CN106434414A - Online pH change rate monitoring based HCDC (high cell density cultivation) method for lactic acid bacteria - Google Patents
Online pH change rate monitoring based HCDC (high cell density cultivation) method for lactic acid bacteria Download PDFInfo
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Abstract
The invention particularly discloses an online pH change rate monitoring based HCDC (high cell density cultivation) method for lactic acid bacteria. The method comprises steps as follows: S1, strains are cultured in a fermentation tank equipped with a pH sensor and a lye fed-batch system; S2, during culture, pH in the fermentation process keeps stable by the pH sensor and the lye fed-batch system; S3, in the culture process of S2, the lye fed-batch system is stopped at set intervals, and the pH change rate of a fermentation liquid over a period of time is measured by the pH sensor, so that the pH change rate is measured; S4, the proliferation stage of lactic acid bacteria, the supplementing time and canning time during HCDC of the lactic acid bacteria are judged according to the change trend of pH change rate obtained in S3. The method can avoid pollution caused by on-line sampling and is not limited by components of a medium, result lagging caused by measurement of the number of viable bacteria is avoided, and accordingly, the method has the advantages of being convenient, visual and real-time and can be applied in HCDC of the lactic acid bacteria.
Description
Technical field
The present invention relates to bioprocess controls and optimizes engineering field, in particular it relates to a kind of become based on on-line monitoring pH
The lactic acid bacteria high-cell-density cultivation method of rate.
Background technology
At present, lactic acid bacteria and its fermentation have become as the core of fermented dairy product and other fermented foods.Meanwhile, lactic acid
Some bacterial strains in bacterium, because it is to healthy and helpful and be referred to as " probio " by hat, answer apparatus in bread and cheese and health food
There are bright prospects.In recent years, the product with lactic acid bacteria/probiotic beverage as main carriers is just gradually being broken through in China lactic acid bacteria market
General layout, the product of the diversification such as baby milk powder, pickles, candy, cheese, probiotics preparation will open up the new market space.I
Continuous 3 annual growths of state lactic acid bacteria/probio industry, more than 25%, are the industries of Fast Growth.Global lactic acid bacteria/benefit at present
Raw bacterium industry production value is 30,000,000,000 dollars.Therefore, lactic acid bacteria powder, as the biological product of high added value, has considerable society
Can economic benefit and good ecological benefits.
Either as throw type leaven（direct vat set, DVS）Or the lactic acid bacteria as raw materials for production
Powder, the final goal that it produces is to obtain highly active lactic acid bacteria concentrate.And reach height during lactic acid bacteria Multiplying culture
Cell density is cultivated（high cell density cultivation, HCDC）, then it is to prepare high-activity lactic acid bacteria concentrate
The most important condition and the most important thing.
The production model of high-cell-density cultivation have in batches, feed supplement and continuous send out three kinds.The industrial production of lactic acid bacteria at present
On, mainly adopt fed-batch culture technology, its core is the supply mode of nutriment and the maintenance of optimal yeastiness,
Suppression production concentration can be made to be controlled by controlling feed rate, thus improving cell concentration.Meanwhile, the method is simple, raw
Produce potentiality high.Therefore, for fed-batch culture technology, its crucial control point is to determine feed supplement time, highest cell
Density moment, fermentation termination.Also imply that during peak and need thalline is put because the cell density in nutrient solution reaches
Tank and collection, thus the highest cell density moment can consider and be equal to fermentation termination.If in addition, being related to fermentation in industrial production
Scale is amplified step by step in addition it is also necessary to determine the culture transferring time.In recent years, fed-batch culture Control Cooling mainly includes parameter preset
Nonfeedback control feed supplement and feedback control feed supplement.The former includes fed-batch, constant speed feed supplement, speed change feed supplement and index feed supplement etc.
Feed rate control method；The latter is the feed process of more advanced tool feedback control system, reversed between being further subdivided into
Feedback control, including based on dissolved oxygen constant, pH is constant, CO2The indirect feedback of rate of release and cell concentration controls and is based on bottom
The direct feedback of thing concentration controls.
Realize the optimal control of lactic acid bacteria incubation, give full play to the potentiality of bacterial classification, be High Density Cultivation technology
High boundary.But the bioprocess of bacterial strain propagation often will be related to hundreds and thousands of physical processes and chemistry is anti-in incubation
Should, the complexity of bacterium cellular biochemical variable detection, so that some important parameters in incubation is automatically controlled far from meeting fermentation
Requirement.Therefore, there is following characteristics and problem in lactic acid bacteria high-density culture process：
（1）Kinetic model is in the non-linear of height, and typically common bacterial strain propagation will be adjusted phase, logarithmic phase, stationary phase
And decline phase（As shown in Figure 1）.
This curve the affecting of culture process also to be subject in incubation, as kept pH constant to bacterial strain different times
Impact is different；As feed supplement causes quadratic logarithm or multiple logarithmic phase, and for example after bacterial strain activation inoculation, bacterial strain propagation may transition
Spending adjustment period is directly entered logarithmic phase etc.；
（2）With the difference of bacterial strain or condition of culture or batch fermentation, the kinetic parameters of process usually come and go, and are in
Now strong time variation feature, even cannot be carried out quantitative for some bioprocess with Mathematical Modeling to dynamic characteristic
Description；
（3）Except some simple physics and chemical state variable, outside temperature, pH, pressure, partial pressure, oxyty, absolutely
Most of biological aspect variables（As biomass, nutrient concentrations, Metabolites Concentration, biologically active etc.）, it is to be difficult to online
Measurement.Although the developing rapidly so that the on-line measurement of some biological aspects becomes of bioelectrode and sensor technology in the last few years
For may, but the factor such as measurement noise, stability, harsh Operation and Maintenance condition, price still governs them actual raw
Application in product；
（4）Finally, due to being related to many physical processes and chemical reaction, its role and influence each other must for bioprocess
So create the feature that the speed of response is slow, on-line measurement is with significantly time lag of bioprocess.
The above-mentioned characteristic of the bioprocess of bacterial strain propagation is so that the Traditional control based on linear kinetic model is managed with optimizing
By the requirement being difficult in adapt to and meeting bioprocess control and optimization.
High Density Cultivation for the purpose of bacterial strain propagation, biomass（biomass）Be most important be also the most direct result
Index.This index is mainly offline inspection at present, and most common off-line checking method is dry cell weight method, microscopic counting
Method, optical densitometric method（OD）And viable bacteria counting method.In these methods, dry cell weight method, microscope count method and optical densitometric method are all no
Method makes a distinction to strain whole-cell and bacterial strain living cells, and gained biomass is not effective biomass；Dry cell weight method and light
Densimetry is affected significantly by medium component, and reliability is unstable.Viable bacteria counting method, as colony counting method are although accuracy
Height, takes oversize, needs 48-72h could obtain count results.Optical densitometric method also can achieve the on-line monitoring of biomass sometimes,
But it is affected by the impact such as culture medium turbidity, fluorescence, viscosity, impedance, temperature and limit.For example online laser nephelometer is easily subject to
Bubble in zymotic fluid is to measurement signal disturbance, thus affecting accuracy and the reliability measuring.Therefore, biomass is direct
On-line checking, is still difficult to application during all important industrial fermentations at present.
Meanwhile, in actual production, offline inspection needs on-line period.Close envelope because fermentation tank is in incubation
State, if be constantly measured by sampling by sample tap, not only complex operation, and because tank internal gas pressure balances ability discharging, just
Air must be passed through in tank, this is easily caused miscellaneous bacteria and invades therewith and pollutes, and pollute and cause in microorganism culture industry
Loss and harm the hugest.Meanwhile, workman is had high demands, need expertly to carry out loaded down with trivial details sterilizing sampling sterilizing behaviour
Make, the careless slightly risk just having microbiological contamination and pressure inside the tank mutation, these risks increase with the increase of the sampling frequency.Therefore
Need to find a kind of new, safely and effectively parameter to be weighing the proliferative conditions of bacterial strain in fermentation tank.
Content of the invention
The present invention is directed to above-mentioned the deficiencies in the prior art, provides a kind of lactic acid bacteria based on on-line monitoring pH rate of change high thin
Born of the same parents' density cultural method.
The above-mentioned purpose of the present invention is achieved by the following technical programs.
A kind of lactic acid bacteria high-cell-density cultivation method based on on-line monitoring pH rate of change, specifically includes following steps：
S1. lactic acid bacteria high-cell-density cultivation is carried out using the fermentation tank equipped with pH sensor and alkaline stream adding system；
S2. pass through pH sensor in incubation and alkaline stream adding system keeps the pH of lactic acid bacteria culture solution in fermentation tank stable；
S3. in the incubation of step S2, close alkaline stream adding system every 0.5h～1.0h, stop alkaline stream and add, thus
Measure pH rate of descent, measure and restart alkaline stream adding system after terminating；
S4. during the variation tendency of the pH rate of descent according to S3 gained judges lactic acid bacteria high-cell-density cultivation, lactic acid bacteria increases
Grow situation, and then judge the batch feeding time, spend kind of the time and put the tank time.
Preferably, described alkaline stream adding system is the auto-feeding alkali lye pH control system being associated with pH setting value.
Preferably, described alkali lye is 25% (w/w) ammonia spirit, 20～25% (w/w) NaOH solution, 20～25% (w/w)
Na2CO3Solution or 20～25% (w/w) (NH4)2CO3Solution.
Preferably, the pH stability range in described step S2 is 5.7～6.0.
Preferably, described lactic acid bacteria strains are Lactobacillus plantarum（Lactobacillus plantarum）, rhamnose breast
Bacillus（Lactobacillus rhamnosus）Or animal bifidobacteria（Bifidobacterium animalis）.
Preferably, in step S3, the computing formula of pH rate of descent is：
；
pH1：The pH of nutrient solution when timing initiates；
pH2：The pH of nutrient solution at the end of timing；
t：Timing duration/min；
PH rate of descent：pH/min.
Preferably, the variation tendency according to pH rate of descent described in step S4 refers to judging lactic acid bacteria proliferative conditions：Work as bacterium
When strain propagation is in the lag phase, the pH decline rate score of bacterial strain is very low and increasess slowly；When strain culturing is in logarithmic phase, bacterium
Rate score is higher and rapid development for the pH change of strain.
Preferably, when judging the batch feeding time, spend kind of the time and put tank according to described pH rate of descent described in step S4
Between refer to：, when adjustment period, bacterial strain propagation is slow, and metabolic rate is low, few using the carbon source in culture medium, Lactic Acid Secretion for bacterial strain
Less, pH in culture medium fall off rate and amplitude are few, and alkali lye magnitude of recruitment is few；
A kind of lactic acid bacteria high-cell-density cultivation method based on on-line monitoring pH rate of change that the present invention provides, is based on so
Design：In logarithmic phase, bacterial strain increases rapidly bacterial strain, and metabolism is vigorous, is promptly entered using the carbon source in culture medium and nitrogen source
Line splitting is bred, and Lactic Acid Secretion amount is many, and pH in culture medium fall off rate and amplitude all constantly increase, and alkali lye magnitude of recruitment also increases therewith
Increase soon；In stationary phase, bacterial strain division growth quantity is equal to decline The dead quantity, therefore living cells quantity stable, overall generation
Thank to speed and pH fall off rate is stable；In decline phase, number of viable drastically declines, and bacterial strain metabolic capability weakens, acid producing ability
Decline, pH fall off rate and amplitude diminish, and alkali lye magnitude of recruitment also tails off.
Therefore, pH is combined with time parameter, using simplest switch（on-off）The means controlling, can controlling
To calculate the product acid situation of the lactic acid bacteria in certain time point nutrient solution thus reflecting that the proliferative conditions of bacterial strain and metabolism are lived
Power, i.e. pH fall off rate.
Further, pH fall off rate be can be used for fed-batch culture control as a kind of indirect feedback, pass through
PH rate of descent to set the feed supplement time and to put the tank time to judge bacterial strain propagation logarithmic phase and the flex point of stationary phase.
The present invention compared with prior art, has the advantages that：
（1）Intuitively real-time：1. need 48-72h compared to viable bacteria counting method, using calculating and the monitoring of pH rate of descent, Ke Yi
Line reflects the proliferative conditions of lactic acid bacteria strains during lactic acid bacteria high-cell-density cultivation in real time；Can accurately, immediately sentence
Disconnected feed supplement time, mistake are planted the time and are put the main technologic parameters such as tank time, it is to avoid because carbon source deficiency causes bacterial strain to fail, bacterium
Strain vigor and viable bacteria amount decline；3. effectively shorten incubation time, it is to avoid consumption and energy consumption when causing Operation delay to bring, save and produce
Cost, improve production efficiency.
（2）Reliable and stable：1. pH sensor have developed into ripe, measured value be not subject to culture medium temperature, turbidity, viscosity etc. refer to
Mark impact, applied widely；2. the sensing equipment of pH and time and human error are all less, and measured value accuracy and reliability are equal
Higher；3. what the method reflected is the metabolic condition of viable bacteria, and the bacterium cell that do not become feeble and die is affected.
（3）Portable safety：1. adopt calculating and the monitoring of pH rate of descent, skip the sampling link of conventional monitoring, permissible
Substantially reduce and in sweat, sample the risk polluting；2. also reduce manually loaded down with trivial details operation simultaneously, more convenient.
Brief description
Fig. 1 bacterial strain growth curve figure.
Viable count and pH rate of descent change curve in Fig. 2 incubation.
Fig. 3 20L seed tank culture stage pH rate of change.
Fig. 4 200L fermentation tank culture stage pH rate of change.
Fig. 5 500L seed tank culture stage pH rate of change.
Fig. 6 1500L fermentation tank culture stage pH rate of change.
Fig. 7 10L anaerobic fermentation tank cultivation stage pH rate of change.
Specific embodiment
With reference to Figure of description and specific embodiment, the present invention is made and further elaborating, described embodiment
It is served only for explaining the present invention, be not intended to limit the scope of the present invention.Test method used in following embodiments is such as no special
Different explanation, is conventional method；The material that used, reagent etc., if no special instructions, for the reagent commercially obtaining
And material.
Embodiment 1 pH rate of descent is verified with viable bacteria exponential model
With Lactobacillus rhamnosus for verifying bacterial strain, carry out the high-cell-density cultivation of 20L fermentation tank, keeping temperature and pH are constant,
Measure pH rate of descent and viable count in incubation, compareed, result is as shown in Figure 2.
As seen from Figure 2, in bacterial strain breeding, the growth curve of pH rate of descent and viable count is in lag phase and logarithm
Phase fits like a glove, and meets the expection of modelling.Simultaneously it can be seen that when viable count was bred to logarithmic phase latter stage, pH declines
To close to zero, this is a large amount of propagation due to thalline to rate bust, and the carbon source in culture medium is depleted, and bacterial strain cannot produce acid and lead
Cause, continue culture it can be found that viable count is declined due to poor nutritional in nutrient solution, therefore feed supplement can be judged by this flex point
Time or put the tank time, reach the on-line monitoring to lactic acid bacteria fed-batch high-cell-density cultivation.
Embodiment 2
The first step is amplified fermentation tank and is entered using equipped with the 20L seeding tank of pH sensor and 25% ammoniacal liquor auto-feeding system and 200L
Row Lactobacillus plantarum（Lactobacillus plantarum）High-cell-density cultivation；
Pass through pH sensor in second step incubation and ammoniacal liquor auto-feeding system keeps Lactobacillus plantarum culture in fermentation tank
The pH of liquid stablizes 5.7；
3rd step, in the incubation of second step, closes ammoniacal liquor auto-feeding system every 0.5h, stops ammonia aqua stream and adds, from
And measure pH rate of descent, measure and can be again started up alkaline stream adding system after terminating.
The computing formula of pH rate of descent is：
；
pH1：The pH of nutrient solution when timing initiates；
pH2：The pH of nutrient solution at the end of timing；
t：Timing duration/min；
PH rate of descent：pH/min；
The variation tendency of the pH rate of descent according to the 3rd step gained for the 4th step judges Lactobacillus plantarum high-cell-density cultivation mistake
Lactic acid bacteria proliferative conditions in journey, and then judge the batch feeding time, spend kind of the time and put the tank time.The pH rate of descent of final gained
Variation tendency as shown in Figure 3 and Figure 4.
This culture, takes 12.5 hours, final viable count 1.1 × 10 altogether10Cfu/mL, has reached wanting of High Density Cultivation
Ask.
Embodiment 3
The first step amplifies fermentation tank using equipped with the 500L seeding tank of pH sensor and 20%NaOH auto-feeding system and 1500L
Carry out Lactobacillus rhamnosus（Lactobacillus rhamnosus）High-cell-density cultivation；
Pass through pH sensor in second step incubation and 20%NaOH auto-feeding system keeps Lactobacillus plantarum in fermentation tank
The pH of nutrient solution stablizes 5.8；
3rd step, in the incubation of second step, closes NaOH solution auto-feeding system every 0.5h, thus measuring under pH
Fall rate, measures and can be again started up alkaline stream adding system after terminating.
The computing formula of pH rate of descent is：
；
pH1：The pH of nutrient solution when timing initiates；
pH2：The pH of nutrient solution at the end of timing；
t：Timing duration/min；
PH rate of descent：pH/min；
The variation tendency of the pH rate of descent according to the 3rd step gained for the 4th step judges Lactobacillus rhamnosus high-cell-density cultivation
During lactic acid bacteria proliferative conditions, and then judge the batch feeding time, spend kind of time and put the tank time.The pH of final gained declines
The variation tendency of rate is as shown in Figure 5 and Figure 6.
This culture, takes 14 hours, final viable count 2.1 × 10 altogether10Cfu/mL, has reached wanting of High Density Cultivation
Ask.
Embodiment 4
The first step carries out animal bifid bar using the 10L anaerobic fermentation tank equipped with pH sensor and 25%NaOH auto-feeding system
Bacterium（Bifidobacterium animalis）High-cell-density cultivation；
Pass through pH sensor in second step incubation and 25%NaOH auto-feeding system keeps animal bifid bar in fermentation tank
The pH of bacteria culture fluid stablizes 6.0；
3rd step, in the incubation of second step, closes NaOH solution auto-feeding system every 0.5h, thus measuring under pH
Fall rate, measures and can be again started up alkaline stream adding system after terminating.
The computing formula of pH rate of descent is：
；
pH1：The pH of nutrient solution when timing initiates；
pH2：The pH of nutrient solution at the end of timing；
t：Timing duration/min；
PH rate of descent：pH/min；
The variation tendency of the pH rate of descent according to the 3rd step gained for the 4th step judges animal bifidobacteria high-cell-density cultivation
During lactic acid bacteria proliferative conditions, and then judge batch feeding time and put the tank time.The change of the pH rate of descent of final gained
Trend is as shown in Figure 7.
This culture, takes 10 hours, final viable count 5.8 × 10 altogether10Cfu/mL, has reached wanting of High Density Cultivation
Ask.
Claims (7)
1. a kind of lactic acid bacteria high-cell-density cultivation method based on on-line monitoring pH rate of change is it is characterised in that include as follows
Step：
S1. lactic acid bacteria high-cell-density cultivation is carried out using the fermentation tank equipped with pH sensor and alkaline stream adding system；
S2. pass through pH sensor in incubation and alkaline stream adding system keeps the pH of lactic acid bacteria culture solution in fermentation tank stable；
S3. in the incubation of step S2, close alkaline stream adding system every 0.5h～1.0h, stop alkaline stream and add, thus
Measure pH rate of descent, measure and restart alkaline stream adding system after terminating；
S4. during the variation tendency of the pH rate of descent according to S3 gained judges lactic acid bacteria high-cell-density cultivation, lactic acid bacteria increases
Grow situation, and then judge the batch feeding time, spend kind of the time and put the tank time.
2. cultural method according to claim 1 it is characterised in that described alkali lye be 25% (w/w) ammonia spirit, 20～
25% (w/w) NaOH solution, 20～25% (w/w) Na2CO3Solution or 20～25% (w/w) (NH4)2CO3Solution.
3. cultural method according to claim 1 it is characterised in that the pH stability range in described step S2 be 5.7～
6.0.
4. cultural method according to claim 1 is it is characterised in that described lactic acid bacteria strains are Lactobacillus plantarum, mouse
Lee's sugar lactobacillus or animal bifidobacteria.
5. cultural method according to claim 1 it is characterised in that in described step S3 pH rate of descent computing formula
For：
；
pH1：The pH of nutrient solution when timing initiates；
pH2：The pH of nutrient solution at the end of timing；
t：Timing duration/min；
PH rate of descent：pH/min.
6. cultural method according to claim 1 is it is characterised in that become according to the change of pH rate of descent in described step S4
Gesture refers to judging lactic acid bacteria proliferative conditions：When bacterial strain propagation is in the lag phase, the pH decline rate score of bacterial strain is very low and increases
Long slow；When strain culturing is in logarithmic phase, the pH of bacterial strain change rate score is higher and rapid development.
7. cultural method according to claim 1 it is characterised in that walk judges according to pH rate of descent in described rapid S4 point
Batch feed supplement time, spend kind of the time and put the tank time and refer to：During logarithmic phase, when pH change rate score bust to very low when, as divide
Criticize the feed supplement time；After feed supplement, pH declines rate score and can uprush, and is rear logarithmic phase；After batch feeding terminates, pH declines rate score again
Secondary bust, as crosses kind, culture transferring or puts the tank time.
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| WO2023077683A1 (en) * | 2021-11-04 | 2023-05-11 | 江南大学 | Cell culture state on-line estimation and replenishment optimization regulation and control method |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101245324A (en) * | 2007-02-13 | 2008-08-20 | 丁之铨 | High-density cultivation method for lactobacillus |
| CN101967454A (en) * | 2009-07-27 | 2011-02-09 | 上海斯哒米纳生物科技有限公司 | High-intensity culture method for lactobacilli |
-
2016
- 2016-07-08 CN CN201610543411.4A patent/CN106434414A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101245324A (en) * | 2007-02-13 | 2008-08-20 | 丁之铨 | High-density cultivation method for lactobacillus |
| CN101967454A (en) * | 2009-07-27 | 2011-02-09 | 上海斯哒米纳生物科技有限公司 | High-intensity culture method for lactobacilli |
Non-Patent Citations (1)
| Title |
|---|
| 范瑞等: "乳酸菌活菌数对酸乳理化特性的影响", 《中国乳品工业》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023077683A1 (en) * | 2021-11-04 | 2023-05-11 | 江南大学 | Cell culture state on-line estimation and replenishment optimization regulation and control method |
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Application publication date: 20170222 |