Microfluidic Cell Isolation via Size-Based Filtration
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Solution Overview
Problem
Current cell sorting systems face limitations in isolating and analyzing cells due to issues such as cell damage, inability to perform multiplex assays, and inefficiencies in sample preparation, particularly in flow cytometry and conventional microfluidic devices, which hinder widespread adoption for personalized medicine and drug testing.
Innovation Solution
A microfluidic system with a substrate featuring an array of wells and channels that allows for individual cell capture and retention without antibodies, enabling multiplex assays and maintaining cell viability through controlled fluid flow and reagent delivery, facilitating real-time tracking and downstream analysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional microfluidic devices use cell-specific antibodies for cell selection, then specific cell types can be captured, but cell viability is compromised and non-expressing cells cannot be captured
Solution Approach 1:
The patent replaces the biochemical mechanism (antibody-antigen binding) with a mechanical size-based filtration system. The porous substrate physically separates cells based on size differences, capturing target cells while allowing smaller cells and debris to pass through, thereby maintaining cell viability without requiring cell-specific antibodies.
Solution Approach 2:
The invention changes the selection parameter from biochemical (antigen expression) to physical (cell size). By controlling the pore size of the substrate, the system can selectively capture cells of specific sizes, enabling both viable cell isolation and the capture of cells that do not express specific antigens.
2Measurement precision
If flow cytometry is used for cell identification and sorting, then cells can be sorted by specific markers, but multiple analyses cannot be performed on the same cell and observation is limited to the sorting point
Solution Approach 1:
The system performs preliminary cell isolation and capture on the porous substrate before any analysis is conducted. This allows the same isolated cell to be subjected to multiple different assays and analyses sequentially, enabling multiplex testing without requiring the cell to be sorted and re-isolated for each assay type.
Solution Approach 2:
The porous substrate serves as a universal platform that can accommodate multiple different assay types and analysis methods. The same captured cell can be analyzed using different stains, reagents, and detection methods, making the system versatile for various research and diagnostic applications.
3Reliability
If cellular filters are used to separate sample components by size, then cell damage is minimized, but specific cell identification and individual cell retrieval are not possible
Solution Approach 1:
The system segments the filtration and identification functions into distinct components: the porous substrate performs size-based separation to maintain cell integrity, while the imaging system provides subsequent specific cell identification. This segmentation allows both gentle size-based filtering and precise optical identification to be achieved without compromising either function.
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 effectively isolates and analyzes cells in single-cell or cluster format, enabling multiple assays and maintaining cell viability, thereby supporting advanced cellular analysis and personalized medicine applications.
Implementation Method 1
controlled fluid flow and reagent delivery
Implementation Method 2
receiving a process reagent at the array, thereby facilitating diffusive delivery of the process reagent to the cell population
Implementation Method 3
transmitting heat, through the substrate, to the cell population
Data Source
AI summary
A system and method for isolating and analyzing single cells, comprising: a substrate having a broad surface; a set of wells defined at the broad surface of the substrate, and a set of channels, defined by the wall, that fluidly couple each well to at least one adjacent well in the set of wells; and fluid delivery module defining an inlet and comprising a plate, removably coupled to the substrate, the plate defining a recessed region fluidly connected to the inlet and facing the broad surface of the substrate, the fluid delivery module comprising a cell capture mode.