Microfluidic Size-Based Separation of Dissociated Tissue Cells
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Solution Overview
Problem
Current diagnostic tools face challenges in accurately representing genetically heterogeneous cancer cells and different cell types within a tumor mass due to the reliance on small, localized tumor sampling, leading to inefficient sequencing and analysis, particularly when dealing with mixed populations of tumor and normal cells.
Innovation Solution
A method involving the homogenization and dissociation of tissue samples followed by size-based sorting using microfluidic devices, such as deterministic lateral displacement or hydrodynamic filtration, to separate tumor cells from normal cells without the need for staining, allowing for the enrichment of tumor and normal cell populations for further analysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Device complexity
If small, localized tumor sampling is used for diagnostic analysis, then the complexity of the diagnostic process is reduced, but the accuracy of representing tumor heterogeneity deteriorates
Solution Approach 1:
The patent segments the tumor tissue into individual cellular particles through homogenization and dissociation, allowing each cell to be separately analyzed. This segmentation enables comprehensive representation of tumor heterogeneity by examining many individual cells rather than a small localized sample, thereby improving measurement precision while managing complexity through automated microfluidic processing
Solution Approach 2:
The patent replaces complex mechanical staining and sorting systems with a streamlined microfluidic approach that uses size-based separation. This substitution reduces diagnostic process complexity by eliminating multiple staining steps and complex sorting procedures while maintaining or improving tumor heterogeneity representation through automated cellular particle analysis
2Ease of operation
If mixed populations of tumor and normal cells are analyzed together, then the ease of operation is improved, but the productivity of sequencing and analysis deteriorates
Solution Approach 1:
The patent extracts tumor cells from the mixed population of tumor and normal cells using size-based separation in microfluidic devices. By taking out the tumor cell subset, the system enables focused sequencing and analysis on relevant cells, improving productivity by avoiding wasted sequencing capacity on normal cells while maintaining ease of operation through automated separation
Solution Approach 2:
The patent changes the physical parameter of cell size to enable separation of tumor cells from normal cells. By utilizing the size difference between tumor and normal cellular particles, the system achieves automatic enrichment of tumor cells, improving sequencing productivity without complicating the operational workflow
3Measurement precision
If staining is conducted prior to sorting to identify tumor cells, then the measurement precision of cell identification is improved, but the device complexity and time required for the process worsen
Solution Approach 1:
The patent replaces the complex biochemical staining and fluorescence detection system with a simpler mechanical size-based separation system. By using microfluidic devices that separate cells based on physical size differences, the system achieves tumor cell enrichment without requiring staining reagents, fluorescence microscopy, or complex sorting instrumentation, thereby reducing device complexity while maintaining adequate identification accuracy
Solution Approach 2:
The patent employs disposable microfluidic chips for size-based separation, replacing expensive and complex staining and sorting equipment. These disposable devices perform tumor cell enrichment through simple size-based physics, reducing overall device complexity and cost while achieving the necessary cell identification and separation functionality
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
This approach enables more accurate representation of tumor heterogeneity, reduces sequencing costs, and simplifies downstream analyses like flow cytometry by providing enriched populations of tumor and normal cells, facilitating better therapeutic approaches and resistance prediction.
Implementation Method 1
sorting using microfluidic devices, such as deterministic lateral displacement or hydrodynamic filtration
Implementation Method 2
sorting using microfluidic devices, such as deterministic lateral displacement or hydrodynamic filtration
Data Source
AI summary
The present disclosure provides a method of separating cellular particles from a tissue sample and then sorting the cellular particles into two or more cellular particle populations.