Sliding-Filter Bioreactor for Closed-Loop Cell Culture Harvesting
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing bioreactors are unsatisfactory for cell culturing as they require multiple manipulations, risk contamination, are not suitable for lab bench use, and are costly due to large volumes and expensive ingredients, necessitating large-scale equipment and chemical transfection methods.
Innovation Solution
A bioreactor with a culturing tank, filter, and medium management system that allows for automated cell culture, volume adjustment, and separation of cells from medium without transfer, enabling small-scale bioproduction on a lab bench, using electroporation for efficient transfection and reducing human intervention.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If large volume bioreactors are used for bioproduction, then production volume is increased, but device size becomes too large for lab bench and cost increases
Solution Approach 1:
The bioreactor is divided into two functional compartments: a lower compartment for cell culture and an upper compartment for medium processing. This segmentation allows the system to achieve large production volumes through continuous operation rather than requiring a single large chamber, enabling lab bench-scale operation with enhanced productivity.
Solution Approach 2:
The system implements continuous medium extraction and replacement, allowing the cell culture process to proceed without interruption. Fresh medium is continuously supplied to maintain nutrient levels and remove waste products, enabling sustained high-density cell culture and increasing overall productivity within a compact footprint.
2Productivity
If multiple manipulations are performed for cell culture and lysis, then cell culture process is completed, but contamination risk increases
Solution Approach 1:
The system combines cell culture, medium exchange, and cell harvesting functions within a single sealed bioreactor system. The filter assembly integrates separation and containment functions, allowing cells to be cultured and then harvested without opening the system or transferring to external equipment, thereby eliminating contamination risks associated with multiple manipulations.
Solution Approach 2:
The bioreactor system performs self-contained operations including automated medium extraction through the filter, fresh medium injection, and cell harvesting. The system requires no external intervention for these critical steps, maintaining sterility through automated closed-loop operation and eliminating human handling that could introduce contaminants.
3Productivity
If expensive active ingredients are used in large quantities for large volume culture, then cell culture is maintained, but cost increases
Solution Approach 1:
The continuous medium exchange system maintains optimal nutrient concentrations throughout the culture process by continuously removing metabolites and supplying fresh medium. This prevents nutrient depletion and waste accumulation, allowing sustained high-density cell growth with efficient use of expensive active ingredients rather than requiring large initial volumes.
Solution Approach 2:
The system enables high cell density culture by dynamically controlling medium composition and exchange rates. By maintaining optimal physiological parameters through continuous monitoring and adjustment, the system achieves high productivity in a small volume, reducing the total quantity of expensive active ingredients required compared to conventional large-volume batch culture.
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
Enables continuous production and harvesting of biological compounds, reduces contamination risk, decreases costs, and increases safety by automating the process, particularly suitable for Point of Care production of CAR-T cells.
Implementation Method 1
a filter (120) disposed in the culturing tank (110) so that the filter (120) separates the culturing tank (110) into an upper compartment (110a) and a lower compartment (110b), the filter (120) being configured to confine the at least one cell in the lower compartment (110b)
Implementation Method 2
an agitating device (180) disposed in the lower compartment (110b) and configured to agitate the medium
Implementation Method 3
an extraction device in fluidic communication with the culturing tank, the extraction device being configured to extract the medium out of the upper compartment of the culturing tank
Implementation Method 4
a filling device in fluidic communication with the culturing tank, the filling device being configured to inject fresh medium in the upper compartment of the culturing tank
Data Source
Figure 1
Figure 2~3
Figure 4A~4I
AI summary
The present disclosure relates to a bioreactor for cell culturing, the bioreactor comprising: a culturing tank, a sliding filter, an extraction device configured to extract medium out of the culturing tank, a filling device configured to inject fresh medium in the culturing tank, and an agitating device.