JPH02107182A - Hollow fiber for bioreactor - Google Patents
Hollow fiber for bioreactorInfo
- Publication number
- JPH02107182A JPH02107182A JP25837288A JP25837288A JPH02107182A JP H02107182 A JPH02107182 A JP H02107182A JP 25837288 A JP25837288 A JP 25837288A JP 25837288 A JP25837288 A JP 25837288A JP H02107182 A JPH02107182 A JP H02107182A
- Authority
- JP
- Japan
- Prior art keywords
- hollow fiber
- zeolite
- bioreactor
- polymeric material
- polysulfone
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000012510 hollow fiber Substances 0.000 title claims abstract description 39
- 229910021536 Zeolite Inorganic materials 0.000 claims abstract description 16
- HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical compound O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000010457 zeolite Substances 0.000 claims abstract description 16
- 239000000463 material Substances 0.000 claims abstract description 12
- 229920002492 poly(sulfone) Polymers 0.000 abstract description 9
- 239000004695 Polyether sulfone Substances 0.000 abstract description 4
- 229920006393 polyether sulfone Polymers 0.000 abstract description 4
- 239000002033 PVDF binder Substances 0.000 abstract description 3
- 210000004102 animal cell Anatomy 0.000 abstract description 3
- 238000000034 method Methods 0.000 abstract description 3
- 238000002156 mixing Methods 0.000 abstract description 3
- 239000003960 organic solvent Substances 0.000 abstract description 3
- 229920002981 polyvinylidene fluoride Polymers 0.000 abstract description 3
- 238000001891 gel spinning Methods 0.000 abstract description 2
- 239000007788 liquid Substances 0.000 abstract description 2
- 229920002239 polyacrylonitrile Polymers 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract 1
- 235000013311 vegetables Nutrition 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 9
- 239000000047 product Substances 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000009987 spinning Methods 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 229910010293 ceramic material Inorganic materials 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 239000007836 KH2PO4 Substances 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229920001600 hydrophobic polymer Polymers 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 230000010220 ion permeability Effects 0.000 description 1
- 239000013586 microbial product Substances 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- DQWPFSLDHJDLRL-UHFFFAOYSA-N triethyl phosphate Chemical compound CCOP(=O)(OCC)OCC DQWPFSLDHJDLRL-UHFFFAOYSA-N 0.000 description 1
- 230000002747 voluntary effect Effects 0.000 description 1
- 238000004804 winding Methods 0.000 description 1
Landscapes
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Immobilizing And Processing Of Enzymes And Microorganisms (AREA)
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は、植物、動物細胞の高密度培養及び培養液の透
過速度を向上させ、バイオリアクターとして有効に用い
られる中空糸に関する。DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a hollow fiber that improves the high-density culture of plant and animal cells and the permeation rate of a culture solution, and is effectively used as a bioreactor.
従来、植物細胞、動物細胞、微生物などを培養するバイ
オリアクターにあっては、中空糸素材としてポリサルホ
ン、ポリフッ化ビニリデンなどの高分子素材が利用され
ていた。一方、セラミックス素材も利用され、粒子間の
空隙を利用して口過する方法が採用されていた。Conventionally, in bioreactors for culturing plant cells, animal cells, microorganisms, etc., polymeric materials such as polysulfone and polyvinylidene fluoride have been used as hollow fiber materials. On the other hand, ceramic materials were also used, and a method of passing through the mouth using the voids between particles was adopted.
しかしながら、高分子素材からなる中空糸では中空糸の
孔径が小さく、また一般の疎水性高分子では細胞及び産
生物との親和性が悪く、孔径が小さく、口過効率が低い
という難点があった。微生物は一般に、産生物が高濃度
になると増殖速度が低下する傾向があるため細胞の高密
度培養には限界があった。However, hollow fibers made of polymeric materials have small pore diameters, and general hydrophobic polymers have poor affinity with cells and products, resulting in small pore diameters and low filtration efficiency. . Microorganisms generally have a tendency to slow down their growth rate when the concentration of their products is high, so there has been a limit to high-density culture of cells.
また、セラミックス素材は口過効率は高いが、空隙率が
４０％程度しかなく、細胞及び産生物との親和性も充分
でなかった。Further, although the ceramic material has a high porosity efficiency, the porosity is only about 40%, and the affinity with cells and products is not sufficient.
そこで、細胞や細菌が産生ずる物質を速やかに透過し、
細胞の吸着性が高く、高密度培養が可能なバイオリアク
ター用中空糸が求められていた。Therefore, substances produced by cells and bacteria can quickly pass through,
There has been a need for hollow fibers for bioreactors that have high cell adsorption properties and enable high-density culture.
本発明は上記課題を解決する中空糸を提供することを目
的とし、その構成は、３〜５０重量％のゼオライトを含
有する高分子素材を用いることを特徴とする。The present invention aims to provide a hollow fiber that solves the above problems, and its structure is characterized by using a polymeric material containing 3 to 50% by weight of zeolite.
本発明に係る中空糸はゼオライトを、ポリサルホン、ポ
リフッ化ビニリデン、ポリエーテルスルホン、ポリアク
リロニトリルなどの高分子素材の有機溶媒溶液と均一に
混合し、乾湿式法により中空糸状に成形して中空糸とし
たものである。有機溶媒としては、ジメチルアセトアミ
ド、ジメチルホルムアミド、トリエチルホスフェートな
どが使用される。紡糸速度は５〜２０ｍ／ｍｉｎが好ま
しい。The hollow fibers according to the present invention are produced by uniformly mixing zeolite with an organic solvent solution of a polymeric material such as polysulfone, polyvinylidene fluoride, polyethersulfone, or polyacrylonitrile, and forming the mixture into a hollow fiber shape using a dry-wet method. This is what I did. As the organic solvent, dimethylacetamide, dimethylformamide, triethyl phosphate, etc. are used. The spinning speed is preferably 5 to 20 m/min.
中空糸用のドープ液の組成は、１００重量部中ゼオライ
ト１〜１０重量部に対し高分子素材５〜２０重量部、残
部を溶媒としたものであり、好ましくは、ゼオライト３
〜７重量部、高分子素材１０〜１８重量部である。ゼオ
ライトが１重量部以下ではゼオライトの口過効率促進効
果が発現せず、１０重量部以上では紡糸が困難になる。The composition of the dope solution for hollow fibers is 1 to 10 parts by weight of zeolite in 100 parts by weight, 5 to 20 parts by weight of polymeric material, and the remainder being a solvent, preferably 3 to 3 parts by weight of zeolite.
~7 parts by weight, and 10 to 18 parts by weight of the polymeric material. If the amount of zeolite is less than 1 part by weight, the zeolite does not have the effect of promoting filtration efficiency, and if it is more than 10 parts by weight, spinning becomes difficult.
得られた中空糸の組成は３〜５０重量％、好ましくは１
５〜３５重量％のゼオライトを含有する。The composition of the obtained hollow fibers is 3 to 50% by weight, preferably 1
Contains 5-35% by weight of zeolite.
本発明中空糸を使用する中空糸モジュールは上記中空糸
を、両端を閉塞した反応管に反応管と平行に、両端を反
応管端部に開口させて収納し、該開口部の一方を口過液
の集合管とする。他方の開口部は窒素供給管と連結し、
通常は閉塞しているが間歇的に開口し、窒素ガスを逆流
させて中空糸の目詰まりを防止することが好ましい。ま
た、開口部の両端から口過液を採集してもよい。The hollow fiber module using the hollow fibers of the present invention stores the hollow fibers in a reaction tube with both ends closed, parallel to the reaction tube, with both ends opened at the end of the reaction tube, and one of the openings is opened at the end of the reaction tube. It is used as a collecting pipe for liquid. The other opening is connected to the nitrogen supply pipe,
Although it is normally closed, it is preferable to open it intermittently to allow nitrogen gas to flow back and prevent clogging of the hollow fibers. Alternatively, oral fluid may be collected from both ends of the opening.
培養器は別に設け、この培養器内の一定量の反応液を反
応管側壁に設けた反応液供給口から供給し、反応液排出
口から排出させ、この間に反応液中の産生物質が中空糸
で口過されて集合管を通過して別容器に採集されるよう
にしてもよい。An incubator is provided separately, and a certain amount of the reaction solution in this incubator is supplied from the reaction solution supply port provided on the side wall of the reaction tube, and is discharged from the reaction solution outlet. Alternatively, the sample may be passed through the mouth, passed through a collecting pipe, and collected in a separate container.
本発明はゼオライトのイオン交換性能、優れた細胞吸着
性および溶液の透過性を利用し、従来の高分子素材にゼ
オライトを配合して紡糸して得られた中空糸である。本
発明中空糸を使用したモジュールを用いれば、微生物の
産生物の透過効率が高く、産生物を培養液から効率よく
口過分離し、高密度培養を可能にするものである。The present invention utilizes zeolite's ion exchange performance, excellent cell adsorption properties, and solution permeability, and is a hollow fiber obtained by blending zeolite into a conventional polymeric material and spinning it. When the module using the hollow fibers of the present invention is used, the permeation efficiency of microbial products is high, the products are efficiently separated from the culture solution, and high-density culture is possible.
このように高口過性中空糸モジュールに反応液を通過さ
せることにより、培養液中の産生物比率が減少し、細胞
の高密度培養が可能になるので、バイオリアクターとし
ての有効な利用が図れる。By passing the reaction solution through the high porosity hollow fiber module in this way, the ratio of products in the culture solution is reduced and cells can be cultured at high density, making it possible to effectively use the module as a bioreactor. .
〔実施例１〕
ポリサルホン＜ ＵＣＣ社製品Ｐ−１７００） １５
ｇ 。[Example 1] Polysulfone < UCC product P-1700) 15
g.
ゼオライト５ｇ及びジメチルホルムアミド８０ｇの混合
物からなるドープ液をゲル化浴温度１０℃、巻取速度１
０ｍ／分で乾湿式紡糸して内径１ｍｍ、外径２ｍｍ、長
さ１８ｃｍ、空隙率４５％のゼオライト中空糸を得た。A dope solution consisting of a mixture of 5 g of zeolite and 80 g of dimethylformamide was heated at a gelling bath temperature of 10°C and a winding speed of 1.
A zeolite hollow fiber having an inner diameter of 1 mm, an outer diameter of 2 mm, a length of 18 cm, and a porosity of 45% was obtained by dry-wet spinning at 0 m/min.
この中空糸１０本を収納したモジュールを製造した。A module containing 10 of these hollow fibers was manufactured.
別に比較例として同一寸法のポリサルホン中空糸を１０
本収納したモジュールの透過性を比較した。両者共０．
１Ｍ ＫＨ２ＰＯ４を中空糸内に０．１ＭＫ２ＨＰＯ，
を中空糸外側に供給し、中空糸内のｐＨの経時変化を比
較して第１図に示した。本発明中空糸を使用した場合に
は、中空糸のイオン透過性が優れているため、Ｋ ２
ＨＰ Ｏａが中空糸内に速やかに浸入し、ｐＨが急上昇
している。Separately, as a comparative example, 10 polysulfone hollow fibers of the same size were used.
The permeability of the stored modules was compared. Both are 0.
1M KH2PO4 into the hollow fiber, 0.1MK2HPO,
was supplied to the outside of the hollow fiber, and the changes in pH inside the hollow fiber over time are compared and shown in FIG. When the hollow fiber of the present invention is used, since the hollow fiber has excellent ion permeability, K2
HP Oa quickly penetrates into the hollow fibers, causing a rapid rise in pH.
〔実施例２〕
実施例１の中空糸及びポリサルホン中空糸を各々０．５
ｇ採り、大腸菌１０”個／ｃｃ含有する培養液１００ｍ
１に３０分間浸漬した後遠心分離した。[Example 2] The hollow fibers and polysulfone hollow fibers of Example 1 were each 0.5
100m of culture solution containing 10" E. coli/cc
1 for 30 minutes and then centrifuged.
培養液上清を１０’倍に希釈しＬ−ｂｒｏｔｈ培地に植
菌しコロニー数を比較した。この操作を２回行いその結
果を第１表に示した。The culture supernatant was diluted 10' times and inoculated into L-broth medium, and the number of colonies was compared. This operation was performed twice and the results are shown in Table 1.
第 １ 表
第１表より本発明中空糸は大腸菌に対しても優れた付着
性を有することが理解される。Table 1 It is understood from Table 1 that the hollow fibers of the present invention have excellent adhesion to E. coli.
ゼオライトを含有する高分子素材からなる本発明中空糸
を使用することにより、培養液の口過速度が向上し、細
胞の高密度培養が可能になり、目的とする産生物を高収
率で得ることができる。By using the hollow fiber of the present invention made of a polymeric material containing zeolite, the overvelocity of the culture solution is improved, enabling high-density culture of cells and obtaining the desired product at a high yield. be able to.
第１図は中空糸内ｐＨの変化を示すグラフであり、○は
本発明中空糸を使用した場合であり、・はポリサルホン
中空糸を使用した場合である。
手続補正書
平成１年６月２７日
特許庁長官 吉 １）文 毅 殿
１、事件の表示
昭和６３年特許願第２５８３７２号
２、発明の名称
バイオリアクター用中空糸
３、補正をする者
事件との関係 特許出願人
住所 東京都港芝大門−丁目１２番１５号名称 エヌオ
ーケー株式会社
４、代理人 ■１５０
住所 東京都渋谷区広尾−丁目１１番５号時
間
（ｈｒ）
電話 ０３−２８０−２３０６番（外１名）５、補正命
令の日付 自発
６、補正の対象 明細書の発明の詳細な説明の欄７、
補正の内容
（１）明細書、１頁の１５行、２頁の１８から１９行、
５頁の２行、９行及び下３行、６頁の未行の「ポリサル
ホン」を「ポリサルホン」にそれぞれ訂正する。
（２）同、２頁の１９行から未行の「ポリエーテルスル
ホン」を「ポリエーテルスルホン」に訂正する。
以上FIG. 1 is a graph showing the change in pH inside the hollow fiber, where ◯ indicates the case where the hollow fiber of the present invention was used, and ◯ indicates the case where the polysulfone hollow fiber was used. Procedural amendment June 27, 1999 Director General of the Japan Patent Office Yoshi 1) Takeshi Moon1, Indication of the case 1988 Patent Application No. 2583722, Name of the invention Hollow fiber for bioreactor 3, Person making the amendment Case and Relationship Patent Applicant Address: 12-15, Minato Shiba Daimon-chome, Tokyo Name: NOK Co., Ltd. 4, Agent ■150 Address: 11-5, Hiroo-chome, Shibuya-ku, Tokyo Hours (hr) Telephone: 03-280-2306 (1 other person) 5. Date of amendment order Voluntary 6. Subject of amendment Detailed explanation of the invention in the specification 7.
Contents of amendment (1) Specification, line 15 on page 1, lines 18 to 19 on page 2,
Correct the missing words "Polysulfone" in lines 2 and 9 on page 5 and in the bottom 3 lines and page 6 to "polysulfone". (2) From page 2, line 19, the missing "polyether sulfone" is corrected to "polyether sulfone."that's all
Claims (1)
なるバイオリアクター用中空糸。A hollow fiber for bioreactors made of a polymeric material containing 3 to 50% by weight of zeolite.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP25837288A JPH02107182A (en) | 1988-10-15 | 1988-10-15 | Hollow fiber for bioreactor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP25837288A JPH02107182A (en) | 1988-10-15 | 1988-10-15 | Hollow fiber for bioreactor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH02107182A true JPH02107182A (en) | 1990-04-19 |
Family
ID=17319331
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP25837288A Pending JPH02107182A (en) | 1988-10-15 | 1988-10-15 | Hollow fiber for bioreactor |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH02107182A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8158411B2 (en) | 2006-08-21 | 2012-04-17 | Samsung Electronics Co., Ltd. | Method of separating microorganism using nonplanar solid substrate and device for separating microorganism using the same |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63196280A (en) * | 1987-02-12 | 1988-08-15 | Sumitomo Electric Ind Ltd | Substrate for cell culture |
-
1988
- 1988-10-15 JP JP25837288A patent/JPH02107182A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63196280A (en) * | 1987-02-12 | 1988-08-15 | Sumitomo Electric Ind Ltd | Substrate for cell culture |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8158411B2 (en) | 2006-08-21 | 2012-04-17 | Samsung Electronics Co., Ltd. | Method of separating microorganism using nonplanar solid substrate and device for separating microorganism using the same |
| US8557564B2 (en) | 2006-08-21 | 2013-10-15 | Samsung Electronics Co., Ltd. | Method of separating microorganism using nonplanar solid substrate and device for separating microorganism using the same |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6001585A (en) | Micro hollow fiber bioreactor | |
| CN101703893B (en) | Hollow fiber ultrafiltration composite membrane, preparation method and application thereof | |
| JPH03164169A (en) | Cell culture | |
| JPH09511392A (en) | High performance cell culture bioreactor and method | |
| CN109012181B (en) | A kind of synthetic method and gained permeable membrane of the modified Cellulose acetate forward osmotic membrane of ZIF-8 | |
| JP2661848B2 (en) | Culture method and culture device | |
| JP2003510042A (en) | Cell culture method, membrane module, use of membrane module and reaction system for cell culture | |
| JPH02107182A (en) | Hollow fiber for bioreactor | |
| JPS63157978A (en) | Method and apparatus for culturing animal cell | |
| CN106497760A (en) | Biogas membrance separation purifying plant | |
| JPH01222768A (en) | Bioreactor | |
| JPS63240774A (en) | Bioreactor | |
| Wang et al. | Immobilization of Anabaena azollae in hallow fibre photobioreactors for ammonia production | |
| CN105002723A (en) | High-photocatalytic-activity modified-honeycomb-stone-doped polylactic acid-polypropylene biological film composite fiber carrier material and preparation method thereof | |
| JPH03505965A (en) | bioreactor equipment | |
| JP6952297B2 (en) | Hollow fiber membrane for cell culture and cell culture method | |
| CN1321741A (en) | Hematopoietic device using hollow fibre to simulate bone marrow | |
| CN109319947A (en) | A kind of biofilm reactor | |
| JPH01124375A (en) | Material for bioreactor | |
| WO2001058501A1 (en) | Apparatus and process for removal of carbon dioxide in a bioreactor system | |
| JPH0398571A (en) | Cell culture container and cell culture | |
| CN209442982U (en) | Microorganism fermentation tank | |
| CN217459409U (en) | In-situ culture device for tubular bacterial cellulose hydrogel | |
| KR102176005B1 (en) | Floating photobioreactor comprising selectively permeable membranes for inhibiting biofouling | |
| JP2984748B2 (en) | Method for culturing microorganisms using air-permeable membrane |