JP2017035472A - Liquid treatment device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a liquid treatment device which can simply perform a set of operations from a priming process to a separation/recovery process of a liquid to be treated while simultaneously performing the priming process of a hollow fiber membrane module and a flow passage.SOLUTION: A liquid treatment device in the invention includes: a hollow fiber membrane module; a supply flow passage for supplying a liquid to be treated or a priming liquid to the hollow fiber membrane module; a first switching mechanism for switching the liquid to be injected to the hollow fiber membrane module; a rotating pump for sending the liquid; an air vent provided in the supply flow passage; a first space liquid recovery flow passage, branched into a recovery flow passage which makes a liquid in a first space pass for recovering the liquid that has been subjected to a separation treatment and a discharge flow passage for discharging an unnecessary liquid; a second space liquid recovery flow passage for recovering a liquid in a second space that is discharged from the hollow fiber membrane module; and a second switching mechanism for switching the flow passage of the liquid in the first space that is discharged from the hollow fiber membrane module.SELECTED DRAWING: Figure 2

Description

  The present invention relates to a liquid processing device.

  Solid-liquid separation that separates the liquid dispersed in the liquid from the liquid is used in various fields such as separation of cells and cell culture medium, such as removal of sludge in waste water and recovery of synthetic fine particles.

  Among these, as a method of solid-liquid separation, for example, a method of separating substances according to the pore size of the membrane using a separation membrane such as a hollow fiber membrane is known. In this case, the target solid component and liquid component can be separated by appropriately setting the pore size of the membrane. So far, a plasma separation membrane module used in extracorporeal circulation has been reported for separation of blood cells and plasma proteins with a hollow fiber membrane (Patent Document 1). Further, a method of washing platelets which are blood cells using a hollow fiber membrane (Patent Document 2), a method of washing cells from blood products during surgery (Patent Document 3), and concentrating cells in a cell culture solution (Patent Document 4) has been reported.

  Here, when a solute is removed from a liquid using a hollow fiber membrane module provided with a hollow fiber membrane, the liquid to be treated is connected by connecting a supply source of the liquid to be treated, the hollow fiber membrane module, and a recovery container through a flow path. Is processed by a hollow fiber membrane module. If substances derived from the manufacturing process remain in this flow path or hollow fiber membrane, the liquid to be treated after separation / recovery may be adversely affected. And the hollow fiber membrane module needs to be thoroughly washed. In addition, when gas is present in the liquid to be treated or the flow path, the hollow fiber membrane may be blocked by bubbles due to the gas in the hollow fiber membrane. In some cases, the solid in the membrane cannot be recovered. In order to prevent these problems, a process called priming (priming process), which is a process of cleaning the flow path and the hollow fiber membrane module with a liquid called a priming liquid before use and removing air, is essential.

  Normally, when priming a hollow fiber membrane module filled with an initial filling liquid, in order to prevent air bubbles remaining in the flow channel from being injected into the hollow fiber membrane module, the flow channel and the hollow fiber membrane module are Although it is separately primed in a state where it is not connected, a method of priming the module and the flow channel in a state where the hollow fiber membrane module filled with the initial filling liquid and the flow channel are connected has also been reported, For example, a method for priming the hollow fiber membrane module and the flow path using forward / reverse rotation of a rotary pump in a closed closed flow path has been reported (Patent Document 5).

Japanese Patent Laid-Open No. 1-171566 JP 2012-261982 A JP-A-7-136244 Japanese Patent Application No. 2015-12837 JP2012-152286A

  Patent Documents 1 to 4 describe a method for removing solutes such as plasma, platelets, cells, proteins, and turbids from a liquid using a separation membrane such as a hollow fiber membrane. The way to do is not considered.

  Patent Document 5 describes a method of simply performing priming in a state in which the flow channel and the hollow fiber membrane module are connected. However, it is necessary to form a loop in the flow channel before the priming process. Since it is necessary to change the connection to cancel the loop, the process is interrupted by changing the connection. In addition, since the priming is automated using forward and reverse rotations of the rotary pump, there is a possibility that the air remaining during the reverse rotation flows back again.

  Therefore, the present invention can easily perform a series of operations from the priming step to the separation / recovery step of the liquid to be processed while simultaneously performing the priming step of the hollow fiber membrane module filled with the initial filling liquid and the flow path. Another object is to provide a liquid processing device.

As a result of intensive studies to solve the above problems, the present inventors have found the following inventions (1) to (8).
(1) A case having three openings, a first space liquid inlet, a first space liquid outlet, and a second space liquid outlet, and a hollow fiber membrane for separating and treating the liquid to be treated, The first space inlet and the first space liquid outlet are in communication with the first space, and are arranged inside the case so as to partition the first space on the surface side and the second space on the outer surface side. A two-space liquid discharge port communicates with the second space, and is connected to the hollow fiber membrane module and the first space injection port, and a supply channel for supplying a liquid to be treated or a priming solution to the hollow fiber membrane module A first switching mechanism that is provided in the supply flow path and switches the liquid to be injected into the hollow fiber membrane module, and a rotary pump that is provided in the supply flow path and rotates in one direction to feed liquid And provided in the supply flow path, A first air vent capable of injecting or discharging the body and the first space liquid discharge port are connected to allow the liquid in the first space discharged from the hollow fiber membrane module to pass therethrough and collect the separated liquid. Connected to the first spatial liquid recovery flow channel branched to the recovery flow channel for discharging and the discharge flow channel for discharging unnecessary liquid, and the second spatial liquid discharge port, from the hollow fiber membrane module A second space liquid recovery flow path for recovering the liquid in the discharged second space, and a liquid in the first space discharged from the hollow fiber membrane module provided in the first space liquid recovery flow path. A liquid processing device provided with a second switching mechanism for switching a flow path.
(2) A case having three openings, a first space liquid inlet, a first space liquid outlet, and a second space liquid outlet, and a hollow fiber membrane for separating and treating the liquid to be treated, The first space inlet and the first space liquid outlet are in communication with the first space, and are arranged inside the case so as to partition the first space on the surface side and the second space on the outer surface side. A two-space liquid discharge port communicates with the second space, and is connected to the hollow fiber membrane module and the first space injection port, and a supply channel for supplying a liquid to be treated or a priming solution to the hollow fiber membrane module A first switching mechanism that is provided in the supply flow path and switches the liquid to be injected into the hollow fiber membrane module, and a rotary pump that is provided in the supply flow path and rotates in one direction to feed liquid And provided in the supply flow path, A first air vent capable of injecting or discharging a body, and a first space liquid recovery channel connected to the first space liquid discharge port and recovering the liquid in the first space discharged from the hollow fiber membrane module; , Connected to the second space liquid discharge port, allows the liquid in the second space discharged from the hollow fiber membrane module to pass through, and discharges the recovery flow path for recovering the separated liquid and unnecessary liquid A second space liquid recovery channel that branches into a discharge channel for performing the operation, and a liquid in the second space that is provided in the second space liquid recovery channel and is discharged from the hollow fiber membrane module. A liquid processing device provided with a second switching mechanism for switching a flow path.
(3) A second air vent capable of injecting or discharging gas into the second space is provided, and the hollow fiber membrane module communicates with the second space and can be connected to the second air vent. The liquid processing device according to (1) or (2), comprising a discharge port.
(4) The liquid treatment according to any one of (1) to (3), wherein the first air vent includes an air trap chamber, an air vent channel connected to the air trap chamber, and an opening / closing mechanism for the air vent channel. device.
(5) A cock or click chip is provided at least at one of the connection sites of the hollow fiber membrane module and the supply channel, the hollow fiber membrane module and the recovery channel, or the hollow fiber membrane module and the discharge channel. The liquid processing device according to any one of (1) to (4).
(6) The liquid treatment device according to any one of (1) to (5), wherein an air vent is provided in the first space inlet side case of the hollow fiber membrane module.
(7) The liquid treatment device according to any one of (1) to (6), wherein platelets and plasma proteins are separated and collected from the platelet preparation.
(8) A liquid processing method using the liquid processing device according to any one of (1) to (7), in which a first priming step for filling a priming liquid in the supply channel and the above-mentioned filling with an initial filling liquid A second priming step of discharging the initial filling liquid in the second space of the hollow fiber membrane module from the second space liquid outlet and filling the second space with the priming liquid, and filling with the initial filling liquid Replacing the initial filling liquid in the first space of the hollow fiber membrane module by injecting a priming liquid from the first space inlet, and replacing the initial filling liquid from the first space liquid outlet. A third priming step to be discharged; a separation treatment step for injecting a liquid to be treated into the hollow fiber membrane module to carry out a separation treatment; and a separation-treated liquid obtained by the separation treatment step A liquid recovery method including a separation process-completed liquid recovery step of recovering the body through the recovery flow path of the first spatial liquid recovery flow path while discharging the body from the first spatial liquid discharge port.

  In the liquid processing method of (8), for example, i) a case having three openings of a first space inlet, a first space liquid outlet, and a second space liquid outlet, and a hollow for separating and processing the liquid to be processed The hollow fiber membrane is disposed inside the case so as to partition the first space on the inner surface side and the second space on the outer surface side, and the first space inlet and the first space liquid The discharge port communicates with the first space, the second space liquid discharge port communicates with the second space, and is connected to the hollow fiber membrane module and the first space injection port. A supply flow path for supplying a liquid to be treated or a priming liquid, a first switching mechanism provided in the supply flow path for switching the liquid to be injected into the hollow fiber membrane module, and provided in the supply flow path, A rotary pump that rotates in one direction A first air vent provided in the supply channel and capable of injecting or discharging gas into the supply channel and connected to the first space liquid outlet, and in the first space discharged from the hollow fiber membrane module A first spatial liquid recovery flow path that branches into a recovery flow path for allowing liquid to pass through and recovering the separated liquid and a discharge flow path for discharging unnecessary liquid; and the second spatial liquid A second space liquid recovery channel connected to a discharge port for recovering the liquid in the second space discharged from the hollow fiber membrane module; and the hollow fiber membrane provided in the first space liquid recovery channel. A liquid processing method using a liquid processing device provided with a second switching mechanism for switching a liquid flow path in a first space discharged from a module, wherein the first priming liquid is filled in the supply flow path. Priming process and initial filling liquid A second priming step of discharging an initial filling liquid in the second space of the filled hollow fiber membrane module from the second space liquid outlet and filling the second space with a priming liquid; Replacing the initial filling liquid in the first space of the hollow fiber membrane module filled with the filling liquid by injecting a priming liquid from the first space inlet, and replacing the initial filling liquid from the first space liquid outlet A third priming step for discharging, a separation treatment step for injecting the liquid to be treated into the hollow fiber membrane module and performing a separation treatment, and a separation-treated liquid obtained by the separation treatment step as the first space liquid. A liquid treatment method including a separated liquid recovery step which is discharged from the discharge port and recovered through the recovery flow path included in the first spatial liquid recovery flow path; ii) the first space injection port, the first And a hollow fiber membrane for separating and treating the liquid to be treated, the hollow fiber membrane comprising a first space on the inner surface side and a first space on the outer surface side. The first space inlet and the first space liquid outlet are in communication with the first space, and the second space liquid outlet is the second space. A hollow fiber membrane module in communication with the first space inlet, a supply flow path for supplying a liquid to be treated or a priming liquid to the hollow fiber membrane module, and a supply flow path provided in the supply flow path A first switching mechanism that switches the liquid to be injected into the hollow fiber membrane module, a rotary pump that is provided in the supply flow path and rotates in one direction to feed liquid, and is provided in the supply flow path. The gas can be injected into or discharged from the supply channel. 1 air vent, a first space liquid recovery channel connected to the first space liquid discharge port and recovering the liquid in the first space discharged from the hollow fiber membrane module, and the second space liquid discharge port A recovery flow path for recovering the separated liquid and a discharge flow path for discharging the unnecessary liquid, allowing the liquid in the second space discharged from the hollow fiber membrane module to pass through. A second space liquid recovery channel that is branched, and a second switch that is provided in the second space liquid recovery channel and switches the channel of the liquid in the second space discharged from the hollow fiber membrane module. A liquid processing method using a liquid processing device provided with a mechanism, the first priming step for filling a priming liquid in the supply channel, and the hollow fiber membrane module filled with an initial filling liquid First in the second space A second priming step of discharging the filling liquid from the second space liquid outlet and filling the second space with the priming liquid, and the first space of the hollow fiber membrane module filled with the initial filling liquid. A third priming step in which the initial filling liquid is replaced by injecting a priming liquid from the first space inlet, and the initial filling liquid is discharged from the first space liquid outlet; A separation process step for injecting into the module and performing a separation process, and a separation-processed liquid obtained by the separation process step is discharged from the second space liquid discharge port and the second space liquid recovery channel has A liquid processing method including a separated liquid recovery step of recovering through a flow path is applicable.

  According to the present invention, a series of operations from the priming process to the separation / collection process of the liquid to be processed can be easily performed while simultaneously performing the priming process of the hollow fiber membrane module filled with the initial filling liquid and the flow path. Therefore, it is possible to provide a liquid processing device that can recover a specific solid or solute component from the liquid to be processed at a high rate.

  In order to efficiently prime the hollow fiber outer space, it is usually efficient to use a flow path and a liquid feeding system connected only to the second space on the outer surface side of the hollow fiber membrane. Since it is necessary to prepare an additional flow path and a rotary pump for connection to only two spaces, the structure is complicated. However, in the present invention, the configuration of the flow path is further simplified by performing the priming only by injecting the priming liquid from the first space on the inner surface side of the hollow fiber membrane. In addition, since the priming liquid is injected after the initial filling liquid in the second space is first discharged, the amount of the priming liquid used for cleaning the second space can be reduced to improve the priming efficiency.

The schematic of the hollow fiber membrane module used for the liquid processing device of this invention. 1 is a schematic view of a liquid processing device according to an embodiment of the present invention. The operation | movement flowchart figure of the liquid processing device which concerns on embodiment of this invention. FIG. 1 is a schematic diagram 1 of a liquid processing device according to another embodiment of the present invention. FIG. 3 is a schematic view 2 of a liquid processing device according to another embodiment of the present invention. FIG. 3 is a schematic view of a liquid processing device according to another embodiment of the present invention. FIG. 4 is a schematic view of a liquid processing device according to another embodiment of the present invention.

  The liquid treatment device of the present invention includes a case having three openings, a first space injection port, a first space liquid discharge port, and a second space liquid discharge port, and a hollow fiber membrane for separating and processing the liquid to be processed, The hollow fiber membrane is arranged inside the case so as to partition the first space on the inner surface side and the second space on the outer surface side, and the first space inlet and the first space liquid outlet are the first space. The second space liquid outlet is connected to the hollow fiber membrane module, which is in communication with the second space, and the first space inlet, and the liquid to be treated or the priming liquid is supplied to the hollow fiber membrane module. A supply flow path to be supplied; a first switching mechanism provided in the supply flow path for switching a liquid to be injected into the hollow fiber membrane module; and provided in the supply flow path, rotated in one direction and fed. A rotary pump for liquid and the supply channel A first air vent capable of injecting or discharging gas into the supply channel, and connected to the first space liquid outlet, allowing the liquid in the first space discharged from the hollow fiber membrane module to pass through, Connected to the first space liquid recovery channel that branches into a recovery channel for recovering the separated liquid and a discharge channel for discharging unnecessary liquid, and to the second space liquid outlet A second space liquid recovery channel for recovering the liquid in the second space discharged from the hollow fiber membrane module, and the first space liquid recovery channel provided in the first space liquid recovery channel and discharged from the hollow fiber membrane module. A second switching mechanism for switching the liquid flow path in the first space is provided.

  The liquid treatment device of the present invention includes a case having three openings, a first space injection port, a first space liquid discharge port, and a second space liquid discharge port, and a hollow fiber membrane that separates the liquid to be processed. The hollow fiber membrane is disposed inside the case so as to partition the first space on the inner surface side and the second space on the outer surface side, and the first space inlet and the first space liquid outlet are the first space. The second space liquid discharge port communicates with the first space, and is connected to the hollow fiber membrane module and the first space injection port, which communicates with the second space. A supply flow path for supplying liquid, a first switching mechanism provided in the supply flow path for switching the liquid to be injected into the hollow fiber membrane module, and provided in the supply flow path and rotating in one direction. A rotary pump that feeds liquid and the supply flow A first air vent provided in the gas passage for injecting or discharging gas into the supply flow path and the first space liquid discharge port connected to the first space vent and collecting the liquid in the first space discharged from the hollow fiber membrane module Connected to the first space liquid recovery flow path and the second space liquid discharge port, for allowing the liquid in the second space discharged from the hollow fiber membrane module to pass therethrough and for recovering the separated liquid A second spatial liquid recovery channel branched into a recovery channel and a discharge channel for discharging unnecessary liquid; and provided in the second spatial liquid recovery channel and discharged from the hollow fiber membrane module And a second switching mechanism for switching the liquid flow path in the second space.

  Here, examples of the liquid to be treated in the present invention include cell components, synthetic fine particles, inorganic fine particles, and vesicle dispersions. Further, the liquid to be treated may contain a cell culture medium and plasma. The liquid to be treated is not limited to these, and may include rainwater, seawater, earth and sand liquid in the environment, and the like. Cell components may be, for example, animal cells, microorganisms, plant cells, and cell suspensions composed of somatic cells, living body germ cells, somatic stem cells, induced pluripotent stem cells, and embryonic hepatocytes. These cells may be those obtained by treating or culturing living tissue. In addition, blood cells derived from living organisms or cultures, blood products such as platelet products and erythrocyte products, and cell suspension liquids or liquid components such as plasma and ascites may also be used.

  In addition, the initial filling liquid in the present invention is a liquid filled in an unused hollow fiber membrane module, and is not particularly limited. For example, an electrolyte solution or the like is used.

  In addition, the priming solution in the present invention refers to a cell culture or differentiation medium, plasma, a blood product preservation solution, a buffer such as an infusion, a specific gravity adjusting solution, etc., but is not limited thereto, and is a liquid such as pure water. Including. In addition, the priming liquid and the liquid for cleaning and collecting the separated liquid may be different types.

  Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the drawings, but the present invention is not limited to these aspects. Further, the ratios of the drawings do not necessarily match those described.

  A liquid processing device according to an embodiment of the present invention will be described with reference to FIGS. 1 and 2. FIG. 1 is a schematic view of a hollow fiber membrane module used in a liquid processing device.

  The hollow fiber membrane module shown in FIG. 1 is formed by bundling a plurality of hollow fiber membranes 1 that are tubular membranes and installing them inside a cylindrical case 8. The inside of the case 8 is hollow fiber. The membrane 1 is partitioned into a first space 2 connected to the inner surface side of the hollow fiber membrane 1 and a second space 3 connected to the outer surface side of the hollow fiber membrane 1. In FIG. 1, the hatched portion in the case 8 indicates the first space 2, and the white portion indicates the second space 3. The case 8 has four openings: a first space inlet 4, a first space liquid outlet 5, an air outlet 6, and a second space liquid outlet 7. Here, the first space 2 communicates with the first space inlet 4 disposed at the upper part of the case 8 and the first space liquid outlet 5 disposed at the lower part of the case 8. Further, the second space 3 communicates with the air discharge port 6 disposed above the side surface of the case 8 and the second space liquid discharge port 7 disposed below the side surface of the case 8.

  Here, the material of the hollow fiber membrane 1 in the present invention is preferably a polysulfone polymer such as polysulfone or polyethersulfone, or a polymer material such as polymethyl methacrylate. Among these, a polysulfone-based polymer is preferably used from the viewpoint of water permeability of the hollow fiber membrane 1 and the like.

In the hollow fiber membrane module of the present invention, when processing biologically derived particles such as platelet preparations, cells and proteins, the membrane surface area is preferably 0.02 m ² or more with respect to 100 mL of the liquid to be processed. More preferably, it is 5 m ² or more. Moreover, in order to prevent cells and proteins from adhering to the membrane surface and increasing loss, the membrane surface area should not be too large. Specifically, the membrane surface area is preferably 2.0 m ² or less, and 1.0 m ^2. The following is more preferable. In addition, when processing particles derived from living bodies, it is preferable that the membrane surface has a hydrophilic polymer, and the presence of the hydrophilic polymer with respect to all molecules up to a depth of 10 nm on the surface of the hollow fiber membrane 1. It is preferable that a rate is 40-70 mass% or less.

  The film surface referred to here is a surface in contact with the liquid to be processed. The abundance of the hydrophilic polymer can be measured by X-ray photoelectron spectroscopy. The hydrophilic polymer here means a polymer having a solubility in water of 25 ° C. of preferably 0.001% by weight or more, more preferably 0.01% by weight or more, and further preferably 0.1% by weight or more. Specific examples include polyvinyl pyrrolidone, polyethylene glycol, polypropylene glycol, polyvinyl alcohol, polyvinyl acetate, polyacrylamide and copolymers thereof, such as vinyl alcohol / vinyl acetate copolymer, vinyl pyrrolidone / Examples thereof include vinyl acetate copolymer and ethylene glycol / vinyl alcohol copolymer. From the viewpoint of reducing adhesion of blood components, the hydrophilic polymer present on the membrane surface includes vinyl alcohol / vinyl acetate copolymer, vinyl pyrrolidone / vinyl acetate copolymer, ethylene glycol / vinyl alcohol copolymer. Copolymers such as are preferably used.

  Further, from the viewpoint of reducing the elution of the hydrophilic polymer from the hollow fiber membrane and preventing the activation of blood components, the hydrophilic polymer in the hollow fiber membrane is preferably cross-linked. Specifically, the cross-linked polymer that is insoluble in the good solvent for the polymer constituting the hollow fiber membrane is preferably 10% or more, more preferably 30% or more of the polymer weight of the entire membrane. In order to reduce adhesion of blood components, the cross-linked polymer ratio is preferably 80% or less, and more preferably 50% or less.

The area of the hollow fiber membrane in the present invention can be changed depending on the amount of the liquid to be processed. In addition, the pore diameter of the hollow fiber membrane, the permeation performance of water from the inside to the outside of the hollow fiber membrane, and the target to be separated can be changed. As an example, when separating a platelet preparation with a volume of 100 to 800 mL containing 2.0 × 10 ^{11 to} 4.0 × 10 ¹¹ platelets into platelets and plasma proteins, the membrane surface area is 0.3 to It is preferably 2.5 m ² . The pore diameter on the membrane surface is preferably 0.02 to 2 μm, and more preferably 0.05 to 1.5 μm. Permeability of water is preferably ^{5000~13000mL / mmHg / hr / m 2} , more preferably ^{8000~12000mL / mmHg / hr / m 2} .

  In extracorporeal circulation such as an artificial kidney and a plasma separator, blood is filtered by so-called crossflow. On the other hand, since the liquid to be treated is totally filtered by the hollow fiber membrane module in the application of the present invention, the combination of the flow path and the hollow fiber membrane module is also important. In particular, when the liquid to be treated is a blood component, cells and proteins may be activated, which is particularly important. Therefore, the end face length of the hollow fiber membrane is preferably 10 cm or more, and more preferably 15 cm or more. Further, the end face length of the hollow fiber membrane is preferably 35 cm or less, and more preferably 27 cm or less. The end face length of the hollow fiber membrane here refers to the length between both ends of the hollow fiber membrane fixed between the cases.

  FIG. 2 is a schematic view of a liquid processing device according to an embodiment of the present invention. The liquid treatment device shown in FIG. 2 is formed by connecting a plurality of flow paths to a hollow fiber membrane module. The first space inlet 4 of the hollow fiber membrane module is connected to a liquid supply channel 23 for supplying a liquid to be treated or a priming liquid to the hollow fiber membrane module, and the first space liquid outlet 5 Connected to the first spatial liquid recovery flow path 9 that branches into a recovery flow path 9a that allows the liquid in the space to pass through and recovers the separated liquid and a discharge flow path 9b that discharges unnecessary liquid. Yes. The air discharge port 6 is connected to a second air vent channel 10 of the second air vent, and the second space liquid discharge port 7 is a second space liquid discharge for collecting the liquid in the second space. The flow path 11 is connected.

  Note that the second air vent in the present invention includes the second air vent channel 10 and an electromagnetic valve 106 that is an opening / closing mechanism of the second air vent channel 10, thereby allowing gas to enter the second space. Injection and draining can be performed.

  In the present embodiment, the hollow fiber membrane module has an air exhaust port 6, and the air in the second space is exhausted by connecting to the second air vent channel 10 of the second air vent through the air exhaust port 6. Although it is possible, the second air vent need not be provided. In that case, the air outlet 6 is not disposed in the hollow fiber membrane module, and the hollow fiber membrane module and the second air vent are not connected. The second air vent is more suitable for priming the second space.

  In this embodiment, the hollow fiber membrane module has an air vent 26 (third air vent) in the first space inlet side case (header) portion, and air in the first space can be discharged through the air outlet 26. However, the first space inlet side case may not have an air vent. In that case, the first space inlet side case of the hollow fiber membrane module is connected only to the liquid supply channel 23 for supplying the liquid to be processed or the priming liquid. The electromagnetic valve 113 controls the discharge and sealing of the gas from the first space inlet side case portion air vent 26. The first space inlet side case air vent 26 is not limited to a tubular shape, and may be a filter that allows only gas to pass therethrough. The first space inlet side case air vent (third air vent) of the hollow fiber membrane module is more suitable for removing gas generated in the first space.

  Further, a liquid processing device according to another embodiment of the present invention is a liquid processing device having a circuit configuration capable of adjusting a priming liquid and a replacement / cleaning liquid for a liquid to be processed by mixing different solutions. is there. With this circuit, it becomes possible to adjust the priming liquid and the liquid to be processed and the cleaning liquid, and dilute the liquid to be processed using the liquid adjusted before supplying the hollow fiber membrane module. FIG. 6 is a schematic view of a liquid processing device according to another embodiment of the present invention. The liquid processing device shown in FIG. 6 has a circuit for replacement and cleaning liquid adjustment of the priming liquid and the liquid to be processed, and performs a series of processes from the adjustment of the priming liquid and the dilution of the liquid to be processed and the recovery of the liquid It can be carried out.

  The circuit for replacing the priming liquid and the liquid to be processed / adjusting the cleaning liquid has a priming stock solution supply source A28 and a priming stock solution supply source B29, which are connected to the priming stock solution supply flow path 30, and are connected by a rotary pump 27. The liquid can be fed to the priming liquid supply source 15 or the liquid supply source 16 through the priming liquid supply flow path 22 or the liquid supply path 21 to be processed at an arbitrary ratio.

  The priming liquid supply source 15 adjusted by mixing the priming liquid supply undiluted solution by the above process can be connected to the priming liquid supply channels 22 and 21b, the liquid supply channels 21a and 21b to be processed, and the liquid supply channel 23. The priming liquid adjusted from the priming liquid supply source 15 can be injected into the hollow fiber membrane module using the rotary pump 19.

  Further, the liquid supply source 16 to be processed is supplied by the rotary pump 19 through the priming liquid supply channels 22 and 22b and the liquid supply channels 21a and 21 to be processed. It is possible to add and dilute the liquid in any proportion. In addition, the priming undiluted solution supply source A28 and the priming undiluted solution supply source B29 are fed by the rotary pump 27 through the priming undiluted solution supply channel 30 and the to-be-treated liquid supply channels 21 and 21b, and diluted. It is possible.

  The liquid source 16 to be processed that has been diluted by the above process can be connected to the liquid supply channels 21 and 21a to be processed, the priming liquid supply channels 22a and 22b, and the liquid supply channel 23. The liquid to be treated diluted from 16 can be injected into the hollow fiber membrane module using the rotary pump 19.

  Further, downstream of the liquid supply flow path 23a upstream of the air trap chamber, the liquid supply flow path 23b downstream of the air trap chamber is connected to the air trap chamber 12 of the first air vent described later. Connected. Further downstream of the liquid supply flow path 23b downstream of the air trap chamber is connected to the first space inlet 4 of the hollow fiber membrane module, from which liquid can be supplied to the hollow fiber membrane module.

  In the liquid processing device according to another embodiment of the present invention, a circuit is branched between the air vent 26 and the air trap chamber 12 to the first space inlet 4 in the first space inlet side case portion of the hollow fiber membrane module. The liquid supply channel 23 c is connected to the first space inlet 4 from this branch point, and the liquid supply channel 23 d is a liquid processing device having a circuit connected to the first space liquid outlet 5. In this liquid processing device, priming can be performed in a state where it is connected to a dry hollow fiber membrane module that does not contain the initial filling liquid. Therefore, it is more preferable when using a dry hollow fiber membrane. FIG. 7 is a schematic view of a liquid processing device according to another embodiment of the present invention.

  The liquid supply channel 23b has a branch between the air trap chamber 12 and the first space inlet 4, and branches into the liquid supply channels 23c and 23d. The liquid supply channel 23c controls the flow of the liquid into the liquid supply channel 23c by opening and closing the electromagnetic valve 110. The liquid supply channel 23d controls the flow of the liquid in the liquid supply channel 23d by opening and closing the electromagnetic valves 111 and 112.

  For example, when performing priming in the first space 3 of the dry hollow fiber membrane module not including the initial filling liquid, the liquid supply flow channel 23d is opened by opening the electromagnetic valves 111 and 112 and closing 110 and 105. Thus, the priming liquid can be sent from the first space liquid outlet 5 to the first space inlet 4 to replace the inside of the first space 3 with the priming liquid. At this time, the gas existing in the hollow fiber membrane can be discharged from the air vent 26 to the first space inlet side case portion of the hollow fiber membrane module. Subsequently, in the priming of the second space of the hollow fiber membrane module, the priming liquid is sent from the first space 3 to the second space via the hollow fiber membrane, and the priming liquid is sent to the first space inlet 4. Priming can be performed by discharging the gas from the second air vent channel 10 through the air discharge port 6.

  Here, the supply flow path in this invention is comprised with the following flow paths. The liquid supply flow path 23 can be connected to the priming liquid supply source 15, and is connected to a priming liquid supply flow path 22 for injecting the priming liquid sent from the priming liquid supply source 15 into the hollow fiber membrane module. ing. The liquid supply channel 21 to be processed can be connected to the liquid supply source 16 to be processed and is connected to the liquid supply channel 23. The to-be-processed liquid supply channel 21 and the priming liquid supply channel 22 are formed integrally with a liquid supply channel 23 through which both liquids can be fed. A rotary pump 19 is provided in the liquid supply flow path 23a upstream of the air trap chamber, and the rotary pump 19 rotates in one direction to send the liquid to be processed or the priming liquid to the hollow fiber membrane module. it can. Further, downstream of the liquid supply flow path 23a upstream of the air trap chamber, the liquid supply flow path 23b downstream of the air trap chamber is connected to the air trap chamber 12 of the first air vent described later. Connected. Further downstream of the liquid supply flow path 23b downstream of the air trap chamber is connected to the first space inlet 4 of the hollow fiber membrane module, from which liquid can be supplied to the hollow fiber membrane module.

  Further, in the liquid supply channel 23, a first air vent that is provided in the liquid supply channel 23 and can inject or discharge gas into the liquid supply channel 23 is provided. The first air vent includes an air trap chamber 12 connected to the liquid supply passage 23, a first air vent passage 13 connected to the air trap chamber 12, and an electromagnetic valve that is an opening / closing mechanism for the first air vent passage 13. 104, and the first air vent channel 13 is arranged to branch from above the air trap chamber 12. The liquid to be treated is injected into the hollow fiber membrane module from the liquid supply channel 23a upstream of the air trap chamber, through the air trap chamber 12, and through the liquid supply channel 23b downstream of the air trap chamber. When priming the supply flow path 23 or injecting the liquid to be processed into the hollow fiber membrane module, the air trap chamber 12 traps bubbles in the supply flow path and the liquid to be processed. The air vent channel 13 can be discharged out of the channel. Therefore, it is possible to prevent air lock due to air injection into the hollow fiber membrane module. The amount of bubbles trapped in the air trap chamber 12 when the liquid to be treated is injected into the hollow fiber membrane module is proportional to the volume of the air trap chamber 12, but is generally preferably 5 mL or more and 50 mL or less, and is preferably 5 mL or more and 30 mL. The following is more preferable. As an example, when 2 L is sent using M-sol, which is a foamable liquid, as the liquid to be processed, the capacity of the air trap chamber is preferably 10 mL or more. Further, the first air vent can not only discharge the gas in the supply flow path but also inject it.

  When priming is performed in a state where the flow path is connected to the hollow fiber membrane module filled with the initial filling liquid, the gas in the flow path is injected into the hollow fiber membrane module to become an air lock, and the liquid after separation treatment This causes a reduction in the recovery rate. However, in the liquid processing device according to the present invention, by having the first air vent upstream of the flow path connected to the internal space of the hollow fiber membrane module, injection of bubbles into the hollow fiber membrane module is effectively prevented. Has been.

  In the embodiment according to the present invention, the air vent has a function of injecting and discharging gas and a function of maintaining airtightness by opening and closing the flow path by an external pressure type pinch valve.

  Here, the first space liquid recovery flow path 9 is connected to the first space liquid discharge port 5 communicating with the first space 2 and can recover the liquid in the first space. In addition, the first space liquid recovery flow path 9 is branched into two flow paths by a branch 14, one is a recovery flow path 9 a that can be connected to the first liquid recovery container 17, and the other is This is a discharge channel 9b that can be connected to the second liquid recovery container 18. Here, in the liquid processing device, whether the liquid in the first space passes through the first space liquid discharge port 5 and flows into the first space liquid discharge channel 9 by opening and closing the electromagnetic valves 105, 108 and 109. Whether or not the liquid in the first space is caused to flow in the recovery flow path 9a or the discharge flow path 9b is controlled. For example, when performing the priming in the first space 2, the solenoid valves 105 and 109 are opened so that the priming liquid flows in the discharge flow path 9b, and the second liquid recovery for recovering unnecessary liquid therefrom. It can flow into the container 18. Here, the electromagnetic valves 108 and 109 can function as a second switching mechanism that switches the flow path of the liquid in the first space discharged from the hollow fiber membrane module.

  Here, the second space liquid discharge channel 11 is connected to the second space liquid discharge port 7 communicating with the second space 3, and can recover the liquid in the second space 3. Here, the liquid processing device controls whether or not the liquid in the second space is caused to flow from the second space liquid discharge port 7 into the second space liquid discharge channel 11 by opening and closing the electromagnetic valve 107. . For example, when performing priming in the second space 3, the solenoid valve 107 is opened to cause the priming liquid to flow into the second space liquid discharge flow path 11 and to collect unnecessary liquid therefrom. It can be made to flow into the liquid recovery container 18.

  The flow path in the liquid processing device of the present invention includes the first space liquid discharge flow path 9 or the second space liquid discharge flow path 11 connected to the first space discharge outlet 5 or the second space liquid discharge opening 7. It is also possible to install a new rotary pump and perform cross flow filtration. In that case, it is possible to again inject the liquid to be processed into the hollow fiber membrane module from the first space discharge port 5 or the second space liquid discharge port 7 and perform the separation process. When cross-flow filtration is performed, it is newly installed in the first space liquid discharge channel 9 or the second space liquid discharge channel 11 connected to the first space discharge port 5 or the second space liquid discharge port 7. The flow rate of the pump of the liquid injected into the first space is set to be larger than the flow rate of the pump.

  Between each flow path connected with the hollow fiber membrane module in the liquid processing device of this invention, the connector which can connect / disconnect each can be provided. In particular, when the hollow fiber membrane module filled with the initial filling liquid is connected to the dry flow channel, the hollow fiber membrane module and the supply flow channel, the hollow fiber membrane module and the recovery flow channel, or the hollow fiber membrane module It is preferable that a click tip or a cock is provided in at least one place of the connection part of the discharge channel. When the click chip or cock 24 is provided, the liquid in the module in the hollow fiber membrane can be held without flowing out into the flow path, and the performance change due to the drying of the hollow fiber membrane can be prevented. And is more preferably used. In order to prevent drying of the hollow fiber membrane, each of the three connection portions of the hollow fiber membrane module and the supply circuit and discharge circuit of the first space inside the hollow fiber membrane and the discharge circuit of the second space inside the hollow fiber membrane More preferably, a click tip or a cock is provided.

  The end of the flow path in the liquid processing device of the present invention is connected to a container that is the priming liquid supply source 15 or the liquid supply source 16 to be processed or a container that is the first liquid recovery container 17 or the second liquid recovery container 18. It is equipped with a tube that can be connected aseptically as possible with a plastic needle or tube provided in a container. Further, by providing a filter 25 having a pore diameter of 0.22 μm or less at the end of the air vent, it is possible to maintain the sterility in the flow path, and it is used more suitably.

  The flow path in the liquid processing device of the present invention has a first space inlet side case air vent 26 of the hollow fiber membrane module, and discharges the gas in the first space. With this first space air vent, it is possible to prevent air lock of the hollow fiber membrane except for bubbles generated from the space inside the hollow fiber membrane in use, such as when foaming liquid is used, Since the contact between the gas and the cell can be reduced in the first space, it is more suitably used when using a foamable liquid or when handling cells or biomolecules whose properties change due to contact with the gas. It is done. Examples of effervescent liquids include citric acid-added bicanate infusion (BRS-A solution) and M-sol infusion that generate and release carbonic acid. Cells activated by contact with gas include platelets, and biomolecules include amphipathic proteins, lipids, and nucleic acids.

  Further, a liquid processing device according to another embodiment of the present invention is a liquid processing device having a circuit configuration capable of adjusting a priming liquid and a replacement / cleaning liquid for a liquid to be processed by mixing different solutions. is there. By this circuit, the priming liquid and the liquid to be treated are replaced and cleaned, and the liquid to be treated is diluted by adding the liquid to be treated before supplying the hollow fiber membrane module or other liquid, thereby diluting the liquid to be treated. It becomes possible. Therefore, a series of processes from the adjustment of the priming liquid and the dilution of the liquid to be processed to the processing and collection of the liquid to be processed can be performed. As a cleaning / replacement liquid for the priming liquid and the liquid to be treated, the generation and release of carbonic acid occurs, and liquid such as infusion whose composition changes over time after adjustment, especially citric acid-added bicanate infusion (BRS-A liquid) and M -More preferable when using sol infusion.

  In the liquid processing device according to another embodiment of the present invention, a circuit is branched between the air vent 26 and the air trap chamber 12 to the first space inlet 4 in the first space inlet side case portion of the hollow fiber membrane module. The liquid supply channel 23 c is connected to the first space inlet 4 from this branch point, and the liquid supply channel 23 d is a liquid processing device having a circuit connected to the first space liquid outlet 5. In this liquid processing device, it is possible to perform priming in a state of being connected to a dry hollow fiber membrane module that does not contain the initial filling liquid. In particular, since liquid is fed from below the hollow fiber membrane module and gas is discharged from above with respect to the direction of gravity, efficient priming is possible. Therefore, it is used more suitably when priming is performed in a state where the dry hollow fiber membrane module not containing the initial filling liquid and the circuit are connected.

  As the material of the flow path in the liquid processing device of the present invention, vinyl chloride, polyolefin, silicone, fluorinated rubber, or the like can be used, but is not limited to these materials. However, when the flow path switching determination is performed by the optical sensor, vinyl chloride which is a material having higher transparency is preferable.

  As a flow path in the liquid processing device of the present invention, cells and proteins are activated when the linear velocity in the flow path during liquid feeding is high. Further, when the flow path volume is large, liquid loss occurs, so it is necessary to set it to an appropriate value. When the liquid to be treated contains a blood component, the inner diameter of the flow path is preferably 1.0 to 7.0 mm, and more preferably 2.5 to 4.0 mm. Moreover, it is preferable that the linear velocity in a flow path is 3-30 cm / sec, and it is more preferable that it is 6-20 cm / sec. In addition, when the flow path is switched using an external pressure type pinch valve, the hardness is deformable by the external pressure, and further, the hardness naturally recovers the shape when released from the external pressure. Therefore, the hardness (Shore A) of the flow path is preferably 20 to 100, but can be changed by adjusting the pressure applied to the pinch valve.

  In addition, the length of the supply flow path in the present invention is preferably shorter in order to reduce the loss of the liquid to be processed and, in the case of blood components, to reduce activation. In particular, in the case of blood components, the activation in the hollow fiber membrane module is large, but if it is activated before entering the hollow fiber membrane module, the activation in the hollow fiber membrane is further enhanced. End up. For this reason, the length of the supply flow path from the liquid supply source 16 to be processed to the first space inlet 4 is preferably 200 cm or less, more preferably 170 cm or less.

  On the other hand, from the viewpoint of operability, the length of the supply flow path 23 from the liquid source 16 to be processed to the first space inlet 4 needs to be 90 cm or more. In addition, since the branching of the flow path causes activation of blood components, the number of branches in all flow paths of the liquid processing device is preferably 5 or less, and more preferably 2 or less. In addition, the shape of the branching portion of the flow path is preferably three or less and more preferably two or less.

  In addition, since blood components are activated upon contact with air, it is necessary to minimize the amount of gas remaining in the channel after channel priming. For this purpose, the length of the liquid supply flow path 23b downstream from the air trap chamber that connects the air vent chamber 12 to the first space inlet 4 of the hollow fiber membrane module should be shorter, specifically 150 mm. The following is preferable, and it is more preferable that it is 100 mm or less. Furthermore, in order to prevent the separated liquid collected from the first space discharge port 5 from being injected into the discharge flow path 9b for discharging unnecessary liquid and being lost, the first space discharge flow path 9 has a branch. 14 to the second switching mechanism, the length between the electromagnetic valve 109 (channel opening / closing portion) in the discharge channel 9b is preferably shorter, specifically, 1500 mm or less, and more preferably 750 mm or less. It is more preferable that

  As an example, when recovering a substance held inside the hollow fiber membrane, when collecting the separated liquid from the first space inside the hollow fiber membrane, by providing a branch in the recovery flow path, The priming liquid for cleaning the hollow fiber membrane module and the separated liquid recovered from the first space inside the hollow fiber membrane can be independently discharged into containers connected to separate flow paths. Therefore, it is possible to obtain a separation-treated liquid having a high purity or substance concentration without mixing the priming liquid into the separation-treated liquid. In addition, when filtering solutes such as platelets that are likely to lose their quality as the time retained in the hollow fiber membrane increases, the separation flow is switched between the initial flow and the final flow of the separated liquid. It is possible to collect high-quality cells by collecting them in separate containers.

  In the liquid processing device of the present invention, switching of the type of liquid to be sent or switching of the flow path is performed by opening and closing the flow path by an external pressure type pinch valve, and the contact between the liquid in the flow path and the valve machine is performed via the flow path. It is preferable to carry out non-contact. Selection of the type of liquid to be fed or switching of the flow path is performed by determining the turbidity or liquid feeding time, liquid weight, and electric conductivity of the liquid being sent or discharged. The liquid processing device of the present invention can also be used in combination with an apparatus equipped with optical, weight, time, pressure, and electrical conductivity sensors for determining the switching of the liquid to be fed.

  The liquid treatment device of the present invention can be sterilized by ethylene oxide gas, high-pressure steam, γ-ray irradiation, or the like. It is also possible to connect the hollow fiber membrane module and the flow path after sterilization by different methods.

  The liquid treatment device of the present invention can be used for separating any liquid to be treated, but it is preferably used for blood components including blood cells and cells that are activated when contacted with bubbles. Can do.

  Moreover, the liquid processing device which concerns on another embodiment of this invention is a liquid processing device which connected the flow path which has a branch to the 2nd space discharge port. Thereby, the processed liquid in the second space can be collected with high accuracy using the second switching mechanism. FIG. 4 is a schematic view of a liquid processing device according to another embodiment of the present invention. The liquid treatment device shown in FIG. 4 is formed by connecting a plurality of flow paths to a hollow fiber membrane module. The first space inlet 4 of the hollow fiber membrane module is connected to a liquid supply channel 23 for supplying a liquid to be treated or a priming liquid to the hollow fiber membrane module, and the first space liquid outlet 5 The first space liquid recovery flow path 9 that recovers the liquid in the space is connected. The air discharge port 6 is connected to the second air vent channel 10 of the second air vent, and the second space liquid discharge port 7 is the liquid in the second space discharged from the hollow fiber membrane module. Is connected to the second space liquid discharge channel 11 which branches into a recovery channel 11a for recovering the separated liquid and a discharge channel 11b for discharging unnecessary liquid.

  In the liquid processing device according to another embodiment of the present invention, the second spatial liquid recovery channel 11 is branched into two channels on the downstream side by the branch 14, and one side is the first liquid recovery container 17. And the other is a discharge channel 11b connectable to the second liquid recovery container 18. Here, the liquid processing device determines whether or not the liquid in the second space flows from the second space liquid discharge port 7 into the second space liquid discharge channel 11 by opening and closing the electromagnetic valves 107, 108 and 109. Control is performed as to whether or not the liquid in the two spaces flows into the recovery channel 11a or the discharge channel 11b. For example, when performing priming in the second space 3, by opening the solenoid valves 105 and 109, the priming liquid flows into the recovery channel 11b, and the second liquid recovery container recovers unnecessary liquid therefrom. 18 can flow. Here, the electromagnetic valves 108 and 109 can function as a second switching mechanism that switches the flow path of the liquid in the second space discharged from the hollow fiber membrane module.

The liquid processing method for recovering the liquid after separation processing in the first space using the liquid processing device according to the embodiment of the present invention is exemplified by the following steps (1) to (5).
(1) a first priming step of filling the priming liquid in the supply flow path;
(2) The filling liquid in the second space of the hollow fiber membrane module filled with the initial filling liquid is discharged from the second space liquid discharge port and recovered through the second space liquid recovery flow path. A second priming step for filling the second space with the priming solution;
(3) The filling liquid in the first space of the hollow fiber membrane module filled with the initial filling liquid is replaced by injecting a priming liquid from the first space inlet, and from the first space liquid outlet. A third priming step of recovering the filling liquid discharged from the first space liquid discharge port through the discharge channel of the first space liquid recovery channel while discharging the initial filling liquid;
(4) A separation process step of injecting a liquid to be treated into the hollow fiber membrane module and performing a separation process;
(5) The separation-processed liquid that is recovered through the recovery flow path of the first spatial liquid recovery flow path while discharging the liquid that has been subjected to the separation process obtained in the separation process step from the first spatial liquid discharge port. Collection process.

Moreover, when the liquid processing method which collect | recovers the liquid by which the separation process in the 2nd space was collect | recovered using the liquid processing device which concerns on another embodiment of this invention is illustrated by the following process (6)-(10). Done.
(6) a first priming step that fills the supply channel with a priming liquid;
(7) While discharging the filling liquid in the second space of the hollow fiber membrane module filled with the initial filling liquid from the second space liquid discharge port and collecting it through the second space liquid recovery channel, A second priming step for filling the second space with the priming solution;
(8) The filling liquid in the first space of the hollow fiber membrane module filled with the initial filling liquid is replaced by injecting a priming liquid from the first space injection port, and from the first space liquid discharge port. A third priming step of recovering the initial filling liquid discharged from the first space liquid discharge port through the discharge channel of the first space liquid recovery channel while discharging the initial filling liquid;
(9) A separation process step of injecting a liquid to be treated into the hollow fiber membrane module and performing a separation process;
(10) The separation-processed liquid that collects the separation-processed liquid obtained in the separation process step through the recovery channel of the second space liquid recovery channel while discharging it from the second inter-liquid discharge port. Collection process.

Using the liquid processing device according to the embodiment of the present invention, the priming liquid is adjusted and the liquid to be processed is diluted, the liquid to be processed is fed into the first space, and the separation-processed liquid in the first space is performed. If the liquid processing method which collect | recovers is illustrated, it will be performed by the following process (1)-(8).
(1) a priming solution adjustment step of supplying priming solution supply sources A and B to the priming solution supply source at an arbitrary ratio and adjusting the priming solution;
(2) a first liquid to be processed dilution step for sending an arbitrary amount of the adjusted priming liquid to the liquid to be processed;
(3) a second liquid to be processed dilution step for sending an arbitrary amount of the priming stock solution supply source A or B to the liquid supply source to be processed;
(4) a first priming step for filling the adjusted priming liquid in the supply channel;
(5) The filling liquid in the second space of the hollow fiber membrane module filled with the initial filling liquid is discharged from the second space liquid discharge port and recovered through the second space liquid recovery flow path. A second priming step for filling the adjusted priming liquid in the second space;
(6) The filling liquid in the first space of the hollow fiber membrane module filled with the initial filling liquid is replaced by injecting a priming liquid adjusted from the first space injection port, and the first space liquid A third priming step of recovering the filling liquid discharged from the first space liquid discharge port through the discharge channel of the first space liquid recovery channel while discharging the initial filling liquid from the discharge port;
(7) A separation process step of injecting a diluted liquid to be processed into the hollow fiber membrane module and performing a separation process;
(8) The separation-processed liquid that is recovered through the recovery flow path of the first spatial liquid recovery flow path while discharging the liquid that has been subjected to the separation process obtained in the separation process step from the first spatial liquid discharge port. Collection process.

Illustrating a liquid processing method that uses a liquid processing device according to an embodiment of the present invention to recover a separated liquid in a first space using a dry hollow fiber membrane module that does not include an initial filling liquid The following steps (1) to (6) are performed.
(1) a first priming step of filling the priming liquid in the supply flow path;
(2) The priming liquid is fed to the first space through the liquid supply flow path 23d through the first space of the dry hollow fiber membrane module not including the initial filling liquid, and the air vent is provided to the first space inlet side case portion. A second priming step of discharging gas from 26 and filling the first space with a priming liquid;
(3) The second space of the hollow fiber membrane module is fed from the first space through the hollow fiber membrane, discharged from the second space air discharge port, a third priming step,
(4) The filling liquid in the first space of the hollow fiber membrane module filled with the initial filling liquid is replaced by injecting a priming liquid from the first space inlet, and from the first space liquid outlet. A fourth priming step of recovering the filling liquid discharged from the first space liquid discharge port through the discharge channel of the first space liquid recovery channel while discharging the initial filling liquid;
(5) a separation process step of injecting a liquid to be treated into the hollow fiber membrane module and performing a separation process;
(6) The separation-processed liquid that is recovered through the recovery flow path of the first spatial liquid recovery flow path while discharging the liquid that has been subjected to the separation process obtained in the separation process step from the first spatial liquid discharge port. Collection process.

  Separation process in which the priming is performed in a state where the hollow fiber membrane module filled with the initial filling liquid and the flow path not filled with the liquid in the liquid processing device according to the embodiment of the present invention are connected and held in the first space A more specific method for recovering the used liquid will be described with reference to FIGS. All solenoid valves not described shall be closed.

Step (1) First priming step:
The channel priming for filling the priming liquid in the priming liquid supply channel 22 and the liquid supply channel 23 is performed in the next step. First, by rotating the rotary pump 19 in one direction with the electromagnetic valves 101 and 104 opened, the priming liquid in the priming liquid supply source 15 is supplied to the priming liquid supply channel 22, the liquid supply channel 23, and the trap chamber. 12 is fed. At the same time, the gas in the liquid supply channel 23 and the trap chamber 12 is discharged through the first air vent channel 13. When the liquid supply flow path 23 and the air trap chamber 12 are filled with the priming liquid, the gas-liquid interface is detected by the optical sensor 112 installed in the first air vent flow path 13, and the priming liquid is filled in the flow path. When the completion is determined, the liquid feeding is stopped.

Step (2) Second priming step:
The second space priming is to fill the second space with the priming liquid while discharging the initial filling liquid in the second space of the hollow fiber membrane module filled with the initial filling liquid from the second space liquid discharge port 7. Perform in the next step. First, the electromagnetic valves 106 and 107 are opened, and the initial filling liquid in the second space is discharged from the second space discharge port 7 by the gas injected from the second air vent channel 10. The discharged initial filling liquid is recovered in the second liquid recovery container 18 through the second space discharge channel 11. Completion of the discharge of the initial filling liquid in the second space is detected by detecting the gas-liquid interface with the optical sensor 114 installed in the second space discharge flow path 11, and the completion of the discharge of the initial filling liquid in the hollow fiber membrane module is determined As a result, the injection of gas from the second air vent channel 10 is stopped (1. second space initial liquid discharging step). After this step, with the solenoid valves 101, 103, 106 opened, the rotary pump 19 is rotated in one direction, and the priming liquid is injected into the second space from the first space injection port 4, Is discharged from the second air vent channel 10 and the second space is filled with the priming liquid. When the second space is filled with the priming liquid, the gas-liquid interface is detected by the optical sensor 113 installed in the second air vent flow path 10, and the completion of filling of the priming liquid in the flow path is determined. The liquid feeding is stopped (2. Second priming liquid filling step).

Step (3) Third priming step:
The initial filling liquid in the first space of the hollow fiber membrane module filled with the initial filling liquid is replaced by injecting the priming liquid from the first space injection port 4, and the initial filling from the first space liquid discharge port 5 is performed. The first space priming for discharging the liquid is performed in the following process. First, the rotary pump 19 is rotated in one direction with the solenoid valves 101 and 103, 105, 109 opened, and the priming liquid is injected into the first space. The initial filling liquid in the first space is discharged from the first space discharge port 5 and is collected in the second liquid recovery container 18 through the first space discharge flow path 9 and the discharge flow path 9b. The initial filling liquid is replaced with the priming liquid. At this time, since the electromagnetic valve 108 is closed, the initial filling liquid is directed to the discharge channel 9b. Completion of priming of the first space is completed by injecting a larger amount of priming liquid than the volume of the first space.

Process (4) Processed liquid separation process The process of injecting the liquid to be processed into the hollow fiber membrane module and performing the separation process is performed in the following process. First, the rotary pump 19 is operated with the solenoid valves 102, 103, and 107 opened, and the liquid to be processed in the liquid supply source 16 to be processed passes through the hollow liquid membrane through the liquid supply circuit 21 and the liquid supply passage 23. The liquid to be treated is injected into the module and separated by the hollow fiber membrane module. The filtrate that has flowed into the second space through the hole of the hollow fiber membrane is discharged from the second space discharge port 7 and is recovered in the second liquid recovery container 18 through the second space discharge channel 11. The separation of the liquid to be processed is completed by detecting the gas-liquid interface with the optical sensor 110 installed in the liquid to be processed supply circuit 21 and determining the completion of the liquid supply of the liquid to be processed. The liquid feeding is stopped (1. liquid separation process step). In order to improve the purity of the separated liquid recovered from the first space containing the substance that has not been filtered by the hollow fiber membrane after this step, a washing step is further performed. The cleaning process is performed in the following process. First, the rotary pump 19 is rotated in one direction with the electromagnetic valves 101, 103, and 107 opened, and the priming liquid in the priming liquid supply source 15 passes through the priming liquid supply circuit 22 and the liquid supply flow path 23 to form a hollow fiber membrane. The priming solution is injected into the module and filtered by the hollow fiber membrane module. The filtrate that has flowed into the second space through the hole of the hollow fiber membrane is discharged from the second space discharge port 7 and is recovered in the second liquid recovery container 18 through the second space discharge channel 11. Completion of the cleaning process is detected by detecting a change in the color tone of the filtrate by the optical sensor 114 installed in the second space discharge flow path 11, and the completion of the cleaning is determined, or the priming liquid is fed by a specified volume. When it is determined that the liquid has been fed, the liquid feeding is stopped (2. Washing step).

Process (5) Separation-processed liquid recovery process The separation-processed liquid recovery process for recovering the separation-processed liquid obtained by the separation process from the first space is performed in the following process. First, the electromagnetic valves 106 and 107 are opened, and the initial filling liquid in the second space is discharged from the second space discharge port 7 by the gas injected from the second air vent channel 10. The discharged initial filling liquid is recovered in the second liquid recovery container 18 through the second space discharge channel 11. The completion of the discharge of the initial filling liquid in the second space is determined by the detection of the gas-liquid interface by the optical sensor 114 installed in the second space discharge flow path 11 to the completion of the discharge of the initial filling liquid in the second space. The gas injection from the second air vent channel 10 is stopped (1. second space filling liquid discharging step). After this step, the rotary pump 19 is rotated in one direction with the electromagnetic valves 101 and 103, 105, 108 opened, and the priming liquid is injected into the first space from the first space injection port 4, so that the first space The separated liquid is discharged from the first space liquid discharge port 5 and is collected in the first liquid collection container 17 through the first space collection channel 9 and the collection channel 9a. At this time, since the electromagnetic valve 109 is closed, the separated liquid is directed to the recovery flow path 9a. Completion of the recovery is determined by detecting a change in color tone by the optical sensor 111 installed in the recovery flow path 9a, or by determining that the liquid to be processed has been supplied by a specified volume. Are stopped (2. Separation-treated liquid recovery step (liquid feeding) in the first space). Furthermore, when raising the density | concentration of the liquid after separation processing collect | recovered from 1st space, the following process is performed. First, the solenoid valves 104 and 103, 105, 108 are opened, and gas is injected from the first air vent channel 13 into the first space through the liquid supply channel 23b downstream of the air trap chamber. The separated liquid in the first space pushed away by the injected gas is discharged from the first space discharge port 5. The discharged separated liquid is collected in the first liquid collection container 17 through the first space collection channel 9 and the collection channel 9a. At this time, since the electromagnetic valve 109 is closed, the separated liquid is directed to the recovery flow path 9a. Completion of the recovery is determined by detecting the gas-liquid interface of the optical sensor 111 installed in the recovery flow path 9a, and the completion of the discharge of the separated liquid in the first space is determined. The gas injection is stopped (4. Separation-treated liquid recovery step (gas injection) in the first space).

  Here, when priming the space inside the hollow fiber membrane, it is efficient to inject the priming liquid only into the space inside the hollow fiber membrane (first space). It is necessary to avoid mixing the components retained in the space inside the hollow fiber membrane with the priming liquid during recovery, and it is necessary to change the recovery container. In the method of the present invention, the third priming step In the above, since a mechanism for separately collecting the initially filled liquid inside the hollow fiber membrane and the separated liquid through the branch of the flow path is provided, it is possible to improve the purity of the collected separated liquid. .

  When recovering the separated liquid in the space inside the hollow fiber membrane (first space), it is efficient to inject a gas into the first space and discharge the separated liquid. In the method of the present invention, it is possible to inject a gas by the first air vent in the supply flow path, so that it is possible to improve the concentration of the target component in the recovered separated liquid. .

  When the processing liquid is fed into the space inside the hollow fiber membrane (first space), bubbles generated from the space inside the hollow fiber membrane in use, such as when foaming liquid is used, are generated in the first of the hollow fiber membrane module. It is efficient to discharge from the space inlet side case portion air vent 26. In the method of the present invention, since air bubbles in the first space can be removed from the first space inlet side case portion air vent 26, air lock of the hollow fiber membrane due to the air bubbles in the first space is prevented, and the recovered separation It is possible to improve the concentration of the target component in the treated liquid. Furthermore, since the activation of cells, particularly platelets, due to the bubbles in the first space is suppressed, it becomes possible to suppress the activation of the cells in the collected separated liquid.

Hereinafter, although this invention is demonstrated using an experimental result, this invention is not limited to this form. In the treatment described in the examples, a platelet preparation of 100 to 700 mL containing 2.0 to 2.9 × 10 ¹¹ platelets is separated into platelets and plasma proteins by a hollow fiber membrane module, An example will be described in which the retained platelets are suspended in a storage solution injected into the first space to obtain a liquid that has been separated in the first space and recovered from the first space. The platelet recovery rate was calculated according to the following formula 1 based on the volume of the liquid to be processed and the separation-treated liquid recovered from the first space and the platelet count concentration in each liquid.

  Platelet recovery rate (%) = (platelet concentration in the separation-processed recovery liquid recovered from the first space × volume of the separation-processed recovery liquid recovered from the first space) ÷ (platelet in the liquid to be processed (Concentration × volume of liquid to be treated) × 100 Formula 1

  The platelet concentration was measured by a multi-item automatic blood cell counter (XT1800i; manufactured by Sysmec). Furthermore, regarding platelet activation, CD62P on the platelet surface was measured as an activation marker. The platelets in the pre-treatment platelet preparation fixed with paraformaldehyde and the platelets in the collected recovery solution within 10 minutes after the treatment were washed, and anti-CD61-perCP and anti-CD62P-PE (BD Biosciences, San Jose) , USA) and using a flow cytometer (FACS Canto II, BDBiosciences, San Jose, CA, USA), CD62P in platelets determined to be platelets by forward scatter and backscatter and platelet-specific CD61 labeling. The percentage of platelets labeled with was measured, and the percentage of activated platelets in each liquid was measured. More specifically, a cutoff value is set so that 0.5% to 1.0% or less of platelets becomes positive by labeling with anti-CD61-perCP and control IgG. The percentage of activated platelets was calculated as positive platelets (activated platelets). The percentage of platelet activation before and after treatment with this device was determined by the following formula 2.

  Platelet activation ratio = (percentage of activated platelets in the collected recovery solution collected from the first space) / (percentage of activated platelets in the platelet preparation before treatment) Formula 2

  The hollow fiber membrane module used in each example, the priming liquid, and the liquid feeding speed are all the same unless individually described for each example. In Examples and Comparative Examples, a buffer was used as the priming solution. As a buffer, Vicanate (trademark registered) infusion solution (Otsuka Pharmaceutical Factory Co., Ltd.) to which 5% ACD-A was added was used.

(Creation of hollow fiber membrane module)
A mixture of 15 parts by weight of polysulfone (P3500; Solvay), 8 parts by weight of polyvinylpyrrolidone (K90; ISP), 75 parts by weight of dimethylacetamide (hereinafter “DMAc”) and 2 parts by weight of water After mixing and dissolving at 50 ° C., the solution kept at 50 ° C. was used as a film forming stock solution. Further, a core solution was prepared by adding 30 parts by weight of polyvinylpyrrolidone (K30; ISP) to a mixed liquid composed of 80 parts by weight of DMAC and 20 parts by weight of water and mixing and dissolving them.

  Using an orifice type double cylindrical die with an outer diameter of 1.0 mm / inner diameter of 0.7 mm, a film-forming stock solution was discharged from the outer cylinder and a core liquid was simultaneously discharged from the inner cylinder, and the length was set to 30 ° C. After passing through a dry section of 80 mm in length, it is immersed in a 90 ° C. coagulation bath containing a mixed liquid consisting of 90 parts of water and 10 parts of DMAC, and further washed with warm water in an 80 ° C. hot water bath. Was wound around a cassette frame to obtain a wet hollow fiber membrane. When the film forming speed was 40 m / min, the inner diameter of the hollow fiber membrane was 300 μm, and the film thickness of the hollow fiber membrane was 80 μm.

The hollow fiber membranes 4580 pieces were assembled in a cylindrical plastic module having a diameter of 44 × 220 mm so that the membrane surface area was about 0.85 m ^2, and both ends were potted with urethane resin. Then, a hollow fiber membrane module was prepared by opening the hollow fiber membrane and attaching a header.

(Create liquid device)
A liquid supply passage for supplying a liquid to be treated or a priming liquid to the hollow fiber membrane module is connected to the first space inlet of the hollow fiber membrane module, and a first space liquid outlet of the hollow fiber membrane module is connected to the first space liquid outlet. A first space liquid recovery flow path that is branched into a recovery flow path that allows liquid in one space to pass through and recovers the separated liquid and a discharge flow path that discharges unnecessary liquid was connected. In addition, a second air vent channel is connected to the air outlet of the hollow fiber membrane module, and the second space liquid recovers the liquid in the second space to the second space liquid outlet of the hollow fiber membrane module. The discharge channel was connected. Further, a priming liquid supply source and a liquid treatment source are connected to the liquid supply flow path, and a first liquid treatment container and a second liquid treatment container are connected to the first spatial liquid recovery flow path. Connected. Furthermore, the second liquid collection container was connected to the second space liquid outlet.

  The liquid feeding speed of this liquid device was 35 mL / min during platelet feeding / washing liquid, and 250 mL / min during recovery, and the following Examples and Comparative Examples were performed.

  The inner diameter of the used flow path is 3.4 mm, and unless otherwise specified, the length 23b of the flow path from the first air vent to the first space exhaust inlet is 100 mm, and the first space liquid recovery flow path The length between the branch 14 of 9 and the flow path opening / closing part 109 as the second switching mechanism in the first space discharge flow path 9b is 750 mm. Further, the liquid supply flow path 23a in the first space is 975 mm, and the liquid supply flow path 21 to be processed and the priming liquid supply flow path 22 are 650 mm and 850 mm, respectively. The length of the first air vent channel 13 is 230 mm, and a filter having a pore diameter of 0.22 μm or less is provided at the end of the channel not connected to the air trap chamber 12. The channel length of the second air vent channel 10 is 300 mm, and a filter having a pore diameter of 0.22 μm or less is provided at the end of the channel not connected to the air outlet 6. The length of the second space liquid discharge channel 11 is 350 mm. The capacity of the air trap chamber 12 is 20 mL.

Example 1
The priming of the flow path uses a supply flow path having an air vent between the liquid supply source to be processed and the first space inlet, injects a buffer from the priming liquid supply source, and discharges the gas in the flow path from the air vent. At the same time, the supply channel was filled with a buffer. Here, the length of the flow path from the first air vent to the first space exhaust introduction port was 100 mm. Subsequently, a buffer was injected into the second space and the first space from the first space inlet of the hollow fiber membrane module, and the initial filling liquid was discharged from the hollow fiber membrane module. The initial filling liquid is discharged from the second space liquid discharge port through the second space liquid discharge channel, and from the first space liquid discharge port through the discharge channel, and is collected in the second liquid recovery container. It was. The priming of the hollow fiber membrane module was completed by filling the buffer while discharging the initial filling liquid. Next, separation treatment was performed by injecting a platelet preparation as a liquid to be treated into the first space. Thereafter, while injecting the buffer into the first space, the second switching mechanism switches the flow path from the discharge flow path to the recovery flow path, and passes from the first space liquid discharge port to the first liquid recovery container through the recovery flow path. The liquid (recovered liquid) that was discharged and separated in the first space was recovered.

As a result, as described in Table 1 below, the platelet recovery rate in Example 1 was 96%, and the platelet activation ratio was 1.4. The platelet concentration in the collected liquid collected from the first space after the separation treatment was 124 × 10 ⁴ cells / μL, and the volume of the collected liquid was 199 mL.

(Example 2)
The priming of the flow path uses a supply flow path having an air vent between the liquid supply source to be processed and the first space inlet, sends a buffer from the priming liquid supply source, and discharges the gas in the flow path from the air vent. And the flow path was filled with a buffer. Here, the length of the flow path from the first air vent to the first space exhaust introduction port was 150 mm. Subsequently, a buffer was injected from the first space inlet of the hollow fiber membrane module into the second space and the first space, and the initial filling liquid was discharged from the hollow fiber membrane module. The initial filling liquid is discharged from the second space liquid discharge port through the second space liquid discharge channel, and from the first space liquid discharge port through the discharge channel, and is collected in the second liquid recovery container. It was. The priming of the hollow fiber membrane module was completed by filling the buffer while discharging the initial filling liquid. Next, separation treatment was performed by injecting a platelet preparation as a liquid to be treated into the first space. Thereafter, while injecting the buffer into the first space, the second switching mechanism switches the flow path from the discharge flow path to the recovery flow path, and the first liquid recovery container passes through the recovery flow path from the first space liquid discharge port. The liquid (recovered liquid) after the separation process in the first space was recovered.

As a result, as described in Table 1 below, the platelet recovery rate in Example 2 was 92% and the platelet activation ratio was 1.9. In addition, the platelet concentration in the collected liquid collected from the separated first space was 120 × 10 ⁴ cells / μL, and the volume of the collected liquid was 198 mL.

(Example 3)
The priming of the flow path uses a supply flow path having an air vent between the liquid supply source to be processed and the first space inlet, injects a buffer from the priming liquid supply source, and discharges the gas in the flow path from the air vent. At the same time, the flow path was filled with a buffer. Subsequently, a buffer was injected from the first space inlet of the hollow fiber membrane module into the second space and the first space, and the initial filling liquid was discharged from the hollow fiber membrane module. The initial filling liquid is discharged from the second space liquid discharge port through the second space liquid discharge channel, and from the first space liquid discharge port through the discharge channel, and is collected in the second liquid recovery container. It was. The priming of the hollow fiber membrane module was completed by filling the buffer while discharging the initial filling liquid. Here, the length between the branch 14 of the first space liquid recovery flow path 9 and the flow path opening / closing portion 109, which is the second switching mechanism in the first space discharge flow path 9b, is the second switching mechanism. It was 1500 mm. Next, separation treatment was performed by injecting a platelet preparation as a liquid to be treated into the first space. Thereafter, while injecting the buffer into the first space, the second switching mechanism switches the flow path from the discharge flow path to the recovery flow path, switches from the first space liquid discharge port to the recovery flow path, and passes through the recovery flow path. It discharged | emitted to 1 liquid collection | recovery container, and collection | recovery of the liquid (collected liquid) after the separation process in 1st space was performed.

As a result, as described in Table 1 below, the platelet recovery rate in Example 3 was 93% and the platelet activation ratio was 1.5. The platelet concentration in the collected liquid collected from the first space after the separation treatment was 122 × 10 ⁴ cells / μL, and the volume of the collected liquid was 197 mL.

Example 4
The priming of the flow path uses a flow path having an air vent between the liquid supply source to be processed and the first space inlet, injects a buffer from the priming liquid supply source, discharges the gas in the flow path from the air vent, The buffer was filled in the flow path. Subsequently, a buffer was injected from the first space inlet of the hollow fiber membrane module into the second space and the first space, and the initial filling liquid was discharged from the hollow fiber membrane module. The initial filling liquid is discharged from the second space liquid discharge port through the second space liquid discharge channel, and from the first space liquid discharge port through the discharge channel, and is collected in the second liquid recovery container. It was. The priming of the hollow fiber membrane module was completed by filling the buffer while discharging the initial filling liquid. Next, separation treatment was performed by injecting a platelet preparation as a liquid to be treated into the first space. Thereafter, while injecting the buffer into the first space, the second switching mechanism switches the flow path from the discharge flow path to the recovery flow path, and the first liquid recovery container passes through the recovery flow path from the first space liquid discharge port. The liquid (recovered liquid) after the separation process in the first space was recovered. Here, the end face length of the hollow fiber membrane was 28 cm, the number of yarns was 3430, and the surface area of the hollow fiber membrane was 0.85 m ² .

As a result, as described in Table 1 below, the platelet recovery rate in Example 4 was 94% and the platelet activation ratio was 1.9. The platelet concentration in the collected liquid collected from the separated first space was 121 × 10 ⁴ cells / μL, and the volume of the collected liquid was 203 mL.

(Example 5)
The priming of the flow path uses a supply flow path having an air vent between the liquid supply source to be processed and the first space inlet, injects a buffer from the priming liquid supply source, and discharges the gas in the flow path from the air vent. At the same time, the supply channel was filled with a buffer. Here, the length of the flow path from the first air vent to the first space exhaust introduction port was 100 mm. Subsequently, a buffer was injected into the second space and the first space from the first space inlet of the hollow fiber membrane module, and the initial filling liquid was discharged from the hollow fiber membrane module. The initial filling liquid is discharged from the second space liquid discharge port through the second space liquid discharge channel, and from the first space liquid discharge port through the discharge channel, and is collected in the second liquid recovery container. It was. The priming of the hollow fiber membrane module was completed by filling the buffer while discharging the initial filling liquid. Next, separation treatment was performed by injecting a platelet preparation as a liquid to be treated into the first space. Thereafter, while injecting the buffer into the first space, the second switching mechanism switches the flow path from the discharge flow path to the recovery flow path, and passes from the first space liquid discharge port to the first liquid recovery container through the recovery flow path. The liquid (recovered liquid) that was discharged and separated in the first space was recovered. During this time, bubbles generated in the first space were always removed from the air vent (third air vent) 26 of the first space inlet side case portion of the hollow fiber membrane module.

As a result, as described in Table 1 below, the platelet recovery rate in Example 5 was 96%, and the platelet activation ratio was 1.3. In addition, the platelet concentration in the collected liquid collected from the separated first space was 124 × 10 ⁴ / μL in the separated liquid collected from the first space, and the volume of the collected liquid was 198 mL. The

(Example 6)
Adjustment of the priming liquid and dilution of the liquid to be treated were performed, and the priming of the flow path and the hollow fiber membrane module was performed using the adjusted priming liquid.
As the priming stock solution supply source, Vicanate infusion solution and ACD-A solution were used, and these solutions were mixed at a ratio of 95% and 5% to obtain an adjusted priming solution. As a liquid to be treated, add the above-prepared priming liquid to platelet preparation (200 mL) 1.5 times the amount of platelet preparation (300 mL), and further add ACD-A solution 0.25 times the amount of platelet preparation (50 mL). In addition, the liquid to be treated was diluted.

  The priming of the flow path uses a supply flow path having an air vent between the liquid supply source to be processed and the first space inlet, injects a buffer from the priming liquid supply source, and discharges the gas in the flow path from the air vent. At the same time, the supply channel was filled with a buffer. Here, the length of the flow path from the first air vent to the first space exhaust introduction port was 100 mm. Subsequently, a buffer was injected into the second space and the first space from the first space inlet of the hollow fiber membrane module, and the initial filling liquid was discharged from the hollow fiber membrane module. The initial filling liquid is discharged from the second space liquid discharge port through the second space liquid discharge channel, and from the first space liquid discharge port through the discharge channel, and is collected in the second liquid recovery container. It was. The priming of the hollow fiber membrane module was completed by filling the buffer while discharging the initial filling liquid. Next, separation treatment was performed by injecting a platelet preparation as a liquid to be treated into the first space. Thereafter, while injecting the buffer into the first space, the second switching mechanism switches the flow path from the discharge flow path to the recovery flow path, and passes from the first space liquid discharge port to the first liquid recovery container through the recovery flow path. The liquid (recovered liquid) that was discharged and separated in the first space was recovered.

As a result, as described in Table 1 below, the platelet recovery rate in Example 6 was 94% and the platelet activation ratio was 1.8. The platelet concentration in the collected liquid collected from the separated first space was 120 × 10 ⁴ cells / μL, and the volume of the collected liquid was 197 mL.

(Example 7)
A dry hollow fiber membrane module that does not contain the initial filling liquid and a device in which the liquid supply channel 23b has a branch were used.

  The priming of the flow path uses a supply flow path having an air vent between the liquid supply source to be processed and the first space inlet, injects a buffer from the priming liquid supply source, and discharges the gas in the flow path from the air vent. At the same time, the supply channel 23a was filled with a buffer. Here, the combined length of the liquid supply channels 23b and 23c downstream of the air trap chamber was 100 mm. Subsequently, the priming liquid is supplied to the first space through the liquid supply channel 23b and the liquid supply channel 23d, the gas is discharged from the air vent 26 to the first space inlet side case portion, and the priming is performed to the first space. Filled with liquid. Further, the second space of the hollow fiber membrane module was fed from the first space through the hollow fiber membrane, and discharged from the second space air discharge port, thereby priming the second space. The filling liquid in the first space is replaced by injecting the priming liquid from the first space injection port, and the initial filling liquid is discharged from the first space liquid discharge port. The discharged filling liquid was recovered through the discharge channel included in the first space liquid recovery channel, thereby completing the priming of the hollow fiber membrane module. Next, separation treatment was performed by injecting a platelet preparation as a liquid to be treated into the first space. Thereafter, while injecting the buffer into the first space, the second switching mechanism switches the flow path from the discharge flow path to the recovery flow path, and passes from the first space liquid discharge port to the first liquid recovery container through the recovery flow path. The liquid (recovered liquid) that was discharged and separated in the first space was recovered. During this time, bubbles generated in the first space were always removed from the air vent 26 of the first space inlet side case portion of the hollow fiber membrane module.

As a result, as described in Table 1 below, the platelet recovery rate in Example 5 was 92%, and the platelet activation ratio was 1.5. The platelet concentration in the collected liquid collected from the first space after the separation treatment was 120 × 10 ⁴ cells / μL, and the volume of the collected liquid was 196 mL.

(Comparative Example 1)
As Comparative Example 1, the liquid treatment was performed using a liquid treatment device having no air vent in the supply flow path. In the priming of the flow path, a buffer was injected from a priming liquid supply source, whereby the gas in the supply flow path was discharged from the first space injection port to the hollow fiber membrane module, and the flow path was filled with the buffer. Subsequently, a buffer was injected from the first space inlet of the hollow fiber membrane module into the second space and the first space, and the initial filling liquid was discharged from the hollow fiber membrane module. The initial filling liquid is discharged from the second space liquid discharge port through the second space liquid discharge channel, and from the first space liquid discharge port through the discharge channel, and is collected in the second liquid recovery container. It was. The priming of the hollow fiber membrane module was completed by filling the buffer while discharging the initial filling liquid. Next, separation treatment was performed by injecting a platelet preparation as a liquid to be treated into the first space. Thereafter, the first liquid recovery is performed from the first space liquid discharge port through the recovery flow path by switching the flow path from the discharge flow path to the recovery flow path by the second switching mechanism while injecting the buffer into the first space. It was discharged into a container, and the separated liquid (recovered liquid) in the first space was recovered.

As a result, as described in Table 1 below, the platelet recovery rate in Comparative Example 1 was 81%, and the platelet activation ratio was 3.0. The platelet concentration in the collected liquid collected from the first space after the separation treatment was 90.2 × 10 ⁴ cells / μL, and the volume of the collected liquid was 194 mL.

(Comparative Example 2)
As Comparative Example 2, the liquid treatment was performed using a liquid treatment device having no branch in the first space recovery flow path. The priming of the flow path uses a flow path having an air vent between the liquid supply source to be processed and the first space inlet, injects a buffer from the priming liquid supply source, discharges the gas in the flow path from the air vent, The buffer was filled in the flow path. Subsequently, the hollow fiber membrane module was primed by injecting a buffer into the second space and the first space from the first space inlet of the hollow fiber membrane module. The initial filling liquid in the second space was recovered from the second space liquid discharge port to the second liquid recovery container through the second space liquid discharge channel. The initial filling liquid in the first space was recovered from the first space discharge port to the first liquid recovery container through the first space recovery channel and the recovery channel, thereby completing the priming. Next, separation treatment was performed by injecting a platelet preparation as a liquid to be treated into the first space. Thereafter, while injecting the buffer into the first space, the buffer is discharged from the first space liquid outlet to the first liquid recovery container through the first space recovery channel and the recovery channel, and the separation processing in the first space is completed. Liquid (collected liquid) was collected.

As a result, as described in Table 1 below, the platelet recovery rate in Comparative Example 2 was 95%, and the platelet activation ratio was 1.4. The platelet concentration of the separated liquid collected from the first space was 82.1 × 10 ⁴ cells / μL, and the volume of the collected liquid was 263 mL.

  From Example 1 and Comparative Example 1, when the supply channel had an air vent, the platelet recovery rate was improved and platelet activation was reduced. This is due to the priming process in which air bubbles are prevented from being mixed into the flow channel and the hollow fiber membrane module by the flow channel having the air vent. Therefore, it is clear that the platelet recovery rate can be increased by suppressing the air lock of the hollow fiber membrane module. It is also clear that platelet activation before and after the separation process can be suppressed by reducing the chance of contact between the platelet and gas in the hollow fiber membrane module.

  From Example 1 and Comparative Example 2, when the first space recovery flow path has a plurality of branches, the platelet concentration in the separated liquid recovered from the first space is increased, and the volume of the recovered liquid is increased. I was able to prevent it. By having a plurality of branches in the first space recovery flow path, it is possible to recover the initial filling liquid and the separated liquid in separate containers, and the target component in the separated liquid This is because it is possible to prevent some platelets from being diluted with the initial filling liquid during priming. Furthermore, since it is possible to prevent impurities derived from the manufacturing process contained in the initial filling liquid in the hollow fiber membrane module in the priming liquid from being mixed into the separated liquid, high purity can be obtained. It is a thing.

  From Example 1 and Example 2, when the circuit length from the air trap chamber 12 in the supply flow path to the first space inlet 4 (liquid supply flow path 23b downstream of the air trap chamber) is short, more platelets are collected. The rate was improved and activation was suppressed. This is because when the circuit length from the air trap chamber 12 to the first space injection port 4 in the supply flow path (liquid supply flow path 23b downstream of the air trap chamber) is shorter, bubbles are injected into the hollow fiber membrane module. It is clear that it is more preferable to reduce the amount.

  When the length between the branch 14 of the first space liquid recovery flow path 9 and the flow path opening / closing part 109 as the second switching mechanism in the first space discharge flow path 9b is short from the first and third embodiments. , Platelet recovery rate improved. This is because separation is recovered from the first space as the length between the branch 14 of the first space recovery channel 9 and the channel switching unit 109 in the discharge channel 9b, which is the second switching mechanism, is shorter. When the treated liquid passes through the first space recovery channels 9 and 9a, the shorter one is used to reduce loss due to a decrease in the amount of recovered liquid during recovery due to injection from the branch 14 into another channel 9b. It is clear that is more preferred.

  From Example 1 and Example 4, when the end face length of the hollow fiber membrane was short, platelet activation was suppressed. This is because when the membrane area is the same, the higher the number of yarns and the shorter the end face length of the hollow fiber membrane, the lower the platelet concentration and linear velocity in the hollow fiber. It is clear that a module shape having a short end face length of the yarn membrane is more preferable.

  From Example 1 and Example 5, when there was the 3rd air vent of the 1st space inlet side case part of a hollow fiber membrane module, the platelet recovery rate improved and the activation of platelet was suppressed. It is clear that the platelet recovery rate can be increased by suppressing the air lock of the hollow fiber membrane module. It is also clear that platelet activation before and after the separation process can be suppressed by reducing the chance of contact between the platelet and gas in the hollow fiber membrane module. This is because the air lock in the hollow fiber membrane was suppressed because the air bubbles in the first space were removed, and the contact between the air bubbles and the platelets in the first space was reduced, and the activation of platelets by the air bubbles was suppressed. It is. From this, it is clear that the module shape having the third air vent of the first space inlet side case portion is more preferable.

  From Example 1 and Example 6, it has a circuit for replacement and cleaning liquid adjustment of priming liquid and liquid to be processed, and performs a series of processing from adjustment of priming liquid and dilution of liquid to be processed and recovery of liquid. Similar results were also obtained. From this, it is clear that it is more preferable to have a circuit configuration for preconditioning / dilution in order to easily perform a series of processes from the adjustment of the priming liquid and the liquid to be processed to the processing and collection of the liquid to be processed It is.

  From Example 1 and Example 7, the same results as in the case of using the hollow fiber membrane module containing the initial filling liquid were obtained even when the dry hollow fiber membrane module containing no initial filling liquid was used. From this, it is clear that it is more preferable to have a branch in the liquid supply channel when using a dry hollow fiber membrane module that does not contain the initial filling liquid.

  The present invention makes it possible to easily perform a series of operations for separating a specific solid or solute component from a liquid by using a hollow fiber membrane module and recovering it at a high recovery rate.

DESCRIPTION OF SYMBOLS 1 ... Hollow fiber membrane, 2 ... 1st space, 3 ... 2nd space, 4 ... 1st space injection port, 5 ... 1st space liquid discharge port, 6 ... Air Discharge port, 7 ... second space liquid discharge port, 8 ... case, 9 ... first space recovery channel, 9a ... first space recovery channel branch downstream, 9b ... first Spatial discharge flow path, 10 ... second air vent flow path, 11 ... second spatial liquid discharge flow path, 11a ... recovery flow path, 11b ... discharge flow path, 12 ... air trap Chamber, 13 ... first air vent channel, 14 ... branch, 15 ... priming liquid supply source, 16 ... processed liquid supply source, 17 ... first liquid recovery container, 18 ... Second liquid recovery container, 19 ... Rotary pump, 21 ... Processed liquid supply flow path, 22 ... Priming liquid supply flow path, 23 ... Liquid Supply channel, 23a ... Liquid supply channel upstream of the air trap chamber, 23b ... Liquid supply channel downstream of the air trap chamber, 24 ... Cock, 25 ... Filter, 26 ... First Space inlet side case (hetter) part air vent (third air vent), 27... Rotating pump 2, 28... Priming stock solution supply source A, 29. Stock solution supply channel, 101-117 ... solenoid valve, 200-206 ... optical sensor

Claims (8)

A case having three openings, a first space inlet, a first space liquid outlet, and a second space liquid outlet, and a hollow fiber membrane for separating and treating the liquid to be treated, the hollow fiber membrane on the inner surface side The first space is arranged inside the case so as to partition the first space and the second space on the outer surface side, the first space inlet and the first space liquid outlet communicate with the first space, and the second space. The space liquid outlet is in communication with the second space, a hollow fiber membrane module;
A supply flow path connected to the first space inlet for supplying a liquid to be treated or a priming liquid to the hollow fiber membrane module;
A first switching mechanism that is provided in the supply flow path and switches a liquid to be injected into the hollow fiber membrane module;
A rotary pump that is provided in the supply flow path and rotates in one direction to feed liquid;
A first air vent that is provided in the supply channel and capable of injecting or discharging gas to the supply channel;
It is connected to the first space liquid discharge port, allows the liquid in the first space discharged from the hollow fiber membrane module to pass therethrough, and discharges a recovery flow path for recovering the separated liquid and unnecessary liquid. A first spatial liquid recovery channel that branches into a discharge channel for
A second space liquid recovery flow path that is connected to the second space liquid discharge port and recovers the liquid in the second space discharged from the hollow fiber membrane module;
A second switching mechanism that is provided in the first space liquid recovery flow path and switches the flow path of the liquid in the first space discharged from the hollow fiber membrane module;
A liquid processing device comprising: A case having three openings, a first space inlet, a first space liquid outlet, and a second space liquid outlet, and a hollow fiber membrane for separating and treating the liquid to be treated, the hollow fiber membrane on the inner surface side The first space is arranged inside the case so as to partition the first space and the second space on the outer surface side, the first space inlet and the first space liquid outlet communicate with the first space, and the second space. The space liquid outlet is in communication with the second space, a hollow fiber membrane module;
A supply flow path connected to the first space inlet for supplying a liquid to be treated or a priming liquid to the hollow fiber membrane module;
A first switching mechanism that is provided in the supply flow path and switches a liquid to be injected into the hollow fiber membrane module;
A rotary pump that is provided in the supply flow path and rotates in one direction to feed liquid;
A first air vent that is provided in the supply channel and capable of injecting or discharging gas to the supply channel;
A first space liquid recovery channel connected to the first space liquid outlet and recovering the liquid in the first space discharged from the hollow fiber membrane module;
Connected to the second space liquid discharge port, allows the liquid in the second space discharged from the hollow fiber membrane module to pass therethrough, and discharges a recovery flow path for recovering the separated liquid and unnecessary liquid. A second spatial liquid recovery channel branched into a discharge channel for
A second switching mechanism that is provided in the second space liquid recovery flow path and switches the flow path of the liquid in the second space discharged from the hollow fiber membrane module;
A liquid processing device comprising: A second air vent capable of injecting or discharging gas into the second space is provided;
The liquid processing device according to claim 1, wherein the hollow fiber membrane module includes an air discharge port that communicates with the second space and can be connected to a second air vent.   The liquid processing device according to claim 1, wherein the first air vent includes an air trap chamber, an air vent channel connected to the air trap chamber, and an opening / closing mechanism for the air vent channel.   At least one of the connection part of the hollow fiber membrane module and the supply channel, the connection part of the hollow fiber membrane module and the recovery channel, or the connection part of the hollow fiber membrane module and the discharge channel The liquid processing device according to claim 1, comprising a cock or a click chip.   The liquid processing device according to claim 1, wherein a third air vent is provided in the first space inlet side case of the hollow fiber membrane module.   The liquid processing device according to claim 1, wherein platelets and plasma proteins are separated and collected from the platelet preparation. A liquid processing method using the liquid processing device according to claim 1,
A first priming step for filling a priming liquid in the supply channel;
A second priming that discharges the initial filling liquid in the second space of the hollow fiber membrane module filled with the initial filling liquid from the second space liquid discharge port and fills the second space with the priming liquid. Process,
Replacing the initial filling liquid in the first space of the hollow fiber membrane module filled with the initial filling liquid by injecting a priming liquid from the first space inlet, and from the first space liquid outlet A third priming step for discharging the initial filling liquid;
A separation process step of injecting a liquid to be treated into the hollow fiber membrane module and performing a separation process;
A separation-processed liquid recovery step for recovering the separated liquid obtained in the separation process step through the recovery flow path of the first spatial liquid recovery flow path while discharging the liquid from the first spatial liquid discharge port; ,
A liquid processing method comprising: