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Control of cell growth through a temperature feedback loop

a technology of cell growth and feedback loop, which is applied in the direction of biomass after-treatment, specific use bioreactor/fermenter, biochemistry apparatus and processes, etc., can solve the problems that standard offline measurement techniques fail to capture important data such as the exact cell peak time and density

Inactive Publication Date: 2019-10-03
BRISTOL MYERS SQUIBB CO
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent text describes a method for controlling the growth of cells in a bioreactor by measuring the viable cell density and adjusting the temperature to control the growth rate. This leads to a more consistent and stable growth of cells, which is important for the production of biological products.

Problems solved by technology

In addition standard offline measurement techniques fail to capture important data such as the exact cell peak time and density.
This can make cell density based process decisions such as temperature shifting difficult to time.

Method used

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  • Control of cell growth through a temperature feedback loop
  • Control of cell growth through a temperature feedback loop
  • Control of cell growth through a temperature feedback loop

Examples

Experimental program
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Effect test

example 1

[0074]The following example describes the use of a biomass capacitance probe to precisely control cell growth as measured through the capacitance probe by modulating reactor temperature.

Cell Line and Cell Culture Medium

[0075]A BMS-proprietary cell culture medium and a proprietary recombinant CHO cell line expressing IgG antibodies were used for the experiments. The cell culture medium was chemically defined and fully serum and protein free. Recombinant IgG producing CHO cells were maintained in suspension culture in 250-mL, 1-L and 3 L shake flasks. A CO2 shaker incubator (Kuhner) was used for incubation at 36.5° C., 150 rpm at a CO2 concentration of 5%.

Bench-Style Bioreactors and Cultivation Conditions

[0076]Bench scale reactor cultivations were carried out in 5-L stirred tank reactors (Sartorius). All the 5-L reactors were equipped with two 45° pitched tri-blade impellers, pH, DO (dissolved oxygen) and biomass capacitance probes. The working volume of the 5-L bioreactor was 4.5 L. ...

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Abstract

The present invention relates to the use of online biomass capacitance monitoring in cultures as a way to control the growth of cells through the use of a temperature control loop. In certain embodiments, a biomass capacitance probe is used to measure the cell density, and a predetermined growth curve is used to adjust the temperature in the culture.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority to U.S. Provisional Application No. 62 / 650,430, filed Mar. 30, 2018, which is incorporated herein by reference in its entirety.BACKGROUND OF THE INVENTION[0002]Understanding cell growth is critical for developing efficient and robust bioreactor processes. Due to exponential growth characteristics, small perturbations in process conditions such as inoculation density, media composition, and pH can have large impacts on cell density and process performance. In addition standard offline measurement techniques fail to capture important data such as the exact cell peak time and density. This can make cell density based process decisions such as temperature shifting difficult to time.[0003]There is a need in the art for mechanisms to dynamically adjust cell growth to precisely control the timing of cell growth from inoculation to peak.SUMMARY OF THE INVENTION[0004]In some embodiments, the invention is directed t...

Claims

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Application Information

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IPC IPC(8): C12M1/36C12M1/34
CPCC12M41/46C12M41/48C12M41/12C12M41/36
Inventor ARON, KATHRYN L.SWANBERG, JEFFREY
Owner BRISTOL MYERS SQUIBB CO