Cell culture control system, cell culture control method, and non-transitory computer readable storage medium

Patent metadata

Field	Value
Publication number	US-9783774-B2
Application number	US-201514700301-A
Country	US
Kind code	B2
Filing date	Apr 30, 2015
Priority date	May 19, 2014
Publication date	Oct 10, 2017
Grant date	Oct 10, 2017

Abstract

A cell culture control system includes a controller configured to control parameters of a culture fluid which exists in a processor in accordance with a control value which is preliminarily set, a generator configured to generate time-series data by using a concentration value of the metabolic substances in the culture fluid, the concentration value of the metabolic substances being detected by a sensor, an extractor configured to extract a characteristic point of the time-series data generated by the generator, and a control value setter configured to change the control value in accordance with the characteristic point extracted by the extractor.

First claim

What is claimed is:

1. A cell culture control system comprising:
a control unit configured to control a supply operation of supplying additives to a tank for containing a culture fluid in which cells are cultured, the additives being feed agents or augmenting agents;
a controller configured to control the control unit to control parameters of the culture fluid which exists in the tank in accordance with a control value which is preliminarily set;
a sensor configured to detect a cell density, a concentration value of metabolic substances, and a concentration value of nutrient sources in the culture fluid which exists in the tank by using near-infrared spectroscopy;
a calculator configured to calculate a specific rate of the cell density, a specific rate of the concentration value of the metabolic substances, and a specific rate of the concentration value of the nutrient sources based on the cell density, the concentration value of the metabolic substances, and the concentration value of the nutrient sources detected by the sensor;
a generator configured to generate time-series data in accordance with the specific rate of the cell density, the specific rate of the concentration value of the metabolic substances, and the specific rate of the concentration value of the nutrient sources calculated by the calculator;
an extractor which comprises a simulator configured to calculate a predicted value of the time-series data in accordance with the time-series data generated by the generator, the extractor being configured to extract a characteristic point of the time-series data or a characteristic point of the predicted value, the characteristic point being a peak point or a shift point of the time-series data or the predicted value; and
a control value setter configured to change the control value in accordance with the characteristic point extracted by the extractor,
wherein the control value setter is configured to determine an adding amount of additives to be added to the tank based on an adding amount of additives stored in the control value setter at a timing of an output from the extractor, and
wherein the controller is configured to control the control unit to supply the additives to the tank in accordance with the adding amount of the additives determined by the control value setter.

2. The cell culture control system according to claim 1 , wherein
in a case where the cells in the culture fluid grow, lactic acid increases,
the sensor is configured to detect a concentration value of the lactic acid in the culture fluid,
the calculator is configured to calculate a specific production rate of the lactic acid in accordance with the concentration value of the lactic acid detected by the sensor,
a sign of the specific production rate of the lactic acid is shifted from positive to negative at a shift point,
the extractor is configured to extract the shift point as the characteristic point, and
the control unit is configured to add feed agents or augmenting agents into the culture fluid as the additives in accordance with the shift point extracted by the extractor.

3. The cell culture control system according to claim 1 , wherein
the sensor is configured to detect a concentration value of ammonia in the culture fluid,
the extractor is configured to output a shift point of a trend of the concentration value of the ammonia detected by the sensor as the characteristic point, and
the control unit is configured to add feed agents or augmenting agents into the culture fluid as the additives in accordance with the output from the extractor.

4. The cell culture control system according to claim 1 , wherein
the control value setter is configured to switch the control value from a first control value to a second control value at a timing of outputting from the extractor, and
the controller is configured to control the control unit, which is disposed between a supply source of the additives and the tank, perform a supply operation and a block operation in accordance with the second control value switched by the control value setter.

5. The cell culture control system according to claim 4 , wherein
the control value corresponds to the concentration value of the nutrient sources detected by the sensor, and
the control unit is configured to add the nutrient sources into the culture fluid in accordance with the output from the extractor, and make the concentration value of the nutrient sources correspond to the second control value.

6. The cell culture control system according to claim 4 , wherein
the sensor is configured to detect a pH value of the culture fluid which exists in the tank,
the control value corresponds to the pH value of the culture fluid detected by the sensor, and
the control unit is configured to add pH adjusting material into the culture fluid in accordance with the output from the extractor, and make the pH value of the culture fluid correspond to the second control value.

7. The cell culture control system according to claim 6 , wherein
in a case where the pH value detected by the sensor is lower than the second control value, the control unit adds alkali solution as the pH adjusting material into the culture fluid,
in a case where the pH value detected by the sensor is higher than the second control value, the control unit adds CO 2 gas as the pH adjusting material into the culture fluid.

8. The cell culture control system according to claim 4 , wherein
the sensor is configured to detect an osmotic pressure value of the culture fluid which exists in the tank,
the control value corresponds to the osmotic pressure value of the culture fluid detected by the sensor, and
the control unit is configured to add osmotic pressure adjusting material into the culture fluid in accordance with the output from the extractor, and make the osmotic pressure value of the culture fluid correspond to the second control value.

9. The cell culture control system according to claim 8 , wherein
in a case where the second control value is lower than the osmotic pressure value of the culture fluid detected by the sensor, the control unit adds natrium chloride as the osmotic pressure adjusting material into the culture fluid.

10. The cell culture control system according to claim 4 , wherein
the sensor is configured to detect a temperature value of the culture fluid which exists in the tank,
the control value corresponds to the temperature value of the culture fluid detected by the sensor, and
the control unit is configured to control a temperature adjuster in accordance with the output from the extractor, and make the temperature value of the culture fluid correspond to the second control value.

11. The cell culture control system according to claim 4 , wherein
the sensor is configured to detect a concentration value of dissolved oxygen of the culture fluid which exists in the tank,
the control value corresponds to the concentration value of the dissolved oxygen of the culture fluid detected by the sensor, and
the control unit is configured to control a gas flow adjuster in accordance with the output from the extractor, and make the concentration value of the dissolved oxygen of the culture fluid correspond to the second control value.

12. The cell culture control system according to claim 1 , wherein
the calculator comprises an averager configured to calculate a representative value by averaging the output from the sensor in a predetermined period, and
the averager calculates a rate component of the representative value based on the representative value calculated by the calculator.

13. The cell culture control system accor

Assignees

• Yokogawa Electric Corp

Inventors

• Namatame Tetsushi
• Shimoda Souichirou
• Suzuki Yasuyuki
• Izaki Fumiaki

Classifications

• C12M41/38

  of metabolites or enzymes in the cells · CPC title

• C12M41/48 Primary

  Automatic or computerized control (automatic analysis G01N35/00) · CPC title

• C12M41/40

  of pressure · CPC title

• C12M41/00

  Means for regulation, monitoring, measurement or control, e.g. flow regulation (controlling or regulating chemical, physical or physicochemical processes B01J19/0006; heating or cooling apparatus for laboratory use B01L7/00; electro optical investigation of individual particles, flow cytometers G01N15/14; automatic analysis G01N35/00; controlling or regulating in general G06N) · CPC title

• C12M41/32

  of substances in solution · CPC title