JP2021023149A - Method for supplying cell-containing liquid, device for supplying cell-containing liquid, and method for manufacturing cell-containing product - Google Patents

Method for supplying cell-containing liquid, device for supplying cell-containing liquid, and method for manufacturing cell-containing product Download PDF

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JP2021023149A
JP2021023149A JP2019141196A JP2019141196A JP2021023149A JP 2021023149 A JP2021023149 A JP 2021023149A JP 2019141196 A JP2019141196 A JP 2019141196A JP 2019141196 A JP2019141196 A JP 2019141196A JP 2021023149 A JP2021023149 A JP 2021023149A
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cell
container
containing liquid
liquid
main pipe
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JP7346141B2 (en
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真代 湯本
Masayo Yumoto
真代 湯本
古野 哲生
Tetsuo Furuno
哲生 古野
輝 黒木
Teru Kuroki
輝 黒木
崇史 瀧尻
Takashi TAKIJIRI
崇史 瀧尻
正通 阿部
Masamichi Abe
正通 阿部
八木 良樹
Yoshiki Yagi
良樹 八木
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Rohto Pharmaceutical Co Ltd
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Abstract

To provide a method for supplying a cell-containing liquid that is capable of filling a certain amount of a cell-containing liquid in a container in a short time and is less likely to affect the qualities of cells, such as homogeneity and viability, between multiple containers.SOLUTION: For a combination of a main pile 22, which is a series of pipelines; a plurality of branch pipes 23, which are pipelines branched laterally from the main pipe 22; and a plurality of containers B connected to the plurality of branch pipes 23, the main pipe 22 is filled with a cell-containing liquid L in which living cells are dispersed in a state where the plurality of branch tubes 23 are closed. After that, by opening the plurality of branch pipes 23, the containers B are supplied from the main pipe 22 through the respective branch pipes 23.SELECTED DRAWING: Figure 1

Description

本発明は、生存細胞を含有する液体を容器に供給する際の、細胞含有液の供給方法、細胞含有液の供給装置、細胞含有製品の製造方法に関する。 The present invention relates to a method for supplying a cell-containing liquid, a device for supplying the cell-containing liquid, and a method for producing a cell-containing product when supplying a liquid containing viable cells to a container.

近年、人体の様々な部位の組織、細胞、受精卵等を用いて細胞の分離及び/もしくは細胞培養を行い、調製された細胞を再生医療に使用することが実用化されている。調製された細胞は、調製場所から、例えば、医療機関や研究機関等の使用場所へと運ばれる。この際、生存細胞を含有する液体が容器に充填された、細胞含有製品の形体とすることが考えられる。容器に充填された細胞含有製品であれば、流通ルートに乗せることが容易となる。また、容器に充填することにより細胞等の品質を保つことが可能となる。 In recent years, it has been put into practical use that cells are separated and / or cell culture is performed using tissues, cells, fertilized eggs and the like of various parts of the human body, and the prepared cells are used for regenerative medicine. The prepared cells are transported from the place of preparation to a place of use such as a medical institution or a research institution. At this time, it is conceivable that the container is filled with a liquid containing viable cells to form a cell-containing product. If the cell-containing product is packed in a container, it can be easily put on the distribution route. Further, by filling the container, it is possible to maintain the quality of cells and the like.

ここで、例えば特許文献1には、生体試料に係る液体を容器に充填する方法が記載されている。この方法は、複数の容器のそれぞれの収容室の底部が実質的に同じ高さとされ、液体がそれぞれの収容室を順に流れるように接続されて送液される方法である。 Here, for example, Patent Document 1 describes a method of filling a container with a liquid related to a biological sample. In this method, the bottoms of the respective storage chambers of a plurality of containers are set to substantially the same height, and the liquids are connected so as to flow through the respective storage chambers in order to be fed.

特開2018−126195号公報JP-A-2018-126195

この方法において、液体の容器への供給は、上流側の容器から下流側の容器へ時間差をおいてなされる。このため、異なる容器への充填が時間的に前後することにより細胞の均質性や生存率等の品質に影響を与える可能性があった。 In this method, the liquid is supplied to the container with a time lag from the container on the upstream side to the container on the downstream side. For this reason, filling of different containers may affect quality such as cell homogeneity and viability by changing the time.

そこで本発明は、短時間で、一定量の細胞含有液を容器に充填でき、細胞の均質性や生存率等の品質に影響を与えにくい細胞含有液の供給方法、細胞含有液の供給装置、細胞含有製品の製造方法を提供することを課題とする。 Therefore, according to the present invention, a method for supplying a cell-containing liquid, which can fill a container with a certain amount of the cell-containing liquid in a short time and does not easily affect the quality such as cell homogeneity and viability, a cell-containing liquid supply device, An object of the present invention is to provide a method for producing a cell-containing product.

本発明は、一連の管路である本管と、前記本管から側方に分岐した管路である複数の支管と、前記複数の支管に接続された複数の容器と、の組み合わせに対し、生存細胞が分散している細胞含有液を、前記複数の支管が閉鎖された状態で前記本管に充填し、その後、前記複数の支管を開放することにより、前記本管から各支管を介して各容器に供給する、細胞含有液の供給方法である。 The present invention relates to a combination of a main pipe, which is a series of pipelines, a plurality of branch pipes, which are pipelines branched laterally from the main pipe, and a plurality of containers connected to the plurality of branch pipes. The cell-containing liquid in which the living cells are dispersed is filled in the main pipe in a state where the plurality of branch pipes are closed, and then the plurality of branch pipes are opened, so that the main pipe is used via each branch pipe. This is a method of supplying a cell-containing liquid to be supplied to each container.

また、本発明は、容器に生存細胞が分散している細胞含有液が充填された細胞含有製品の製造方法であって、一連の管路である本管と、前記本管から側方に分岐した管路である複数の支管と、前記複数の支管に接続された複数の前記容器と、の組み合わせに対し、細胞含有液を、前記複数の支管が閉鎖された状態で前記本管に充填し、その後、前記複数の支管を開放することにより、前記本管から各支管を介して各容器に供給する、細胞含有製品の製造方法である。 Further, the present invention is a method for producing a cell-containing product in which a container is filled with a cell-containing solution in which viable cells are dispersed, and the main is a series of pipelines and the main is branched laterally from the main. The main pipe is filled with a cell-containing liquid in a state where the plurality of branch pipes are closed for a combination of the plurality of branch pipes which are the pipelines and the plurality of containers connected to the plurality of branch pipes. After that, by opening the plurality of branch pipes, the cell-containing product is supplied from the main pipe to each container via each branch pipe.

これらの方法によれば、細胞含有液を本管に充填し、その後、各支管を介して各容器に供給することで、複数の容器に同時に細胞含有液を供給できるので、供給条件を均一にできる。 According to these methods, by filling the main pipe with the cell-containing liquid and then supplying the cell-containing liquid to each container via each branch pipe, the cell-containing liquid can be supplied to a plurality of containers at the same time, so that the supply conditions can be made uniform. it can.

また、前記容器は、細胞含有液の前記供給に伴い膨張する容器であって、前記容器は、細胞含有液を出し入れする出入口部を有し、周縁部のうち前記出入口部が形成された部分以外は液密及び気密に閉鎖されており、前記出入口部を介して細胞含有液が前記容器に供給された後に、前記出入口部から、前記容器の内部にある空気を排出するものであってもよい。 Further, the container is a container that expands with the supply of the cell-containing liquid, and the container has an entrance / exit portion for taking in / out the cell-containing liquid, and the peripheral portion other than the portion where the entrance / exit portion is formed. Is liquid-tight and airtightly closed, and after the cell-containing liquid is supplied to the container through the inlet / outlet portion, the air inside the container may be discharged from the inlet / outlet portion. ..

これによれば、細胞含有液が容器に供給された後に、出入口部から、容器の内部にある空気を排出することで、充填後に残留した空気が細胞含有液に悪影響を及ぼすことを防止できる。 According to this, after the cell-containing liquid is supplied to the container, the air inside the container is discharged from the inlet / outlet portion, so that the air remaining after filling can be prevented from adversely affecting the cell-containing liquid.

また、本発明は、生存細胞が分散している細胞含有液を容器に入れるための、細胞含有液の供給装置であって、細胞含有液を貯留する貯留部と、前記貯留部に接続された、一連の管路である本管と、前記本管から側方に分岐した管路である複数の支管と、前記貯留部から前記本管に対して細胞含有液を供給する送液ポンプと、前記複数の支管に設けられた複数の開閉弁と、制御部と、を備え、前記制御部は、前記複数の開閉弁を閉鎖した上で前記送液ポンプを運転させることで、細胞含有液を前記貯留部から前記本管に供給し、細胞含有液が前記本管に充填された後、前記複数の開閉弁を開放して、前記本管から各支管を介して各容器に細胞含有液を供給する、細胞含有液の供給装置である。 Further, the present invention is a cell-containing liquid supply device for putting a cell-containing liquid in which viable cells are dispersed into a container, and is connected to a storage portion for storing the cell-containing liquid and the storage portion. A main line, which is a series of pipelines, a plurality of branch pipes, which are pipelines branched laterally from the main line, and a liquid feed pump that supplies cell-containing liquid from the storage unit to the main line. A plurality of on-off valves provided in the plurality of branch pipes and a control unit are provided, and the control unit closes the plurality of on-off valves and then operates the liquid feed pump to release cell-containing liquid. After supplying the cell-containing liquid from the storage unit to the main pipe and filling the main pipe with the cell-containing liquid, the plurality of on-off valves are opened, and the cell-containing liquid is supplied from the main pipe to each container via each branch pipe. It is a supply device for a cell-containing liquid to be supplied.

この構成によれば、細胞含有液を本管に充填し、その後、各支管を介して各容器に供給することで、複数の容器に同時に細胞含有液を供給できるので、供給条件を均一にできる。 According to this configuration, by filling the main pipe with the cell-containing liquid and then supplying the cell-containing liquid to each container via each branch pipe, the cell-containing liquid can be supplied to a plurality of containers at the same time, so that the supply conditions can be made uniform. ..

また、前記本管の、前記貯留部が接続された側とは反対側に設けられた液回収ポンプを備え、前記容器は、細胞含有液の前記供給に伴い膨張する容器であって、前記容器は、細胞含有液を出し入れする出入口部を有し、周縁部のうち前記出入口部が形成された部分以外は液密及び気密に閉鎖されており、前記制御部は、前記出入口部を介して細胞含有液が前記容器に供給された後に、前記液回収ポンプを運転させることで、前記容器の前記出入口部から、前記容器の内部にある空気を排出するものであってよい。 Further, the main body is provided with a liquid recovery pump provided on the side opposite to the side to which the storage portion is connected, and the container is a container that expands with the supply of the cell-containing liquid. Has an entrance / exit portion for taking in and out a cell-containing liquid, and is closed in a liquid-tight and airtight manner except for a portion of the peripheral portion where the entrance / exit portion is formed, and the control unit is a cell via the entrance / exit portion. By operating the liquid recovery pump after the contained liquid is supplied to the container, the air inside the container may be discharged from the inlet / outlet portion of the container.

この構成によれば、細胞含有液が容器に供給された後に、出入口部から、容器の内部にある空気を排出することで、充填後に残留した空気が細胞含有液に悪影響を及ぼすことを防止できる。 According to this configuration, after the cell-containing liquid is supplied to the container, the air inside the container is discharged from the inlet / outlet portion, so that the air remaining after filling can be prevented from adversely affecting the cell-containing liquid. ..

本発明によると、複数の容器への細胞含有液の供給条件を均一にできる。よって、短時間で、一定量の細胞含有液を容器に充填でき、しかも複数の容器間での細胞の均質性や生存率等の品質に影響を与えにくい、細胞含有液の供給方法、細胞含有液の供給装置、細胞含有製品の製造方法を提供できる。 According to the present invention, the conditions for supplying the cell-containing liquid to a plurality of containers can be made uniform. Therefore, a certain amount of cell-containing liquid can be filled in a container in a short time, and the quality such as cell homogeneity and viability between a plurality of containers is not easily affected. It is possible to provide a liquid supply device and a method for producing a cell-containing product.

本発明の一実施形態に係る細胞含有製品の製造装置の構成を概略的に示す図である。It is a figure which shows schematic structure of the manufacturing apparatus of the cell-containing product which concerns on one Embodiment of this invention. 同製造装置の要部を、容器の側方から見た図である。It is the figure which looked at the main part of the manufacturing apparatus from the side of a container. 図2におけるIII−III矢視図である。It is a view of the arrow III-III in FIG. 同製造装置のブロック図である。It is a block diagram of the manufacturing apparatus.

以下、本発明の一実施形態に係る細胞含有製品の製造装置1(以下、単に「製造装置」という)について説明すると共に、細胞含有製品の製造方法についても説明する。細胞含有製品とは、容器Bに生存細胞が分散している細胞含有液が充填されたものである。この製造装置1は、製造装置1の外部で調製された細胞に関し、細胞含有製品の外装となる容器Bに対して生存細胞が分散している細胞含有液Lを供給して、細胞含有液Lが充填された細胞含有製品を製造するための装置である。この装置は、複数の容器のそれぞれに対して規定量の細胞含有液Lが供給されることにより、分注がなされる。この製造装置1は、細胞含有液Lの充填に着目した場合は、充填装置でもある。 Hereinafter, the cell-containing product manufacturing apparatus 1 (hereinafter, simply referred to as “manufacturing apparatus”) according to the embodiment of the present invention will be described, and a method for producing the cell-containing product will also be described. The cell-containing product is a container B filled with a cell-containing solution in which living cells are dispersed. The manufacturing apparatus 1 supplies the cell-containing liquid L in which the living cells are dispersed to the container B which is the outer cover of the cell-containing product with respect to the cells prepared outside the manufacturing apparatus 1, and the cell-containing liquid L It is a device for producing a cell-containing product filled with. In this device, dispensing is performed by supplying a specified amount of cell-containing liquid L to each of a plurality of containers. This manufacturing apparatus 1 is also a filling apparatus when focusing on the filling of the cell-containing liquid L.

本実施形態の製造装置1は、液供給部2、容器配置部3、制御部4(図4参照)を備えている。液供給部2は細胞含有液Lを容器Bに向けて供給する部分であって、主に、貯留部21、本管22、支管23、送液ポンプ24、液回収ポンプ25、本管開閉弁(上流弁26、下流弁27)、複数の支管開閉弁28…28を備える。制御部4は製造装置1における各部を制御する。 The manufacturing apparatus 1 of the present embodiment includes a liquid supply unit 2, a container arrangement unit 3, and a control unit 4 (see FIG. 4). The liquid supply unit 2 is a portion that supplies the cell-containing liquid L toward the container B, and is mainly a storage unit 21, a main pipe 22, a branch pipe 23, a liquid feed pump 24, a liquid recovery pump 25, and a main on-off valve. (Upstream valve 26, downstream valve 27), and a plurality of branch pipe on-off valves 28 ... 28 are provided. The control unit 4 controls each unit in the manufacturing apparatus 1.

貯留部21は、容器Bに向けて供給する前の細胞含有液Lを貯留しておく容器(タンク)211を有する。本実施形態の容器211は、細胞含有液Lを入れるための入口を有し、この入口は開閉できる蓋212により閉じられている。なお、例えば貯留部21に接続された配管から細胞含有液Lが直接的に導入されるよう構成されていてもよく、この場合、細胞含有液Lを入れるための入口は不要である。また、貯留部21は、容器211の内部に撹拌部213を有する。この撹拌部213は例えば回転する羽根を有しており生存細胞の分散状態を保つために細胞含有液Lを撹拌する。また、図示していないが、貯留部21は温度調整部を有する。温度調整部は、貯留部21に当接するように設けられた冷却ジャケットや冷却板であり、細胞含有液Lを一定温度(低温)に維持する。このため、細胞含有液Lは冷却された状態(本実施形態では4℃)で容器Bに向けて送り出される。なお、ここでは貯留部21における温度調整部について言及したが、製造装置1の全体の温度を調整する全体温度調整部(図示しない)を設けることもでき、こうすることにより、移動中の細胞含有液Lも一定温度(低温)に維持されるので望ましい。本実施形態の貯留部21は、容器211としてのスピナーフラスコと、スピナーフラスコが載置される台であって、温度調整部としての冷却台を備えている。 The storage unit 21 has a container (tank) 211 for storing the cell-containing liquid L before being supplied to the container B. The container 211 of the present embodiment has an inlet for containing the cell-containing liquid L, and this inlet is closed by a lid 212 that can be opened and closed. For example, the cell-containing liquid L may be directly introduced from the pipe connected to the storage unit 21, and in this case, an inlet for the cell-containing liquid L is not required. Further, the storage unit 21 has a stirring unit 213 inside the container 211. The stirring unit 213 has, for example, rotating blades and stirs the cell-containing liquid L in order to maintain the dispersed state of the living cells. Further, although not shown, the storage unit 21 has a temperature adjusting unit. The temperature adjusting unit is a cooling jacket or a cooling plate provided so as to come into contact with the storage unit 21, and maintains the cell-containing liquid L at a constant temperature (low temperature). Therefore, the cell-containing liquid L is sent out toward the container B in a cooled state (4 ° C. in this embodiment). Although the temperature adjusting unit in the storage unit 21 has been mentioned here, it is also possible to provide an overall temperature adjusting unit (not shown) that adjusts the overall temperature of the manufacturing apparatus 1, thereby containing moving cells. The liquid L is also desirable because it is maintained at a constant temperature (low temperature). The storage unit 21 of the present embodiment includes a spinner flask as a container 211 and a table on which the spinner flask is placed, and includes a cooling table as a temperature control unit.

本管22は、一連の管路であって、貯留部21に接続される管路である。本実施形態では樹脂製(具体的には軟質樹脂)のチューブが用いられている。図2に示すように、本管22は、複数のチューブが接続部材で接続されて一連に構成されている。本実施形態では図1に示したように、本管22のうち、支管23が分岐している部分が平行して3本設けられており、各本管22の上流側と下流側では3本が1本に集約され、集約管22Aとなっている。また、3本という本数は一例に過ぎず、本数は製造装置1の仕様に合わせて種々に決定できる。本実施形態の本管22は、集約管22Aとなっている上流側221と下流側222が共に貯留部21に接続されていて、図1に示すように循環路を構成している。循環路とすることにより、容器Bへの充填終了後の余剰の細胞含有液Lを貯留部21で回収できるため有利である。前述のように全体温度調整部を設けた場合には、余剰の細胞含有液Lも一定温度(低温)に維持されることから、この細胞含有液Lを再利用に供することが可能である。 The main pipe 22 is a series of pipes and is connected to the storage unit 21. In this embodiment, a resin tube (specifically, a soft resin) is used. As shown in FIG. 2, the main 22 is formed in a series by connecting a plurality of tubes with connecting members. In the present embodiment, as shown in FIG. 1, three main pipes 22 are provided in parallel with branch pipes 23, and three main pipes 22 are provided on the upstream side and the downstream side of each main pipe 22. Are integrated into one to form an aggregation pipe 22A. Further, the number of three is only an example, and the number can be variously determined according to the specifications of the manufacturing apparatus 1. In the main pipe 22 of the present embodiment, both the upstream side 221 and the downstream side 222, which are the centralized pipe 22A, are connected to the storage section 21, and form a circulation path as shown in FIG. The circulation path is advantageous because the surplus cell-containing liquid L after the filling of the container B is completed can be recovered in the storage unit 21. When the overall temperature adjusting unit is provided as described above, the surplus cell-containing liquid L is also maintained at a constant temperature (low temperature), so that the cell-containing liquid L can be reused.

支管23は、本管22から側方に分岐した管路であって、容器Bに接続される管路である。本実施形態では樹脂製(具体的には軟質樹脂)のチューブが用いられている。本管22から複数の支管23…23が分岐している。複数の支管23…23は、内径寸法及び長さが同一である。本実施形態では、図1に示した平行する部分における3本の本管22のそれぞれから、図2に示すように10本の支管23が分岐している。なお、10本という本数は一例に過ぎず、支管23の分岐本数は製造装置1の仕様に合わせて種々に決定できる。 The branch pipe 23 is a pipe line that branches laterally from the main pipe 22 and is connected to the container B. In this embodiment, a resin tube (specifically, a soft resin) is used. A plurality of branch pipes 23 ... 23 branch from the main pipe 22. The plurality of branch pipes 23 ... 23 have the same inner diameter dimension and length. In the present embodiment, 10 branch pipes 23 are branched from each of the three main pipes 22 in the parallel portion shown in FIG. 1 as shown in FIG. The number of 10 is only an example, and the number of branches of the branch pipe 23 can be variously determined according to the specifications of the manufacturing apparatus 1.

本管22と複数の支管23…23とは組み合わされて1組のアセンブリーとして形成されることができる。このようにアセンブリー化しておくことにより、1回目の充填作業を終了してから2回目の充填作業を行う前の本管22と支管23との交換(交換は原則的に、充填作業の各回ごとに行われる)を、1組のアセンブリー全体の交換で行うことができるため、配管を接続する作業負担を低減できる。 The main pipe 22 and the plurality of branch pipes 23 ... 23 can be combined to form a set of assemblies. By assembling in this way, the main pipe 22 and the branch pipe 23 are replaced after the first filling work is completed and before the second filling work is performed (replacement is in principle every time of the filling work). Since this can be done by exchanging the entire set of assemblies, the work load of connecting the pipes can be reduced.

ここで、容器Bについて説明する。本実施形態で用いられる容器Bは、公知の輸液袋(点滴バッグ等)と同じ構成を有しており、対向する2枚の柔軟な樹脂フィルムの周縁部が接着されたことにより、液密及び気密に閉鎖されて構成されている。よって容器Bは膨張可能な容器であって、細胞含有液Lの供給に伴い膨張する柔軟な袋である。この袋は後述のように、エア抜きの際は収縮する。つまり、容器Bは袋状であり容積が変化するものである。この構成から、2枚の樹脂フィルムの対向間隔と、内部の液体充填量との間には相関関係がある。容器Bの平面形状は特に限定されないが、長方形状(略長方形状)または長円形状とされることが多い。本実施形態の容器Bは、図3に示すような略長方形状であって、一辺(充填を行う際における配置状態での上辺)に複数(本実施形態では3箇所)の口部が設けられている。本実施形態では、3箇所のうち2箇所(図3における左側と略中央側の口部)は栓B1によって閉鎖されている。そして他の1箇所が出入口部B2とされ、充填を行う際において細胞含有液Lの出し入れに用いられる。出入口部B2は、容器Bの有する一辺における中心よりも端部側(図3では右側)に位置する。ところで、栓B1の外周部には周方向に溝B11が形成されている。この溝B11は、図2及び図3に示すように容器配置部3において対向配置された一対の棒から形成された、一対の袋係止部34に引っ掛けられることで、容器配置部3に対して容器Bを位置決めできる。このため、溝B11は袋係止部34に対応した形状とされている。図3に示すように、出入口部B2には出入口チューブB21が一体に設けられている。この出入口チューブB21は、細胞含有液Lの充填終了後に、途中の位置で閉鎖されて切断される。 Here, the container B will be described. The container B used in the present embodiment has the same structure as a known infusion bag (drip bag, etc.), and is liquidtight and liquid-tight due to the peripheral portions of two flexible resin films facing each other being adhered to each other. It is airtightly closed. Therefore, the container B is an expandable container and is a flexible bag that expands with the supply of the cell-containing liquid L. This bag shrinks when bleeding air, as described below. That is, the container B has a bag shape and its volume changes. From this configuration, there is a correlation between the facing distance between the two resin films and the amount of liquid filled inside. The planar shape of the container B is not particularly limited, but is often rectangular (substantially rectangular) or oval. The container B of the present embodiment has a substantially rectangular shape as shown in FIG. 3, and is provided with a plurality of (three places in the present embodiment) mouth portions on one side (upper side in the arranged state at the time of filling). ing. In the present embodiment, two of the three locations (the mouth portion on the left side and the mouth portion on the substantially central side in FIG. 3) are closed by the plug B1. The other one is used as the entrance / exit portion B2, and is used for taking in / out the cell-containing liquid L when filling. The entrance / exit portion B2 is located on the end side (right side in FIG. 3) of the center on one side of the container B. By the way, a groove B11 is formed in the circumferential direction on the outer peripheral portion of the plug B1. As shown in FIGS. 2 and 3, the groove B11 is hooked on a pair of bag locking portions 34 formed from a pair of rods arranged opposite to each other in the container arrangement portion 3, so that the groove B11 is hooked on the container arrangement portion 3. Can position the container B. Therefore, the groove B11 has a shape corresponding to the bag locking portion 34. As shown in FIG. 3, the entrance / exit tube B21 is integrally provided in the entrance / exit portion B2. The entrance / exit tube B21 is closed and cut at an intermediate position after the filling of the cell-containing liquid L is completed.

送液ポンプ24は押出ポンプとして機能し、細胞含有液Lを加圧して貯留部21から本管22に対して供給する。液回収ポンプ25は吸引ポンプとして機能し、本管22中の細胞含有液Lを吸引することにより、容器Bへの充填後における余剰の細胞含有液Lを回収して貯留部21に戻す。更に液回収ポンプ25は、細胞含有液Lが容器Bに供給された後に、容器Bの内部にある空気を前記余剰の細胞含有液Lと共に吸引することで、容器Bから排出する。 The liquid feed pump 24 functions as an extrusion pump, pressurizes the cell-containing liquid L, and supplies it from the storage unit 21 to the main 22. The liquid recovery pump 25 functions as a suction pump, and by sucking the cell-containing liquid L in the main pipe 22, the surplus cell-containing liquid L after filling the container B is collected and returned to the storage unit 21. Further, the liquid recovery pump 25 discharges the cell-containing liquid L from the container B by sucking the air inside the container B together with the excess cell-containing liquid L after the cell-containing liquid L is supplied to the container B.

送液ポンプ24及び液回収ポンプ25は、チューブ(本実施形態では本管22を構成するチューブ)の外側をローラ等の押圧手段によりしごくことで送液を行う公知のチューブポンプが用いられている。このため、各ポンプの内部に直接細胞含有液Lが接触しないため、各ポンプ24,25において細胞含有液Lが汚染されることがない。 As the liquid feed pump 24 and the liquid recovery pump 25, a known tube pump that feeds liquid by squeezing the outside of the tube (the tube constituting the main pipe 22 in this embodiment) with a pressing means such as a roller is used. .. Therefore, since the cell-containing liquid L does not come into direct contact with the inside of each pump, the cell-containing liquid L is not contaminated in the pumps 24 and 25.

本管開閉弁は、本管22において、複数の支管23…23の分岐位置よりも上流側及び下流側に設けられていて、本管22を開閉できる。本管開閉弁は、本管22の上流側に設けられた上流弁26と、本管22の下流側に設けられた下流弁27から構成されている。各支管開閉弁28は、各支管23に設けられていて、各支管23を開閉できる。各開閉弁26〜28の開閉と送液ポンプ24及び液回収ポンプ25の選択的な動作との組み合わせにより、本管22内への細胞含有液Lの充填、本管22及び支管23を介した容器Bへの細胞含有液Lの供給、支管23及び本管22を介した容器Bのエア抜きを順次行うことができる。各開閉弁26〜28は、アクチュエータ等によるチューブ外部からの押圧でチューブ内の流路空間を押しつぶすことにより、閉鎖を行う公知のピンチバルブが用いられている。このため、本管22及び支管23が有するチューブは、外部からの押圧により変形する柔軟な材料で形成されている。 The main pipe on-off valve is provided on the upstream side and the downstream side of the branch positions of the plurality of branch pipes 23 ... 23 in the main pipe 22, and can open and close the main pipe 22. The main on-off valve is composed of an upstream valve 26 provided on the upstream side of the main 22 and a downstream valve 27 provided on the downstream side of the main 22. Each branch pipe opening / closing valve 28 is provided in each branch pipe 23, and each branch pipe 23 can be opened / closed. By combining the opening and closing of each on-off valve 26 to 28 and the selective operation of the liquid feed pump 24 and the liquid recovery pump 25, the cell-containing liquid L is filled into the main pipe 22 via the main pipe 22 and the branch pipe 23. The cell-containing liquid L can be supplied to the container B, and the air in the container B can be sequentially bleeded through the branch pipe 23 and the main pipe 22. As each on-off valve 26 to 28, a known pinch valve that closes by crushing the flow path space in the tube by pressing from the outside of the tube by an actuator or the like is used. Therefore, the tubes included in the main pipe 22 and the branch pipe 23 are made of a flexible material that is deformed by external pressure.

容器配置部3は、少なくとも細胞含有液Lの供給開始から供給終了にわたって複数の容器B…Bを支持する部分である。図2に示すように、水平方向に一定間隔を空けて配置された、複数のブロック状の側方部材31と、水平方向に延び、複数の側方部材31の下端部に当接するように設けられた平板状の底部材32とを備える。図3に示すように、側方部材31と底部材32とは側方視(容器B基準では平面視)で傾斜して設けられている。側方部材31と底部材32とは平板状の後方部材33に固定されている。この固定により、2枚の隣り合う側方部材31は一定距離に保たれている。容器配置部3には、隣り合う側方部材31の組に対応して、当該組の上方に一対の袋係止部34が設けられている。袋係止部34は容器Bの一部を係止するものであって、本実施形態では後方部材33から突出する棒状体(具体的には丸棒)である。この一対の袋係止部34に容器Bの栓が引っ掛けられることで、容器配置部3に対して容器Bの位置決めがされる。容器Bは容器配置部3に配置されると、底部材32と側方部材31に当接した状態となる。ただし、底部材32に接しないように容器Bを配置することもできる。 The container arrangement portion 3 is a portion that supports a plurality of containers B ... B at least from the start of supply of the cell-containing liquid L to the end of supply. As shown in FIG. 2, a plurality of block-shaped side members 31 arranged at regular intervals in the horizontal direction are provided so as to extend in the horizontal direction and abut on the lower ends of the plurality of side members 31. The flat plate-shaped bottom member 32 is provided. As shown in FIG. 3, the side member 31 and the bottom member 32 are provided so as to be inclined in a lateral view (a plan view based on the container B reference). The side member 31 and the bottom member 32 are fixed to the flat plate-shaped rear member 33. By this fixing, the two adjacent side members 31 are kept at a constant distance. The container arranging portion 3 is provided with a pair of bag locking portions 34 above the pair of adjacent side members 31. The bag locking portion 34 locks a part of the container B, and is a rod-shaped body (specifically, a round bar) protruding from the rear member 33 in the present embodiment. By hooking the stopper of the container B on the pair of bag locking portions 34, the container B is positioned with respect to the container arranging portion 3. When the container B is arranged in the container arrangement portion 3, the container B is in contact with the bottom member 32 and the side member 31. However, the container B may be arranged so as not to come into contact with the bottom member 32.

2枚の隣り合う側方部材31により、対向する一対の壁面31A,31Aが形成される。各壁面31Aは垂直の平面とされていて、一対の壁面31A,31Aは平行に対向している。この一対の壁面31A,31Aの間に、細胞含有液Lが充填される前の容器Bが配置される。側方部材31により形成される各壁面31Aは、容器Bにおいて、細胞含有液Lの供給に伴い自由に膨張する領域(つまり、容器Bにおける周縁部で2枚の柔軟な樹脂フィルムが接着されたことで自由な膨張が規制されることにより、他の部分よりも膨張量が小さくなる部分を除いた領域)よりも外方まで設けられている。 A pair of facing wall surfaces 31A and 31A are formed by the two adjacent side members 31. Each wall surface 31A is a vertical plane, and the pair of wall surfaces 31A and 31A face each other in parallel. A container B before being filled with the cell-containing liquid L is arranged between the pair of wall surfaces 31A and 31A. Each wall surface 31A formed by the side member 31 has a region in the container B that freely expands with the supply of the cell-containing liquid L (that is, two flexible resin films are adhered to the peripheral portion of the container B). As a result, free expansion is restricted, so that the region is provided to the outside of the region (excluding the portion where the amount of expansion is smaller than that of other portions).

そして、対向する一対の壁面31A,31Aの間の下方には、容器Bを下方から支持する底面32Aが形成される。この底面32Aは、底部材32における上面が該当する。底部材32が傾斜していることから、前記底面32Aは、一対の壁面31A,31Aと交差する線に着目すると、一方(図3における右方)が高くて他方(同左方)が低くなっているように傾斜した面となる。 A bottom surface 32A that supports the container B from below is formed below the pair of wall surfaces 31A and 31A that face each other. The bottom surface 32A corresponds to the top surface of the bottom member 32. Since the bottom member 32 is inclined, one (right side in FIG. 3) of the bottom surface 32A is high and the other (left side) is low when focusing on the line intersecting the pair of wall surfaces 31A and 31A. The surface is inclined as if it were.

容器配置部3にある複数の容器B…Bに対して細胞含有液Lを供給すると、各容器Bは膨張していく。ところが、容器Bは一対の壁面31A,31Aに挟まれているから、特に前記「自由に膨張する領域」において、容器Bを構成する樹脂フィルムが各壁面31Aに密着した後は、容器Bが更には膨張しなくなる。つまり、一対の壁面31A,31Aにより袋内部の空間容積の拡大がその時点で規制される。これに対応して、一対の壁面31A,31Aの対向距離に応じた容量の細胞含有液Lが容器Bに充填されることになる(そして、それ以上の充填はされなくなる)。 When the cell-containing liquid L is supplied to the plurality of containers B ... B in the container arrangement portion 3, each container B expands. However, since the container B is sandwiched between the pair of wall surfaces 31A and 31A, the container B is further moved after the resin film constituting the container B is brought into close contact with each wall surface 31A, particularly in the "freely expanding region". Does not expand. That is, the pair of wall surfaces 31A and 31A regulates the expansion of the space volume inside the bag at that time. Correspondingly, the container B is filled with the cell-containing liquid L having a volume corresponding to the facing distance between the pair of wall surfaces 31A and 31A (and no further filling is performed).

次に、本実施形態に係る細胞含有製品の製造方法(細胞含有液Lの充填方法)の工程を説明する。まず、容器配置部3の対向する一対の壁面31A,31Aの間に差し込むようにして、複数(図2に示す例では10個)の容器Bを配置する。この際、出入口部B2が上端(詳しくは袋内部の空間における上端)に位置するように、容器Bが傾斜して一対の壁面31A,31Aの間に配置される。これと共に、貯留部21の容器211に細胞含有液Lを入れる。また、本管22を送液ポンプ24及び液回収ポンプ25に取り付けた上で、本管22における上流側及び下流側の集約管22Aを貯留部21に接続する。また、各支管23に容器Bを接続する。この接続により、チューブを有する本管22及び各支管23の組は、貯留部21及び容器Bに接続される。更に、この組は液回収ポンプ25にも接続される。また、各開閉弁26〜28を動作できるようにセットする。 Next, the steps of the method for producing the cell-containing product (method for filling the cell-containing liquid L) according to the present embodiment will be described. First, a plurality of containers B (10 in the example shown in FIG. 2) are arranged so as to be inserted between the pair of opposite wall surfaces 31A and 31A of the container arrangement unit 3. At this time, the container B is inclined and arranged between the pair of wall surfaces 31A and 31A so that the entrance / exit portion B2 is located at the upper end (specifically, the upper end in the space inside the bag). At the same time, the cell-containing liquid L is placed in the container 211 of the storage unit 21. Further, after the main pipe 22 is attached to the liquid feeding pump 24 and the liquid recovery pump 25, the upstream side and downstream side centralizing pipes 22A of the main pipe 22 are connected to the storage unit 21. Further, the container B is connected to each branch pipe 23. By this connection, the main 22 having the tube and the set of each branch pipe 23 are connected to the storage portion 21 and the container B. Further, this set is also connected to the liquid recovery pump 25. In addition, each on-off valve 26 to 28 is set so as to be able to operate.

次に、本管開閉弁のうち上流弁26を閉鎖、下流弁27を開放、全ての支管開閉弁28…28を開放、の各状態とした上で液回収ポンプ25を運転する。これにより充填前の容器Bから空気を抜く作業である予備エア抜きを一定時間行う。所定時間経過後、全ての支管開閉弁28…28を閉鎖する。 Next, the liquid recovery pump 25 is operated after the upstream valve 26 of the main on-off valve is closed, the downstream valve 27 is opened, and all the branch on-off valves 28 ... 28 are opened. As a result, preliminary air bleeding, which is the work of bleeding air from the container B before filling, is performed for a certain period of time. After a lapse of a predetermined time, all the branch on-off valves 28 ... 28 are closed.

ここで、前記「所定時間」とは、あらかじめ設定された固定的な時間であって、各動作(ここでは予備エア抜き)が達成されたと見込まれる時間に対応して設定されている(以下、別の動作でも同じ)。このように本実施形態の制御部4は、充填状況をリアルタイムで検知することなく、いわば「見込時間」で各開閉弁26〜28を制御したり細胞含有液Lの供給を停止したりする管理をしている。このように本実施形態では、刻々と充填状況を検知して、細胞含有液Lの供給量をフィードバックするような制御と比べると、相対的に緩い条件で充填制御を行うことができるので、制御に係る設計コストを低減できて有利である。 Here, the "predetermined time" is a fixed time set in advance, and is set corresponding to a time in which each operation (here, preliminary air bleeding) is expected to be achieved (hereinafter, hereafter. Same for other operations). In this way, the control unit 4 of the present embodiment controls each on-off valve 26 to 28 or stops the supply of the cell-containing liquid L in the so-called "expected time" without detecting the filling status in real time. I am doing. As described above, in the present embodiment, the filling control can be performed under relatively loose conditions as compared with the control in which the filling status is detected every moment and the supply amount of the cell-containing liquid L is fed back. It is advantageous because the design cost related to the above can be reduced.

次に、本管開閉弁のうち上流弁26を開放し、送液ポンプ24及び液回収ポンプ25を運転する。これにより貯留部21の細胞含有液Lが、空であった本管22に送り込まれて、本管22の内部が細胞含有液Lで満たされる。これにより、本管22(特に、本管22のうちで、複数の支管23…23が分岐している部分)の内部に細胞含有液Lが充填される。所定時間経過後、送液ポンプ24及び液回収ポンプ25を停止すると共に、本管開閉弁のうち下流弁27を閉鎖する。 Next, the upstream valve 26 of the main on-off valve is opened, and the liquid feed pump 24 and the liquid recovery pump 25 are operated. As a result, the cell-containing liquid L of the reservoir 21 is sent to the empty main 22, and the inside of the main 22 is filled with the cell-containing liquid L. As a result, the cell-containing liquid L is filled inside the main 22 (particularly, the portion of the main 22 where the plurality of branch pipes 23 ... 23 are branched). After a lapse of a predetermined time, the liquid feed pump 24 and the liquid recovery pump 25 are stopped, and the downstream valve 27 of the main on-off valves is closed.

次に、全ての支管開閉弁28…28を開放すると共に、送液ポンプ24を運転する。全ての支管開閉弁28…28の開放は、制御部4により同時に(一斉に)なされる。これにより、最初に本管22に充填されていた細胞含有液L、次に、貯留部21から本管22を介して送られた細胞含有液Lが支管23に供給される。このようにして、支管23及び出入口部B2を介して細胞含有液Lが前記容器Bに供給され、容器Bを膨張させ、一対の壁面31A,31Aの対向距離に応じた容量の細胞含有液Lが容器Bに充填される。容器Bの膨張は、一対の壁面31A,31Aにより規制されるため、各容器Bに規定量の細胞含有液Lが充填された後(つまり、一対の壁面31A,31Aに容器Bが密着した後)において、各容器Bには細胞含有液Lを受容する空間は無くなるため、細胞含有液Lは各容器Bに入っていかなくなる。なお、この時点で下流弁27は閉鎖されているから、各容器Bに入らない細胞含有液Lは本管22(そのうち下流弁27の上流側)及び支管23に滞留する。 Next, all the branch pipe on-off valves 28 ... 28 are opened, and the liquid feed pump 24 is operated. All the branch on-off valves 28 ... 28 are opened at the same time (simultaneously) by the control unit 4. As a result, the cell-containing liquid L that was first filled in the main pipe 22 and then the cell-containing liquid L that was sent from the storage unit 21 via the main pipe 22 are supplied to the branch pipe 23. In this way, the cell-containing liquid L is supplied to the container B via the branch pipe 23 and the entrance / exit portion B2, the container B is expanded, and the cell-containing liquid L having a volume corresponding to the facing distance between the pair of wall surfaces 31A and 31A. Is filled in the container B. Since the expansion of the container B is regulated by the pair of wall surfaces 31A and 31A, after the container B is filled with the specified amount of the cell-containing liquid L (that is, after the container B is in close contact with the pair of wall surfaces 31A and 31A). ), Since there is no space for receiving the cell-containing liquid L in each container B, the cell-containing liquid L cannot enter each container B. Since the downstream valve 27 is closed at this point, the cell-containing liquid L that does not enter each container B stays in the main pipe 22 (of which, the upstream side of the downstream valve 27) and the branch pipe 23.

本実施形態では、一対の壁面31A,31Aの対向距離に応じた容量の細胞含有液Lを、供給に伴って(つまり、供給の成り行きで)容器Bに充填できるので、供給中に供給速度を変化させる必要がない。また、本実施形態では、細胞含有液Lを本管22に充填し、その後、各支管23を介して各容器Bに供給することで、複数の容器B…Bに同時に細胞含有液Lを供給できるので、供給条件を均一にできる。このため、細胞含有液Lの供給状況により、複数の容器B…B間での細胞の均質性や生存率等の品質に影響を与えにくく、その上薬効、薬理効果の高い良質な製品を供給できる。 In the present embodiment, the cell-containing liquid L having a volume corresponding to the facing distance between the pair of wall surfaces 31A and 31A can be filled in the container B with the supply (that is, in the flow of the supply), so that the supply rate can be adjusted during the supply. No need to change. Further, in the present embodiment, the cell-containing liquid L is filled in the main pipe 22 and then supplied to each container B via each branch pipe 23, whereby the cell-containing liquid L is supplied to the plurality of containers B ... B at the same time. Therefore, the supply conditions can be made uniform. Therefore, depending on the supply status of the cell-containing liquid L, it is difficult to affect the quality such as cell homogeneity and survival rate between a plurality of containers B ... B, and a high-quality product having high medicinal and pharmacological effects is supplied. it can.

細胞含有液Lの供給に当たり、規定量の細胞含有液Lを確実に各容器Bに充填するため(充填不足を防止するため)、貯留部21からは規定量よりも多い量の細胞含有液Lが供給される。所定時間経過後、送液ポンプ24を停止すると共に、本管開閉弁のうち上流弁26、及び、全ての支管開閉弁28…28を閉鎖する。 When supplying the cell-containing liquid L, in order to surely fill each container B with the specified amount of the cell-containing liquid L (to prevent insufficient filling), the amount of the cell-containing liquid L larger than the specified amount is received from the storage unit 21. Is supplied. After a lapse of a predetermined time, the liquid feed pump 24 is stopped, and the upstream valve 26 of the main main on-off valve and all the branch on-off valves 28 ... 28 are closed.

次に、本管開閉弁のうち下流弁27を開放した上で液回収ポンプ25を運転する。この際、複数の支管開閉弁28…28のうち、例えば最上流側の1台のみが開放される。これにより、開放された支管23に対応する容器Bにつき、出入口部B2から内部にある空気を排出するエア抜きが行われる。エア抜きにより、充填後に容器Bに残留した空気が細胞含有液Lに悪影響を及ぼすことを防止できる。所定時間経過後、複数の支管開閉弁28…28のうち開放されていた1台が閉鎖されて、他の1台のみが開放され、この開放された支管23に対応する容器Bにつきエア抜きが行われる。これが他の支管23においても順次行われる。なお、このエア抜きは、複数の容器B…Bで同時に行うと、空気及び細胞含有液Lの吸い出しが多量になされる容器Bと、吸い出しが少量にとどまる容器Bができてしまい、ばらつきが生じるため、容器B一つずつで順次行われる。最後のエア抜きについて所定時間経過後、液回収ポンプ25を停止し、本管開閉弁のうち下流弁27を閉鎖する。 Next, the liquid recovery pump 25 is operated after opening the downstream valve 27 of the main on-off valve. At this time, of the plurality of branch pipe on-off valves 28 ... 28, for example, only one on the most upstream side is opened. As a result, the container B corresponding to the opened branch pipe 23 is evacuated to discharge the air inside from the inlet / outlet portion B2. By bleeding air, it is possible to prevent the air remaining in the container B after filling from adversely affecting the cell-containing liquid L. After a lapse of a predetermined time, one of the plurality of branch pipe on-off valves 28 ... 28 that had been opened was closed, and only the other one was opened, and air was bleeded from the container B corresponding to the opened branch pipe 23. Will be done. This is also sequentially performed in the other branch pipes 23. If this air bleeding is performed in a plurality of containers B ... B at the same time, there will be a container B in which a large amount of air and the cell-containing liquid L are sucked out and a container B in which the sucking out is limited to a small amount, resulting in variation. Therefore, it is carried out sequentially in each container B. After a predetermined time has elapsed for the final air bleeding, the liquid recovery pump 25 is stopped, and the downstream valve 27 of the main on-off valves is closed.

その後、容器配置部3から容器Bを取り出し、容器Bの出入口部B2に一体に設けられた出入口チューブB21を溶着等により閉鎖した上で切断する。これにより、細胞含有製品が出来上がる。出来上がった細胞含有製品は必要に応じて冷凍され、流通に供されて、細胞含有製品中の細胞が使用される。 After that, the container B is taken out from the container arranging portion 3, and the inlet / outlet tube B21 integrally provided at the inlet / outlet portion B2 of the container B is closed by welding or the like and then cut. As a result, a cell-containing product is completed. The finished cell-containing product is frozen as needed, put on the market, and the cells in the cell-containing product are used.

以上、本実施形態によると、供給中に供給速度を変化させる必要がない。よって、簡素な構成でありながら短時間で、一定量の細胞含有液Lを容器Bに充填でき、しかも、細胞の均質性や生存率等の品質に影響を与えにくく、その上薬効、薬理効果の高い良質な製品を供給できる。 As described above, according to the present embodiment, it is not necessary to change the supply rate during supply. Therefore, although it has a simple structure, a certain amount of cell-containing liquid L can be filled in the container B in a short time, and the quality such as cell homogeneity and survival rate is not easily affected, and moreover, medicinal effect and pharmacological effect. We can supply high quality products.

以上、本発明の一実施形態につき説明したが、本発明は前記実施形態に限定されるものではなく、本発明の要旨を逸脱しない範囲で種々の変更が可能である。 Although one embodiment of the present invention has been described above, the present invention is not limited to the above-described embodiment, and various modifications can be made without departing from the gist of the present invention.

本管22は、前記実施形態では循環路を構成していた。しかしこれに限定されず、例えば貯留部21から出た細胞含有液Lが本管22を一方向に流れて貯留部21に戻らないような構成であってもよい。 The main 22 constitutes a circulation path in the above embodiment. However, the present invention is not limited to this, and for example, the cell-containing liquid L discharged from the storage unit 21 may be configured so as not to flow in one direction through the main 22 and return to the storage unit 21.

また、容器配置部3において側方部材31を移動可能としたり、別体の装着板を着脱可能に設けたりすることで、一対の壁面31A,31A間の間隔を調整可能とすることもできる。この場合、一対の壁面31A,31A間の間隔に応じて充填容量の調整が可能である。 Further, the distance between the pair of wall surfaces 31A and 31A can be adjusted by making the side member 31 movable in the container arranging portion 3 or providing a separate mounting plate so as to be detachable. In this case, the filling capacity can be adjusted according to the distance between the pair of wall surfaces 31A and 31A.

また、容器配置部3における底面32Aは、前記実施形態では傾斜面であったが、容器Bの形状によっては水平面とすることもできる。 Further, although the bottom surface 32A of the container arrangement portion 3 is an inclined surface in the above embodiment, it may be a horizontal surface depending on the shape of the container B.

また、容器配置部3における各壁面31Aは前記実施形態では平面であった。しかしこれに限定されず、例えば湾曲した面であってもよい。 Further, each wall surface 31A in the container arrangement portion 3 was a flat surface in the above embodiment. However, the present invention is not limited to this, and for example, it may be a curved surface.

また、細胞含有液Lの充填対象である容器は硬質の瓶(ガラス、硬質樹脂製の瓶等)であってもよい。この場合の容器は、装着した蓋により閉鎖されるものであってもよい。この場合、容器配置部3は単に容器を置く部分とできる。ただし、製造装置1において、充填量を一定にする機構または制御が必要となる。 Further, the container to be filled with the cell-containing liquid L may be a hard bottle (glass, hard resin bottle, etc.). The container in this case may be closed by the attached lid. In this case, the container arranging portion 3 can be simply a portion on which the container is placed. However, in the manufacturing apparatus 1, a mechanism or control for keeping the filling amount constant is required.

1…製造装置、2…液供給部、3…容器配置部、4…制御部、21…貯留部、22…本管、22A…本管(集約管)、23…支管、24…送液ポンプ、25…液回収ポンプ、26…本管開閉弁(上流弁)、27…本管開閉弁(下流弁)、28…開閉弁、支管開閉弁、31…側方部材、31A…壁面、32…底部材、32A…底面、33…後方部材、34…袋係止部、211…貯留部における容器、212…蓋、213…撹拌部、221…上流側、222…下流側、B…容器、B1…栓、B11…溝、B2…出入口部、B21…出入口チューブ、L…細胞含有液 1 ... Manufacturing equipment, 2 ... Liquid supply unit, 3 ... Container arrangement unit, 4 ... Control unit, 21 ... Storage unit, 22 ... Main pipe, 22A ... Main pipe (consolidation pipe), 23 ... Branch pipe, 24 ... Liquid feed pump , 25 ... Liquid recovery pump, 26 ... Main on-off valve (upstream valve), 27 ... Main on-off valve (downstream valve), 28 ... On-off valve, branch on-off valve, 31 ... Side member, 31A ... Wall surface, 32 ... Bottom member, 32A ... bottom surface, 33 ... rear member, 34 ... bag locking part, 211 ... container in storage part, 212 ... lid, 213 ... stirring part, 221 ... upstream side, 222 ... downstream side, B ... container, B1 ... Plug, B11 ... Groove, B2 ... Doorway, B21 ... Doorway tube, L ... Cell-containing liquid

Claims (6)

一連の管路である本管と、
前記本管から側方に分岐した管路である複数の支管と、
前記複数の支管に接続された複数の容器と、の組み合わせに対し、
生存細胞が分散している細胞含有液を、前記複数の支管が閉鎖された状態で前記本管に充填し、その後、前記複数の支管を開放することにより、前記本管から各支管を介して各容器に供給する、細胞含有液の供給方法。
The main, which is a series of pipelines,
A plurality of branch pipes, which are pipelines branched laterally from the main pipe,
For a combination of a plurality of containers connected to the plurality of branch pipes,
The cell-containing liquid in which the living cells are dispersed is filled in the main pipe in a state where the plurality of branch pipes are closed, and then the plurality of branch pipes are opened, so that the main pipe is used via each branch pipe. A method of supplying a cell-containing liquid to be supplied to each container.
前記容器は、細胞含有液の前記供給に伴い膨張する容器であって、
前記容器は、細胞含有液を出し入れする出入口部を有し、周縁部のうち前記出入口部が形成された部分以外は液密及び気密に閉鎖されており、
前記出入口部を介して細胞含有液が前記容器に供給された後に、前記出入口部から、前記容器の内部にある空気を排出する、請求項1に記載の細胞含有液の供給方法。
The container is a container that expands with the supply of the cell-containing liquid.
The container has an entrance / exit portion for taking in and out the cell-containing liquid, and is closed liquidtightly and airtightly except for the portion of the peripheral portion where the entrance / exit portion is formed.
The method for supplying a cell-containing liquid according to claim 1, wherein the cell-containing liquid is supplied to the container through the inlet / outlet portion, and then the air inside the container is discharged from the inlet / outlet portion.
生存細胞が分散している細胞含有液を容器に入れるための、細胞含有液の供給装置であって、
細胞含有液を貯留する貯留部と、
前記貯留部に接続された、一連の管路である本管と、
前記本管から側方に分岐した管路である複数の支管と、
前記貯留部から前記本管に対して細胞含有液を供給する送液ポンプと、
前記複数の支管に設けられた複数の開閉弁と、
制御部と、を備え、
前記制御部は、前記複数の開閉弁を閉鎖した上で前記送液ポンプを運転させることで、細胞含有液を前記貯留部から前記本管に供給し、細胞含有液が前記本管に充填された後、前記複数の開閉弁を開放して、前記本管から各支管を介して各容器に細胞含有液を供給する、細胞含有液の供給装置。
A cell-containing liquid supply device for putting a cell-containing liquid in which living cells are dispersed into a container.
A storage unit that stores cell-containing fluid and
A main pipe, which is a series of pipelines connected to the storage unit,
A plurality of branch pipes, which are pipelines branched laterally from the main pipe,
A liquid feed pump that supplies cell-containing liquid from the reservoir to the main
A plurality of on-off valves provided in the plurality of branch pipes and
With a control unit
The control unit closes the plurality of on-off valves and then operates the liquid feed pump to supply the cell-containing liquid from the storage unit to the main pipe, and the cell-containing liquid is filled in the main pipe. After that, the cell-containing liquid supply device for opening the plurality of on-off valves and supplying the cell-containing liquid from the main pipe to each container via each branch pipe.
前記本管の、前記貯留部が接続された側とは反対側に設けられた液回収ポンプを備え、
前記容器は、細胞含有液の前記供給に伴い膨張する容器であって、
前記容器は、細胞含有液を出し入れする出入口部を有し、周縁部のうち前記出入口部が形成された部分以外は液密及び気密に閉鎖されており、
前記制御部は、前記出入口部を介して細胞含有液が前記容器に供給された後に、前記液回収ポンプを運転させることで、前記容器の前記出入口部から、前記容器の内部にある空気を排出する、請求項3に記載の細胞含有液の供給装置。
A liquid recovery pump provided on the side of the main pipe opposite to the side to which the storage portion is connected is provided.
The container is a container that expands with the supply of the cell-containing liquid.
The container has an entrance / exit portion for taking in and out the cell-containing liquid, and is closed in a liquid-tight and airtight manner except for the portion of the peripheral portion where the entrance / exit portion is formed.
The control unit discharges the air inside the container from the inlet / outlet portion of the container by operating the liquid recovery pump after the cell-containing liquid is supplied to the container via the inlet / outlet portion. The cell-containing liquid supply device according to claim 3.
容器に生存細胞が分散している細胞含有液が充填された細胞含有製品の製造方法であって、
一連の管路である本管と、
前記本管から側方に分岐した管路である複数の支管と、
前記複数の支管に接続された複数の前記容器と、の組み合わせに対し、
細胞含有液を、前記複数の支管が閉鎖された状態で前記本管に充填し、その後、前記複数の支管を開放することにより、前記本管から各支管を介して各容器に供給する、細胞含有製品の製造方法。
A method for producing a cell-containing product in which a container is filled with a cell-containing solution in which living cells are dispersed.
The main, which is a series of pipelines,
A plurality of branch pipes, which are pipelines branched laterally from the main pipe,
For the combination of the plurality of containers connected to the plurality of branch pipes,
A cell containing a cell-containing solution is filled in the main pipe in a state where the plurality of branch pipes are closed, and then supplied to each container from the main pipe via each branch pipe by opening the plurality of branch pipes. Manufacturing method of contained products.
前記容器は、細胞含有液の前記供給に伴い膨張する容器であって、
前記容器は、細胞含有液を出し入れする出入口部を有し、周縁部のうち前記出入口部が形成された部分以外は液密及び気密に閉鎖されており、
前記出入口部を介して細胞含有液が前記容器に供給された後に、前記出入口部から、前記容器の内部にある空気を排出する、請求項5に記載の細胞含有製品の製造方法。
The container is a container that expands with the supply of the cell-containing liquid.
The container has an entrance / exit portion for taking in and out the cell-containing liquid, and is closed in a liquid-tight and airtight manner except for the portion of the peripheral portion where the entrance / exit portion is formed.
The method for producing a cell-containing product according to claim 5, wherein the cell-containing liquid is supplied to the container through the doorway, and then the air inside the container is discharged from the doorway.
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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH11513247A (en) * 1995-09-08 1999-11-16 バクスター・インターナショナル・インコーポレイテッド Apparatus for transporting a flexible container and method for transferring fluid to a container
JP2018030610A (en) * 2016-08-24 2018-03-01 大日本印刷株式会社 Divided injection device and method for manufacturing package

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH11513247A (en) * 1995-09-08 1999-11-16 バクスター・インターナショナル・インコーポレイテッド Apparatus for transporting a flexible container and method for transferring fluid to a container
JP2018030610A (en) * 2016-08-24 2018-03-01 大日本印刷株式会社 Divided injection device and method for manufacturing package

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