Bidirectional Flow Column for High-Viability Cell Purification
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Solution Overview
Problem
Current methods for purifying biological cells, such as those using magnetic beads, are inefficient in capturing viable cells at high concentrations and often result in cell damage or death due to shear stress and physical trapping within column matrices, leading to low purity and viability issues, especially when dealing with large sample volumes and circulating tumor cells.
Innovation Solution
The use of a column technology with a solid phase, such as a chromatography medium, that allows for rapid bidirectional flow to capture and recover cells without physical trapping, utilizing frits to minimize backpressure and maintain cell integrity, enabling high-purity and high-concentration cell isolation in a short time frame.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If magnetic beads are used to capture cells, then cell selection is improved, but cell viability deteriorates due to shear stress and physical trapping
Solution Approach 1:
The patent extracts the harmful magnetic beads from the system and replaces them with a magnetic-free column containing solid phase particles. This removes the source of shear stress and physical trapping while maintaining cell capture capability through affinity binding between cells and the solid phase medium.
Solution Approach 2:
The patent replaces the mechanical magnetic bead-based capture system with a chemical/biochemical affinity-based column system. Instead of using magnetic forces and physical trapping, the system uses specific binding interactions between cell surface markers and ligands on the solid phase particles, eliminating mechanical stress on cells.
2Measurement precision
If conventional column methods are used, then cell capture is achieved, but processing speed deteriorates and cells are trapped in the matrix
Solution Approach 1:
The patent applies local quality by creating specific functional zones within the column - the solid phase particles are distributed to provide localized capture sites throughout the column matrix. This allows cells to be captured efficiently at multiple points along the flow path rather than requiring slow diffusion to a single capture zone, significantly improving processing speed.
Solution Approach 2:
The patent uses porous solid phase particles with controlled pore structures that allow rapid cell access to binding sites while preventing cell entrapment. The porous structure provides high surface area for cell capture but with open pathways that enable fast flow rates and prevent cells from becoming trapped in the matrix.
3Quantity of substance
If high concentration cell samples are processed, then sample throughput is improved, but cell purity deteriorates due to insufficient separation
Solution Approach 1:
The patent implements continuous flow processing where sample, wash buffers, and elution buffers continuously pass through the column. This continuous action allows high concentration samples to be processed rapidly while maintaining separation efficiency - the continuous flow ensures that non-specifically bound material is constantly washed away while specifically bound cells remain captured, achieving both high throughput and high purity.
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 isolates viable cells with high purity and concentration, maintaining cell integrity even after multiple passes through the column, allowing for rapid processing of large samples and improving cell viability compared to existing technologies.
Implementation Method 1
The solid phase can be a chromatography medium such as a gel resin. Following capture, the column is washed to remove material that is not specifically bound to the column medium.
Implementation Method 2
utilizing frits to minimize backpressure and maintain cell integrity, enabling high-purity and high-concentration cell isolation in a short time frame
Data Source
AI summary
This invention relates to devices and methods for purifying biological cells. For example, viable tumor, stem, immune and sperm cells can be purified from a complex biological sample using a column, including a pipette tip column. Cells can be purified in a sealed chromatographic system. Methods of the invention can aid research, diagnosis and treatment of cancer.