Multistage Cell Culture System with Closed-System Liquid Handling
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Solution Overview
Problem
Current cell culture systems face challenges such as temperature fluctuations, contamination, and spatial restrictions when handling multilayer cell culture containers, which require a high-grade clean environment and manual handling, leading to labor-intensive operations and potential cell damage.
Innovation Solution
A cell culture system with a multistage-shelf-type cell culture container and a drive mechanism that maintains closed-system lines, allowing for posture changes within an incubator, reducing the need for manual handling and minimizing contamination risks by maintaining a sterile environment and controlling humidity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If the cell culture container is removed from the incubator for medium replacement, then the operation can be performed, but the cells are stimulated by temperature drop and may be damaged
Solution Approach 1:
The patent extracts the harmful operation (removing container from incubator) by implementing an in-incubator medium replacement system. The liquid supply/discharge device performs all necessary operations within the incubator environment, eliminating the need to take out the cell culture container and avoiding temperature shock to cells.
Solution Approach 2:
The patent introduces an intermediary liquid supply/discharge device that operates within the incubator. This intermediary device handles medium replacement through closed-system lines, allowing operation without direct manual handling of the container and protecting cells from temperature fluctuations.
2Ease of operation
If the cell culture container is manually transferred, then the operation can be completed, but the culture medium may be shaken causing cells to be peeled off or stimulated
Solution Approach 1:
The system enables self-service operation where the liquid supply/discharge device automatically performs medium replacement without requiring manual transfer of the heavy multilayer container. The carriage device with fixing member secures the container in place, and all liquid handling is performed in situ, eliminating vibrations and impacts from manual handling.
3Stability of the object's composition
If the cell culture container is kept in the incubator for medium replacement, then cell stability is maintained, but the reconnection of tubes may cause contamination
Solution Approach 1:
The patent implements continuous closed-system lines that remain connected throughout the medium replacement process. The liquid supply/discharge device connects to the cell culture container through sealed ports, maintaining continuous sterile barriers and eliminating the opening/closing cycles that would compromise sterility and introduce contamination risk.
Solution Approach 2:
The system maintains the sterile incubator atmosphere as an inert environment throughout the operation. All connections and liquid handling occur within this controlled atmosphere without exposing the system to external air, effectively using the sterile environment as a protective barrier against contamination.
4Productivity
If a multilayer type cell culture container is used, then culture capacity is increased, but the weight becomes heavy making manual transfer difficult
Solution Approach 1:
The system eliminates the need for manual transfer of the heavy multilayer container by implementing automated operations. The carriage device with fixing member secures the container, and the liquid supply/discharge device performs all medium replacement tasks in place, allowing the system to serve itself without human physical intervention.
5Ease of operation
If CO2 gas is introduced into the incubator during tube attachment, then liquid feeding is enabled, but the gas leaks and humidifies the room causing rusting
Solution Approach 1:
The system uses continuous closed-system lines that remain connected throughout the operation. CO2 gas is introduced only into the specific container being serviced through sealed ports, not into the general incubator atmosphere. This localized approach prevents gas leakage into the room and subsequent humidity-related rusting problems.
Data Source
AI summary
According to one embodiment of the present disclosure, a cell culture system includes: a cell culture container; a liquid storage part configured to store a liquid including a culture medium or a reagent to be supplied to the cell culture container; and a cell collection part configured to collect cells cultured in the cell culture container, wherein the cell culture container, the liquid storage part, and the cell collection part are connected by spatially closed-system lines at least during a period from feeding of the liquid to the cell culture container to removal of the cultured cells, and wherein the cell culture container is arranged in an incubator in a form of a multistage shelf including a liquid supply/discharge port.