JPH0655131B2 - Biochemical reaction method - Google Patents
Biochemical reaction methodInfo
- Publication number
- JPH0655131B2 JPH0655131B2 JP2205989A JP2205989A JPH0655131B2 JP H0655131 B2 JPH0655131 B2 JP H0655131B2 JP 2205989 A JP2205989 A JP 2205989A JP 2205989 A JP2205989 A JP 2205989A JP H0655131 B2 JPH0655131 B2 JP H0655131B2
- Authority
- JP
- Japan
- Prior art keywords
- reaction
- reaction tank
- baffles
- cylindrical
- biochemical reaction
- 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.)
- Expired - Lifetime
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M27/00—Means for mixing, agitating or circulating fluids in the vessel
- C12M27/14—Rotation or movement of the cells support, e.g. rotated hollow fibers
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M27/00—Means for mixing, agitating or circulating fluids in the vessel
- C12M27/18—Flow directing inserts
- C12M27/22—Perforated plates, discs or walls
Abstract
Description
【発明の詳細な説明】 （産業上の利用分野） この発明は多孔質構造を持った素材で成る筒状容器を内
面にバッフルを設けた生化学反応を行なう反応槽内で回
転させる生化学反応方法に関し、さらに詳しくは上記筒
状容器を液体相で空のまま又は内部に固定化生体触媒を
収容して回転撹拌させることを特徴とする生化学反応方
法に関する。（なおここにいう生化学反応とは、酵素反
応は勿論のこと、微生物や動，植物細胞など総べての培
養，発酵，反応をいう。） （従来の技術） 従来、一般的な培養，発酵，反応方法として羽根撹拌を
使用せる完全混合型反応器による方法がよく知られてお
り、また固定化生体触媒の培養，発酵，反応方法として
は、完全混合型反応器，エアリフト型反応器，カラム充
填型反応器，中空糸膜型反応器，回転円盤型反応器等に
よる方法がある。そしてエアリフト型など流動層型反応
器によるものでは流動による菌体への酸素・基質の供給
が促進され、物質移動は良好になるが反応率が低いとい
う欠点がある。また充填率を増すと流動性が悪くなる。
大体流動性が保てるのは充填率0.3以下とされている。
これに対してカラム充填型などの固定層型反応器による
場合は充填率が高く、反応率も高いが、物質移動が悪く
なるので増殖速度，生産速度ともに上がらないもので、
いずれも一長一短がある。TECHNICAL FIELD The present invention relates to a biochemical reaction in which a cylindrical container made of a material having a porous structure is rotated in a reaction tank for carrying out a biochemical reaction in which an inner surface is provided with a baffle. More particularly, the present invention relates to a biochemical reaction method characterized in that the tubular container is left empty in the liquid phase, or the immobilized biocatalyst is housed in the liquid container and rotatively stirred. (The biochemical reaction mentioned here means not only an enzymatic reaction but also all cultures, fermentations, reactions of microorganisms, animals, plant cells, etc.) (Prior art) Conventional general culture, As a fermentation and reaction method, a method using a perfect mixing type reactor that uses blade stirring is well known, and as a method for culturing, fermentation and reacting an immobilized biocatalyst, a perfect mixing type reactor, an air lift type reactor, There are methods such as column packed reactor, hollow fiber membrane reactor, and rotating disk reactor. Further, a fluidized bed reactor such as an air lift type has a drawback that the supply of oxygen / substrate to the bacterial cells is promoted by the flow and the mass transfer is improved, but the reaction rate is low. Further, if the filling rate is increased, the fluidity becomes worse.
It is said that the fluidity can be maintained at a filling rate of 0.3 or less.
On the other hand, in the case of a fixed bed type reactor such as a column packing type, the packing rate is high and the reaction rate is also high, but since mass transfer deteriorates, neither the growth rate nor the production rate increases.
Both have advantages and disadvantages.
（発明が解決しようとする問題点） 一般的に従来のジャーファメンターに代表される生化学
反応器では、基質や酸素などの物質移動が、反応の律速
になる場合が多く、また一般的に固定化生体触媒の培
養，発酵，反応において、固定化生体触媒が物理的な剪
断力などで崩壊し、その活性が低下することが知られて
いる。そして粘度が高い溶液中で固定化生体触媒を使用
する場合には、基質や酸素などの物質移動が困難で、か
つ固定化生体触媒と高粘性溶液との分離，回収が困難で
あるなどの問題があった。(Problems to be Solved by the Invention) Generally, in a biochemical reactor represented by a conventional jar-famenter, mass transfer of a substrate or oxygen is often the rate-determining reaction, and generally, It is known that the immobilized biocatalyst is destroyed by physical shearing force or the like during the culture, fermentation, and reaction of the immobilized biocatalyst, and the activity thereof is reduced. When using an immobilized biocatalyst in a highly viscous solution, it is difficult to transfer substances such as substrates and oxygen, and it is difficult to separate and recover the immobilized biocatalyst from the highly viscous solution. was there.
ここに言う固定化生体触媒は、増殖可能な細胞を含むも
のである。The immobilized biocatalyst referred to herein includes cells that can grow.
（問題点を解決するための手段） この発明は上記問題点を解決するためになされたもので
あって、生化学反応容器内の物質移動速度を速くするだ
けでなく、固定化生体触媒を劣化させることなく、高密
度に使用できる固定化生体触媒を使用した培養，発酵，
反応方法をも提供することにある。(Means for Solving Problems) The present invention has been made to solve the above problems, and not only increases the mass transfer rate in the biochemical reaction vessel, but also deteriorates the immobilized biocatalyst. Culture, fermentation using immobilized biocatalyst that can be used at high density without
It is also to provide a reaction method.
所謂この発明は、流体の流通移動良好な多孔質構造を持
った素材で形成した容器またはその容器に固定化生体触
媒を充填包括したものを液体中で回転し、液体を撹拌さ
せて培養，発酵，反応させることを特徴とする生化学反
応方法である。The so-called present invention is a container formed of a material having a porous structure with good fluid flow and movement, or a container in which the immobilized biocatalyst is filled and rotated in a liquid, and the liquid is stirred to culture and ferment. , A biochemical reaction method characterized by reacting.
さらに詳しくはこの発明は、多孔質構造を持った素材で
成る筒状容器または内部に固定化生体触媒が収容された
同筒状容器を回転軸に取付け、内面に軸方向の細長いバ
ッフルを設けた生化学的反応を行なう反応槽内で回転さ
せ、液体を撹拌させて培養，発酵，反応を行なうことを
特徴とする生化学反応方法である。More specifically, according to the present invention, a cylindrical container made of a material having a porous structure or the cylindrical container containing an immobilized biocatalyst inside is attached to a rotary shaft, and an axially elongated slender baffle is provided on the inner surface. It is a biochemical reaction method characterized by culturing, fermentation and reaction by rotating a liquid in a reaction tank for biochemical reaction and stirring a liquid.
次にこの発明を図面に示す実施例装置について詳しく説
明する。Next, a detailed description will be given of an apparatus according to an embodiment of the present invention shown in the drawings.
先ず１は、内面に軸方向の細長い４枚（数枚）のバッフ
ル７を（放射状に）設けた生化学的反応を行なうガラス
製円筒状の反応槽で、上部に流出，入口３，２を有す
る。そして該反応槽１内には外面上部中央部に設けられ
たモーター４の軸５が垂設されている。６は、例えばセ
ラミックス，ウレタンフォーム，ガラス，金属（ステン
レス鋼）などの材料でなる多孔質または綱目（ネット）
構造を持った流体移動の良好な第１，２図（実施例１）
及び第３図（実施例２）に示すような円筒状の筒状容器
であるが、ＥＧＳＴＲ（本発明の生化学反応容器を便宜
的にＥＧＳＴＡＲと呼ぶ）の回転軸方向の流体移動を良
くするために第４図に例示したドーナツ形の筒状容器６
にするか、あるいは図示してないが回転軸のまわりにウ
レタンフォームなどの多孔質構造を持ったスペーサーを
入れたり固定化生体触媒９をドーナツ状に配置するなど
してもよい。First, 1 is a cylindrical glass-made reaction tank for biochemical reaction in which four axially elongated baffles 7 (several) are provided (radially) on the inner surface. Have. A shaft 5 of a motor 4 provided in the central portion of the upper surface of the outer surface is vertically installed in the reaction tank 1. 6 is a porous or corrugated (net) made of a material such as ceramics, urethane foam, glass, metal (stainless steel), etc.
1 and 2 (Structure 1) in which the structure has a good fluid movement.
And a cylindrical tubular container as shown in FIG. 3 (Example 2), which improves fluid movement in the rotation axis direction of the EGSTR (the biochemical reaction container of the present invention is conveniently called EGSTAR). The donut-shaped cylindrical container 6 illustrated in FIG.
Alternatively, although not shown, a spacer having a porous structure such as urethane foam may be inserted around the rotating shaft, or the immobilized biocatalyst 9 may be arranged in a donut shape.
（実施例１） 第１図に示すように多孔質構造をもった流通移動の良好
な素材で成る円筒状の筒状容器６を反応槽１内の液体相
で空のまま強制的に回転させることによって例えば酸素
移動容量係数を高くすることが可能となり、液体を撹拌
させて培養，発酵，反応が有効に行える。(Example 1) As shown in FIG. 1, a cylindrical cylindrical container 6 made of a material having a porous structure and having good flow movement is forcibly rotated in an empty state in a liquid phase in a reaction tank 1. As a result, for example, the oxygen transfer capacity coefficient can be increased, and the liquid can be stirred to effectively perform the culture, fermentation, and reaction.
（実施例２） 第３図に示すように筒状容器６内に固定化生体触媒９を
収容して反応槽１内の液体相で強制的に回転させると、
液体流を矢印のように万偏なく円滑に流動させて撹拌
し、筒状容器６内の固定化生体触媒９を培養，発酵，反
応させる。Example 2 As shown in FIG. 3, when the immobilized biocatalyst 9 was housed in the cylindrical container 6 and forcedly rotated by the liquid phase in the reaction tank 1,
The liquid flow is smoothly and uniformly stirred as shown by the arrow, and the immobilized biocatalyst 9 in the cylindrical container 6 is cultured, fermented, and reacted.
そして筒状容器６内の固定化生体触媒９は物理的な剪断
力などで崩壊劣化することなく、その他の原因がなけれ
ば長時間の連続運転に供することができる。当然、酸素
移動容量係数も高い。Then, the immobilized biocatalyst 9 in the cylindrical container 6 does not collapse and deteriorate due to physical shearing force, etc., and can be continuously operated for a long time unless there are other causes. Naturally, the oxygen transfer capacity coefficient is also high.
（実施例３） 実施例１の筒状容器６を市販のジャーファメンターにセ
ットし、亜硫酸ソーダ法で酸素移動容量係数を他の方法
と比較測定したところ、１ｖｖｍの通気量で次のような
結果を得た。(Example 3) The cylindrical container 6 of Example 1 was set in a commercially available jar-famenter, and the oxygen transfer capacity coefficient was measured by comparison with other methods by the sodium sulfite method. I got the result.
ＥＧＳＴＡＲ（７００ｒｐｍ） １．２００ｈ-1 プロペラ撹拌型（同上） ２００ｈ-1 エアーリフト型 ４０ｈ-1 （実施例４） 市販アルギン酸２ｇ，水100ｇ，市販パン酵母20ｇの割
合で混合し、通常通り塩化カルシウム溶液中に適下して
パン酵母を包括固定化したアルギン酸カルシウムゲルを
作る。EGSTAR (700 rpm) 1. 200 h -1 propeller stirring type (same as above) 200 h -1 air lift type 40 h -1 (Example 4) 2 g of commercially available alginic acid, 100 g of water, and 20 g of commercially available baker's yeast were mixed in a ratio of calcium chloride as usual. A calcium alginate gel in which baker's yeast is entrapped and immobilized in a solution is prepared.
また市販のスポンジ（１〜３mm径）で実施例１のような
筒状容器を作り、その中にパン酵母を包括固定化したア
ルギン酸カルシウムゲル（４〜５mm径）一杯充填した。A cylindrical container as in Example 1 was made from a commercially available sponge (1 to 3 mm in diameter) and filled with a whole amount of calcium alginate gel (4 to 5 mm in diameter) in which baker's yeast was entrapped and immobilized.
そしてこのアルギン酸カルシウムゲルを包括固定した筒
状容器を第３図のように市販のミニジャーファメンター
にセットし、撹拌及び回転によるゲルの崩壊とパン酵母
の漏洩を、分光光度計で測定した。なお同時に完全混合
型（ＣＳＴＲ）とエアリフト型（ＡＡＣＲ）の装置に、
同じ割合で上記ゲルを入れ、実験に供した。その結果、
第５図の図表からも明らかなように本発明のもの（便宜
的にＥＧＳＴＲＡＲと呼ぶ反応器）は非常に有利である
ことがわかった。Then, as shown in FIG. 3, the tubular container in which the calcium alginate gel was entrapped and fixed was set in a commercially available mini jar fermenter, and gel collapse and baker's yeast leakage due to stirring and rotation were measured with a spectrophotometer. In addition, at the same time, the equipment of perfect mixing type (CSTR) and air lift type (AACR),
The gel was added at the same ratio and used for the experiment. as a result,
As is clear from the chart of FIG. 5, the one of the present invention (reactor for convenience called EGSTRAR) was found to be very advantageous.
なおまた実施例２の場合において、第３図に示すように
回転軸５にプロペラ８を取付けると、矢印の液体流の流
動作用が助勢される。Furthermore, in the case of the second embodiment, when the propeller 8 is attached to the rotary shaft 5 as shown in FIG. 3, the flow action of the liquid flow indicated by the arrow is assisted.
（発明の効果） この発明は、例えば酸素移動容量係数を高くすることが
可能となり、液体相の物質移動を従来法より極端に良く
することができる卓抜した効果がある。さらにこの発明
では反応槽内面に軸方向の細長いバッフルを設けたか
ら、これにより凝集防止と共に軸方向の液体流動混合を
促進させることができ反応処理を助勢できる優れた効果
がある。かつ固定化生体触媒をさらに包括固定化し、液
体中で強制的に回転撹拌操作できるようにしたため、従
来からの問題であった固定化生体触媒の強度の悪さと培
養，発酵，反応槽内での物質移動の悪さとを解消するこ
とができる。また従来から使用されている装置が若干の
改良でそのままこの発明方法に使用でき産業的にも有益
である。(Effects of the Invention) The present invention has an outstanding effect that, for example, the oxygen transfer capacity coefficient can be increased and the mass transfer of the liquid phase can be made extremely better than the conventional method. Further, in the present invention, since the axially elongated slender baffle is provided on the inner surface of the reaction vessel, this has an excellent effect of preventing aggregation and promoting liquid flow mixing in the axial direction and assisting the reaction treatment. Moreover, since the immobilized biocatalyst was further entrapped and immobilized so that it could be forcibly rotated and stirred in a liquid, the poor strength of the immobilized biocatalyst, which was a problem in the past, and culture, fermentation, and reaction in a reaction tank Poor mass transfer can be eliminated. Further, the apparatus used conventionally can be used as it is in the method of the present invention with some improvements, and is industrially useful.
第１図はこの発明の実施例１装置の縦断面図、第２図は
同横断面図、第３図は同実施例２装置の縦断面図、第４
図は筒状容器の別の実施例の一部欠截した斜視図、第５
図はこの発明と従来法とを比較した光学的透過度の図表
である。 １…反応層、２…気体等の流入口、（通気は通常のスパ
ージャーを使用可能）３…流出口、４…モーター、５…
軸、６…筒状容器、７…バッフル、８…プロペラ、９…
固定化生体触媒、FIG. 1 is a vertical cross-sectional view of a first embodiment of the present invention, FIG. 2 is a horizontal cross-sectional view of the same, and FIG. 3 is a vertical cross-sectional view of the second embodiment of the present invention.
FIG. 5 is a partially cutaway perspective view of another embodiment of the cylindrical container, FIG.
The figure is a table of optical transmittance comparing the present invention with a conventional method. DESCRIPTION OF SYMBOLS 1 ... Reaction layer, 2 ... Inlet for gas, etc. (a normal sparger can be used for ventilation) 3 ... Outlet, 4 ... Motor, 5 ...
Shaft, 6 ... Cylindrical container, 7 ... Baffle, 8 ... Propeller, 9 ...
Immobilized biocatalyst,
Claims (3)
回転軸に取付け、内面に軸方向の細長いバッフルを設け
た生化学的反応を行なう反応槽内で回転させ、液体を撹
拌させて培養、，発酵，反応を行なうことを特徴とする
生化学反応方法。1. A cylindrical container made of a material having a porous structure is attached to a rotary shaft, and the liquid is agitated by rotating in a reaction tank for biochemical reaction in which an elongated slender baffle is provided on the inner surface. A biochemical reaction method characterized by carrying out culture, fermentation, and reaction.
いる請求項１記載の生化学反応方法。2. The biochemical reaction method according to claim 1, wherein the immobilized biocatalyst is contained in a cylindrical container.
記載の生化学反応方法。3. The tubular container is a donut-shaped container.
The described biochemical reaction method.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2205989A JPH0655131B2 (en) | 1989-01-31 | 1989-01-31 | Biochemical reaction method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2205989A JPH0655131B2 (en) | 1989-01-31 | 1989-01-31 | Biochemical reaction method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH02203780A JPH02203780A (en) | 1990-08-13 |
| JPH0655131B2 true JPH0655131B2 (en) | 1994-07-27 |
Family
ID=12072339
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2205989A Expired - Lifetime JPH0655131B2 (en) | 1989-01-31 | 1989-01-31 | Biochemical reaction method |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0655131B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11192076B2 (en) | 2017-03-06 | 2021-12-07 | Spinchem Ab | Flow-promoting device, a reactor arrangement and the use of such flow-promoting device |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL101792A (en) * | 1992-05-05 | 1996-08-04 | Interpharm Lab Ltd | Bioreactor and basket therefor |
| JP3639007B2 (en) * | 1995-08-22 | 2005-04-13 | 京都水研株式会社 | Stirred tank type bioreactor |
| SE537934C2 (en) * | 2013-10-25 | 2015-11-24 | Nordic Chemquest Ab | reactor Construction |
| CN109694825A (en) * | 2019-02-20 | 2019-04-30 | 湖南省肿瘤医院 | A kind of mold for cultivating 3D cell ring |
| KR102096500B1 (en) * | 2019-12-17 | 2020-04-02 | 주식회사 이뮤니스바이오 | Doughnut-shaped cell culture bag and cell culture system with it |
-
1989
- 1989-01-31 JP JP2205989A patent/JPH0655131B2/en not_active Expired - Lifetime
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11192076B2 (en) | 2017-03-06 | 2021-12-07 | Spinchem Ab | Flow-promoting device, a reactor arrangement and the use of such flow-promoting device |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH02203780A (en) | 1990-08-13 |
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