Fixing Rare Circulating Cells for Size Exclusion Filtration
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Solution Overview
Problem
Current methods for isolating rare circulating cells, such as circulating tumor cells, from biological fluids face challenges due to their elastic nature, which allows them to pass through filters with smaller pores, compromising recovery rates, and the heterogeneity of biological properties limits the effectiveness of enrichment techniques based on cell surface markers.
Innovation Solution
Fixing rare circulating cells with a fixative like formaldehyde increases their rigidity, allowing for their isolation and enrichment using size exclusion techniques like filtration through filter membranes with specific pore sizes, independent of their biological properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If size exclusion techniques (filtration) are used to isolate rare circulating cells, then cell recovery is improved, but cell elasticity causes cells to pass through smaller pores reducing recovery
Solution Approach 1:
The patent applies preliminary fixation treatment to rare circulating cells before filtration to increase their rigidity. By pre-fixing cells with formaldehyde or other fixatives, the cells become less elastic and more likely to be retained by filter membranes during subsequent size exclusion techniques, thereby improving recovery rates
Solution Approach 2:
The patent changes the physical parameter of cell rigidity through chemical fixation. By treating cells with fixatives that cross-link cellular proteins, the cells transition from an elastic state to a rigid state, making them more suitable for size exclusion-based isolation and improving their retention on filters
2Measurement precision
If enrichment techniques based on cell surface markers are used, then specific cell types can be targeted, but heterogeneity of biological properties limits effectiveness
Solution Approach 1:
The patent extracts the limitation of biological property heterogeneity by shifting from biology-based enrichment to physics-based size exclusion. By removing dependence on cell surface markers and biological characteristics, the method achieves universal applicability across different cell types while maintaining isolation effectiveness through physical size differences
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 fixation method significantly improves the recovery rate of rare circulating cells by preventing them from passing through filters, achieving higher retention and purity, as demonstrated by improved recovery rates in experiments using formaldehyde pretreatment.
Implementation Method 1
fixation of a rare circulating cell may increase the rigidity of the cell
Implementation Method 2
Rare circulating cells can be recovered from a sample using, for example, size exclusion techniques (e.g., filtration)
Data Source
AI summary
Traditionally, enriching or isolating rare circulating cells from a sample has proven difficult as rare circulating cells can be heterogeneous, which limits the use of techniques based on biological properties (e.g., cell surface markers), and can be flexible, which hinders techniques based on physical properties (e.g., diameter size). Methods disclosed herein are capable of enriching or isolating rare circulating cells are minimally impacted by heterogeneity or flexibility of rare circulating cells, and therefore, overcome disadvantages observed with prior techniques. For example, a method for enriching or isolating rare circulating cells from a sample of a subject including fixing one or more rare circulating cells in a sample to create a fixed sample, and isolating the one or more rare circulating cell from the fixed sample using a size exclusion technique is disclosed.