Aqueous Multiphase System for Mammalian Cell Separation
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Solution Overview
Problem
Current methods for separating cultured mammalian cells from contaminants in cell cultures, such as bacteria and nonviable cells, often require antibiotics that can interfere with cell processes and result in the disposal of valuable cell populations, which is inefficient and wasteful.
Innovation Solution
A density-based method using an aqueous multiphase system (AMPS) with a polyethylene glycol (PEG)-Ficoll system, where the physical properties are tuned to separate mammalian cells from contaminants based on their respective densities, allowing cells to be recovered from the liquid-liquid interface while contaminants sediment at the bottom of the container.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antibiotics are used to treat or prevent contamination, then contamination is controlled, but cell processes are interfered with and antibiotic resistance develops
Solution Approach 1:
The patent extracts and removes contaminants from the cell culture using density-based centrifugal separation. Contaminants are separated from viable cells based on density differences, allowing selective removal of harmful elements without affecting the cells, thereby eliminating the need for antibiotics that would interfere with cell processes.
Solution Approach 2:
The patent introduces an aqueous multiphase system as an intermediary medium between the cell culture and the separation process. This intermediary system enables selective separation of contaminants from cells through density gradients, providing a alternative to direct antibiotic treatment that avoids harmful effects on cell processes.
2Reliability
If contaminated cultures are destroyed with bleach, then contaminants are eliminated, but valuable cell populations are disposed of
Solution Approach 1:
The patent extracts and removes only the contaminants from the cell culture through density-based centrifugal separation. By separating contaminants from viable cells based on density differences, the method eliminates contaminants while preserving and recovering valuable cell populations, avoiding their disposal.
Solution Approach 2:
The patent implements a process to discard contaminants while recovering viable cells. Through density-based separation, contaminants are discarded at the bottom of the centrifuge tube while viable cells are recovered from the interface region, enabling reuse of valuable cell populations that would otherwise be lost.
3Reliability
If density-based separation is used, then cells and contaminants are separated effectively, but the system complexity increases
Solution Approach 1:
The patent utilizes changes in density as a key parameter to achieve separation. By adjusting the density characteristics of the aqueous multiphase system, viable cells and contaminants are separated based on their inherent density differences. This parameter-based approach provides effective separation using a relatively simple centrifugal process rather than complex multi-step systems.
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
This method effectively enriches viable cell populations, reduces the need for antibiotics, and preserves the viability and growth rates of recovered cells, enabling the reuse of cultures that would otherwise be discarded.
Implementation Method 1
The top liquid phase has a top liquid density that is different than a bottom liquid density of the bottom liquid phase... In response to the centrifuging and in accordance with the respective density, the cultured mammalian cells are separated from the contaminants
Implementation Method 2
The container, containing the liquid and the cover medium, is, then, centrifuged for a second time period subsequent to the first time period
Implementation Method 3
The container, containing the liquid and the cover medium, is, then, centrifuged for a second time period... In response to the centrifuging and in accordance with the respective density
Data Source
AI summary
A method is directed to separating contaminants from mammalian cells in an aqueous multiphase system, and includes loading a container with a liquid having a top liquid phase and a bottom liquid phase. A cover medium is inserted in the container with a mixture of cultured mammalian cells and contaminants. The container is incubated and centrifuged for respective periods of time. In response to the centrifuging, the cells are separated from the contaminants in accordance with the respective density of the cells, the contaminants, and each liquid phase, resulting in the cells being located at a liquid-to-liquid interface between the top liquid phase and the bottom liquid phase and the contaminants being located at the bottom of the container.