Offset Pore Microfiltration Device for Circulating Tumor Cell Separation
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Solution Overview
Problem
Current cell separation methods, particularly for circulating tumor cells from blood, face challenges such as low recovery rates, variability in surface antigen expression, and mechanical trauma during filtration, which limits the efficiency and viability of captured cells.
Innovation Solution
A microfiltration device with a top and bottom porous membrane, both formed from parylene and assembled using microfabrication techniques, where the pores in the top membrane are offset from those in the bottom membrane, reducing cell membrane tension and enhancing capture efficiency while maintaining cell viability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Device complexity
If a single porous membrane is used for cell filtration, then the device structure is simple, but the cell capture efficiency is limited and mechanical trauma occurs
Solution Approach 1:
The single membrane is divided into two separate porous membranes (top and bottom) with different pore sizes. The top membrane has larger pores (e.g., 10 μm) while the bottom membrane has smaller pores (e.g., 8 μm), creating a segmented filtration system that improves capture efficiency while reducing mechanical stress on captured cells.
Solution Approach 2:
The invention transitions from a two-dimensional single-membrane filtration to a three-dimensional dual-membrane structure with a gap between them. This dimensional change creates a capture zone where cells are trapped between the membranes, significantly improving capture efficiency while the gap reduces mechanical trauma.
2Productivity
If pore sizes are optimized for maximum cell capture, then capture efficiency increases, but mechanical trauma to cell membranes increases
Solution Approach 1:
The filtration function is segmented into two membranes with different pore sizes. The top membrane's larger pores allow cells to pass through with minimal trauma, while the bottom membrane's smaller pores provide the primary capture mechanism, distributing the mechanical stress across two structures rather than one.
Solution Approach 2:
The gap between the two membranes acts as a cushioning zone that absorbs mechanical stress. When cells are captured, the gap provides space that reduces the direct mechanical trauma to cell membranes, preserving cell viability while maintaining capture efficiency.
3Productivity
If dense pore arrangement is used to increase capture efficiency, then more cells are captured, but pore fusion occurs and efficiency decreases
Solution Approach 1:
The pore density requirement is segmented between two membranes. The top membrane can have lower pore density with larger pores, while the bottom membrane has higher pore density with smaller pores. This segmentation allows each membrane to be manufactured with appropriate pore characteristics without requiring extremely high precision in a single membrane.
Solution Approach 2:
The dual-membrane structure acts as a composite filtration system where two different membrane configurations work together. This composite approach allows optimization of each membrane's pore structure independently, achieving high overall capture efficiency while avoiding the pore fusion problems that would occur in a single high-density membrane.
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 device achieves high capture efficiency of viable circulating tumor cells with reduced mechanical trauma, allowing for efficient separation and further analysis, such as immunofluorescent staining and cell viability tests, with up to 86% capture efficiency and maintaining cell integrity for extended periods.
Implementation Method 1
microfiltration device having a top porous membrane and a bottom porous membrane... Filtering may be provided through the capture of cells within the pores of the top membrane or within a gap between the top membrane and the bottom membrane
Data Source
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Figure 3~4C
Figure 5A~5E
AI summary
A microfiltration apparatus and method for separating cells, such as circulating tumor cells, from a sample using a microfiltration device having a top porous membrane and a bottom porous membrane. The porous membranes are formed from parylene and assembled using microfabrication techniques. The porous membranes are arranged so that the pores in the top membrane are offset from the pores in the bottom membrane.