Parylene Membrane Filters for Circulating Tumor Cell Recovery
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Solution Overview
Problem
Current filtration technologies are inadequate for efficiently capturing circulating tumor cells from blood due to low recovery rates and lengthy processing times, especially when dealing with low concentrations of cells in large blood volumes, as they often have randomly distributed holes that result in large openings and fused defects.
Innovation Solution
The development of parylene membrane filters with precisely controlled geometric designs, including size, shape, and density of holes, which allow for high-efficiency capture of circulating tumor cells while allowing red blood cells to pass through, using a substrate comprising parylene polymer deposited through a highly-conformal vapor deposition process.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If commercially available polycarbonate filters are used for mechanical filtration of blood, then large sample volumes can be processed, but the recovery rate is low due to randomly distributed holes with large openings and fused defects
Solution Approach 1:
The patent replaces the mechanical punching method used to create filter holes with a laser-based fabrication method. This substitution eliminates the random distribution and fused defects characteristic of mechanically punched holes, producing precise, uniformly distributed holes with controlled dimensions that maintain structural integrity while enabling effective cell filtration.
Solution Approach 2:
The patent changes the hole size parameter from the large, uncontrolled openings in commercial filters to precisely controlled smaller holes (e.g., 5-15 micrometers in diameter). This parameter change ensures that holes are small enough to capture circulating tumor cells effectively while maintaining uniform distribution and avoiding fused defects, thereby improving recovery rates.
2Reliability
If existing filtration methods are used to capture circulating tumor cells, then filtration can be performed, but the processing time is extended to hours
Solution Approach 1:
The patent replaces conventional mechanical filtration systems with a laser-fabricated membrane filter system. This substitution enables faster processing by creating a more efficient filtration structure with precise hole distribution and optimal size, reducing the time required to process blood samples from hours to minutes while maintaining high capture capability.
3Productivity
If membrane filters with larger hole openings are used, then processing speed increases, but the capture efficiency of small tumor cells decreases
Solution Approach 1:
The patent optimizes the hole size parameter to a specific range (5-15 micrometers in diameter) that balances filtration speed and capture efficiency. This parameter optimization ensures holes are small enough to effectively capture small circulating tumor cells while maintaining sufficient open area for adequate fluid flow and processing speed.
Solution Approach 2:
The patent implements uniform distribution of holes across the membrane surface, ensuring consistent local quality throughout the filter. This uniform distribution prevents localized clogging and maintains steady flow rates, achieving both high capture efficiency and sustained filtration speed throughout the processing period.
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 parylene membrane filters achieve greater than 80% recovery with high enrichment factors, processing samples in less than 10 minutes, outperforming existing methods by providing a cost-effective and reliable means for CTC monitoring with minimal human intervention.
Implementation Method 1
a substrate comprising parylene polymer deposited through a highly-conformal vapor deposition process
Implementation Method 2
A mechanical filter can be used to remove, filter, collect, concentrate and analyze particles and cells in a variety of fluid medium
Data Source
Figure 1A~1C
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AI summary
The invention provides parylene membrane filters (110), filter devices and methods of making them and using them in the mechanical separation of cells and particles by size. The provision of parylene membrane filters with high figures of merit and finely controlled hole sizes (125, 135) allows the separation of cells and particles in a variety of biological and other fluids according to size.