JP7390677B2 - Cell suspension processing equipment - Google Patents

Description

The present invention relates to a cell suspension processing device for concentrating cells.

BACKGROUND ART Cell suspension processing has conventionally been performed in which cells are concentrated using a circulation circuit that includes at least a storage container, a pump, and a hollow fiber membrane filter (see, for example, Patent Document 1). As the concentration process progresses, the concentration of cells in the cell suspension in the storage container increases. Then, when the concentration of the cell suspension in the storage container reaches a predetermined concentration, the cell concentration process is completed.

JP2015-42167A

By the way, when the concentration process is completed, many cells exist in the storage container, but some cells also remain in the circulation circuit.

Therefore, an object of the present invention is to recover cells remaining in the circulation circuit after the completion of the concentration treatment in a cell concentration treatment using a circulation circuit including at least a storage container, a pump, and a hollow fiber membrane filter.

In order to solve the above technical problem, according to one aspect of the present invention,
A cell suspension processing device that concentrates a cell suspension,
a circulation circuit in which a cell suspension circulates;
a first filling liquid supply source that supplies filling liquid to the circulation circuit;
The circulation circuit is
a hollow fiber membrane filter that filters and concentrates the cell suspension;
a storage container having an inlet port and an outlet port and storing a cell suspension;
a pump that is provided on the downstream side in the circulation direction of the cell suspension with respect to the storage container and on the upstream side in the circulation direction with respect to the hollow fiber membrane filter, and that circulates the cell suspension;
a first valve provided on the downstream side in the circulation direction with respect to the storage container and on the upstream side in the circulation direction with respect to the pump,
the first filling liquid supply source is connected to a portion of the circulation circuit between the first valve and the pump;
After the concentrated cell suspension is stored in the storage container, with the first valve closed and the pump driven in normal rotation, the first filling liquid supply source starts the circulation. By starting the supply of fill liquid to the circuit, the fill liquid pushes the cell suspension remaining in the part of the circulation circuit from the pump to the inlet port of the storage vessel in the circulation direction towards the storage vessel. sink,
further comprising a first optical sensor provided near the inlet port of the storage container to detect the color and/or turbidity of the cell suspension;
When the first optical sensor detects a change in color and/or turbidity of the cell suspension, the pump is stopped and the first filling liquid supply source stops supplying filling liquid to the circulation circuit. A cell suspension processing device is provided.

Moreover, according to another aspect of the present invention,
A cell suspension processing device for concentrating a cell suspension, the device comprising:
a circulation circuit in which a cell suspension circulates;
a filling liquid supply source that supplies filling liquid to the circulation circuit;
The circulation circuit is
a hollow fiber membrane filter that filters and concentrates the cell suspension;
a storage container having an inlet port and an outlet port and storing a cell suspension;
a pump that is provided on the downstream side in the circulation direction of the cell suspension with respect to the storage container and on the upstream side in the circulation direction with respect to the hollow fiber membrane filter, and that circulates the cell suspension;
a valve provided on the downstream side in the circulation direction with respect to the hollow fiber membrane filter and on the upstream side in the circulation direction with respect to the storage container,
the filling liquid supply source is connected to a portion of the circulation circuit between the pump and the valve ;
After the concentrated cell suspension is stored in the storage container, the filling liquid supply source is supplied to the circulation circuit with the valve closed and the pump driven in reverse. By starting the supply of the filling liquid, the filling liquid moves the cell suspension remaining in the portion of the circulation path from the outlet port of the storage container to the pump toward the storage container in a direction opposite to the circulation direction. A cell suspension processing device is provided.

According to the present invention, in a cell concentration process using a circulation circuit including at least a storage container, a pump, and a hollow fiber membrane filter, cells remaining in the circulation circuit after completion of the concentration process can be recovered.

Front perspective view of a cell suspension processing device according to an embodiment of the present invention Front perspective view of the cell suspension processing device from different perspectives Rear perspective view of cell suspension processing device Rear perspective view of the cell suspension processing device from different perspectives Front view of cell suspension processing device Rear view of cell suspension processing device Right side view of cell suspension processing device Left side view of cell suspension processing device Plan view of cell suspension processing device Front view of a cell suspension processing device with an example of a cell concentration washing circuit set up Schematic diagram of an example cell concentration washing circuit A perspective view of a portion of a cell suspension processing device showing multiple hooks. Block diagram showing the control system of the cell suspension processing device Diagram for explaining the first treatment step in an example of cell suspension treatment Diagram for explaining the second treatment step following the first treatment step Diagram for explaining the third treatment step following the second treatment step Diagram for explaining the fourth treatment step following the third treatment step Diagram for explaining the fifth treatment step following the fourth treatment step Diagram for explaining the sixth treatment step following the fifth treatment step Diagram for explaining the seventh treatment step following the sixth treatment step Diagram for explaining the eighth treatment step following the seventh treatment step Diagram for explaining the ninth treatment step following the eighth treatment step Diagram for explaining the 10th treatment step following the 9th treatment step Diagram for explaining the 11th treatment step following the 10th treatment step A perspective view showing an example of a pinch device Diagram showing the pressure fluctuation of the cell suspension being supplied to the circulation circuit when an accumulator is present (example) and when it is not present (comparative example) Diagram showing the pressure fluctuation of the cell suspension during cell washing in the case where an accumulator is present (example) and when it is not present (comparative example)

A cell suspension processing device according to one aspect of the present invention is a cell suspension processing device that concentrates a cell suspension, and includes a circulation circuit in which the cell suspension circulates, and a filling liquid in the circulation circuit. a first filling liquid supply source for supplying the cell suspension, the circulation circuit comprising a hollow fiber membrane filter for filtering and concentrating the cell suspension, an inlet port and an outlet port, a storage container for storing the cell suspension, and a pump that is provided downstream in the circulation direction of the cell suspension with respect to the storage container and upstream in the circulation direction with respect to the hollow fiber membrane filter and circulates the cell suspension. , a first valve provided on the downstream side in the circulation direction with respect to the storage container and on the upstream side in the circulation direction with respect to the pump, and the first filling liquid supply source is provided in the circulation direction. connected to a portion between the first valve and the pump in the circuit, and after the concentrated cell suspension is stored in the storage container, the first valve is closed and the pump is connected. is driven in normal rotation, the first filling liquid supply source starts supplying filling liquid to the circulation circuit, so that the filling liquid flows through the circulation circuit from the pump to the inlet port of the storage container. The cell suspension remaining in the portion is forced toward the storage container in the circulation direction.

According to this aspect, in a cell concentration process using a circulation circuit including at least a storage container, a pump, and a hollow fiber membrane filter, cells remaining in the circulation circuit after completion of the concentration process can be recovered.

The cell suspension processing device may further include a first optical sensor provided near the inlet port of the storage container to detect the color and/or turbidity of the cell suspension; When a first optical sensor detects a change in color and/or turbidity of the cell suspension, the pump is stopped and the first filling liquid source stops supplying filling liquid to the circulation circuit. do.

The first filling liquid supply source may be a filling liquid supply source for priming the circulation circuit and the hollow fiber membrane filter.

Another aspect of the cell suspension processing apparatus is a cell suspension processing apparatus that concentrates a cell suspension, and includes a circulation circuit in which the cell suspension circulates, and a filling liquid is supplied to the circulation circuit. a filling liquid supply source, the circulation circuit comprising a hollow fiber membrane filter for filtering and concentrating the cell suspension, and an inlet port and an outlet port for storing the cell suspension. a container, a pump that is provided on the downstream side in the circulation direction of the cell suspension with respect to the storage container and on the upstream side in the circulation direction with respect to the hollow fiber membrane filter and circulates the cell suspension; a valve provided on the downstream side in the circulation direction with respect to the thread membrane filter and on the upstream side in the circulation direction with respect to the storage container, and the filling liquid supply source is provided in the circulation circuit. Connected to the part between the pump and the valve , after the concentrated cell suspension is stored in the storage container, the valve is closed and the pump is driven in reverse. Then, the filling liquid supply source starts supplying the filling liquid to the circulation circuit, whereby the cell suspension remaining in the portion of the circulation path from the outlet port of the storage container to the pump is removed by the filling liquid. The liquid is forced toward the storage container in a direction opposite to the circulation direction.

According to this aspect, in a cell concentration process using a circulation circuit including at least a storage container, a pump, and a hollow fiber membrane filter, cells remaining in the circulation circuit after completion of the concentration process can be recovered.

The cell suspension processing device may further include an optical sensor that is provided near the outlet port of the storage container and detects the color and/or turbidity of the cell suspension ; When an optical sensor detects a change in the color and/or turbidity of the cell suspension, the pump is stopped and the fill fluid source stops supplying fill fluid to the circulation circuit.

The filling liquid supply source is a filling liquid supply source for supplying filling liquid into the hollow fiber membrane filter located between the pump and the valve to prime the hollow fiber membrane filter. There may be.

Embodiments of the present invention will be described below with reference to the drawings. However, more detailed explanation than necessary may be omitted. For example, detailed explanations of well-known matters or redundant explanations of substantially the same configurations may be omitted. This is to avoid unnecessary redundancy in the following description and to facilitate understanding by those skilled in the art.

The inventor(s) provide the accompanying drawings and the following description in order for those skilled in the art to fully understand the present invention, and do not intend to limit the subject matter recited in the claims. It's not something you do.

1 to 9 show the appearance of a cell suspension processing device according to an embodiment of the present invention.

Specifically, FIG. 1 is a front perspective view of the cell suspension processing device. FIG. 2 is a front perspective view of the cell suspension processing device from a different perspective. FIG. 3 is a rear perspective view of the cell suspension processing device. FIG. 4 is a rear perspective view of the cell suspension processing device from a different perspective. FIG. 5 is a front view of the cell suspension processing device. FIG. 6 is a rear view of the cell suspension processing device. FIG. 7 is a right side view of the cell suspension processing device. FIG. 8 is a left side view of the cell suspension processing device. FIG. 9 is a plan view of the cell suspension processing device.

Note that although an XYZ orthogonal coordinate system is shown in the drawings, this is for facilitating understanding of the embodiments of the invention and is not intended to limit the invention. Further, the X-axis direction is the front-rear direction of the cell suspension processing device, the Y-axis direction is the left-right direction, and the Z-axis direction is the height direction. Regarding "left and right", the front view of the cell suspension processing device is used as a reference.

A cell suspension processing apparatus 10 according to the present embodiment shown in FIGS. 1 to 9 is an apparatus for concentrating and washing cells as cell suspension processing. Note that FIGS. 1 to 9 show the cell suspension processing apparatus 10 in a state before attaching bags, tubes, etc. used for cell suspension processing, that is, the main body of the cell suspension processing apparatus 10. "Cell suspension" refers to cells such as platelets and megakaryocytes suspended in a liquid medium. Note that the embodiments of the present invention do not limit the cells or culture medium.

Moreover, the "concentration" process refers to a process that removes medium components by filtering the cell suspension so that the concentration of cells in the cell suspension increases. In addition, the "washing" treatment involves washing the concentrated cell suspension with medium components such as physiological saline or buffered physiological saline or Ringer's solution such as bicarbonate Ringer's solution (Bikanate Infusion; manufactured by Otsuka Pharmaceutical Factory Co., Ltd.). Albumin such as blood preservation solution (ACD-A solution; manufactured by Terumo Corporation) or ACD-A solution and human serum albumin preparation (HAS; manufactured by CSL Behring Co., Ltd.) in Ringer's bicarbonate solution or ACD-A solution, human serum albumin preparation and anti-inflammatory agent. Refers to the process of replacing the liquid with a replacement liquid such as a solution containing an oxidizing agent.

As shown in FIGS. 1 to 9, the cell suspension processing device 10 according to the present embodiment includes a base section 12, a column section 14 provided on the base section 12, and a column section 14 provided on the column section 14. It is composed of first and second arm parts 16A and 16B.

The base portion 12 of the cell suspension processing device 10 is a desk-like structure and includes a plurality of casters 18 . The entire cell suspension processing apparatus 10 is movable by the plurality of casters 18. Further, a handle 20 for a user to operate the cell suspension processing device 10 that moves via a plurality of casters 18 is provided on the left side of the base portion 12. Thereby, the layout of the cell suspension processing device 10 can be easily changed.

The columnar part 14 of the cell suspension processing device 10 is a columnar structure that is provided on the base part 12 and extends upward from the base part 12 (in the Z-axis direction). Although details will be described later, a cell processing circuit for processing cells, specifically a cell concentration and washing circuit for carrying out concentration processing and washing processing of cells, is provided on the front side of this columnar portion 14.

The first and second arm portions 16A and 16B of the cell suspension processing device 10 extend laterally from the top of the columnar portion 14, in the case of this embodiment, in the horizontal direction (Y-axis direction). ing. The first arm portion 16A extends to the right, and the second arm portion 16B extends to the left. Although the details will be described later, the first and second arm sections 16A and 16B are configured such that a plurality of bags used for cell concentration processing and washing processing can be suspended therefrom.

From here on, a cell concentration and washing circuit for concentrating and washing cells will be described.

FIG. 10 is a front view of a cell suspension processing apparatus in which an example cell concentration washing circuit is set. FIG. 11 is a schematic configuration diagram of an example of a cell concentration washing circuit.

As shown in FIG. 11, the cell concentration and washing circuit 30 includes a circulation circuit 32 in which the cell suspension circulates during the concentration process and the washing process.

The circulation circuit 32 includes a hollow fiber membrane filter 34 that filters the cell suspension, a storage bag 36 that stores the concentrated cell suspension (concentrate), an outlet port 36b of the storage bag 36, and the hollow fiber membrane filter. 34, and a second connecting tube 40 that connects the outlet port 34b of the hollow fiber membrane filter 34 and the inlet port 36a of the storage bag 36.

The hollow fiber membrane filter 34 is a device that filters and concentrates the cell suspension circulating in the circulation circuit 32, and is replaceably attached to the front of the columnar part 14 of the cell suspension processing device 10. . The hollow fiber membrane filter 34 also has an inlet port 34a through which the cell suspension flows in, an outlet port 34b through which the cell suspension concentrated by filtration flows out, and filtration caused by filtration. A filtrate discharge port 34c is provided for discharging the liquid. A filtrate discharge port 34c of the hollow fiber membrane filter 34 is connected to a filtrate tank 44 via a connecting tube 42.

As shown in FIG. 1, the filtrate tank 44 is mounted on a trolley 46 disposed within the base portion 12 of the cell suspension processing device 10. By moving the trolley 46, the filtrate tank 44 containing the filtrate can be moved to an appropriate location.

Furthermore, in the case of this embodiment, the hollow fiber membrane filter 34 includes an introduction port 34d for introducing a filling liquid for priming into the inside. The introduction port 34d is connected via a connecting tube 48 to a filling liquid bag 50 for supplying filling liquid for priming.

The filling fluid bag 50 is filled with a blood preservation solution (ACD-A solution; Contains filling liquids such as ACD-A solution, ACD-A solution, human serum albumin preparation, and a solution containing an antioxidant. The container is made of, for example, a resin material and has flexibility. Further, although details will be described later, the filling liquid bag 50 is suspended from the first arm portion 16A.

The storage bag 36 is a container (storage container) that stores a cell suspension during cell concentration processing and washing processing, and is made of, for example, a resin material and has flexibility. Furthermore, although details will be described later, the storage bag 36 is suspended from the second arm portion 16B. Furthermore, the storage bag 36 has an inlet port 36a through which the cell suspension from the hollow fiber membrane filter 34 flows in, and an outlet port 36b through which the cell suspension flows out toward the hollow fiber membrane filter 34. Be prepared.

The first connecting tube 38 is a flexible tube made of a transparent resin material, and connects the outlet port 36b of the storage bag 36 and the inlet port 34a of the hollow fiber membrane filter 34.

Further, the first connecting tube 38 is branched at two places, that is, two branch tubes 38a and 38b are connected. One of the branch tubes 38a is a culture solution tank (cell suspension tank) that supplies the cell suspension stored in the storage bag 36 to the circulation circuit 32. (suspended liquid supply source) 52. Note that the culture solution tank 52 is arranged outside the cell suspension processing device 10. The other branch tube 38b is connected to a filling liquid bag 54 for supplying filling liquid for priming to the circulation circuit 32, although the details will be described later.

The filling fluid bag 54 is filled with a blood preservation solution (ACD-A solution; Contains filling liquids such as ACD-A solution, ACD-A solution, human serum albumin preparation, and a solution containing an antioxidant. The container is made of, for example, a resin material and has flexibility. Further, although details will be described later, the filling liquid bag 54 is suspended from the second arm portion 16B.

Like the first connecting tube 38, the second connecting tube 40 is a flexible tube made of a transparent resin material, and connects the outlet port 34b of the hollow fiber membrane filter 34 and the inlet of the storage bag 36. Connect to port 36a.

Further, the second connecting tube 40 is branched at two places, that is, two branch tubes 40a and 40b are connected. One of the branch tubes 40a has a replacement liquid bag (a replacement liquid bag) for supplying a replacement liquid for washing the cells in the concentrated cell suspension, that is, a replacement liquid to be replaced with the medium components of the cell suspension, to the circulation circuit 32. 56 (substitute liquid supply source). The other branch tube 40b is connected to a waste liquid bag 58 that collects the filling liquid after priming, although the details will be described later.

The replacement fluid bag 56 is a blood preservation solution (ACD-A solution; Terumo) mixed with Ringer's solution or Ringer's bicarbonate solution such as physiological saline or buffered physiological saline solution or Ringer's bicarbonate solution (Bikanate Infusion; manufactured by Otsuka Pharmaceutical Factory). Container containing replacement liquids such as ACD-A solution, human serum albumin preparation, and solution containing antioxidants It is made of, for example, a resin material and has flexibility. Further, although details will be described later, the substitution liquid bag 56 is suspended from the first arm portion 16A.

The waste liquid bag 58 is a container for collecting the filling liquid after priming, and is made of, for example, a resin material and has flexibility. Further, although details will be described later, the waste liquid bag 58 is suspended from the second arm portion 16B.

The cell concentration washing circuit 30 including the circulation circuit 32 includes a plurality of pumps 60 to 64, a plurality of valves 66 to 78, a plurality of pressure sensors 80 to 84, and a plurality of pressure sensors 80 to 84 to perform cell concentration and washing processes. Flow rate sensors 86 to 88 are provided.

The circulation circuit 32 of the cell concentration and washing circuit 30 is provided with a pump 60 and three valves 66 to 70.

The pump 60 in the circulation circuit 32 is mainly a pump for circulating the cell suspension within the circulation circuit 32, and is, for example, a roller pump. The pump 60 is disposed downstream in the circulation direction CD of the cell suspension with respect to the storage bag 36 and upstream in the circulation direction CD with respect to the hollow fiber membrane filter 34, that is, in the first connection tube 38. It is provided. Further, the pump 60 is attached to the front of the columnar section 14 of the cell suspension processing device 10.

The three valves 66-70 in the circulation circuit 32 are, for example, pinch valves that pinch close the first and second connecting tubes 38, 40. In the three valves, two valves 66, 68 are provided on the first connecting tube 38. Specifically, the valve 66 is disposed between the branch points of each of the two branch tubes 38a, 38b, and the valve 68 is disposed between the storage bag 36 and the branch point of the branch tube 38a. . The remaining valves 70 are provided on the second connecting tube 40 and are specifically arranged between the branch point of the branch tube 40b and the storage bag 36. Furthermore, these three valves 66 to 70 are attached to the front of the columnar section 14 of the cell suspension processing device 10.

The pump 62 provided outside the circulation circuit 32 is a pump for delivering the filtrate of the hollow fiber membrane filter 34 to the filtrate tank 44, and is, for example, a roller pump. The pump 62 is provided in the connecting tube 42 that connects the filtrate discharge port 34c of the hollow fiber membrane filter 34 and the filtrate tank 44. Further, the pump 62 is attached to the front of the columnar section 14 of the cell suspension processing device 10.

The pump 64 provided outside the circulation circuit 32 is a pump for delivering the substitution liquid in the substitution liquid bag 56 toward the circulation circuit 32, and is, for example, a roller pump. The pump 64 is provided in the branch tube 40a that connects to the second connecting tube 40. Further, the pump 64 is attached to the right side of the columnar section 14 of the cell suspension processing device 10.

The valve 72 provided outside the circulation circuit 32 is a valve that cuts off the connection between the circulation circuit 32 and the culture solution tank 52, and is, for example, a pinch valve. The valve 72 is provided on the branch tube 38a that connects to the first connecting tube 38. Further, the valve 72 is attached to the front of the columnar part 14 of the cell suspension processing device 10.

The valve 74 provided outside the circulation circuit 32 is a valve that cuts off the connection between the circulation circuit 32 and the filling liquid bag 54, and is, for example, a pinch valve. The valve 74 is provided in the branch tube 38b that connects to the first connection tube 38. Further, the valve 74 is attached to the front of the columnar part 14 of the cell suspension processing device 10.

The valve 76 provided outside the circulation circuit 32 is a valve that cuts off the connection between the circulation circuit 32 and the waste liquid bag 58, and is, for example, a pinch valve. The valve 76 is provided in the branch tube 40b that connects to the second connecting tube 40. Further, the valve 76 is attached to the left side surface of the columnar part 14 of the cell suspension processing device 10.

The valve 78 provided outside the circulation circuit 32 is a valve that cuts off the connection between the hollow fiber membrane filter 34 and the filling liquid bag 50, and is, for example, a pinch valve. The valve 78 is provided in the connecting tube 48 that connects the introduction port 34d of the hollow fiber membrane filter 34 and the filling liquid bag 50. Further, the valve 78 is attached to the front of the columnar section 14 of the cell suspension processing device 10.

The pressure sensor 80 is a sensor for detecting the pressure of the cell suspension flowing into the hollow fiber membrane filter 34, and is provided in the first connecting tube 38. Specifically, it is arranged between the pump 60 and the hollow fiber membrane filter 34. Moreover, the pressure sensor 80 is arranged in front of the columnar part 14 of the cell suspension processing device 10.

The pressure sensor 82 is a sensor for detecting the pressure of the cell suspension flowing out from the hollow fiber membrane filter 34, and is provided in the second connection tube 40. Specifically, the pressure sensor 82 is arranged between the hollow fiber membrane filter 34 and the branch point of the branch tube 40a. Moreover, the pressure sensor 82 is arranged in front of the columnar part 14 of the cell suspension processing apparatus 10.

The pressure sensor 84 is a sensor for detecting the pressure of the filtrate discharged from the hollow fiber membrane filter 34, and is provided in the connecting tube 42 that connects the hollow fiber membrane filter 34 and the filtrate tank bag 44. There is. Specifically, the pressure sensor 84 is arranged between the hollow fiber membrane filter 34 and the pump 62. Moreover, the pressure sensor 84 is arranged in front of the columnar part 14 of the cell suspension processing device 10.

The flow rate sensor 86 is a sensor for detecting the flow rate of the concentrated cell suspension flowing out from the hollow fiber membrane filter 34, for example, a clamp-on type sensor, and is provided in the second connecting tube 40. ing. Specifically, the flow rate sensor 86 is arranged between the branch point of the branch tube 40a and the branch point of the branch tube 40b. Further, the flow rate sensor 86 is attached to the front of the columnar section 14 of the cell suspension processing device 10.

The flow rate sensor 88 is a sensor for detecting the flow rate of the filtrate discharged from the hollow fiber membrane filter, for example, a clamp-on type sensor, and is a connecting tube that connects the hollow fiber membrane filter 34 and the filtrate tank 44. 42. Specifically, the flow rate sensor 88 is disposed between the pump 62 and the filtrate tank 44. Further, the flow rate sensor 88 is attached to the front of the columnar section 14 of the cell suspension processing device 10.

As shown in FIG. 10, the plurality of components of the cell concentration washing circuit 30 described above are arranged on the front (some on the side) of the columnar part 14 of the cell suspension processing device 10. Further, the replacement liquid bag 56, the filling liquid bag 50, the waste liquid bag 58, the filling liquid bag 54, and the storage bag 36 are provided side by side in the left-right direction (Y-axis direction). Thereby, when the user is positioned facing the front of the cell suspension processing device 10, the user can confirm the cell concentration washing circuit 30 at a glance. From another perspective, since there are no components or bags of the cell concentration washing circuit 30 on the back side of the columnar body 14 shown in FIG. 6, the back side of the columnar body 14 is brought close to the wall. The cell suspension processing device 10 can be installed in the following manner.

Specifically, as shown in FIG. 10, the replacement liquid bag 56, the filling liquid bag 50, the waste liquid bag 58, the filling liquid bag 54, and the storage bag 36 are suspended from the first and second arm parts 16A and 16B. It's lowered. To this end, the first and second arms 16A, 16B are provided with a plurality of hooks 90, 92 from which these bags are suspended. The first arm portion 16A is provided with two hooks 90 arranged in its extending direction (Y-axis direction), and the second arm portion 16B is provided with two hooks 90 arranged in its extending direction (Y-axis direction). A hook 90 and one hook 92 are provided.

In the case of this embodiment, as shown in FIG. 10, a beam 94 extending in the left-right direction (Y-axis direction) is provided in the first and second arm portions 16A and 16B. The beam 94 is provided with a rail 96 that extends in the left-right direction and supports the plurality of hooks 90 so as to be movable in the left-right direction. Thereby, the distance between the bags suspended from each of the plurality of hooks 90 can be easily adjusted.

The hook 92, unlike the other hooks 90, is not movably mounted on the beam 94. As shown in FIG. 12, the hook 92 is attached to the left end of the beam 94 via a weight sensor 98. This is because the weight of the storage bag 36 suspended from the hook 92 is measured by the weight sensor 98, and also because the storage bag 36 is heavier and larger (for example, 50 liters) than other bags. In addition, in order to fix the position of each of the plurality of hooks 90 similarly to the hook 92, a lock lever 100 for fixing the plurality of hooks 90 at a predetermined position on the rail 96 is provided on each of the hooks 90.

As shown in FIG. 10, the largest storage bag 36 is suspended from the tip of the second arm portion 16B via a hook 92. That is, the storage bag 36 is located at the outermost position. Therefore, there is a possibility that a moving user may come into contact with the storage bag 36. In order to avoid such contact, the handle 20 extends from the base portion 12 to the side of the tip of the second arm portion 16B, as shown in FIGS. 1 and 2, for example. As a result, the handle 20 is deployed to the outside of the storage bag 36, and the handle 20 functions as a guard to avoid contact between the storage bag 36 and the user.

Since a plurality of bags used for cell concentration processing and washing processing are suspended and supported in this way, the installation space (footprint) of the cell suspension processing device 10 can be made compact (the bags can be laid down). (compared to cases where multiple containers containing cell suspensions, etc. are not bags).

Further, as shown in FIGS. 1 and 2, below the hooks 90 and 92, there are a plurality of bags such as the storage bag 36 suspended from these hooks 90 and 92, and below the cell concentration washing circuit 30. , a drain pan 102 is arranged. Specifically, the drain pan 102 has a shape (i.e., a bracket shape) that surrounds the columnar part 14 except for the back surface thereof in a plan view (viewed in the Z-axis direction), and is removably mounted on the base part 12. There is. Thereby, the drain pan 102 can receive the cell suspension leaking from the storage bag 36, the substituent bag 56, or the cell concentration washing circuit 30. As a result, the leaked cell suspension is prevented from falling onto the floor of the room in which the cell suspension processing device 10 is installed. In addition, since the drain pan 102 is removable from the base part 12 of the cell suspension processing apparatus 10, it can be cleaned at a location different from the installation location of the cell suspension processing apparatus 10. Moreover, if a plurality of drain pans 102 are prepared, the cell suspension processing apparatus 10 can be used at a high operating rate.

Cell concentration processing and washing processing using the cell concentration washing circuit 30 are automatically performed.

FIG. 13 is a block diagram showing the control system of the cell suspension processing device.

As shown in FIG. 13, the cell suspension processing device 10 includes a controller 120 that controls a plurality of pumps 60-64 and a plurality of valves 66-78. The controller 120 is, for example, a control board equipped with a CPU. Connected to the controller 120 are a storage device 122 and a touch screen display 124 that is a user interface. The touch screen display 124 is attached to the front of the columnar part 14 of the cell suspension processing device 10, as shown in FIG.

The controller 120 controls the plurality of pumps 60 to 64 and the plurality of valves 66 to 78 necessary for cell concentration processing and washing processing according to a program stored in a storage device 122 such as a memory or a hard disk. . Further, based on the detection results of the plurality of pressure sensors 80 to 84, the plurality of flow rate sensors 86 to 88, and the weight sensor 98, the controller 120 controls the plurality of pumps 60 to 64 and the plurality of valves 66 to 78. . Then, the controller 120 presents information such as the detection results of the plurality of sensors and the currently executed control (processing process) to the user via the touch screen display 124.

From now on, the cell concentration process and washing process executed by the controller 120 will be described with reference to FIGS. 14A to 14K.

First, before the controller 120 starts the cell concentration and washing processes, the cell concentration and washing circuit 30 is set by the user as a preliminary preparation.

As a preliminary preparation, as shown in FIG. Attached to a plurality of pumps 60-64, a plurality of valves 66-78, and a plurality of flow sensors 86,88. These multiple connection tubes and pressure sensors are single-use and are replaced each time cell processing is performed.

Next, as shown in FIG. 10, the filling liquid bag 50 and the replacement liquid bag 56 are hung from the first arm portion 16A via the hook 90 by the user. Further, the waste liquid bag 58, the filling liquid bag 54, and the storage bag 36 are suspended from the second arm portion 16B via hooks 90 and 92. Note that at this time, the storage bag 36 and the waste liquid bag 58 are empty.

Subsequently, as shown in FIGS. 10 and 11, a plurality of bags 36, 50, 54, 56, and 58 are connected to circulation circuit 32 by the user. Further, a branch tube 38a connected to the first connection tube 38 is connected to a culture solution tank 52 located outside the cell suspension processing device 10. Further, a connecting tube 42 connected to the filtrate discharge port 34c of the hollow fiber membrane filter 34 is connected to the filtrate tank 44.

Then, via the touch screen display 124, the user sets conditions related to cell concentration processing and washing processing, such as the rotational speed of the pumps 60 to 64, concentration time, washing time, and the like.

When the preliminary preparation is completed and the user inputs a start instruction to the touch screen display 124, the controller 120 performs a processing step of cleaning the inside of the hollow fiber membrane in the hollow fiber membrane filter 34 as a first processing step. Execute. To this end, as shown in FIG. 14A, the controller 120 opens only the valves 74 and 76 and puts only the pump 60 into operation. In addition, in the figure, the pump indicated by a broken line is in a stopped state, and the valve indicated by a broken line is in a closed state.

During execution of the first treatment step, the filling liquid in the filling liquid bag 54 flows into the hollow fiber membrane filter 34 through the inlet port 34a, and the filling liquid flowing out from the outlet port 34b of the hollow fiber membrane filter 34 is waste liquid. Enter the bag 58. This cleans the inside of the hollow fiber membrane.

Next, as a second processing step, the controller 120 controls the space outside the hollow fiber membrane in the hollow fiber membrane filter 34, that is, the space between the hollow fiber membrane and the cartridge accommodating it. A processing step is executed to clean the space in which the filtrate flows. To this end, as shown in FIG. 14B, the controller 120 opens only the valve 78 and puts only the pump 62 into operation. As a result, the filling liquid in the filling liquid bag 50 flows into the cartridge of the hollow fiber membrane filter 34 through the introduction port 34d, and the filling liquid that has passed through the space inside the cartridge flows out from the filtrate discharge port 34c. It enters the filtrate tank 44. As a result, the inside of the cartridge of the hollow fiber membrane filter (the outside of the hollow fiber membrane) is cleaned.

Next, as a third processing step, the controller 120 executes an air purge processing step of the circuit from the hollow fiber membrane filter 34 to the storage bag 36 (ie, the second connection tube 40). To this end, as shown in FIG. 14C, the controller 120 opens only the valves 70 and 74 and puts only the pump 60 into operation. As a result, the filling liquid in the filling liquid bag 54 flows into the hollow fiber membrane filter 34, and the filling liquid flowing out from the hollow fiber membrane filter 34 enters the storage bag 36. As a result, air is removed from the circuit from the hollow fiber membrane filter 34 to the storage bag 36 (the circuit is filled with the filling liquid).

As a fourth processing step following the third processing step, the controller 120 executes an air removal processing step for the circuit from the storage bag 36 to the culture solution tank 52. To this end, as shown in FIG. 14D, the controller 120 opens only the valves 68, 70, 72, and 74, and puts only the pump 60 into operation. Thereby, the filling liquid in the filling liquid bag 54 passes through the hollow fiber membrane filter 34 and enters the storage bag 36, and the filling liquid in the storage bag 36 enters the culture liquid tank 52. As a result, air is removed from the circuit from the storage bag 36 to the culture solution tank 52 (the circuit is filled with the filling solution).

Next, as a fifth processing step, the controller 120 executes a processing step of supplying the cell suspension (culture solution) processed by the cell concentration washing circuit 30 to the storage bag 36. To this end, as shown in FIG. 14E, the controller 120 opens only the valves 66, 70, and 72, and puts only the pump 60 into operation. Thereby, the cell suspension in the culture solution tank 52 passes through the hollow fiber membrane filter 34 without being filtered, and is stored in the storage bag 36.

As a sixth processing step following the fifth processing step, the controller 120 subsequently executes a processing step of supplying the cell suspension (culture solution) to the storage bag 36. At this time, the cell suspension is supplied to the storage bag 36 while being filtered by the hollow fiber membrane filter 34. To this end, as shown in FIG. 14F, the controller 120 opens only the valves 66, 70, and 72 and puts only the pumps 60 and 62 into operation. Thereby, the cell suspension in the culture solution tank 52 is filtered by the hollow fiber membrane filter 34, and the filtered cell suspension is stored in the storage bag 36.

In this sixth treatment step, the branch tube 40a connected to the second connection tube 40 functions as an accumulator that suppresses the pulsation (pressure fluctuation) of the cell suspension flowing from the culture solution tank 52 to the storage bag 36. do.

Specifically, the operation of the two pumps 60 and 62 causes pulsation in the cell suspension. As a countermeasure, in order to form an accumulator, the branch tube 40a connected to the second connecting tube 40 is pinched and occluded with a pinch device such as forceps 130, as shown in FIG. As a result, the portion 132 of the branch tube 40a from the branch point to the closed position is converted into an accumulator. That is, the air within this accumulator 132 absorbs pressure fluctuations in the cell suspension, thereby suppressing pressure fluctuations.

The effect of the branch tube 40a of the second connecting tube 40 functioning as the accumulator 132 will be explained.

FIG. 16 is a diagram showing the pressure fluctuation of the cell suspension being supplied to the circulation circuit in the case where an accumulator is present (example) and the case where it is not present (comparative example).

The pressure shown in FIG. 16 is the pressure at the inlet port 34a of the hollow fiber membrane filter 34, that is, the pressure detected by the pressure sensor 80. As shown in FIG. 16, although the pressure fluctuates both when an accumulator is present (example) and when an accumulator is not present (comparative example), the fluctuation range is larger in the comparative example. Further, when the 3σ value (3 sigma value) is calculated, the Example is about 1.84 kPa and the Comparative Example is about 2.65 kPa. That is, the degree of pressure fluctuation of the cell suspension is smaller in the example.

Such an accumulator 132 suppresses pulsation (pressure fluctuation) of the cell suspension flowing from the culture solution tank 52 toward the storage bag 36, thereby preventing cells in the cell suspension from being damaged by the pulsation. suppressed.

In addition, in order to suppress the inflow of the cell suspension into the accumulator 132 (i.e., the branch tube 40a), the branch tube 40a is designed to prevent cells passing through its branch point, as shown in area A in FIG. It extends diagonally backward from the branch point with respect to the flow direction of the suspension.

Further, the pinch device that pinches and closes the branch tube 40a in order to make the branch tube 40a function as the accumulator 132 is not limited to the forceps 130 shown in FIG. 15. The pinch device may be a pinch valve, for example.

When the pinch device is the forceps 130, the portion of the branch tube 40a that is pinched and occluded by the forceps 130 can be changed. Therefore, even if the mode of pulsation of the cell suspension is different, if the forceps 130 pinch and occlude the appropriate portion of the branch tube 40a, the pulsation can be appropriately suppressed. Preferably, a scale may be placed on the branch tube 40a, for example, to record the portion of the branch tube 40a that the forceps 130 pinches. Thereby, the branch tube 40a includes a plurality of indicators indicating a plurality of pinch positions to be pinched by the forceps 130. By recording the portion of branch tube 40a that is pinched by forceps 130, substantially the same cell suspension treatment can be performed with high reproducibility.

When a predetermined amount of cell suspension is stored in the storage bag 36 in the sixth processing step, that is, when the weight sensor 98 detects a predetermined weight corresponding to the predetermined amount, the controller 120 ends the sixth processing step. , begins the seventh processing step. As shown in FIG. 14G, in the seventh treatment step, the cell suspension is concentrated by filtration through the hollow fiber membrane filter 34 while circulating through the circulation circuit 32. To this end, the controller 120 opens only the valves 66, 68, and 70 and puts only the pumps 60 and 62 into operation. Thereby, the cell suspension in the storage bag 36 is filtered by the hollow fiber membrane filter 34, and the cell suspension concentrated by the filtration is returned to the storage bag 36. During this seventh treatment step, the weight of the storage bag 36 decreases due to concentration of the cell suspension. Further, the filtrate is sent to the filtrate tank 44 .

When the cell suspension reaches a predetermined concentration in the seventh processing step, that is, when the weight sensor 98 detects a predetermined weight corresponding to the predetermined concentration, the controller 120 ends the seventh processing step and Start the processing step No. 8. As shown in FIG. 14H, in the eighth treatment step, the cell suspension circulates through the circulation circuit 32 without being filtered by the hollow fiber membrane filter 34. This eighth processing step is carried out for several minutes, for example one minute. To this end, the controller 120 opens only the valves 66, 68, and 70, and puts only the pump 60 into operation.

When the eighth treatment step is completed, the controller 120 stops the pump 60 to end the circulation of the cell suspension in the circulation circuit 32. At this time, the concentrated cell suspension, ie, cells, remains in the circulation circuit 32, ie, the first and second connecting tubes 38, 40.

A ninth treatment step is performed to collect the cells remaining in the first and second connecting tubes 38, 40 into the storage bag 36. In this ninth processing step, as shown in FIG. 14I, the controller 120 opens only the valves 70 and 74 and puts only the pump 60 into operation. As a result, the filling liquid in the filling liquid bag 54 is supplied into the circulation circuit 32, and the supplied filling liquid passes through the hollow fiber membrane filter 34 and heads toward the storage bag 36. The filling liquid flowing in this manner sweeps the cell suspension remaining in the portion of the circulation circuit 32 from the pump 60 to the inlet port 36a of the storage bag 36 toward the storage bag 36. As a result, cells remaining in the circulation circuit 32 after the eighth treatment step, that is, after the concentration treatment, are collected into the storage bag 36.

Note that when the filling liquid supplied to the circulation circuit 32 to collect cells remaining in the circulation circuit 32 enters the storage bag 36, the concentration of the cell suspension concentrated to a predetermined concentration in the storage bag 36 increases. descend. Therefore, just before the filling liquid enters the storage bag 36, the supply of the filling liquid to the circulation circuit 32 is stopped (the pump 60 is stopped and the valve 74 is closed).

For example, the time required for the filling liquid in the filling liquid bag 54 to reach the storage bag 36 is determined based on the discharge capacity of the pump 60, the length of the flow path from the filling liquid bag 54 to the storage bag 36, the inner diameter of the tube, etc. The filling liquid arrival time is calculated in advance. When the filling liquid arrival time elapses from the timing at which the filling liquid of the filling liquid bag 54 is supplied to the circulation circuit 32, the supply of the filling liquid is stopped.

For example, if the cell suspension and the filling liquid are distinguishable, the color of the cell suspension in the circulation circuit 32 (i.e., the second connection tube 40) and/or Alternatively, an optical sensor for detecting turbidity is provided.

When the cell suspension is colored red with phenol red and the filling liquid is transparent, the optical sensor detects the cell suspension when the filling liquid reaches the vicinity of the inlet port 36a of the storage bag 36, which is the detection area of the optical sensor. Detects the change in color of the turbid liquid (change from red to a different color).

Furthermore, if the concentrated cell suspension has a high turbidity and has a predetermined concentration, when the filling liquid reaches the vicinity of the inlet port 36a of the storage bag 36, which is the detection area of the optical sensor, the optical sensor detects the change in turbidity. Detect.

When the optical sensor detects a change in color and/or turbidity of the cell suspension, controller 120 stops pump 60 and stops supplying fill fluid from fill fluid bag 54 to circulation circuit 32 .

When the cells remaining in the portion of the circulation circuit 32 from the pump 60 to the inlet port 36a of the storage bag 36 have been collected into the storage bag 36, the controller 120 executes a tenth processing step. In the tenth treatment step, cells remaining in the portion of the circulation circuit 32 from the outlet port 36b of the storage bag 36 to the pump 60 are collected. To this end, as shown in FIG. 14J, the controller 120 opens only the valves 66, 68, and 78, and puts only the pump 60 into operation. However, the controller 120 drives the pump 60 in the reverse direction ( (Roller pump rotor reverses). As a result, the filling liquid in the filling liquid bag 50 is supplied to the hollow fiber membrane filter 34, the supplied filling liquid flows out from the inlet port 34a of the hollow fiber membrane filter 34, and the flowing out filling liquid enters the storage bag 36. Flows toward outlet port 36b. The filling liquid flowing in this way sweeps away the cell suspension remaining in the portion of the circulation circuit 32 from the outlet port 36b of the storage bag 36 to the pump 60 toward the storage bag 36. Thereby, cells remaining in the circulation circuit 32 after the eighth treatment step, that is, after the concentration treatment, are collected into the storage bag 36.

In addition, by the same method as in the ninth processing step (for example, a method using an optical sensor), the filling liquid of the filling liquid bag 50 is supplied to the circulation circuit 32, and the filling liquid is transferred to the outlet port in the storage bag 36. 36b.

When the collection of cells remaining in the circulation circuit 32 is completed (when the ninth and tenth processing steps are completed), the controller 120 executes a cell washing process as an eleventh processing step. To this end, as shown in FIG. 14K, controller 120 opens only valves 66, 68, and 70 and activates all pumps 60, 62, and 64. As a result, the substitution liquid in the substitution liquid bag 56 is supplied to the circulation circuit 32 through which the concentrated cell suspension circulates, and the mixed liquid of the cell suspension and the substitution liquid is filtered by the hollow fiber membrane filter 34. Eventually, the medium components of the cell suspension are replaced by the replacement solution and the cells are washed. When this eleventh processing step is completed, all steps of cell concentration processing and washing processing by the controller 120 are completed.

In this eleventh treatment step, the branch tube 38a of the first connecting tube 38 functions as an accumulator that suppresses the pulsation (pressure fluctuation) of the cell suspension that circulates in the circulation circuit 32 together with the substituting liquid.

Specifically, as shown in FIG. 14K, the operation of the three pumps 60, 62, and 64 causes the cell suspension circulating in the circulation circuit 32 to pulsate. As a countermeasure, the branch tube 38a connected to the first connecting tube 38 is pinched and closed by the valve 72, which is a pinch device, in order to function as an accumulator. Thereby, the portion 134 of the branch tube 38a from the branch point to the closed position is converted into an accumulator.

FIG. 17 is a diagram showing the pressure fluctuation of the cell suspension during cell washing in the case where an accumulator is present (example) and the case where it is not present (comparative example).

The pressure shown in FIG. 17 is the pressure at the inlet port 34a of the hollow fiber membrane filter 34, that is, the pressure detected by the pressure sensor 80. As shown in FIG. 17, although the pressure fluctuates both when an accumulator is present (example) and when an accumulator is not present (comparative example), the fluctuation range is larger in the comparative example. Further, when the 3σ value (3 sigma value) is calculated, the Example is about 1.91 kPa and the Comparative Example is about 2.54 kPa. That is, the degree of pressure fluctuation of the cell suspension is smaller in the example.

Such an accumulator 134 suppresses pulsation (pressure fluctuation) of the cell suspension during cell washing, thereby suppressing damage to cells within the cell suspension due to pulsation.

Note that in order to suppress the cell suspension from flowing into the accumulator 134 (i.e., the branch tube 38a), the branch tube 38a is designed to prevent cells passing through its branch point from flowing into the cell suspension, as shown in area B in FIG. Extending from the branch point in a direction perpendicular to the direction of flow of the suspension.

Further, the pinch device that pinches and closes the branch tube 38a in order to cause the branch tube 38a to function as the accumulator 134 may be a forceps.

When the pinch device that pinches the branch tube 38a is a forceps, the portion of the branch tube 38a that is pinched and occluded by the forceps can be changed. Preferably, a scale may also be provided on the branch tube 38a, for example, to record the portion of the branch tube 38a that the forceps pinch. Thereby, the branch tube 38a includes a plurality of indicators indicating a plurality of pinch positions to be pinched by the forceps.

According to this embodiment, in a cell concentration process using a circulation circuit including at least a storage container, a pump, and a hollow fiber membrane filter, cells remaining in the circulation circuit after completion of the concentration process can be recovered. .

Although the present invention has been described above with reference to the above embodiments, the embodiments of the present invention are not limited thereto.

For example, in the case of the embodiment described above, as shown in FIG. 14J, in order to recover cells remaining in the portion of the circulation circuit 32 from the outlet port 36b of the storage bag 36 to the pump 60, The filling liquid in the liquid bag 50 is supplied to the hollow fiber membrane filter 34. However, embodiments of the present invention are not limited to this. The filling liquid supply source may be connected to a portion of the circulation circuit 32 between the pump 60 and the valve 70.

That is, in a broad sense, the cell suspension processing device according to the embodiment of the present invention is a cell suspension processing device that concentrates a cell suspension, and includes a circulation circuit in which the cell suspension circulates. , a first filling liquid supply source that supplies a filling liquid to the circulation circuit, the circulation circuit having a hollow fiber membrane filter that filters and concentrates the cell suspension, an inlet port and an outlet port. a storage container for storing a cell suspension, provided on the downstream side in the circulation direction of the cell suspension with respect to the storage container and on the upstream side in the circulation direction with respect to the hollow fiber membrane filter; a pump for circulating the suspension; and a first valve provided downstream in the circulation direction with respect to the storage container and upstream in the circulation direction with respect to the pump, the first A filling liquid supply source is connected to a portion between the first valve and the pump in the circulation circuit, and after the concentrated cell suspension is stored in the storage container, the first valve When the valve is closed and the pump is driven in normal rotation, the first filling liquid supply source starts supplying the filling liquid to the circulation circuit, so that the filling liquid flows from the pump to the storage container. The cell suspension remaining in the portion of the circulation circuit up to the inlet port is forced toward the storage container in the circulation direction.

Furthermore, in a broad sense, the cell suspension processing device according to another embodiment of the present invention is a cell suspension processing device that concentrates a cell suspension, and includes a circulation circuit in which the cell suspension circulates. and a filling liquid supply source that supplies a filling liquid to the circulation circuit, and the circulation circuit includes a hollow fiber membrane filter that filters and concentrates the cell suspension, an inlet port, and an outlet port. a storage container for storing a cell suspension, provided on the downstream side in the circulation direction of the cell suspension with respect to the storage container and on the upstream side in the circulation direction with respect to the hollow fiber membrane filter; a pump for circulating the suspension, and a valve provided downstream in the circulation direction with respect to the hollow fiber membrane filter and upstream in the circulation direction with respect to the storage container, A filling liquid supply source is connected to a portion of the circulation circuit between the pump and the valve , and after the concentrated cell suspension is stored in the storage container, the valve is closed. With the valve closed and the pump driven in reverse, the filling liquid supply source starts supplying the filling liquid to the circulation circuit, thereby causing the filling liquid to flow from the outlet port of the storage container to the pump. The cell suspension remaining in the circulation path is forced toward the storage container in a direction opposite to the circulation direction.

The illustrated embodiment will be briefly described below again.
The "main body of the cell suspension processing device" includes a filtration filter 34 approximately in the center of the front. For example, as shown in the reference diagram (Figure 10), a cell suspension processing device is constructed by suspending various bags from the main body of the device and piping the various bags and filtration filters using tube material. be done. The cell suspension processing device is a device for concentrating and washing a cell suspension in which cells such as platelets and megakaryocytes are suspended in a liquid medium, and is used, for example, as follows. First, the inside of the filter and piping is cleaned by circulating the primer contained in the bags 50 and 54 (the used primer is collected in the bag 58 as waste liquid). Next, the cultured cell suspension (culture solution) is supplied from the outside to the bag 36 via the tube 38a. Then, while circulating the cell suspension in the circulation circuit 32, it is filtered (concentrated) by the filter 34 (the filtrate is sent to the filtrate tank 44). Finally, while circulating the concentrated cell suspension within the circulation circuit 32, a replacement liquid in the bag 56 is supplied to replace the medium components of the cell suspension with the replacement liquid. In this way, the entire process of cell concentration and washing is completed.

As mentioned above, a plurality of embodiments have been described as illustrations of the technology of the present invention. To that end, the accompanying drawings and detailed description have been provided.

Therefore, among the components described in the accompanying drawings and detailed description, there are not only components that are essential for solving the problem, but also components that are not essential for solving the problem in order to illustrate the technology. may also be included. Therefore, just because these non-essential components are described in the accompanying drawings or detailed description, it should not be immediately determined that those non-essential components are essential.

Moreover, since the above-described embodiments are for illustrating the technology of the present invention, various changes, substitutions, additions, omissions, etc. can be made within the scope of the claims or equivalents thereof.

INDUSTRIAL APPLICATION This invention is applicable to the apparatus which processes a cell suspension using a circulation circuit.

32 Circulation circuit 34 Hollow fiber membrane filter 36 Storage container 54 Filling liquid supply source (filling liquid bag)
60 pump 66 valve

Claims (5)

A cell suspension processing device that concentrates a cell suspension,
a circulation circuit in which a cell suspension circulates;
a first filling liquid supply source that supplies filling liquid to the circulation circuit;
The circulation circuit is
a hollow fiber membrane filter that filters and concentrates the cell suspension;
a storage container having an inlet port and an outlet port and storing a cell suspension;
a pump that is provided on the downstream side in the circulation direction of the cell suspension with respect to the storage container and on the upstream side in the circulation direction with respect to the hollow fiber membrane filter, and that circulates the cell suspension;
a first valve provided on the downstream side in the circulation direction with respect to the storage container and on the upstream side in the circulation direction with respect to the pump,
the first filling liquid supply source is connected to a portion of the circulation circuit between the first valve and the pump;
After the concentrated cell suspension is stored in the storage container, with the first valve closed and the pump driven in normal rotation, the first filling liquid supply source starts the circulation. By starting the supply of filling liquid to the circuit, the filling liquid forces the cell suspension remaining in the portion of the circulation circuit from the pump to the inlet port of the storage container in the circulation direction toward the storage container. ,
further comprising a first optical sensor provided near the inlet port of the storage container to detect the color and/or turbidity of the cell suspension;
When the first optical sensor detects a change in color and/or turbidity of the cell suspension, the pump is stopped and the first filling liquid supply source stops supplying filling liquid to the circulation circuit. Stop the cell suspension processing device.
The cell suspension processing device according to claim 1, wherein the first filling liquid supply source is a filling liquid supply source for priming the circulation circuit and the hollow fiber membrane filter.
A cell suspension processing device for concentrating a cell suspension, the device comprising:
a circulation circuit in which a cell suspension circulates;
a filling liquid supply source that supplies filling liquid to the circulation circuit;
The circulation circuit is
a hollow fiber membrane filter that filters and concentrates the cell suspension;
a storage container having an inlet port and an outlet port and storing a cell suspension;
a pump that is provided on the downstream side in the circulation direction of the cell suspension with respect to the storage container and on the upstream side in the circulation direction with respect to the hollow fiber membrane filter, and that circulates the cell suspension;
a valve provided on the downstream side in the circulation direction with respect to the hollow fiber membrane filter and on the upstream side in the circulation direction with respect to the storage container,
the filling liquid supply source is connected to a portion of the circulation circuit between the pump and the valve ;
After the concentrated cell suspension is stored in the storage container, the filling liquid supply source is supplied to the circulation circuit with the valve closed and the pump driven in reverse. By starting the supply of the filling liquid, the filling liquid moves the cell suspension remaining in the portion of the circulation path from the outlet port of the storage container to the pump toward the storage container in a direction opposite to the circulation direction. cell suspension processing equipment.
further comprising an optical sensor provided near the outlet port of the storage container to detect the color and/or turbidity of the cell suspension;
When the optical sensor detects a change in color and/or turbidity of the cell suspension, the pump is stopped and the filling liquid source stops supplying filling liquid to the circulation circuit. , The cell suspension processing device according to claim 3.
The filling liquid supply source is a filling liquid supply source for supplying filling liquid into the hollow fiber membrane filter located between the pump and the valve to prime the hollow fiber membrane filter. The cell suspension processing device according to claim 3 or 4.

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