Pre-Conditioned Cell Inoculum Using Electromagnetic Seed Treatment
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Solution Overview
Problem
Conventional cell expansion processes in biomanufacturing and cell culture are time-intensive and costly, with challenges in optimizing cell growth and metabolic processes, especially when scaling up, and applying pulsed electromagnetic signals to large bioreactors is inefficient and requires non-metallic containers, complicating the process.
Innovation Solution
A method involving the application of an electrical or electromagnetic stimulus, such as a pulsed electromagnetic wave, to a cell line sample to create a pre-conditioned cell inoculum that undergoes hereditary metabolic changes, allowing for optimized cell expansion and biomanufacturing without repeated stimulus application, using glass or plastic containers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If pulsed electromagnetic signals are applied to large bioreactors to increase productivity, then protein productivity is improved, but the process becomes more complex and time-consuming due to the need for non-metallic containers and consistent signal application throughout the large volume
Solution Approach 1:
The patent applies pulsed electromagnetic signals during the seed train process (before inoculation) to pre-condition cells for enhanced productivity. This preliminary action modifies cell metabolism in advance, so that when cells are inoculated into the large bioreactor, they already possess improved protein productivity without requiring continuous electromagnetic signal application during the main production phase.
Solution Approach 2:
The patent extracts the electromagnetic signal application step from the main bioreactor process and applies it separately during the seed train phase. This separation allows the use of smaller, more manageable containers during treatment while avoiding the complexity of applying signals uniformly throughout large bioreactor volumes during production.
2Productivity
If pulsed electromagnetic signals are applied to large bioreactors to increase productivity, then protein productivity is improved, but the process requires non-metallic containers which increases cost and operational difficulty
Solution Approach 1:
The electromagnetic signal treatment is performed in advance during the seed train process using small-scale containers, avoiding the need for expensive non-metallic large bioreactors. The pre-conditioned cells are then inoculated into standard metal bioreactors for production, maintaining ease of manufacture while achieving productivity improvements.
3Quantity of substance
If conventional cell expansion processes are used to increase cell numbers for bioreactor inoculation, then adequate cell numbers are achieved, but the process becomes time-intensive and costly with multiple cultivation steps
Solution Approach 1:
The patent applies electromagnetic signals during the seed train process to pre-condition cells for enhanced growth and metabolism. This preliminary treatment accelerates cell expansion rates, reducing the time required to achieve adequate cell numbers for bioreactor inoculation while maintaining cell quality.
Solution Approach 2:
The electromagnetic signal application changes cellular metabolic parameters and growth characteristics, leading to faster cell proliferation rates. This parameter change allows the cell expansion process to be completed more quickly while still achieving the required cell density for inoculation.
4Quantity of substance
If conventional cell expansion processes are scaled up to increase cell numbers, then adequate cell numbers for large bioreactors are achieved, but optimization becomes more difficult and expensive
Solution Approach 1:
The patent applies electromagnetic signal treatment during the seed train process (small scale) to pre-condition cells before they are expanded in large bioreactors. This preliminary optimization at small scale is more manageable and less costly, yet the effects persist through subsequent large-scale expansion, reducing overall optimization difficulty.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The method results in increased protein productivity, ribosomal activity, and reduced cell death, with metabolic changes being permanent and hereditary, thus optimizing the process on a smaller scale and reducing time and costs.
Implementation Method 1
applying an electrical or electromagnetic stimulus, such as an applied electromagnetic field or a transmitted electromagnetic wave and/or one or more stimulus signals to any or any combination of: the cell line sample, the at least first set of passaged cells and/or one or more subsequent sets of passaged cells to create a pre-conditioned cell inoculum
Data Source
AI summary
A method is provided for producing a cell inoculum suitable for use in inoculating a bioreactor in a biomanufacturing or cell culture process. The method includes the steps of taking a cell line sample and undertaking at least one cell passage with said cell line sample to increase the number of cells to form at least a first set of passaged cells. Subsequently said first set and/or one or more subsequent sets of passaged cells is used for optionally inoculating a bioreactor in use. The method further includes the step of applying electrical or electromagnetic stimulus, wave and/or one or more signals to any or any combination of: the cell line sample, the at least first set of passaged cells and/or one or more subsequent sets of passaged cells to create a pre-conditioned cell inoculum. Optionally the pre-conditioned cell inoculum is then used to directly or indirectly inoculate the bioreactor.A cell inoculum composition suitable for use in a biomanufacturing or cell culture process and comprising a population of epigenetically modified cells is also provided. The cells may, for example, be HEK cells or CHO cells.