CN114438035A - CO (carbon monoxide)2Method for controlling culture temperature of IPS cells in incubator - Google Patents
CO (carbon monoxide)2Method for controlling culture temperature of IPS cells in incubator Download PDFInfo
- Publication number
- CN114438035A CN114438035A CN202210067211.1A CN202210067211A CN114438035A CN 114438035 A CN114438035 A CN 114438035A CN 202210067211 A CN202210067211 A CN 202210067211A CN 114438035 A CN114438035 A CN 114438035A
- Authority
- CN
- China
- Prior art keywords
- temperature
- incubator
- heater
- time
- state
- 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.)
- Granted
Links
- 210000004263 induced pluripotent stem cell Anatomy 0.000 title claims abstract description 14
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 title claims description 4
- 229910002091 carbon monoxide Inorganic materials 0.000 title claims description 4
- 238000000034 method Methods 0.000 claims abstract description 13
- 238000004113 cell culture Methods 0.000 claims abstract description 7
- 238000010438 heat treatment Methods 0.000 claims description 6
- 210000004027 cell Anatomy 0.000 description 4
- 230000008859 change Effects 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000008672 reprogramming Effects 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000007877 drug screening Methods 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 210000001778 pluripotent stem cell Anatomy 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000009256 replacement therapy Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000001082 somatic cell Anatomy 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0696—Artificially induced pluripotent stem cells, e.g. iPS
-
- 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
- C12M29/04—Filters; Permeable or porous membranes or plates, e.g. dialysis
-
- 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
-
- 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
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/12—Means for regulation, monitoring, measurement or control, e.g. flow regulation of temperature
- C12M41/18—Heat exchange systems, e.g. heat jackets or outer envelopes
- C12M41/20—Heat exchange systems, e.g. heat jackets or outer envelopes the heat transfer medium being a gas
-
- G—PHYSICS
- G05—CONTROLLING; REGULATING
- G05D—SYSTEMS FOR CONTROLLING OR REGULATING NON-ELECTRIC VARIABLES
- G05D23/00—Control of temperature
- G05D23/19—Control of temperature characterised by the use of electric means
- G05D23/20—Control of temperature characterised by the use of electric means with sensing elements having variation of electric or magnetic properties with change of temperature
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A40/00—Adaptation technologies in agriculture, forestry, livestock or agroalimentary production
- Y02A40/10—Adaptation technologies in agriculture, forestry, livestock or agroalimentary production in agriculture
- Y02A40/25—Greenhouse technology, e.g. cooling systems therefor
Abstract
The invention provides CO2A method for controlling the temperature of IPS cells in an incubator. The method comprises the steps of setting temperature preset values SV at different time periods according to different cell cultures of IPS; by captured CO2Calculating a temperature control deviation value ER between the real-time temperature and a preset temperature value by using the real-time temperature PV inside the incubator; determining the current temperatureThe state of the difference between the temperature and the next set temperature when ER>When 0, the controller controls the heater to operate in a preset state; when ER is 0, the controller controls the heater to operate in a preset state; when ER is present<When 0, the controller controls the heater to operate in a preset state, and in addition, the controller also controls the micro-motion air pump to operate, so that low-temperature air enters the incubator, and CO is introduced2The real-time temperature PV inside the incubator is consistent with the set temperature SV.
Description
Technical Field
The invention relates to the technical field of incubator control, in particular to CO2A method for controlling the temperature of IPS cells in an incubator.
Background
IPS cells are called Induced pluripotent stem cells (Induced pluripotent stem cells), and refer to cells obtained by reprogramming terminally differentiated somatic cells into pluripotent stem cells by introducing a specific transcription factor. The process of recovering differentiated cells to a pluripotent state after being reversed under specific conditions, or forming an embryonic stem cell line, or further developing into a new individual is cell reprogramming. IPS has great potential value in the aspects of cell replacement therapy, the research of pathogenesis, new drug screening, the treatment of clinical diseases such as nervous system diseases, cardiovascular diseases and the like.
The IPS cell culture environment is completely different from the common cell culture environment which is 5% CO2The concentration was adjusted to 37 ℃. While the culture environment of IPS cells is changed in stages during the culture process. The invention realizes automatic control and accurate control of environmental change in each stage.
Disclosure of Invention
In accordance with the technical problems set forth above, there is provided a CO2A method for controlling the temperature of IPS cells in an incubator. The technical means adopted by the invention are as follows:
CO (carbon monoxide)2The method for controlling the culture temperature of the IPS cells in the incubator comprises the following steps:
Further, the specific control method in step 3 is as follows:
ER > 0:
when ER is greater than 0.5, SVK is SV + SV (ER/15) ST, ST is the temperature rise time, and heater control output OUT is PID control output PIDOUT [1- (SV-PV) ];
when ER is more than 0.1 ℃ and less than or equal to 0.5 ℃, stopping controlling other heaters, only starting a bottom heater, and carrying out discontinuous heating control according to a PID output value, wherein BTOUT (PID control output PIDOUT [1+ (SV-PV)) is controlled by the bottom heater, and the discontinuous time T (SV-PV) -0.663I is controlled by the bottom heater;
when SV-PV is less than or equal to 0.1 ℃, the bottom heater controls the output BTOUT to be 0;
when ER is equal to 0, the heater control output OUT is equal to PID control output PIDOUT;
when ER is less than 0, a 2-position 3-way electromagnetic valve and a micro-motion air pump are started to input room-temperature air into the incubator through the HAPA filter, so that the temperature is consistent with the set temperature SV;
when ER < -0.5, SVK (SV + SV (ER/15) × heating time ST, and heater control output OUT (PID control output PIDOUT) [1- (SV-PV) ];
when ER is more than or equal to-0.5 ℃, starting an air pump, simultaneously carrying OUT PWM discontinuous on-off control on a solenoid valve switch according to a PID output value, wherein OUT is PIDOUT (1- (SV-PV)), and the discontinuous time T is 300 (SV-PV) -0.32, when the solenoid valve is opened, air enters an incubator, and when the solenoid valve is closed, the air is emptied through a normally open channel of the solenoid valve;
and when SV-PV is 0.1 ℃, closing the electromagnetic valve and the air pump, and stopping air input.
The invention realizes automatic control and accurate control of environmental change in each stage, and has the advantages of high temperature rise and reduction speed, stable temperature control curve and no overshoot and undershoot. The longest finishing time of heating up to 8 ℃ and cooling down to 8 ℃ is 15 min.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings needed to be used in the description of the embodiments or the prior art will be briefly introduced below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to these drawings without creative efforts.
FIG. 1 is a graph of the temperature control characteristic of the present invention.
FIG. 2 is a graph of the temperature ramp control of the present invention.
FIG. 3 is a temperature drop control curve according to the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are some, but not all, embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The incubator employed in this embodiment includes: the device comprises a main heater, a door heater, a bottom heater, a temperature sensor, an air pump and a controller. The incubator comprises a box body, wherein the main heater, the door heater and the bottom heater are arranged on the box body. The main heater, the door heater, the bottom heater, the temperature sensor and the air pump are connected with the controller. The air pump is connected with the incubator, and a 2-position 3-way electromagnetic valve is arranged between the air pump and the incubator.
The present example discloses a CO2The method for controlling the culture temperature of the IPS cells in the incubator comprises the following steps:
The specific control method of the step 3 is as follows:
ER > 0:
when ER >0.5, SVK ═ SV + SV (ER/15) × ST, ST is the temperature rise time, where SVK is the preset temperature of the next time, in this embodiment, the ST value is a 15-minute time timer, and the heater control output OUT ═ PID control output PIDOUT [1- (SV-PV) ];
when ER is more than 0.1 ℃ and less than or equal to 0.5 ℃, stopping controlling other heaters, only starting a bottom heater, and carrying out discontinuous heating control according to a PID output value, wherein BTOUT (PID control output PIDOUT [1+ (SV-PV)) is controlled by the bottom heater, and the discontinuous time T (SV-PV) -0.663I is controlled by the bottom heater;
when SV-PV is less than or equal to 0.1 ℃, the bottom heater controls the output BTOUT to be 0;
when ER is equal to 0, the heater control output OUT is equal to PID control output PIDOUT;
when ER is less than 0, a 2-position 3-way electromagnetic valve and a micro-motion air pump are started to input room-temperature air at the temperature of 22-25 ℃ into the incubator through the HAPA filter, so that the temperature is consistent with the set temperature SV;
when ER < -0.5, SVK + SV (ER/15) temperature rise time ST, and heater control output OUT PID control output PIDOUT [1- (SV-PV) ];
when ER is more than or equal to-0.5 ℃, starting an air pump, simultaneously carrying OUT PWM discontinuous on-off control on a solenoid valve switch according to a PID output value, wherein OUT is PIDOUT (1- (SV-PV)), and the discontinuous time T is 300 (SV-PV) -0.32, when the solenoid valve is opened, air enters an incubator, and when the solenoid valve is closed, the air is emptied through a normally open channel of the solenoid valve;
and when SV-PV is less than 0.1 ℃, closing the electromagnetic valve and the air pump and stopping air input.
As shown in fig. 2 and fig. 3, when the temperature rise and decrease set value is reached, the maximum completion time of temperature rise and decrease of 8 degrees is 15min, the temperature value is smooth and excessive, and there are no overshoot and undershoot.
Finally, it should be noted that: the above embodiments are only used to illustrate the technical solution of the present invention, and not to limit the same; while the invention has been described in detail and with reference to the foregoing embodiments, it will be understood by those skilled in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some or all of the technical features may be equivalently replaced; and the modifications or the substitutions do not make the essence of the corresponding technical solutions depart from the scope of the technical solutions of the embodiments of the present invention.
Claims (2)
1. CO (carbon monoxide)2The method for controlling the culture temperature of the IPS cells in the incubator is characterized by comprising the following steps:
step 1, setting temperature preset values SV at different time periods according to different cell cultures of IPS;
step 2, passing the obtained CO2The real-time temperature PV inside the incubator calculates the temperature control deviation value ER between the real-time temperature and the temperature preset value, and comprises three states, namely a state 1: next set temperature>Last run temperature, ER>0; state 2: the next set temperature is the last operating temperature, and ER is the last operating temperature0; state 3: next set temperature<Last operating temperature, ER<0；
Step 3, judging the state of the difference between the current temperature and the next set temperature when ER is used>When 0, the controller controls the heater to operate in a preset state; when ER is 0, the controller controls the heater to operate in a preset state; when ER is present<When 0, the controller controls the heater to operate in a preset state, and in addition, the controller also controls the micro-motion air pump to operate, so that low-temperature air enters the incubator, and CO is introduced2The real-time temperature PV inside the incubator is consistent with the set temperature SV.
2. CO according to claim 12The method for controlling the culture temperature of the IPS cells in the incubator is characterized in that the specific control method in the step 3 is as follows:
ER > 0:
when ER is greater than 0.5, SVK is SV + SV (ER/15) ST, ST is the temperature rise time, and heater control output OUT is PID control output PIDOUT [1- (SV-PV) ];
when ER is more than 0.1 ℃ and less than or equal to 0.5 ℃, stopping controlling other heaters, only starting a bottom heater, and carrying out discontinuous heating control according to a PID output value, wherein BTOUT (PID control output PIDOUT [1+ (SV-PV)) is controlled by the bottom heater, and the discontinuous time T (SV-PV) -0.663I is controlled by the bottom heater;
when SV-PV is less than or equal to 0.1 ℃, the bottom heater controls the output BTOUT to be 0;
when ER is equal to 0, the heater control output OUT is equal to PID control output PIDOUT;
when ER is less than 0, a 2-position 3-way electromagnetic valve and a micro-motion air pump are started to input room-temperature air into the incubator through a HEPA filter, so that the temperature is consistent with the set temperature SV;
when ER < -0.5, SVK (SV + SV (ER/15) × heating time ST, and heater control output OUT (PID control output PIDOUT) [1- (SV-PV) ];
when ER is more than or equal to-0.5 ℃, starting an air pump, simultaneously carrying OUT PWM discontinuous on-off control on a solenoid valve switch according to a PID output value, wherein OUT is PIDOUT (1- (SV-PV)), and the discontinuous time T is 300 (SV-PV) -0.32, when the solenoid valve is opened, air enters an incubator, and when the solenoid valve is closed, the air is emptied through a normally open channel of the solenoid valve;
and when SV-PV is less than 0.1 ℃, closing the electromagnetic valve and the air pump and stopping air input.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210067211.1A CN114438035B (en) | 2022-01-20 | 2022-01-20 | CO (carbon monoxide) 2 Culture temperature control method of IPS cells of incubator |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210067211.1A CN114438035B (en) | 2022-01-20 | 2022-01-20 | CO (carbon monoxide) 2 Culture temperature control method of IPS cells of incubator |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114438035A true CN114438035A (en) | 2022-05-06 |
| CN114438035B CN114438035B (en) | 2023-10-20 |
Family
ID=81366864
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210067211.1A Active CN114438035B (en) | 2022-01-20 | 2022-01-20 | CO (carbon monoxide) 2 Culture temperature control method of IPS cells of incubator |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114438035B (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108410726A (en) * | 2018-04-27 | 2018-08-17 | 徐州医科大学 | Portable anaerobic bacteria culture case |
| CN109385374A (en) * | 2018-10-19 | 2019-02-26 | 东南大学 | A kind of minicell culture apparatus and its inside cavity environment control method |
| CN109810896A (en) * | 2019-03-14 | 2019-05-28 | 浙江大学 | A kind of cell culture temperature control device |
| CN111254229A (en) * | 2020-02-25 | 2020-06-09 | 青岛海尔生物医疗股份有限公司 | Carbon dioxide incubator control method and system and carbon dioxide incubator |
| CN113699032A (en) * | 2020-05-22 | 2021-11-26 | 青岛海尔智能家电科技有限公司 | Incubator and control method and device |
-
2022
- 2022-01-20 CN CN202210067211.1A patent/CN114438035B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108410726A (en) * | 2018-04-27 | 2018-08-17 | 徐州医科大学 | Portable anaerobic bacteria culture case |
| CN109385374A (en) * | 2018-10-19 | 2019-02-26 | 东南大学 | A kind of minicell culture apparatus and its inside cavity environment control method |
| CN109810896A (en) * | 2019-03-14 | 2019-05-28 | 浙江大学 | A kind of cell culture temperature control device |
| CN111254229A (en) * | 2020-02-25 | 2020-06-09 | 青岛海尔生物医疗股份有限公司 | Carbon dioxide incubator control method and system and carbon dioxide incubator |
| CN113699032A (en) * | 2020-05-22 | 2021-11-26 | 青岛海尔智能家电科技有限公司 | Incubator and control method and device |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114438035B (en) | 2023-10-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Fox et al. | Maximizing interferon‐γ production by chinese hamster ovary cells through temperature shift optimization: Experimental and modeling: Experimental and modeling | |
| JP4551515B2 (en) | Semiconductor manufacturing apparatus and temperature control method thereof | |
| CN113774207B (en) | Method for controlling protective atmosphere in radiant tube heat treatment furnace | |
| CN114438035A (en) | CO (carbon monoxide)2Method for controlling culture temperature of IPS cells in incubator | |
| Glen et al. | A mechanistic model of erythroblast growth inhibition providing a framework for optimisation of cell therapy manufacturing | |
| CN113621507A (en) | Full-automatic carrying and independent temperature and CO control2Multi-culture-cabin incubator with concentration | |
| Oliveira et al. | Design of a stable adaptive controller for driving aerobic fermentation processes near maximum oxygen transfer capacity | |
| CN108646808B (en) | Temperature control system and temperature control method of dyeing machine | |
| Wen et al. | A novel perfusion system for animal cell cultures by two step sequential sedimentation | |
| CN105865217B (en) | A kind of roaster burner gas flow control method | |
| CN103186151A (en) | Heating furnace control system | |
| Kager et al. | Direct control of recombinant protein production rates in E. coli fed-batch processes by nonlinear feedback linearization | |
| CN113534862B (en) | Gas concentration control system and method for culture cavity | |
| CN114657293B (en) | Automatic control method and device for coal injection rate of iron-smelting blast furnace | |
| JP5001659B2 (en) | Dissolved oxygen control device | |
| JPH11305805A (en) | Process control method and electronic device manufacture using the same | |
| Alimberti et al. | Bioreactor temperature control system using PID controller | |
| Bogle et al. | A process systems engineering view of biochemical process operations | |
| WO2023189007A1 (en) | Culture method and culture device | |
| Foster et al. | A process control system for the fractional precipitation of human plasma proteins | |
| CN218675827U (en) | Oxygen-free oven | |
| Jones et al. | Dissolved Oxygen Control in a Fermentation of Saccharomyces Cerevisiae using an Automatic Tuning PID Controller | |
| CN112503957A (en) | Temperature control method of holding furnace | |
| JPS63188384A (en) | Starting up of high-density continuous culture for cell | |
| JP6031313B2 (en) | Carburizing method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |