in FIG. 10, the fine particles S are taken out from the fine particle forming chamber 10-1. In this case, if the cartridge 20 is left in the centrifuge tube 10a and the second fluid F2 is left in the storage chamber 21, a procedure for removing it is first performed. Further, the cartridge 20 may be taken out from the centrifuge tube 10.

  Thereafter, for example, if the lid 43 of the discharge port 13 ′ is configured to allow the hollow needle to pass therethrough, the hollow needle attached to the collection device 53 having a syringe-type suction function is passed through. The hollow needle has an opening diameter sufficiently larger than the diameter of the fine particles S. In this state, the fine particles S are sucked and collected in the collecting device 53 through the hollow needle. At this time, since the diameter φ of the fine particle S is larger than the opening diameter of the hole of the separation filter 60, the fine particle S does not move to the drainage chamber 10-2, but the discharge port 13 ′ of the fine particle formation chamber 10-1. Recovered from.

  Prior to the collection of the fine particles S, a procedure for washing the fine particles S using a cleaning liquid in the centrifuge tube 10a may be performed. Similarly to the first embodiment, the collection device 53 may be used as a syringe for administering the fine particles S as it is.

<< Effects of Second Embodiment >>
Even in the fine particle production apparatus 2 and the fine particle production method of the second embodiment described above, the fine particles S having the diameter φ corresponding to the centrifugal force G are formed in the sealed centrifuge tube 10a. Until separation from the unreacted reaction liquid L1 can be performed. For this reason, it becomes possible to obtain fine particles having a predetermined particle diameter immediately in a sterile state.

<< Configuration of Fine Particle Manufacturing Apparatus 3 of Third Embodiment >>
FIG. 11 is a configuration diagram showing the fine particle manufacturing apparatus according to the third embodiment. The particle production apparatus 3 of the third embodiment shown in this figure is different from the particle production apparatus of the first embodiment in that a partition plate 70 is provided in the centrifuge tube 10b. Since other configurations are the same as those in the first embodiment, the same components are denoted by the same reference numerals, and redundant description is omitted.

<Centrifuge tube 10b>
The centrifuge tube 10b is a cylindrical tube having an opening 11 with one end as a base end side, and an inner diameter gradually narrowed toward a discharge port 13 provided on the distal end side. The prevention stopper 15, the movement stop stopper 17, and the pin 19 are provided as in the centrifuge tube of the first embodiment. On the distal end side of the centrifuge tube 10b, a partition plate 70, which will be described next, is provided so that the inside of the centrifuge tube 10b is partitioned into a proximal end side and a distal end side.

  In a state where the cartridge 20 is indented, a drain port 61 ′ is provided in a portion closer to the cartridge 20 of the centrifuge tube 10 b than the partition plate 70. The drainage port 61 ′ is configured as a cylindrical tube having a predetermined inner diameter like the discharge port 13, and is thereby easily sealed with the lid 63, and is used for discharging the liquid to the drainage port 61 ′. The aspirator is configured to be easily joined in a sealed state. It is assumed that such a drain port 61 'is provided in a side peripheral portion of the centrifuge tube 10b. The lid 63 that closes the drain port 61 'may be the same as that described in the second embodiment.

  The centrifuge tube 10b configured as described above is also introduced into the centrifuge tube 10b, including the inner walls of the discharge port 13 and the drain port 61 ', the material for the fall prevention stopper 15, the movement stop stopper 17, and the pin 19. It is the same as that of 1st Embodiment that it is comprised with the material which has tolerance with respect to the fluid to be performed.

<Partition plate 70>
The partition plate 70 is provided on the distal end side of the centrifuge tube 10b in a state where the cartridge 20 is indented, and is provided in a state of partitioning the centrifuge tube 10b into the cartridge 20 side and the discharge port 13 side. The partition plate 70 has an opening 71 at a position facing, for example, the drainage port 61 ′, and is provided in a state in which a peripheral edge is fixed to the inner peripheral wall of the centrifuge tube 10b. Further, the partition plate 70 is provided in an inclined state with respect to the cartridge 20, and the inclination is set so that the position of the opening 71 is farthest from the cartridge 20.

  The installation position of the partition plate 70 in the centrifuge tube 10b is a position that does not hinder the formation of the particulate S described below, and a sufficient amount of the particulate S between the partition plate 70 and the outlet 13 is provided. Suppose that it is a position where the space which can be stored is provided. Further, an interval between the partition plate 70 and the cartridge 20 that does not hinder the dropping of the droplet C supplied from the cartridge 20 to the distal end side of the centrifuge tube 10b in the formation of the fine particles S described below. Is maintained.

  The partition plate 70 as described above is preferably made of a material having low adhesion to the fine particles S formed on the distal end side of the centrifuge tube 10b, and the fine particles S on the discharge port 13 side of the centrifuge tube 10b. The movement is facilitated and the recovery rate of the fine particles S is ensured.

<< Method for Producing Fine Particles in Third Embodiment >>
Next, as a method for producing fine particles in the third embodiment, a method for producing fine particles using the above-described fine particle production apparatus 3 will be described in detail with reference to FIGS.

[Fig. 11]
First, as shown in FIG. 11, the reaction solution L1 is stored on the distal end side of the centrifuge tube 10b. In this case, in the description of the fine particle manufacturing method of the first embodiment, the same procedure as that described with reference to FIG. 1 is performed. However, the drainage port 61 ′ is also added as an option as the injection point of the reaction liquid L1.

  The amount of the reaction liquid L1 stored on the distal end side of the centrifuge tube 10b is such that the liquid surface is located above the partition plate 70 and sufficiently lower than the movement stop stopper 17, and is sufficient for the formation of the fine particles S. Suppose that there is.

  Further, the cartridge 20 in which the component-containing solution L2 is stored in the storage chamber 21 is inserted into the centrifuge tube 10b through the opening 11.

  Thereafter, the second fluid F2 is supplied into the centrifuge tube 10b with the cartridge 20 as a bottom surface. Next, the opening 11 is closed by the lid 41 so that the inside of the centrifuge tube 10b is sealed, and a centrifugal force G toward the distal end is applied to the centrifuge tube 10b. As a result, the droplets C of the component-containing solution L2 are dropped from the storage chamber 21 to the reaction solution L1 to form the fine particles S. In this case, in the description of the fine particle manufacturing method of the first embodiment, the same procedure as that described with reference to FIGS. Thereby, fine particles S having a diameter φ corresponding to the centrifugal force G are formed.

  At this time, due to the centrifugal force G, the fine particles S move to the opening 71 closer to the discharge port 13 than the partition plate 70, and the fine particles S are collected from the opening 71 to the discharge port 13 side.

[Fig. 12]
Next, as shown in FIG. 12, after a sufficient amount of fine particles S are formed and the application of the centrifugal force G is finished, the unreacted reaction liquid L1 and the second fluid F2 are discharged from the drain port 61 ′. By discharging, the fine particles S are separated from the reaction liquid L1 and the second fluid F2.

  At this time, prior to the discharge of the reaction liquid L1 and the second fluid F2, the lid 41 is removed from the opening 11 of the centrifuge tube 10b, and the second fluid F2 remaining in the storage chamber 21 of the cartridge 20 is removed or centrifuged. The procedure for taking out the cartridge 20 from the tube 10b may be performed as in the first embodiment.

  Thereafter, the centrifuge tube 10b is tilted so that the opening 71 of the partition plate 70 faces upward and the liquid discharge port 61 'faces downward. At this time, the reaction liquid L1 and the second fluid F2 are poured into the liquid discharge port 61 'while the fine particles S are retained on the discharge port 13 side of the partition plate 70.

  In this state, the reaction liquid L1 and the second fluid F2 are drained from the drain port 61 '. At this time, for example, if the lid 63 of the drainage port 61 ′ is configured so that the hollow needle can be penetrated, the drainage port 61 ′ is used by using the suction device 51 through the hollow needle pierced by the lid 63. The reaction liquid L1 and the second fluid F2 are sucked and drained.

  Thereafter, the fine particles S are collected from the centrifuge tube 10b. In this case, in the description of the method for manufacturing fine particles according to the first embodiment, a hollow needle having an opening diameter sufficiently larger than the diameter of the fine particles S with respect to the lid 43, as in the procedure described with reference to FIG. And the fine particles S are sucked and collected in a syringe-type collecting device through the hollow needle. Alternatively, the lid 43 may be removed, and a collection device having a syringe-type suction function may be directly joined to the discharge port 13, and the fine particles S may be collected by suction.

  Prior to the collection of the fine particles S, a procedure for collecting the fine particles S on the discharge port 13 side by performing a centrifugal treatment may be performed. Further, a procedure for cleaning the fine particles S using a cleaning liquid in the centrifuge tube 10 may be performed. The collecting device 53 may be used as a syringe for administering the fine particles S as it is.

  In collecting the fine particles S, when a small amount of the reaction liquid L1 or the second fluid F2 remains on the discharge port 13 side of the partition plate 70, in the description of the fine particle production method of the first embodiment, As described with reference to FIG. 6, the lid 43 is replaced with a filter having a plurality of holes having an opening diameter smaller than the diameter of the fine particles S, and a syringe-type suction device is joined in a sealed state thereto. Then, the reaction liquid L1 and the second fluid F2 may be sucked by a suction device and removed from the centrifuge tube 10b.

<< Effects of Third Embodiment >>
Even in the fine particle production apparatus 3 and the fine particle production method of the third embodiment described above, the fine particles S having the diameter φ corresponding to the centrifugal force G are formed in the sealed centrifuge tube 10b. Until separation from the unreacted reaction liquid L1 can be performed. For this reason, it becomes possible to obtain fine particles having a predetermined particle diameter immediately in a sterile state.

  In the third embodiment described above, the opening 71 of the partition plate 70 is positioned along the inner peripheral wall of the centrifuge tube 10b, but may be near the axis of the centrifuge tube 10b having a cylindrical tube shape. Even in this case, it is preferable that the opening 71 is inclined with respect to the cartridge 20 so that the opening 71 is farthest from the cartridge 20. With such a configuration, when the formed fine particles S are moved to the discharge port 13 side and subjected to a centrifugal treatment, the fine particles S can be moved most effectively to the discharge port 13 side.

  In addition, the partition plate 70 is provided to be inclined with respect to the cartridge 20 so that the opening 71 is farthest from the cartridge 20. However, if the adhesion between the partition plate 70 and the microparticles S is extremely low, it is easy to move the microparticles S from the opening 71 toward the discharge port 13 by tilting the centrifuge tube 10b. May be provided in parallel to the cartridge 20.

  Further, in each of the above embodiments, the pusher 25 provided in the storage chamber 21 of the cartridge 20 has been described as a plate-like one. However, the pusher 25 may have a configuration in which a columnar part is provided on a plate-like upper surface and the columnar part protrudes from the opening 21 a of the storage chamber 21. In this case, it is preferable that the columnar portion of the pusher 25 is inscribed in the opening 21 a of the storage chamber 21. Accordingly, even when the pusher 25 is pushed into the storage chamber 21 by the centrifugal force G, the second fluid F2 can be prevented from entering and remaining in the storage chamber 21, and the remaining second The trouble of removing the fluid F2 can be saved.

  Further, the driving force for rotating the cartridge 20 may be generated by a power source such as a motor.

1, 2, 3 ... Fine particle production apparatus.
DESCRIPTION OF SYMBOLS 10, 10a, 10b ... Centrifugal tube 10-1 ... Fine particle formation chamber 10-2 ... Drainage chamber 11 ... Opening and taking out of cartridge 20 13, 13 '... Discharge port 15 ... Fall prevention stopper 17 ... Stop stopper for movement DESCRIPTION OF SYMBOLS 19 ... Pin 20 ... Cartridge 20a ... Indentation 21 ... Storage chamber 21a ... Opening of storage chamber 23 ... Droplet pipe 25 ... Pusher 27 ... Supply pipe 29 ... Discharge pipe 31 ... Blade 33 ... Cover which cancels | releases the obstruction | occlusion state of a supply pipe 41, 43 ... lid 43a ... filter 51 ... aspirator 53 ... collection device 60 ... separation filter 61, 61 '... drainage port 63 ... lid 70 ... partition plate 71 ... opening C ... droplet d ... interval F1 ... first Fluid F2 ... Second fluid G ... Centrifugal force L1 ... Reaction liquid L2 ... Component-containing solution S ... Fine particles s1 ... Shell φ ... Fine particle diameter

Claims (13)

A centrifuge tube;
A storage chamber for storing a liquid therein, and a cartridge inserted into the centrifuge tube;
A liquid drop tube provided in a state communicating with the storage chamber on the surface of the cartridge in a state of being indented in the centrifugal tube toward the distal direction of the centrifugal tube;
A discharge port of fine particles provided on the tip side of the centrifuge tube;
A lid for closing the outlet,
The cartridge has a speed corresponding to the centrifugal force about the axis of the centrifuge tube by applying a centrifugal force toward the distal end of the centrifuge tube with the cartridge inserted into the centrifuge tube. Fine particle production equipment that rotates with The fine particle manufacturing apparatus according to claim 1, wherein a pusher that is pressed in a distal direction of the centrifuge tube by the centrifugal force is provided in the storage chamber of the cartridge. The cartridge is
A supply pipe and a discharge pipe communicating with the distal end side and the proximal end side of the centrifugal tube in a state of being indented into the centrifugal tube;
The fine particle production according to claim 1 or 2, wherein a blade that rotates the cartridge by receiving fluid supplied from the supply pipe to the tip side by the centrifugal force is provided on a surface facing the tip side of the centrifuge tube. apparatus. The supply pipe has higher wettability than the discharge pipe with respect to the fluid supplied to the proximal end side of the centrifugal pipe with respect to the cartridge in a state where the cartridge is inserted into the centrifugal pipe. Fine particle production equipment. 5. The fine particle according to claim 3, wherein the cartridge is provided with a lid that closes the supply pipe while being inserted into the centrifuge tube and releases the closed state of the supply pipe by the centrifugal force. manufacturing device. The fine particle manufacturing apparatus according to claim 1, wherein a stopper for stopping movement of the cartridge in the centrifugal tube by the centrifugal force is provided on an inner wall of the centrifugal tube. The microparticle manufacturing apparatus according to any one of claims 1 to 6, wherein the inside of the centrifuge tube is kept sealed. The fine particle manufacturing apparatus according to any one of claims 1 to 7, wherein a filter having a hole having an opening diameter smaller than the diameter of the fine particles is detachably provided at the discharge port. The distal end side of the centrifuge tube is separated by a separation filter having a hole with an opening diameter smaller than the diameter of the fine particles,
The outlet is provided between the cartridge inserted into the centrifuge tube and the separation filter,
The fine particle manufacturing apparatus according to claim 1, wherein a liquid drainage port is provided on a distal end side of the centrifuge tube with respect to the separation filter. On the distal end side of the centrifuge tube, a partition plate that partitions the inside of the centrifuge tube leaving a part of the opening is provided,
The microparticle production apparatus according to claim 1, wherein a liquid drainage port is provided at a position apart from the opening between the cartridge inserted into the centrifuge tube and the partition plate. . A centrifuge tube;
A storage chamber for storing a liquid therein, and a cartridge inserted into the centrifuge tube;
A liquid drop tube provided in a state communicating with the storage chamber on the surface of the cartridge in a state of being indented in the centrifugal tube toward the distal direction of the centrifugal tube;
A discharge port of fine particles provided on the tip side of the centrifuge tube;
A lid for closing the outlet,
The cartridge has a speed corresponding to the centrifugal force about the axis of the centrifuge tube by applying a centrifugal force toward the distal end of the centrifuge tube with the cartridge inserted into the centrifuge tube. A method for producing fine particles using a fine particle production apparatus rotating at
With the discharge port closed with the lid, a reaction solution that reacts and solidifies with a component-containing solution containing a desired component is stored on the distal end side of the centrifuge tube,
The cartridge storing the component-containing solution in the storage chamber is inserted into the centrifuge tube storing the reaction solution,
By applying a centrifugal force toward the distal end of the centrifuge tube to the centrifuge tube in which the reaction liquid is stored and the cartridge is inserted, the component-containing solution in the storage chamber is removed from the droplet tube through the centrifuge. Push and supply to the tip side of the tube, rotate the cartridge relative to the axis of the centrifuge tube, and drop droplets of the component-containing solution supplied from the droplet tube into the reaction solution to form fine particles Form the
A method for producing fine particles, wherein the fine particles are separated from the reaction solution by selectively discharging the reaction solution from the inside of the centrifuge tube. The method for producing fine particles according to claim 11, wherein the inside of the centrifuge tube is kept sealed from the formation of the fine particles to the discharge of the reaction solution. The cartridge is
A supply pipe and a discharge pipe communicating with the distal end side and the proximal end side of the centrifugal tube in a state of being indented into the centrifugal tube;
On the surface toward the tip side of the centrifuge tube is provided with a blade that receives the fluid supplied from the supply tube to the tip side by the centrifugal force and rotates the cartridge,
Before the fine particles are formed, a second fluid that is heavier than the first fluid filling between the cartridge and the reaction solution is supplied to the proximal end side of the centrifuge tube from the cartridge,
13. When forming the fine particles, the cartridge is rotated by applying the centrifugal force to the centrifuge tube to push out the second fluid from the supply tube toward the blades. The manufacturing method of microparticles | fine-particles of description.

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