JPS6158581A - Bioreactor - Google Patents
BioreactorInfo
- Publication number
- JPS6158581A JPS6158581A JP18230084A JP18230084A JPS6158581A JP S6158581 A JPS6158581 A JP S6158581A JP 18230084 A JP18230084 A JP 18230084A JP 18230084 A JP18230084 A JP 18230084A JP S6158581 A JPS6158581 A JP S6158581A
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- Japan
- Prior art keywords
- granules
- reactor
- bioreactor
- porous
- bed
- 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.)
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- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
Description
【発明の詳細な説明】
発明の背景
技術分野
本発明は、バイオリアクターに関する。さらに具体的に
は、本発明は、粒状固定化菌体ないし酵素の充填態様に
主要な特色を有する。圧力損失の少ないノ9イオリアク
ターに関する。BACKGROUND OF THE INVENTION Technical Field The present invention relates to bioreactors. More specifically, the present invention has a main feature in the manner in which granular immobilized bacterial cells or enzymes are packed. This invention relates to a No. 9 ioreactor with low pressure loss.
微生物菌体または酵素を水性ゲルに相持または包接させ
たものの粒状体からなる固定化菌体ないし酵素は、菌体
ないし酵素の有用な形聾として知られていて、この粒状
体を収容した反応器からなるものがバイオリアクターと
して検討されている。Immobilized microbial cells or enzymes consisting of granules of microbial cells or enzymes supported or included in an aqueous gel are known as useful forms of microbial cells or enzymes, and reactions containing these granules are known. A device consisting of a container is being considered as a bioreactor.
バイオリアクターには、様々な種類がある。その中で実
用化された連続式のバイオリアクターのほとんどが、固
定化菌体なりh シ酵票の粒状体・を充填した反応器に
基質溶液を通液させ反応させるIす1謂充填層型反応器
に分類さ+する。ここで、充填層仰反[6器の短所のう
ちで最も太きlfものは、核反応器内において気体(二
酸化炭素等)の発生を伴5反応を実施する場合、特に該
反応器を上向流で通液し実施する場合には、反応器内の
圧力損失経時的に大きくなって、遂には基質溶液ないし
発酵液の流通が停止してしまうということである。There are various types of bioreactors. Most of the continuous bioreactors that have been put into practical use are the so-called packed bed type, in which a substrate solution is passed through a reactor filled with immobilized bacterial cells or granules of fermentation material. Classified as a reactor. Here, packed bed reversal [Among the disadvantages of the 6 reactor, the biggest lf is that when carrying out a 5 reaction involving the generation of gas (carbon dioxide, etc.) in the nuclear reactor, especially when the reactor is When carrying out countercurrent flow, the pressure loss within the reactor increases over time, and eventually the flow of the substrate solution or fermentation liquid stops.
反応器内の圧力損失が経時的に増大する理由の一つは、
固定化菌体ないし酵素の粒状体内部で生化学ないし酵素
反応が進行してその際に粒状体内部に発生する気体(二
酸化炭素等)によって粒状体が低比重化して、反応器上
部で粒状体を支持している目皿に抑圧されるようになり
、さらに、この気体(二酸化炭素等)によって膨張した
粒状体は抑圧によって変形し易くなっているので、目皿
に押圧されて層を成している粒状体は変形して粒状体相
互間の通液空間を失なうに到るからである。One of the reasons why the pressure drop inside the reactor increases over time is because
When a biochemical or enzymatic reaction progresses inside the granules of immobilized bacterial cells or enzymes, the gas (carbon dioxide, etc.) generated inside the granules lowers the specific gravity of the granules, and the granules are removed at the top of the reactor. In addition, the granules expanded by this gas (carbon dioxide, etc.) are easily deformed by the compression, so they are pressed by the perforated plate and form a layer. This is because the granules in the granules are deformed and lose the liquid passage space between the granules.
また気体(二酸化炭素等)は当然のことながら粒状体表
面においても発生するが、この気体(二酸化炭素等)は
粒状体表面に付着してこれを浮上させるべく作用して上
記の問題に加担するばかりでなく、そハ自身の体積相当
分あるいは基質溶液中に遊離したものの体積相当分の基
質溶液の流通量が減少することにt「るのでそれを相殺
すべく基質溶液送入圧力を増大させなければならないと
いう意味においても、反応器内圧力損失の増大を引き起
すことになる。反応器に通気を行ないながら通液を行な
う場合にも、これと同様のことが生ずる。Furthermore, gases (carbon dioxide, etc.) are naturally generated on the surface of the granules, but this gas (carbon dioxide, etc.) adheres to the surface of the granules and acts to make them float, contributing to the above problem. In addition, the flow rate of the substrate solution corresponding to its own volume or the volume of substances liberated in the substrate solution decreases, so the substrate solution feeding pressure is increased to compensate for this. This also causes an increase in the pressure loss within the reactor.The same problem occurs when the reactor is aerated and liquid is passed through the reactor.
このような問題点は既に認識されていて種々の解決策が
提案されているのであるが、本発明者らの知るところで
は必ずしも十分に満足すべきものとはいい離V)。Although these problems have already been recognized and various solutions have been proposed, to the knowledge of the present inventors, they are not necessarily fully satisfactory.
発明の概要
要旨
本発明は上記の点に解決を与えることを目的とし、固定
化菌体ないし酵素の粒状体の床を多孔容器に分割して反
応器内にIヌ容することによってこの目的を達成しよう
とするものである。SUMMARY OF THE INVENTION The present invention aims to solve the above-mentioned problems, and achieves this purpose by dividing a bed of immobilized bacterial cells or enzyme particles into porous containers and placing them in a reactor. This is what we are trying to achieve.
従って、本発明によるノマイオリアクターは、微生物菌
体または酵素を含水ゲルに担持ないし包接させたものの
粒状体の床を内蔵した反応器からなる・Zイオリアクタ
ーにおいて、該粒状体が複数個の多孔容器内に収容され
たもので;l;)ること、を特徴とするものである。Therefore, the bioreactor according to the present invention consists of a reactor containing a bed of granules in which microbial cells or enzymes are supported or included in a hydrogel. It is characterized by being housed in a porous container;
効果
本発明に従って固定化菌体ないし酵素を複数個の多孔容
器に収容して反応器に充填することによって、充填層型
反応器に不可僻であった反応器の圧力1μ失を低くする
ことができるという思いがけない作用によって、充填層
型反応器の圧力損失の増大を防ぎ、高い反応率で長期間
の連続運転を行なうことができるという効果が得られる
〇発明の詳細な説明
含水ゲルに微生物菌体ないし酵素を担持させあるV)は
包接させて固定化したものが公知であることは前記した
ところであるが、それ自身およびその使用の詳細につい
ては各種の放置または総説、たと気ば福井三部、千畑一
部、鈴木周−編「酵素工学」(東京化学同人)、D、W
illiams、 D、M。Effects According to the present invention, by accommodating immobilized bacterial cells or enzymes in a plurality of porous containers and filling them into a reactor, it is possible to reduce the pressure loss of 1 μm in the reactor, which is impossible in a packed bed reactor. This unexpected effect prevents the pressure loss of the packed bed reactor from increasing and enables long-term continuous operation at a high reaction rate.〇Detailed description of the invention As mentioned above, it is known that V) which carries a body or an enzyme is included and immobilized. ``Enzyme Engineering'' (Tokyo Kagaku Doujin), D, W
illiams, D.M.
Munnecke : Biotech、and
B ioeng、 23、 1813− 25(1
981)を参照することができる。Munnecke: Biotech, and
Bioeng, 23, 1813-25 (1
981).
微生物菌体ないし酵素を担持ないし包接した含水ゲルは
粒状体として使用されるが、そのような粒状体の床を内
蔵する反応器からなるバイオリアクターもまた公知であ
る。Hydrogels supporting or encapsulating microbial cells or enzymes are used as granules, and bioreactors comprising reactors incorporating beds of such granules are also known.
本発明で粒状体の床というときは典型的な固定床すなわ
ち充填層型のものの外に流動床であってもよい。反応器
の構造ないし構成を含めてバイオリアクターの詳細につ
いては、上記文献その他を参照することができる。また
、本発明でいう1粒状体」の個々の粒子の形状も合目的
的な任意のものでありうる。1体的には、たとえば、粒
状、柱状(断面は、円形、半円形、方形その他でありう
る)、小嘆片状、短紐状、その他の形状を挙げることが
できる。In the present invention, when referring to a granular bed, a fluidized bed may be used in addition to a typical fixed bed or packed bed type. For details of the bioreactor including the structure and configuration of the reactor, reference can be made to the above-mentioned documents and others. Furthermore, the shape of each particle of the "one granule" as used in the present invention may be any suitable shape. Examples of the shape include granular, columnar (the cross section may be circular, semicircular, rectangular, etc.), flake-like, short string-like, and other shapes.
多孔容器/床の分割
固定化菌体ないし酵素の粒状体からなる床を分割してそ
れぞれを収容すべき多孔容器は、粒状体の通過が不可能
なほど小さくかつ基質容液の通過が可能なほど大きな孔
を有すると共に粒状体を収容した状態で該菌体ないし酵
素による生化学ないし酵素反応に耐えかつこの反応を阻
害しない構造ないし電材の任意のものでありうる。この
容器はその複数個を反応器内に納めてバイオリアクター
を構成するためのものであるから、その形状(複数個の
すべてが同一形状でなくてもよい)はそJlに適したも
のでなげわばならないことはV>うすでもない。Porous container/bed division The porous container in which the bed of immobilized microbial cells or enzyme granules is to be divided and accommodated is so small that the granules cannot pass through, and the substrate solution can pass through. It may have any structure or electrical material that has pores as large as possible and that can withstand biochemical or enzymatic reactions caused by the microbial cells or enzymes while accommodating the granules and does not inhibit this reaction. Since this container is for constructing a bioreactor by housing multiple containers in a reactor, its shape (all containers do not need to be the same shape) must be appropriate for the container. The thing that doesn't matter is V>Uusu.
このようなところから、多孔容器は、ステンレス鋼、ア
ルミニウム等の全域、メタクリル樹脂、ホ蔦ツカ−ボネ
ート、7I?リスチレン、ンJfリオレフイン等のプラ
スチック材、セラミク材、等からなる多孔板あるいは網
で形成されたものが典型的である。そしてその形状は、
筒状(断面は、円形、半円形、四半円形、方形、その他
がある)、球状、半球状、その他がある。From this point of view, porous containers are made of a wide range of materials such as stainless steel, aluminum, methacrylic resin, carbonated carbonate, and 7I? A typical example is a perforated plate or a mesh made of a plastic material such as listyrene or lyolefin, or a ceramic material. And its shape is
There are cylindrical shapes (cross sections include circular, semicircular, quarter circular, square, etc.), spherical, hemispherical, and others.
多孔容器に対する固定化菌体ないし酵素の粒状体の充填
率および反応容器に対する多孔容器の充填率は、任意に
定めることができる。また、多孔容器は相互および反応
器内壁と当接することによって反応器内に固定ないし係
止することも、反応器内に設けた部側によって固定ない
し係止することも、あるいは反応器内で自由に動きうる
よ5にすることも、できる。また基質溶液が粒状体の床
内な効率よく貫流するようにするため、反応器および(
または)粒状体収容容器の内部、外部その他適当な部位
に適当な形状の邪魔板あるいは整流板を設けることもで
きる。The filling rate of the immobilized bacterial cells or enzyme granules to the porous container and the filling rate of the porous container to the reaction container can be arbitrarily determined. In addition, the porous containers can be fixed or locked in the reactor by coming into contact with each other and the inner wall of the reactor, fixed or locked by the side provided in the reactor, or can be fixed or locked freely in the reactor. You can also move to 5. In addition, in order to ensure that the substrate solution flows efficiently through the bed of granules, the reactor and (
Alternatively, a baffle plate or a rectifying plate of an appropriate shape may be provided inside, outside, or other appropriate parts of the granular material storage container.
その他、具体的なことに関しては、後記の実施例を参照
されたい。For other specific details, please refer to Examples below.
実験例
実施例1
第1図(a)に示す様に直径5cmの球状ステンレス鋼
製カザ(網状。網目の大きさ2關X 2 ml )に、
固定化酵母粒状体を充填した。この粒状体は、サツカロ
ミセス・ウノ々ルムを湿重量(水分75%)で16 、
5 W/V%になる様にIW/V%アルギン酸ナトリウ
ムに添加し、これを0.05M塩化カルシウム水溶液中
に滴下して固定化したアルギン酸カル7ウムゲルビーズ
(直径3關)である。これを第1図(blに示す様に、
直径10儂、高さ50cIrLの円筒状カラムに詰めて
(反応器に対する固定化酵母粒状体の充填率50V/’
V%)、加℃で糖度11°Pの麦芽汁を上向流で毎時5
0〜100mjで流したところ、出口(7) :1−1
’ / −k 濃度4〜5 w/’w %、0.02に
9/Cm2(1)圧力損失で定常的に加日間連続運転が
できた。Experimental Examples Example 1 As shown in Figure 1(a), a spherical stainless steel cap (mesh shape, mesh size 2 x 2 ml) with a diameter of 5 cm was placed.
It was filled with immobilized yeast granules. This granular material contains Satucharomyces unonarum with a wet weight (moisture 75%) of 16%,
Calcium alginate gel beads (diameter 3 mm) were added to IW/V% sodium alginate to give a concentration of 5 W/V%, and then dropped into a 0.05 M calcium chloride aqueous solution to be immobilized. As shown in Figure 1 (bl),
Packed into a cylindrical column with a diameter of 10 degrees and a height of 50 cIrL (filling rate of immobilized yeast granules to the reactor was 50 V/'
V%), wort with a sugar content of 11°C at 5°C per hour in an upward flow
When flowing at 0 to 100 mj, outlet (7): 1-1
'/-k concentration of 4 to 5 w/'w %, constant continuous operation for 1 day with a pressure loss of 0.02 to 9/Cm2(1) was possible.
x蔦ノス
第2図(alに示す様に直径7儂、高さ10crrLの
円筒状ステンレス製カザ(網状。網目の大きさ2關×2
龍)の一端に、7ランジ状のジャマ板(外径7.8a、
内径7 cm )をとりつげて、これに実施例1と同様
に調製したアルギン酸カルシウムゲルビーズ(直径31
1I)を充填した。これを第2図(b)に示す様に直径
8cTrL、高さ50αの円筒状カラムに5個直列に詰
めて(反応器に対する固定化酵母粒状体の充填率55V
/’V%)、加℃で10 W/V%シヨ糖液な上向流で
毎時50〜100m1で流したところ、出口のエタノー
ル濃度4〜5W/w%、0 、01 K9/cut2I
J。x Tsuta nosu Figure 2 (As shown in al, a cylindrical stainless steel cap (mesh shape. Mesh size 2 cm x 2
At one end of the dragon, there is a 7-lunge-shaped jammer plate (outside diameter 7.8a,
Calcium alginate gel beads (inner diameter 7 cm) prepared in the same manner as in Example 1 were added to these beads (inner diameter 31 cm).
1I). As shown in Fig. 2(b), five of these were packed in series in a cylindrical column with a diameter of 8 cTrL and a height of 50α (filling ratio of immobilized yeast particles to the reactor was 55V).
/'V%), 10 W/V% sucrose solution was flowed upward at 50 to 100 ml per hour at ℃, the ethanol concentration at the outlet was 4 to 5 W/w%, 0,01 K9/cut2I
J.
下の圧力損失で定常的に14日間連続運転ができた。Steady continuous operation was possible for 14 days with a pressure drop below.
実施例3
第3図(a)に示す様に、縦10cIIL、横1cm、
高さ10儂の直方体状ステンレス鋼製力J(網状。網目
の大きさ2mm X 2 ” )に、実施例1と同様に
調製したアルギン酸カルシウムゲルビーズ(直径3 m
m )を充填した。これを第3図(b)に示す様に縦I
Qcm。Example 3 As shown in Fig. 3(a), the length is 10 cm, the width is 1 cm,
Calcium alginate gel beads prepared in the same manner as in Example 1 (diameter 3 m
m) was filled. This is vertically I as shown in Figure 3(b).
Qcm.
横5 、2儂m、高さ10αの直方体カラムに5個並列
に詰めて(カザ間距離0.24 ) (反応器に対する
固定化酵母粒状体の充填率55 V/V%)、20’C
で糖度11°Pの麦芽汁を上向流で毎時5〜20 tx
tで流したところ、出口のエタノール濃度が4〜5W/
W%、0.01に9/cm2以下の圧力損失で定常的に
加日間連続運転ができた。Five columns were packed in parallel in a rectangular parallelepiped column with a width of 5 m, a height of 10 m, and a height of 10 α.
wort with a sugar content of 11°P in an upward flow of 5 to 20 tx per hour.
When flowing at t, the ethanol concentration at the outlet was 4 to 5 W/
W%, 0.01, and a pressure loss of less than 9/cm2, it was possible to operate steadily for several days.
実施例4
第4図(alに示す様に直径3箔、高さ10crRの円
筒状メタクリル樹脂製容器(多孔状、ノセンチングンー
ト状で直径2111の穴を多数あけたもの)K1固定化
酵紫電状体を充填した。この粒状体は、L−グルタミン
酸膜炭酸紫電(生化学工業(株)製品)50rvを0.
1 M酢酸緩衝液(pH4) 125Il+jK溶解し
、次いでに一カラギーナン159を375酎の水に溶解
してω℃に保温したものと混合し、冷却してからこれに
塩化カリウム0.1W/V%水溶液500itを加えて
ゲル化させ、1辺31IIの立方体に細断した固定化L
−グルタミン酸税炭酸紫電標品である。これを第4図(
b)に示す様に直径9 、5 cWL、高さ10CII
Iの円筒状カラムに7個並列に詰めて(反応器に対する
固定化L−グルタミン酸税炭酸紫電粒状体の充填率45
V/V % )、20 ℃テI W/’V % L
−f /L/ p ミツ酸を含む0.1 M酢酸緩衝液
(pH4)を上向流で毎時5〜213mtで流したとこ
ろ、0.0IKp/cm 9下の圧力4’M失で定常
的に14日間連続運転ができた。Example 4 Figure 4 (As shown in al, a cylindrical methacrylic resin container with a diameter of 3 foils and a height of 10 cr (porous, nocentine-shaped, with many holes of 2111 in diameter)) K1 immobilized fermentation The granules were filled with 50 rv of L-glutamic acid membrane carbonate Shiden (product of Seikagaku Corporation).
Dissolve 1M acetate buffer (pH 4) 125Il+jK, then mix with carrageenan 159 dissolved in 375 liters of water and keep warm at ω℃, cool, and add potassium chloride 0.1W/V% to this. Immobilized L was gelated by adding 500 liters of aqueous solution and chopped into cubes of 31II sides.
- Glutamic acid tax carbonated Shiden standard. This is shown in Figure 4 (
Diameter 9, 5 cWL, height 10CII as shown in b)
7 pieces were packed in parallel in a cylindrical column of I (filling ratio of immobilized L-glutamic acid carbonate purple particles to the reactor was 45
V/V%), 20℃TeI W/'V%L
-f /L/p When a 0.1 M acetate buffer (pH 4) containing mitic acid was flowed upward at a rate of 5 to 213 mt/hour, a constant pressure of 4'M was lost under 0.0 IKp/cm 9. It was possible to operate continuously for 14 days.
比較例
実施例1と同様に調製したアルギン酸カルシウムゲルビ
ーズ(直径3mg+)を実施例2と同様の円筒カラム(
第2図(b))に充填率55 V7V%で充填し、20
℃で糖度11°Pの麦芽汁を上向流で毎時50〜100
rntで流したところ、出口のエタノール濃度は4〜5
W/W%であったが、アルギン酸カルシウムゲルビーズ
はカラム上部に押圧され、これにより変形、圧着化し、
24時間後の圧力損失は2 、 OKy/cm2となり
、運転が不可能となった。Comparative Example Calcium alginate gel beads (diameter 3 mg+) prepared in the same manner as in Example 1 were placed in a cylindrical column (
Fig. 2(b)) was filled with a filling rate of 55 V7V%, and 20
Wort with a sugar content of 11°C in an upward flow of 50 to 100 per hour
When flowing with rnt, the ethanol concentration at the outlet was 4 to 5.
W/W%, but the calcium alginate gel beads were pressed against the top of the column, which deformed and crimped them.
The pressure loss after 24 hours was 2.0Ky/cm2, making operation impossible.
第1〜4図はいずれも本発明ノンイオリアクターの具体
例の説明図である。各図での(alは粒状体収容容器を
、同(b)は粒状体収容容器を反応器内に充填した状態
をそれぞれ示すものである。1 to 4 are explanatory diagrams of specific examples of the non-sulfur reactor of the present invention. In each figure, (al) shows a granule storage container, and (b) shows the state in which the granule storage container is filled in the reactor.
Claims (1)
たものの粒状体の床を内蔵する反応器からなるバイオリ
アクターにおいて、該粒状体が少なくとも2個の多孔容
器内に収容されたものであることを特徴とする、バイオ
リアクター。A bioreactor consisting of a reactor containing a bed of granules in which microbial cells or enzymes are supported or included in a hydrogel, and the granules are housed in at least two porous containers. A bioreactor featuring:
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP18230084A JPS6158581A (en) | 1984-08-31 | 1984-08-31 | Bioreactor |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP18230084A JPS6158581A (en) | 1984-08-31 | 1984-08-31 | Bioreactor |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS6158581A true JPS6158581A (en) | 1986-03-25 |
JPH055470B2 JPH055470B2 (en) | 1993-01-22 |
Family
ID=16115873
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP18230084A Granted JPS6158581A (en) | 1984-08-31 | 1984-08-31 | Bioreactor |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS6158581A (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH02109967A (en) * | 1988-10-20 | 1990-04-23 | Kirin Brewery Co Ltd | Rotary stationary bed-type bioreactor |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS6027698U (en) * | 1983-07-25 | 1985-02-25 | 日東電工株式会社 | enzyme reaction device |
JPS6027699U (en) * | 1983-07-25 | 1985-02-25 | 日東電工株式会社 | Immobilized enzyme container |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS6027699B2 (en) * | 1976-02-23 | 1985-07-01 | 三菱レイヨン株式会社 | Thermosetting coating material |
JPS6027698B2 (en) * | 1976-12-02 | 1985-07-01 | 三菱油化株式会社 | Oil-modified alkyd resin coating composition |
-
1984
- 1984-08-31 JP JP18230084A patent/JPS6158581A/en active Granted
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS6027698U (en) * | 1983-07-25 | 1985-02-25 | 日東電工株式会社 | enzyme reaction device |
JPS6027699U (en) * | 1983-07-25 | 1985-02-25 | 日東電工株式会社 | Immobilized enzyme container |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH02109967A (en) * | 1988-10-20 | 1990-04-23 | Kirin Brewery Co Ltd | Rotary stationary bed-type bioreactor |
Also Published As
Publication number | Publication date |
---|---|
JPH055470B2 (en) | 1993-01-22 |
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