Parylene Membrane Filter for CTC Viability
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Solution Overview
Problem
Current methods for capturing circulating tumor cells (CTCs) using membrane filters face challenges such as low viability due to cell damage during filtration, and existing technologies fail to optimize key parameters like filter geometry, pressure, and filtration time for high efficiency and viability.
Innovation Solution
A filtration system is designed with a parylene membrane substrate having a predetermined geometric design, including hole shape, dimension, and filter opening factor, which balances pressure, filtration duration, and transfilter pressure to maximize the viability and efficiency of capturing live CTCs, using equations to optimize the accumulative viability and time-dependent lysis of cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If single-layer membrane filters are used for CTC filtration, then filtration efficiency is improved, but cell viability deteriorates due to cell damage and lysis
Solution Approach 1:
The single-layer membrane filter is divided into two separate layers: a capture layer with larger pores for efficient CTC capture, and a support layer for structural integrity. This segmentation allows each layer to perform its specific function optimally without compromising cell viability, as the capture layer can be designed with larger pores that reduce mechanical stress on captured cells.
Solution Approach 2:
The invention transitions from a single-layer two-dimensional structure to a multi-layer three-dimensional structure. The dual-layer configuration creates vertical separation of functions, with the capture layer positioned to maximize CTC retention while the support layer provides mechanical strength, thereby resolving the contradiction between filtration efficiency and cell viability.
2Reliability
If dual-layer 3D parylene membrane filters are used, then cell viability is improved, but enrichment efficiency deteriorates due to blood cells trapped in filter gap
Solution Approach 1:
The filter structure is designed with non-uniform pore distribution and varying pore sizes across different layers. The capture layer has larger pores optimized for CTC capture, while the support layer has smaller pores that prevent blood cell trapping. This local quality variation allows the filter to maintain high cell viability while improving enrichment efficiency by preventing unwanted cell accumulation in the filter gap.
3Productivity
If filtration pressure is increased to improve throughput, then productivity is improved, but cell damage increases reducing viability
Solution Approach 1:
The invention employs a dynamic pressure control system that adjusts filtration pressure in real-time based on flow rate and cell capture status. During the filtration process, pressure is optimized to maintain high throughput while automatically reducing when cell capture increases, thereby preventing excessive mechanical stress on cells and maintaining high viability throughout the filtration process.
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 system achieves high viability and enrichment of CTCs, allowing for successful cell culture and drug efficacy screening, with a significant improvement in capture efficiency and viability compared to previous methods, demonstrating a 'golden zone' for optimal filtration conditions.
Implementation Method 1
Size based filtration has been explored for solid-tumor cancers because epithelial CTCs (15-30 μm in diameter) are generally much larger and less deformable than normal blood cells
Implementation Method 2
passing the body fluid under pressure through a filtration system for capturing viable circulating cells
Data Source
Figure 1A~1B
Figure 2A~2D
Figure 3A~3D
AI summary
The present invention provides methods for designing a filtration systems for capturing viable tumor cells, such as circulating tumor cells at high efficiency and high viability. The methods involve development of a set of "key engineering design parameters" that are crucial to achieve high tumor cell viability. These important design parameters include the filter geometry design, fluid delivery method, transfilter pressure and total filtration time.