JP2014097456A - Device and method for dispersing particle - Google Patents

Abstract

PROBLEM TO BE SOLVED: To effectively disperse particles without damaging the particles.SOLUTION: A particle dispersion device 1 includes: a container 2 for accommodating a flock containing liquid; a dispersion nozzle 4 that has a dispersion channel 4a for dispersing flocks by a shear force when the flock containing liquid flows by predetermined introduction pressure; liquid feeding means 7 for feeding the flock containing liquid in the container 2 to the dispersion nozzle 4; and pressure raising means 5 for raising pressure on the flock containing liquid, which is fed by the liquid feeding means 7, to the predetermined introduction pressure before introduction into the dispersion nozzle 4.

Description

  The present invention relates to a particle dispersion apparatus and method.

  Conventionally, the aggregated particle-containing liquid is introduced from the supply port, and a turbulent flow is generated in the aggregated particle-containing liquid in the dispersion channel in which the direction of the channel is forcibly changed. A technique for dispersing is known (for example, see Patent Document 1).

Japanese Patent No. 2788010

However, the technique such as Patent Document 1 has the following problems.
That is, a constant flow pump such as a syringe pump or a peristaltic pump is used to prevent cell infection in order to disperse the cell mass in the cell suspension into isolated cells using this technique.

  When a cell suspension is introduced into a dispersion channel using a constant flow pump and dispersed by a shear force of the flow, the channel resistance of the dispersion channel is significantly higher than the channel resistance between the pump and the dispersion nozzle. Because of the large flow rate, there is a difference between the pump set flow rate and the flow rate in the dispersion channel, and only when the pressure applied to the supply port becomes sufficiently high, the flow rate is sufficient to disperse the cell mass in the dispersion channel. Occur.

  In this case, since the cell mass is dispersed only after a sufficient flow rate is generated in the dispersion channel, the cell mass that has flowed into the dispersion channel from the operation of the pump until the flow rate is increased is not dispersed. There is an inconvenience of passing through the dispersion channel.

  The present invention has been made in view of the above-described circumstances, and an object of the present invention is to provide a particle dispersing apparatus and method capable of effectively dispersing particles without damaging the particles.

In order to achieve the above object, the present invention provides the following means.
One aspect of the present invention is a dispersion nozzle having a container that contains an aggregated particle-containing liquid and a dispersion channel that disperses the aggregated particles by shearing force when the aggregated particle-containing liquid is caused to flow at a predetermined introduction pressure. A liquid feeding means for supplying the aggregated particle-containing liquid in the container to the dispersion nozzle, and the predetermined introduction pressure before introducing the aggregated particle-containing liquid supplied by the liquid supply means into the dispersion nozzle. There is provided a particle dispersing apparatus comprising a pressure increasing means for increasing the pressure.

  According to this aspect, when the aggregated particle-containing liquid stored in the container is supplied toward the dispersion nozzle by the operation of the liquid feeding means, the pressure is increased to the predetermined introduction pressure by the operation of the pressure increase means, and then the dispersion nozzle is supplied. Supplied. As a result, the agglomerated particle-containing liquid supplied to the dispersion nozzle can be made to flow while generating a shearing force capable of dispersing the agglomerated particles, and all particles can be dispersed without waste and without damaging the particles. Can do.

In the above aspect, the liquid feeding means may be a constant flow pump, and the pressure raising means may be a relief valve that is disposed between the container and the dispersion nozzle and is opened at the predetermined introduction pressure. .
By doing so, when the relief valve is closed and the constant flow pump is operated, the relief valve is opened when the introduction pressure reaches a predetermined pressure, and the aggregated particle-containing liquid in the container is dispersed. To be supplied. That is, the aggregated particle-containing liquid can be set to a predetermined introduction pressure from the initial stage of supply to the dispersion nozzle, and can flow in the dispersion channel of the dispersion nozzle while generating a shearing force capable of dispersing the aggregated particles. All particles can be dispersed without waste and without damaging the particles.

Further, in the above aspect, the liquid feeding means is a constant flow pump, and the pressure raising means is a passive valve disposed between the container and the dispersion nozzle and opened at the predetermined introduction pressure. Also good.
By doing so, when the constant flow pump is operated, the passive valve is opened when the introduction pressure reaches a predetermined pressure, and the aggregated particle-containing liquid in the container is supplied to the dispersion nozzle. That is, the aggregated particle-containing liquid can be set to a predetermined introduction pressure from the initial stage of supply to the dispersion nozzle, and can flow in the dispersion channel of the dispersion nozzle while generating a shearing force capable of dispersing the aggregated particles. All particles can be dispersed without waste and without damaging the particles.

Further, in the above aspect, the liquid feeding means is a constant flow pump, and the pressure raising means is filled with a filling means for filling a dummy liquid in a conduit between the container and the dispersion nozzle. A dummy liquid boosting unit that boosts the dummy liquid to the predetermined introduction pressure before the aggregated particle-containing liquid reaches the dispersion nozzle may be provided.
In this way, when the constant flow pump is operated in a state where the dummy liquid is filled in the conduit between the container and the dispersion nozzle by the filling means, the dummy that has not been boosted to the predetermined introduction pressure While the liquid is allowed to pass through the dispersion nozzle, the dummy liquid is pressurized to a predetermined introduction pressure by the dummy liquid pressurizing means, and then the aggregated particle-containing liquid in the container reaches the dispersion nozzle. The liquid can be passed through the dispersion nozzle at a predetermined introduction pressure, and the aggregated particles can be dispersed without waste.

Moreover, in the said aspect, the said dummy liquid pressure | voltage rise means may be a relief valve arrange | positioned in the downstream of the said dispersion | distribution nozzle.
By doing so, the dummy liquid is supplied to the dispersion nozzle while the relief valve is closed, and the relief valve is opened when the pressure is increased to a predetermined introduction pressure. At this point, since the aggregated particle-containing liquid reaches the dispersion nozzle, the aggregated particle-containing liquid can be passed through the dispersion nozzle at a predetermined introduction pressure, and the aggregated particles can be dispersed without waste.

In the above aspect, the dummy liquid booster may be a pipe having a predetermined length disposed between the container and the dispersion nozzle.
In this way, when the constant flow pump is operated, the dummy liquid accommodated in the conduit is first introduced into the dispersion nozzle. The pressure of the dummy liquid is increased to a predetermined introduction pressure by the dummy liquid pressurizing means including a pipe having a predetermined length until the aggregated particle-containing liquid reaches the dispersion nozzle.

  Moreover, in the said aspect, the said liquid feeding means is a 1st syringe which accommodates the said aggregated particle containing liquid between a 1st cylinder and a piston, and the said container is the space in the said 1st syringe. And the discharge port of the first cylinder is closed by a membrane member, and the dummy liquid pressurizing means has a second liquid containing a dummy liquid between the second cylinder using the first syringe as a piston. A needle-shaped member that is a syringe and penetrates the membrane member that has come close may be provided at the discharge port of the second syringe.

  By doing so, when the piston of the first cylinder is pressed to pressurize the agglomerated particle-containing liquid contained in the first syringe, the dummy liquid in the second cylinder is discharged using the first syringe as a piston. Pressurized and a dummy liquid is introduced into the dispersion nozzle from the discharge port. Until the pressure of the aggregated particle-containing liquid reaches a predetermined introduction pressure, only the dummy liquid is supplied to the dispersion nozzle. The membrane member that closes the discharge port of the first syringe by moving the first syringe through the second cylinder is penetrated by the needle-like member provided at the discharge port of the second syringe, The aggregated particle-containing liquid pressurized to a predetermined introduction pressure in the first syringe is discharged from the discharge port of the second syringe and supplied to the dispersion nozzle. Accordingly, the aggregated particle-containing liquid can be passed through the dispersion nozzle at a predetermined introduction pressure, and the aggregated particles can be dispersed without waste.

  Another aspect of the present invention has a dispersion flow path for dispersing aggregated particles by shearing force when the aggregated particle-containing liquid is caused to flow at a predetermined introduction pressure from a container containing the aggregated particle-containing liquid. Provided is a particle dispersion method in which a pipe line to a dispersion nozzle is filled with a dummy liquid, and then the dummy liquid and the aggregated particle-containing liquid are supplied to the dispersion nozzle while increasing the pressure to a predetermined introduction pressure.

  By doing so, the dummy liquid flows in the dispersion channel until the aggregated particle-containing liquid reaches a predetermined introduction pressure, and the aggregated particle-containing liquid is dispersed in a state where the predetermined introduction pressure is reached. Since the flow path can be made to flow, the entire amount of aggregated particles can be dispersed without waste.

  According to the present invention, it is possible to effectively disperse particles without damaging them.

It is a whole lineblock diagram showing the particle dispersion device concerning one embodiment of the present invention. FIG. 2A is an overall configuration diagram of a first modification of the particle dispersion device of FIG. 1, and FIG. It is a whole block diagram which shows the 2nd modification of the particle dispersion apparatus of FIG. It is a whole block diagram which shows the 3rd modification of the particle dispersion apparatus of FIG. It is a whole block diagram which shows the 4th modification of the particle dispersion apparatus of FIG.

A particle dispersion apparatus 1 according to an embodiment of the present invention will be described below with reference to the drawings.
As shown in FIG. 1, the particle dispersion apparatus 1 according to the present embodiment includes a sample container (container) 2 that contains a cell suspension (aggregated particle-containing liquid) containing aggregates, and an outlet of the container 2. Connected to the sample introduction pipe line 3, the dispersion nozzle 4 connected to the sample introduction pipe line 3, the relief valve (pressurizing means) 5 disposed at the introduction port of the dispersion nozzle 4, and the outlet port of the dispersion nozzle 4 A sample outlet line 6 to be arranged and a liquid feeding means 7 for discharging the cell suspension in the sample container 2 to the sample introduction line 3 are provided.

  The dispersion nozzle 4 includes a dispersion flow path 4a that causes the cell suspension introduced from the introduction port to flow and discharge the cell suspension from the discharge port. The dispersion flow path 4a is provided with a branch or a bend, and when a cell suspension is introduced into the introduction port with a predetermined introduction pressure, a shearing force is generated during the flow to cause aggregation in the cell suspension. The lump can be dispersed.

The relief valve 5 is closed when the liquid in the sample introduction line 3 is at a pressure lower than a predetermined equilibrium pressure (introduction pressure), prohibiting the flow of liquid into the dispersion nozzle 4, and the sample introduction line 3. When the liquid inside reaches a predetermined equilibrium pressure, the liquid is opened and the liquid in the sample introduction pipe 3 is introduced into the dispersion nozzle 4.
The liquid feeding means 7 is, for example, a constant flow pump such as a syringe pump or a peristaltic pump.

The operation of the particle dispersing apparatus 1 according to this embodiment configured as described above will be described below.
In order to disperse the aggregate in the cell suspension using the particle dispersion device 1 according to the present embodiment, the cell suspension is accommodated in the sample container 2 and the liquid feeding means 7 is operated. Then, the cell suspension in the sample container 2 is supplied into the sample introduction pipe 3. In the initial state lower than the predetermined equilibrium pressure, the pressure of the cell suspension in the sample introduction pipe 3 increases because the relief valve 5 is closed.

  When the pressure of the cell suspension in the sample introduction pipe 3 reaches a predetermined equilibrium pressure, the relief valve 5 is opened and the cell suspension is introduced into the dispersion channel 4a of the dispersion nozzle 4. The In the dispersion channel 4a, the cell suspension in a state of reaching a predetermined equilibrium pressure is caused to flow, so that the aggregate in the cell suspension is dispersed by the shearing force generated during the flow, and the outlet port To the sample outlet pipe 6.

  That is, according to the particle dispersion apparatus 1 according to the present embodiment, the cell suspension is allowed to flow in the dispersion flow path 4a at a flow rate at which a shearing force required for dispersion is generated from the initial stage when it is introduced into the dispersion nozzle 4. The cell suspension discharged to the sample outlet pipe 6 does not contain undispersed aggregates, and the aggregates in the entire cell suspension in the sample container 2 can be dispersed. There is an advantage.

  In the present embodiment, the relief valve 5 disposed at the introduction port of the dispersion nozzle 4 has been described as an example of the boosting unit. Instead, the relief valve 5 is shown in FIGS. 2 (a) and 2 (b). As described above, a passive valve such as an orifice 8 made of a water repellent material disposed at the inlet of the dispersion nozzle 4 may be adopted. The orifice 8 has a high flow resistance and cannot pass through the cell suspension unless the pressure exceeds a certain pressure. Therefore, only the cell suspension that has reached the equilibrium pressure is introduced into the dispersion nozzle 4 by adjusting the diameter and length of the orifice 8 so that the equilibrium pressure by the dispersion flow path 4a is equal to the passage pressure of the orifice 8. The same effect as the relief valve 5 can be obtained.

  Further, in the present embodiment, as shown in FIG. 3, a relief valve 5 as a pressure increasing means is provided in a sample outlet pipe 6 disposed downstream of the dispersion nozzle 4, and the sample container 2 to the relief valve 5 are provided. The sample introduction pipe line 3, the dispersion flow path 4a, and the sample outlet pipe line 6 are provided with a filling means 9 for filling a dummy liquid such as a cell suspension solvent.

  The filling means 9 is provided in the liquid introduction port 9 a provided in the sample outlet line 6 between the dispersion nozzle 4 and the relief valve 5, and in the sample introduction line 3 between the sample container 2 and the dispersion nozzle 4. And an air vent valve 9b.

  In order to disperse the agglomerates in the cell suspension by the particle dispersing apparatus 1 configured as described above, a dummy liquid is supplied from the liquid inlet 9a of the filling means 9 while the liquid feeding means 7 is stopped. Then, the sample is introduced into the sample outlet line 6, the dispersion channel 4 a and the sample introduction line 3. As a result, the air accumulated in the sample outlet line 6, the dispersion channel 4a, and the sample introduction line 3 is discharged to the outside from the air vent valve 9b, and the sample outlet line 6, the dispersion channel 4a, and the sample introduction line 3 is filled with a dummy liquid.

  In this state, by operating the liquid feeding means 7, the cell suspension and the dummy liquid are pressurized, and when the predetermined introduction pressure is exceeded, the relief valve 5 is released. Since the dispersion flow path 4a is filled with a dummy liquid, the cell suspension does not flow into the dispersion flow path 4a in a state where the predetermined introduction pressure is not exceeded. The agglomerates inside are dispersed by the dispersion nozzle 4.

  Further, in place of the relief valve 5, as shown in FIG. 4, a three-way valve 10 is provided at a portion where a dummy liquid flows from the liquid inlet to the sample outlet pipe 6 so that the sample inlet pipe 3 has a predetermined length. May be set. Here, the predetermined length of the sample introduction pipe line 3 is, for example, a length capable of securing a capacity of 1 to 10 mL, preferably 3 to 7 mL.

  In order to disperse the agglomerates in the cell suspension by the particle dispersing apparatus 1 configured as described above, the three-way valve 10 is switched to allow the dummy liquid to flow through the sample outlet pipe 6, the dispersion flow path 4a, and the sample introduction pipe. After flowing into the passage 3, the liquid feeding means 7 is operated and the three-way valve 10 is switched to release the sample outlet conduit 6. As a result, the cell suspension in the sample container 2 is introduced into the dispersion channel 4 a via the sample introduction pipe 3.

  When the cell suspension starts to flow, the dispersion channel 4a is filled with a dummy liquid, and when the cell suspension reaches the dispersion channel 4a, the cell suspension is predetermined. Reach the pressure of introduction. Also by this, since the whole amount of the cell suspension is caused to flow into the dispersion flow path 4a at a predetermined introduction pressure, the aggregate can be sufficiently dispersed without wasting cells.

Further, as shown in FIG. 5, the liquid feeding means 7 may be constituted by a two-stage syringe.
That is, the first cylinder 11a and the first piston 11b constitute the first syringe 11 that accommodates the cell suspension A therebetween, and the second syringe is used as the second syringe. The second syringe 12 containing the dummy liquid B is formed between the cylinder 12a and the first syringe 11, and the discharge port of the first syringe 11 is configured by the diaphragm 13 that can penetrate, A needle member 14 capable of penetrating the diaphragm may be disposed at the discharge port of the second syringe 12.

  By doing so, the cell suspension A in the first syringe 11 and the dummy liquid B in the second syringe 12 are maintained in an isolated state without being mixed with each other. When the first piston 11b of the first syringe 11 is pushed into the second cylinder 12a, the internal cell suspension A and the dummy liquid B are pressurized while the second cylinder 12a is pressed. The first syringe 11 moves. As a result, the dummy liquid B is introduced into the dispersion channel 4a of the dispersion nozzle 4 through the sample introduction pipe 3, and the introduction pressure into the dispersion channel 4a increases.

  When the diaphragm 13 provided at the tip of the first syringe moves to a position where it contacts the needle member 14, the diaphragm 13 is penetrated by the needle member 14, and the cell suspension A passes through the needle member 14 to the second position. From the discharge port of the syringe 12 into the sample introduction pipe line 3 and the dispersion flow path 4a. At this time, since the pressures of the cell suspension A and the dummy liquid B are increased to a predetermined introduction pressure, the entire amount of the cell suspension A enters the dispersion channel 4a at a predetermined introduction pressure. Since it is allowed to flow in, the aggregate can be sufficiently dispersed without wasting cells.

  In the present embodiment, the cell suspension containing the aggregated cells is exemplified as the aggregated particle-containing liquid. However, the present invention is not limited to this and is applied to any other aggregated particle-containing liquid. Also good.

A Cell suspension (liquid containing aggregated particles)
B Dummy liquid 1 Particle dispersion device 2 Sample container (container)
3 Sample introduction pipe (dummy liquid pressurizing means)
4 Dispersion nozzle 4a Dispersion flow path 7 Liquid feeding means 5 Relief valve (pressure raising means, dummy liquid pressure raising means)
8 Orifice (passive valve, pressure booster)
9 Filling means (pressure boosting means)
11 1st syringe 11a 1st cylinder 11b 1st piston (piston)
12 Second syringe (dummy liquid pressurizing means)
12a Second cylinder 13 Diaphragm (membrane member)
14 Needle member (Needle member)

Claims (8)

A container for containing the aggregated particle-containing liquid;
A dispersion nozzle having a dispersion channel for dispersing the aggregated particles by a shearing force when the aggregated particle-containing liquid is caused to flow at a predetermined introduction pressure;
Liquid feeding means for supplying the aggregated particle-containing liquid in the container to the dispersion nozzle;
A particle dispersion apparatus comprising: a pressure raising means for raising the aggregated particle-containing liquid supplied by the liquid feeding means to the predetermined introduction pressure before being introduced into the dispersion nozzle. The liquid feeding means is a constant flow pump;
2. The particle dispersing apparatus according to claim 1, wherein the pressure increasing means is a relief valve that is disposed between the container and the dispersion nozzle and is opened at the predetermined introduction pressure. The liquid feeding means is a constant flow pump;
The particle dispersing apparatus according to claim 1, wherein the pressurizing unit is a passive valve that is disposed between the container and the dispersion nozzle and is opened at the predetermined introduction pressure. The liquid feeding means is a constant flow pump;
The pressurizing means fills the duct between the container and the dispersion nozzle with a dummy liquid, and the filled dummy liquid before the aggregated particle-containing liquid reaches the dispersion nozzle. The particle dispersion apparatus according to claim 1, further comprising: a dummy liquid boosting unit that boosts the pressure to the predetermined introduction pressure.   The particle dispersion apparatus according to claim 4, wherein the dummy liquid pressurizing unit is a relief valve disposed on the downstream side of the dispersion nozzle.   The particle dispersion apparatus according to claim 4, wherein the dummy liquid pressurizing means is a pipe having a predetermined length disposed between the container and the dispersion nozzle. The liquid feeding means is a first syringe containing the aggregated particle-containing liquid between a first cylinder and a piston;
The container is a space in the first syringe;
A discharge port of the first cylinder is closed by a membrane member;
The dummy liquid pressurizing means is a second syringe containing a dummy liquid between the first cylinder as a piston and a second cylinder;
The particle dispersion apparatus according to claim 4, wherein a needle-like member that penetrates through the membrane member that has come close to the discharge port of the second syringe is provided.   When the aggregated particle-containing liquid is made to flow at a predetermined introduction pressure from the container that stores the aggregated particle-containing liquid, a pipe line from the dispersion nozzle having a dispersion channel that disperses the aggregated particles by shearing force is dummy. A particle dispersion method in which the dummy liquid and the aggregated particle-containing liquid are supplied to the dispersion nozzle while being pressurized to a predetermined introduction pressure after being filled with the liquid.

Images