Perfusion Multi-Well Cell Culture for High-Throughput Protein Production
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Solution Overview
Problem
There is no high throughput model for perfusion-based cell culture using a multi-well plate, limiting the efficiency and scalability of mammalian cell culture systems for recombinant protein production.
Innovation Solution
Culturing mammalian cells in a multi-well plate with specific conditions, including temperature, agitation, and continuous or periodic exchange of liquid culture media, achieves improved viable cell density and recombinant protein production, mimicking large-scale perfusion bioreactors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If traditional fed-batch cell culture systems are used, then the process is well-established and reliable, but high throughput modeling for perfusion-based culture is unavailable, limiting scalability and efficiency
Solution Approach 1:
The invention divides the cell culture process into modular multi-well plate format, where each well functions as an independent mini-bioreactor. This segmentation enables high throughput experimentation (testing multiple conditions simultaneously) while maintaining perfusion-based culture benefits, resolving the contradiction between productivity and complexity by making the system scalable and parallelizable
Solution Approach 2:
The multi-well plate system is designed to perform multiple functions: it serves as both the culture vessel and the perfusion reactor, combining features of traditional bioreactors with high throughput screening capabilities. This multi-functionality allows the same platform to achieve both established reliability and enhanced productivity for recombinant protein production
2Quantity of substance
If perfusion-based cell culture is implemented, then viable cell density and recombinant protein production are substantially improved, but the system complexity increases compared to traditional fed-batch processes
Solution Approach 1:
The invention creates simplified copies of large-scale perfusion bioreactor functionality within multi-well plate format. Each well replicates the essential perfusion characteristics (continuous medium exchange, controlled agitation) at a miniaturized scale, enabling high viable cell densities without the complexity of full-scale bioreactor systems
3Reliability
If continuous medium exchange is performed, then culture performance is accurately modeled for large-scale perfusion, but the operational complexity and time requirements increase
Solution Approach 1:
The system implements continuous or near-continuous medium exchange through automated perfusion protocols, eliminating the need for repeated manual sampling and medium changes. This continuous action maintains accurate perfusion modeling while reducing total time investment by allowing parallel processing across multiple wells simultaneously
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 viable cell densities comparable to large-scale bioreactors, enabling high throughput and efficient recombinant protein production, suitable for high throughput cell culture experiments and quality-by-design studies.
Implementation Method 1
incubating the multi-well plate for a period of time at about 31° C. to about 40° C. and with a rotary agitation of about 320 revolutions per minute (RPM) to about 500 RPM
Data Source
AI summary
Provided herein are methods of culturing a mammalian cell and various methods that utilize these culturing methods. Also provided are multi-well cell culture plates, e.g., for use in perfusion culturing methods.