JPH0428349B2 - - Google Patents
Info
- Publication number
- JPH0428349B2 JPH0428349B2 JP11969087A JP11969087A JPH0428349B2 JP H0428349 B2 JPH0428349 B2 JP H0428349B2 JP 11969087 A JP11969087 A JP 11969087A JP 11969087 A JP11969087 A JP 11969087A JP H0428349 B2 JPH0428349 B2 JP H0428349B2
- Authority
- JP
- Japan
- Prior art keywords
- oxygen
- circulating
- air
- compartment
- flow
- 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
Links
- 239000001301 oxygen Substances 0.000 claims abstract description 109
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 109
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 108
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 24
- 229910002092 carbon dioxide Inorganic materials 0.000 claims description 12
- 239000001569 carbon dioxide Substances 0.000 claims description 12
- 239000007789 gas Substances 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 6
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 5
- 238000000855 fermentation Methods 0.000 claims description 5
- 230000004151 fermentation Effects 0.000 claims description 5
- 229910001882 dioxygen Inorganic materials 0.000 claims description 4
- 239000002912 waste gas Substances 0.000 claims description 3
- 238000001514 detection method Methods 0.000 claims description 2
- 239000007788 liquid Substances 0.000 abstract description 9
- 238000007664 blowing Methods 0.000 abstract description 6
- 239000012530 fluid Substances 0.000 abstract description 5
- 239000012531 culture fluid Substances 0.000 abstract description 4
- 230000001052 transient effect Effects 0.000 abstract 1
- 239000003570 air Substances 0.000 description 38
- 239000000243 solution Substances 0.000 description 11
- 230000001580 bacterial effect Effects 0.000 description 10
- 238000005273 aeration Methods 0.000 description 9
- 230000000694 effects Effects 0.000 description 8
- 239000001963 growth medium Substances 0.000 description 5
- 238000013467 fragmentation Methods 0.000 description 4
- 238000006062 fragmentation reaction Methods 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- 238000012258 culturing Methods 0.000 description 3
- 238000005187 foaming Methods 0.000 description 3
- 230000009036 growth inhibition Effects 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000006096 absorbing agent Substances 0.000 description 2
- 238000010564 aerobic fermentation Methods 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 150000002926 oxygen Chemical class 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 229930000044 secondary metabolite Natural products 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/18—Stationary reactors having moving elements inside
- B01J19/1868—Stationary reactors having moving elements inside resulting in a loop-type movement
- B01J19/1875—Stationary reactors having moving elements inside resulting in a loop-type movement internally, i.e. the mixture circulating inside the vessel such that the upwards stream is separated physically from the downwards stream(s)
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0053—Details of the reactor
- B01J19/0066—Stirrers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/18—Stationary reactors having moving elements inside
-
- 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
- C12M27/02—Stirrer or mobile mixing elements
-
- 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
- C12M27/24—Draft tube
-
- 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
- C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
- C12M29/06—Nozzles; Sprayers; Spargers; Diffusers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00049—Controlling or regulating processes
- B01J2219/00051—Controlling the temperature
- B01J2219/00074—Controlling the temperature by indirect heating or cooling employing heat exchange fluids
- B01J2219/00105—Controlling the temperature by indirect heating or cooling employing heat exchange fluids part or all of the reactants being heated or cooled outside the reactor while recycling
- B01J2219/0011—Controlling the temperature by indirect heating or cooling employing heat exchange fluids part or all of the reactants being heated or cooled outside the reactor while recycling involving reactant liquids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Wood Science & Technology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Health & Medical Sciences (AREA)
- Zoology (AREA)
- Biomedical Technology (AREA)
- Sustainable Development (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
Description
【発明の詳細な説明】
［産業上の利用分野］
本発明は、好気的発酵において低剪断力でかつ
比較的低通気量の条件下でも極めて速い酸素移動
をもたらし、その結果高い酸素利用効率が得られ
るとともに、低通気量化により高菌体濃度培養に
おいても発泡現象を回避し得る発酵槽に関する。Detailed Description of the Invention [Industrial Application Field] The present invention provides extremely fast oxygen transfer in aerobic fermentation under conditions of low shear and relatively low aeration, resulting in high oxygen utilization efficiency. The present invention relates to a fermenter that can avoid foaming even in high bacterial cell concentration culture by reducing the amount of aeration.
［従来の技術］
一般的に、好気的発酵、例えば菌体、酸素、ア
ミノ酸、核酸、さらに二次代謝物としての抗生物
質等の生産を目的とする発酵槽において、好気的
代謝に不可欠な酸素は、液中に常時通気される空
気などの酸素含有ガスから発酵液中へ酸素が溶
解、補給されることによりまかなわれる。[Prior art] In general, in aerobic fermentation, for example, in a fermenter for the purpose of producing bacterial cells, oxygen, amino acids, nucleic acids, and antibiotics as secondary metabolites, Oxygen is supplied by dissolving and replenishing oxygen into the fermentation liquid from an oxygen-containing gas such as air that is constantly aerated into the liquid.
近年、生産性を向上させるため高菌体濃度培養
や大量培養が指向されるとともに工業的発酵槽が
大型化する傾向にある。このような発酵槽の場合
は、空気を通気させることにより得られる酸素移
動では高菌体濃度培養等酸素を多量に要求する微
生物の培養において酸素供給が充分とは云えず、
酸素移動律速となり、支障を来す場合が多い。こ
の酸素律速状態を回避するために、従来、攪拌強
度の増加または通気量の増加などの手段が講じら
れてきた。 In recent years, in order to improve productivity, there has been a trend toward high bacterial cell concentration culture and mass culture, and there has been a trend toward larger industrial fermenters. In the case of such a fermenter, the oxygen transfer obtained by aerating the air is not sufficient for culturing microorganisms that require a large amount of oxygen, such as culturing at a high bacterial cell concentration.
Oxygen transfer becomes rate-limiting and often causes problems. In order to avoid this oxygen rate-limiting state, conventional measures have been taken such as increasing the stirring intensity or increasing the amount of aeration.
しかし、菌体の種類によつては高剪断力下にお
いて菌の破断等を起すことがあつた。また、高通
気量下の高菌体濃度培養等では、培養液の粘度上
昇やそれに伴う発泡現象等が発現するという問題
点があり、これらの酸素移動律速回避手段は好ま
しからざる現象を顕現化させる。さらに、発酵槽
の構造を改善し、効率化をはかる試みが行われて
いるが、酸素移動に空気を使用する限り酸素濃度
約21％の制約があるため酸素移動速度には限界が
ある。このため空気のかわりに酸素富化空気を散
気する方法が試みられている。 However, depending on the type of bacterial cells, rupture of the bacteria may occur under high shearing force. In addition, when culturing at a high bacterial cell concentration under a high aeration rate, there is a problem in that the viscosity of the culture solution increases and foaming phenomena occur as a result, and these oxygen transfer rate-limiting avoidance methods make undesirable phenomena manifest. . Furthermore, attempts are being made to improve the structure of fermenters and increase their efficiency, but as long as air is used for oxygen transfer, there is a limit to the oxygen transfer speed due to the oxygen concentration being limited to approximately 21%. For this reason, attempts have been made to diffuse oxygen-enriched air instead of air.
［発明が解決しようとする問題点］
酸素富化空気を散気する方法には、次のような
欠陥がある。すなわち、培養液の液存酸素濃度が
ある一定値を越えると、生産物の収率は逆に低下
する傾向があり、従来の通気量増大等による酸素
移動速度増加手段によつて酸素供給を効果的なら
しめようとすると、かかる増殖阻害を惹起する危
険性が高い。このため、極めて高濃度の酸素含有
ガスの使用は困難で、一般には酸素濃度25乃至40
％の酸素富化空気が用いられている。したがつ
て、酸素移動律速回避手段としてかかる方法が採
られる限り、一定の限定を越えて効果を期待する
ことができないという欠点をもつている。[Problems to be Solved by the Invention] The method of diffusing oxygen-enriched air has the following deficiencies. In other words, when the concentration of liquid oxygen in the culture medium exceeds a certain value, the yield of the product tends to decrease, so it is difficult to effectively increase the oxygen supply by conventional means of increasing the oxygen transfer rate such as increasing the amount of aeration. If you try to make it a target, there is a high risk of causing such growth inhibition. For this reason, it is difficult to use gas containing extremely high concentrations of oxygen, and generally oxygen concentrations range from 25 to 40.
% oxygen enriched air is used. Therefore, as long as such a method is adopted as a means for avoiding the rate-limiting oxygen transfer, it has the disadvantage that it cannot be expected to be effective beyond a certain limit.
本発明は以上の点に鑑み、酸素と空気とをそれ
ぞれ独立に発酵槽に供給し、前記障害を起こさ
ず、低剪断力、低通気量の条件下においても高酸
素移動速度をもたらし、高菌体濃度培養等にみら
れる酸素移動律速状態に至ることを回避できるの
みならず、発泡現象をも起さない培養を可能とす
る発酵槽を提供する。 In view of the above points, the present invention supplies oxygen and air independently to the fermenter, does not cause the above-mentioned troubles, provides a high oxygen transfer rate even under conditions of low shear force and low aeration rate, and has a high bacterial content. To provide a fermenter which not only can avoid reaching the rate-limiting state of oxygen transfer seen in cell concentration culture, but also enables culture without causing a foaming phenomenon.
［問題点を解決するための手段］
上記問題点を解決するため本発明は次のような
構成を採用した。すなわち、本発明にかかる発酵
槽は、槽内を上向流を形成する区画室と下向流を
形成する区画室に区分し、これら両室を上下両端
部で互いに連通させて循環流路を形成するととも
に、前記上向流を形成する区画室の底部に空気を
噴出する空気噴出ノズルを設け、前記下向流を形
成する区画室の底部には酸素を噴出する酸素噴出
ノズルを設けたことを特徴としている。この発酵
槽に、溶存酸素計または廃ガスラインの酸素分析
計もしくは炭酸ガス分析計等の検出手段を備え、
酸素要求の低い初期工程または後期工程では供給
酸素ガス量を減少させるように制御する制御装置
を設けておけば更に効果的である。[Means for Solving the Problems] In order to solve the above problems, the present invention employs the following configuration. That is, in the fermenter according to the present invention, the inside of the tank is divided into a compartment that forms an upward flow and a compartment that forms a downward flow, and these two chambers are communicated with each other at both upper and lower ends to form a circulation flow path. At the same time, an air jet nozzle for jetting air is provided at the bottom of the compartment forming the upward flow, and an oxygen jet nozzle for spouting oxygen is provided at the bottom of the compartment forming the downward flow. It is characterized by This fermenter is equipped with a detection means such as a dissolved oxygen meter, a waste gas line oxygen analyzer, or a carbon dioxide gas analyzer,
It is more effective if a control device is provided to reduce the amount of oxygen gas to be supplied in the initial step or later step where oxygen demand is low.
本発明の最も特徴とするところは、前記循環流
を生ぜしめ、この循環流に対向して酸素が供給す
る酸素供給装置を具備するところにある。循環流
に対向して酸素が供給されることによつて、極め
て大きい酸素移動速度が得られる。この効果は酸
素射出部の著しい乱れの発生に伴い、酸素と培養
液とのより好適な細分化と接触を惹起し、その結
果として速い酸素移動をもたらすものと考えられ
る。就中前記の如く上向流区画室と下向流区画室
を設け、より好適に培養液を回流させ、後者の下
端部に前記酸素供給装置を設けて、下向きの回流
に対向して酸素を射出させる場合には、前記の循
環流と対向することによつて生ずる好適な細分化
と接触するのみならず、下向流による抵抗によつ
て多数の酸素の気泡が下向流区画室内にホールド
アツプされることにより、気泡の滞留時間が増加
することに起因するものとみられる高酸素移動速
度と高酸素利用率が得られるのでより好ましい。 The most distinctive feature of the present invention is that it is provided with an oxygen supply device that generates the circulation flow and supplies oxygen in opposition to the circulation flow. By supplying oxygen against the circulation flow, extremely high oxygen transfer rates are obtained. This effect is thought to be due to the occurrence of significant turbulence at the oxygen injection part, which induces more suitable fragmentation and contact between oxygen and the culture medium, resulting in rapid oxygen transfer. In particular, as described above, an upward flow compartment and a downward flow compartment are provided to circulate the culture solution more preferably, and the oxygen supply device is provided at the lower end of the latter to counter the downward circulation and supply oxygen. When injecting, not only do they come into contact with the suitable fragmentation caused by opposing the circulating flow, but also a large number of oxygen bubbles are held in the downward flow compartment by the resistance of the downward flow. This is more preferable because a high oxygen transfer rate and a high oxygen utilization rate, which are considered to be caused by an increase in the residence time of bubbles, can be obtained by increasing the air bubbles.
本発明において、槽内の液を循環させる循環手
段として前述の空気の射出によるエアーリフトを
採用する場合には、上述の効果に加えて下記の如
き効果を奏するのでより好適である。すなわち、
酸素と空気の二種の流体からそれぞれ酸素移動が
行われるので、仮りに溶存酸素濃度がたとえば空
気散気に対応する飽和溶存濃度以上となり、菌体
の増殖阻害が生じるとしても、通気されている空
気によつて余剰溶存酸素は速やかに放散されるた
め、増殖阻害が培養に支障を来たす程度に顕現す
るのを防止できる。 In the present invention, when the above-mentioned air lift by injecting air is employed as the circulation means for circulating the liquid in the tank, it is more suitable because the following effects are produced in addition to the above-mentioned effects. That is,
Since oxygen is transferred from two types of fluids, oxygen and air, even if the dissolved oxygen concentration exceeds the saturated dissolved concentration corresponding to air aeration and inhibits the growth of bacterial cells, it is still aerated. Since the excess dissolved oxygen is quickly dissipated by air, growth inhibition can be prevented from manifesting to the extent that it interferes with culture.
攪拌機等の機械的循環手段を採る場合において
も、同様の理由からそれぞれ独立に供給される酸
素と空気の二流体を用いて酸素移動を行わせるこ
とが望ましい。 Even when using mechanical circulation means such as a stirrer, it is desirable to transfer oxygen using two fluids, oxygen and air, which are supplied independently for the same reason.
前述の如く、本発明により高酸素移動速度が得
られる結果、低通気量、低剪断力のもとでより好
適に培養を行うことができる。また高い酸素利用
率が得られるので、培養時に消費される量とほぼ
同量の酸素のみを供給して培養を行うことも、二
酸化炭素濃度増加に伴う阻害現象が生じない培養
においては可能となる。なお培養時に発生する二
酸化炭素濃度は、エタノール資化性菌、アミノ酸
生成菌などのように溶存酸素と同様の阻害作用を
示す場合があるが、この場合には該阻害作用を防
止するに足る量の空気を前記酸素と別個独立に併
せて発酵槽下部より供給することで対処すること
ができる。 As described above, as a result of the high oxygen transfer rate obtained by the present invention, culture can be performed more suitably under low aeration rate and low shear force. In addition, since a high oxygen utilization rate can be obtained, it is possible to perform culture by supplying only the same amount of oxygen as is consumed during culture, as long as the inhibition phenomenon associated with increased carbon dioxide concentration does not occur. . Note that the concentration of carbon dioxide generated during culture may exhibit an inhibitory effect similar to dissolved oxygen, such as in ethanol-assimilating bacteria and amino acid-producing bacteria, but in this case, the concentration of carbon dioxide generated during culture may be sufficient to prevent this inhibitory effect. This can be solved by supplying air from the lower part of the fermenter together with the oxygen.
さらに、高酸素移動速度に起因して大きい応答
速度が得られるため、溶存酸素濃度の制御も容易
となり、過剰酸素濃度の状態に至ることもなく前
記増殖阻害も容易に回避できる。 Furthermore, since a high response speed can be obtained due to the high oxygen transfer rate, it becomes easy to control the dissolved oxygen concentration, and the above-mentioned growth inhibition can be easily avoided without reaching a state of excessive oxygen concentration.
空気の射出による培養液循環手段を採る場合に
は、培養時に消費される量の酸素を供給し、排気
流中の二酸化炭素を吸収装置または吸着装置等、
公知の二酸化炭素除去装置で除去することによつ
て空気流を循環再使用できるが、この際循環空気
流中の酸素の顕著な増加をもたらさず空気中に於
けると同程度の酸素濃度を維持できるので好適で
ある。 When adopting culture medium circulation means by injecting air, supply oxygen in the amount consumed during culture, and use an absorber or adsorption device to absorb carbon dioxide in the exhaust stream.
The air stream can be recycled and reused by removing it with a known carbon dioxide removal device, but this does not result in a significant increase in oxygen in the recycled air stream and maintains the same oxygen concentration as in air. This is suitable because it can be done.
［作用］ 培養液及び菌体への酸素供給能力は dC／dt＝KLa（C*−Ｃ）−QO2Ｘ で表わされる式によつて決る。[Effect] The ability to supply oxygen to the culture solution and bacterial cells is determined by the formula: dC/dt=K La (C * - C) - Q O2 X.
Ｃ：溶存酸素濃度（ｍ・mo102／１）
ｔ：時間（ｈ）
KLa：培養液の酸素移動容量係数（h-1）
C*：飽和溶存酸素濃度（ｍ・mo102／１）
QO2：細胞の酸素の比消費速度（ｍ・mo102／
ｇ・ｈ）
Ｘ：細胞濃度（ｇ／１）
そして（C*−Ｃ）は酸素濃度が大であるほど
大きくなる。酸素を循環流に対向させて単独また
は別個に供給される空気とともに両者独立に供給
するときには、（C*−Ｃ）の増大に起因する酸素
の効率的溶解のみならず、前述した如く、酸素の
射出部における著しい乱れに伴つて生じる好適な
酸素気流の細分化と培養液との接触が得られる。
さらに前述の下向流区画室下端部に下向流に対向
して酸素を射出させる場合には、著しい酸素気泡
のホールドアツプの増加等に起因するものと考え
られる極めて高い酸素移動速度が得られる。 C: Dissolved oxygen concentration (m・mo10 2 /1) t: Time (h) K La : Oxygen transfer capacity coefficient of culture solution (h -1 ) C * : Saturated dissolved oxygen concentration (m・mo10 2 /1) Q O2 : Cellular oxygen specific consumption rate (m・mo10 2 /
g・h) X: Cell concentration (g/1) And (C * -C) increases as the oxygen concentration increases. When oxygen is supplied independently with air that is supplied either alone or separately in opposition to the circulating flow, not only is there an efficient dissolution of oxygen due to an increase in (C * -C), but also an increase in oxygen dissolution as described above. A favorable fragmentation of the oxygen stream and contact with the culture medium is obtained due to significant turbulence at the injection site.
Furthermore, when oxygen is injected into the lower end of the downward flow compartment mentioned above in opposition to the downward flow, an extremely high oxygen transfer rate can be obtained, which is thought to be due to a significant increase in the hold-up of oxygen bubbles. .
酸素のみを発酵槽に導入する場合のみならず、
酸素と空気を予め混合することなく両者独立に培
養液中に導入する場合においても（C*−Ｃ）の
増大に起因する酸素移動速度の増大効果を享受で
きるのは、両流体気泡相互の合一等が予想に反し
起こり難いことによるものとみられる。 Not only when introducing only oxygen into the fermenter,
Even when oxygen and air are introduced into the culture medium independently without being mixed in advance, the effect of increasing the oxygen transfer rate due to the increase in (C * - C) can be enjoyed because of the interaction of the bubbles of both fluids. This appears to be due to the fact that the first prize is unlikely to occur, contrary to expectations.
［実施例］
第１図、第２図に本発明の発酵槽の実施例を示
し、これに基いて本発明をより詳しく具体的に説
明する。[Example] Figures 1 and 2 show examples of the fermenter of the present invention, and the present invention will be specifically explained in more detail based on the examples.
第１図は発酵装置を示し、１が密閉式の発酵槽
でパイプ８および９から基質、工程水、菌体、栄
養剤等からなる培養液Ａをその液面上部に気体空
間Ｂが存在する状態で収納すべく構成されてい
る。槽内部には、それぞれ上端部および下端部で
互に連結した上向流区画室１５と下向流区画室１
４が槽１と同軸的に設けられたドラフト円筒２に
よつて形成されている。槽内の培養液Ａに循環流
を与えるための空気噴射ノズル６が上向流区画室
１５の下端部に設けられ、これに無菌空気導入管
１１および空気濾過器５が接続されている。空気
噴射ノズル６からの空気の噴出により、前記培養
液Ａを上向流区画室１５内を上方へ、次いで反転
して下向流区画室１４内を下方へ回流すべく循環
手段が構成されている。酸素を供給するための噴
出ノズル７が、下向流区画室１４の下端部に循環
液に対向して設けられ、対向噴出によつてもたら
される細分化に加え培養液Ａの下向き循環流れに
よつて浮上しようとする酸素を細分化する状態で
抑えて、ホールドアツプを大きく保持しながら気
泡状酸素を下向流区画室１４に滞留させつつ培養
液中に溶解させるべく、酸素供給装置が構成され
ている。下向流区画室１４を経て供給された酸素
の大部分は消費されるが、なお消費されずに残存
する酸素は前記密閉構成の気体空間Ｂにてエアー
リフト用空気と合体し、培養中発生する炭酸ガス
と共に管１６を経て排気されるように構成されて
いる。要すれば、該排気は二酸化炭素の吸収装置
または吸着装置を経て炭酸ガスを除去し、管１１
へ接続、循環使用する如く構成される。 Fig. 1 shows a fermentation apparatus, in which 1 is a closed fermenter, in which a culture solution A consisting of substrates, process water, bacterial cells, nutrients, etc. is passed through pipes 8 and 9, and a gas space B exists above the liquid level. It is configured to be stored in the same condition. Inside the tank, there are an upward flow compartment 15 and a downward flow compartment 1 connected to each other at the upper and lower ends, respectively.
4 is formed by a draft cylinder 2 provided coaxially with the tank 1. An air injection nozzle 6 for providing a circulating flow to the culture solution A in the tank is provided at the lower end of the upward flow compartment 15, and a sterile air introduction pipe 11 and an air filter 5 are connected to this. A circulation means is configured to cause the culture solution A to flow upwardly in the upward flow compartment 15 and then reversed and circulated downward in the downward flow compartment 14 by blowing air from the air injection nozzle 6. There is. A jet nozzle 7 for supplying oxygen is provided at the lower end of the downward flow compartment 14 facing the circulating fluid, and in addition to the fragmentation brought about by the counter jet, the downward circulating flow of the culture fluid A is also provided. The oxygen supply device is configured to suppress the oxygen that tends to rise to the surface in a fragmented state, maintain a large hold-up, and dissolve the bubbly oxygen into the culture solution while retaining it in the downward flow compartment 14. ing. Most of the oxygen supplied through the downward flow compartment 14 is consumed, but the remaining unconsumed oxygen is combined with the air lift air in the airtight gas space B, and is generated during cultivation. It is configured to be exhausted through a pipe 16 along with carbon dioxide gas. If necessary, the exhaust gas is passed through a carbon dioxide absorber or adsorption device to remove carbon dioxide gas and
It is configured so that it can be connected to and used cyclically.
供給管１０からの酸素の供給量やエアーリフト
用空気による循環回流速度の調整により、前記下
向流区画室１４における気泡状の酸素の滞留時間
を制御することができる。 By adjusting the amount of oxygen supplied from the supply pipe 10 and the circulation rate of the air for air lift, the residence time of the bubble-like oxygen in the downward flow compartment 14 can be controlled.
３は、培養液に発生する熱を培養液を送液ポン
プ４で外部循環し、除去するために設けられた熱
交換器である。 Reference numeral 3 denotes a heat exchanger provided to remove heat generated in the culture solution by circulating the culture solution externally using the liquid feed pump 4.
第２図は、上向流区画室および下向流区画室を
前記ドラフト円筒等の隔壁を設けずに構成された
実施例を示す。電動機１７に連結され駆動される
攪拌機１８で構成された循環手段で槽中央部近傍
に下向流、槽壁部に上向流を発生させ、管１０を
経て槽中央部近傍に設けられた噴出ノズル７から
酸素が下向流に抗して噴出される。槽下部には、
上向流を増強し、前記二酸化炭素による阻害現象
を回避するため管１１を経て供給される空気を噴
出するためのノズル６が設けられている。 FIG. 2 shows an embodiment in which the upward flow compartment and the downward flow compartment are constructed without providing a partition wall such as the draft cylinder. A circulating means composed of an agitator 18 connected to and driven by an electric motor 17 generates a downward flow near the center of the tank and an upward flow on the wall of the tank. Oxygen is ejected from the nozzle 7 against the downward flow. At the bottom of the tank,
A nozzle 6 is provided for blowing out the air supplied via the tube 11 in order to enhance the upward flow and avoid the inhibition phenomenon due to said carbon dioxide.
なお、上記各実施例において、酸素ガスの流量
を溶存酸素計または廃ガスラインの酸素分析計も
しくは炭酸ガス分析計によつて制御する制御装置
を設けることにより、発酵工程の初期や後期の酸
素要求の低い段階では酸素ガスの供給を制限又は
停止して主に空気散気による酸素供給を行なうこ
ととすれば、より経済的な運転を行なうことがで
きる。 In each of the above embodiments, by providing a control device that controls the flow rate of oxygen gas using a dissolved oxygen meter, an oxygen analyzer in the waste gas line, or a carbon dioxide gas analyzer, the oxygen demand at the early and late stages of the fermentation process can be adjusted. If the supply of oxygen gas is limited or stopped at a low stage and oxygen is supplied mainly by air aeration, more economical operation can be achieved.
［発明の効果］
本発明にかかる発酵槽は、空気と酸素を予め混
ざりあわないように槽内に導き、空気を主として
上向流の形成に使用し、酸素を循環流に対向する
ように噴出するので、撹拌動力を節約し、酸素の
液中への移動を効率よく行わせることが可能とな
り、しかも酸素供給量の制御を容易に行うことが
可能となつた。この効果に起因して低通気量化、
低剪断力下でも好適な酸素移動が可能となる。[Effects of the Invention] The fermenter according to the present invention introduces air and oxygen into the tank so that they do not mix in advance, uses the air mainly to form an upward flow, and blows out oxygen in a direction opposite to the circulating flow. Therefore, it has become possible to save stirring power, to efficiently transfer oxygen into the liquid, and to easily control the amount of oxygen supplied. Due to this effect, the amount of airflow is reduced,
Suitable oxygen transfer is possible even under low shear force.
本発明の発酵槽は、上記効果を発現し高生産
性、高酸素利用率で培養を行うことができる経済
性の高い発酵槽となつている。 The fermenter of the present invention exhibits the above-mentioned effects and is a highly economical fermenter that can perform culture with high productivity and high oxygen utilization rate.
第１図は本発明の１実施例の構成説明図、第２
図は、異なる実施例の構成説明図である。
Ａ……培養液、Ｂ……槽上部空間、１……発酵
槽、２……ドラフト円筒、６……空気噴出ノズ
ル、７……酸素噴出ノズル、１７……電動機、１
８……攪拌翼。
FIG. 1 is an explanatory diagram of the configuration of one embodiment of the present invention, and FIG.
The figure is a configuration explanatory diagram of a different embodiment. A...Culture solution, B...Tank upper space, 1...Fermentation tank, 2...Draft cylinder, 6...Air jet nozzle, 7...Oxygen jet nozzle, 17...Electric motor, 1
8... Stirring blade.
Claims (1)
成する区画室に区分し、これら両室を上下両端部
で互いに連通させて循環流路を形成するととも
に、前記上向流を形成する区画室の底部に空気を
噴出する空気噴出ノズルを設け、前記下向流を形
成する区画室の底部には酸素を噴出する酸素噴出
ノズルを設けたことを特徴とする発酵槽。 ２ 溶存酸素計または廃ガスラインの酸素分析計
もしくは炭酸ガス分析計等の検出手段を備え、酸
素要求の低い初期工程または後期工程では供給酸
素ガス量を減少させるように制御する制御装置が
設けられている特許請求の範囲第１項記載の発酵
槽。[Scope of Claims] 1. The inside of the tank is divided into a compartment chamber forming an upward flow and a compartment chamber forming a downward flow, and these chambers are communicated with each other at both upper and lower ends to form a circulation flow path. , an air jet nozzle for jetting air is provided at the bottom of the compartment forming the upward flow, and an oxygen jet nozzle for jetting oxygen is provided at the bottom of the compartment forming the downward flow. fermentation tank. 2. Equipped with a detection means such as a dissolved oxygen meter or an oxygen analyzer or a carbon dioxide gas analyzer in the waste gas line, and a control device that controls the amount of supplied oxygen gas to be reduced in the initial process or late process where oxygen demand is low. A fermenter according to claim 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11969087A JPS63283570A (en) | 1987-05-15 | 1987-05-15 | Fermenter |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11969087A JPS63283570A (en) | 1987-05-15 | 1987-05-15 | Fermenter |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63283570A JPS63283570A (en) | 1988-11-21 |
| JPH0428349B2 true JPH0428349B2 (en) | 1992-05-14 |
Family
ID=14767645
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP11969087A Granted JPS63283570A (en) | 1987-05-15 | 1987-05-15 | Fermenter |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS63283570A (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8811114D0 (en) * | 1988-05-11 | 1988-06-15 | Ici Plc | Fermentation process & apparatus |
| US5798254A (en) * | 1996-09-13 | 1998-08-25 | Praxair Technology, Inc. | Gas driven fermentation method using two oxygen-containing gases |
| US5939313A (en) * | 1997-09-12 | 1999-08-17 | Praxair Technology, Inc. | Stationary vortex system for direct injection of supplemental reactor oxygen |
| HU230026B1 (en) | 2000-10-19 | 2015-05-28 | Lesaffre Et Compagnie | Aerobic fermentation method |
| EP1773976B2 (en) * | 2004-06-04 | 2020-01-01 | Global Life Sciences Solutions USA LLC | Disposable bioreactor systems and methods |
| JP2006121954A (en) * | 2004-10-28 | 2006-05-18 | Japan Science & Technology Agency | Method for producing enzyme degradation product |
| JP6487325B2 (en) * | 2012-10-08 | 2019-03-20 | キャリスタ， インコーポレイテッド | GAS-FED fermentation system |
-
1987
- 1987-05-15 JP JP11969087A patent/JPS63283570A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS63283570A (en) | 1988-11-21 |
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