Microbead Column Filtration for Viable Cell Isolation
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Solution Overview
Problem
Existing methods for isolating circulating rare cells, such as CTCs and CTMs, face challenges in capturing efficiency, purity, and throughput due to variability in cell surface markers, size overlap, cell damage, and complex microfluidic designs, leading to inaccurate results and long processing times.
Innovation Solution
A method using a column with microbeads of specific diameters forming interstices to separate particles by size, minimizing shear stress and clogging, allowing deformable clusters to be captured, and enabling efficient recovery of viable cells through suspension in a buffer solution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If filtration methods with porous filters are used to separate CTCs from other blood cells by size, then isolation purity is improved, but cell damage occurs and throughput is reduced
Solution Approach 1:
The invention employs a porous filtration matrix composed of interconnected pores with controlled size distribution. This matrix allows smaller blood cells to pass through while retaining larger CTCs and CTMs, achieving size-based separation. The porous structure provides multiple flow paths that reduce shear stress on captured cells, minimizing cell damage while maintaining isolation purity.
Solution Approach 2:
The invention utilizes size parameter differences between CTCs/CTM and normal blood cells to achieve separation. By designing the filtration matrix with specific pore size ranges, the system exploits the dimensional parameter variation to selectively retain target particles while allowing other cells to pass, thereby improving isolation purity without requiring complex biochemical markers.
2Manufacturing precision
If filtration methods with porous filters are used to separate CTCs from other blood cells by size, then isolation purity is improved, but processing time increases
Solution Approach 1:
The filtration matrix is designed with a segmented pore size distribution, incorporating multiple pore size ranges within the same structure. This segmentation allows different size fractions of cells to be separated through different pore pathways simultaneously, increasing throughput while maintaining isolation purity for each size category.
Solution Approach 2:
The invention transitions from traditional two-dimensional filter surfaces to a three-dimensional porous matrix structure. This dimensional change provides vastly increased surface area and multiple parallel flow paths, enabling high-volume sample processing while maintaining effective size-based separation and isolation purity.
3Reliability
If microfluidic devices are used for isolation of rare cells, then capturing efficiency is improved, but device complexity increases
Solution Approach 1:
The invention replaces complex microfluidic mechanical systems with a passive porous filtration approach. Instead of using active pumping, valve control, and complex flow dynamics typical of microfluidic devices, the system uses the intrinsic porous structure to achieve size-based separation, significantly reducing device complexity while maintaining capturing efficiency.
Solution Approach 2:
The invention extracts the core separation function from complex microfluidic systems, isolating just the essential size-based filtration mechanism. By removing unnecessary mechanical components and focusing solely on the porous filtration principle, the device achieves high capturing efficiency with minimal complexity.
4Reliability
If immunoaffinity-based enrichment systems are used to isolate CTCs, then capturing efficiency is improved, but isolation purity decreases due to marker variability
Solution Approach 1:
The invention switches from biochemical marker-based separation to physical size parameter-based separation. By exploiting the size difference between CTCs/CTM and normal blood cells, the porous filtration matrix achieves isolation purity without being affected by marker variability, while still maintaining high capturing efficiency through appropriate pore size selection.
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 method achieves high capturing efficiency, purity, and throughput for large sample volumes, preserving cell viability and enabling downstream analysis without clogging or damage.
Implementation Method 1
a first section comprising a first plurality of microbeads of a first diameter, wherein the first plurality of microbeads is retained in the column to prevent the first plurality of microbeads from passing through the lower opening
Implementation Method 2
suspending the retained second portion of particles of the biological sample and the first section in a buffer solution to form a suspension
Data Source
AI summary
A method and an automated liquid handling system for the isolation of particles from a biological sample are provided. A column, a container and a filtration unit which are adapted to be used in such a method and system are provided. The column can include a section comprising a plurality of microbeads retained there.