Microfluidic Cell Isolation Array with Selective Release
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Solution Overview
Problem
Current cell sorting technologies face limitations in isolating and analyzing individual cells, as they often require simultaneous identification and sorting, fail to allow multiple analyses of the same cell, and are unable to perform multiplex assays or capture specific cell subpopulations without cell damage, leading to inefficiencies in cell-specific testing and personalized medicine applications.
Innovation Solution
A microfluidic system with an array of wells and channels that allows for the isolation, retention, and analysis of cells in single-cell or cluster format, enabling multiple assays and optical interrogation, while maintaining cell viability and allowing for selective release and downstream analysis, without the need for antibody-coated wells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If flow cytometry is used for cell identification and sorting, then cell identification and sorting can be performed simultaneously, but multiple analyses of the same cell cannot be conducted and arbitrary cell subpopulation sorting is limited
Solution Approach 1:
The system segments the cell analysis process into distinct functional modules: cell capture in individual wells, optical interrogation for identification, and selective release for downstream analysis. This segmentation allows a single cell to be captured, analyzed multiple times through different optical methods, and then released for additional assays, thereby enabling multiple analyses of the same cell while maintaining high throughput
Solution Approach 2:
The system employs dynamic control of cell retention and release through adjustable retention forces and selective release mechanisms. Cells can be dynamically retained during optical analysis and then selectively released based on identification results, enabling flexible multiple analysis workflows and arbitrary subpopulation sorting without compromising analysis throughput
2Measurement precision
If conventional microfluidic devices use antibody-coated wells for cell selection, then specific antigen-expressing cells can be captured, but cell removal causes damage and non-expressing cells cannot be captured
Solution Approach 1:
The system introduces a reversible cell-surface interaction mechanism as an intermediary between the well surface and cells. This intermediary allows specific antigen-expressing cells to be captured through antibody-antigen binding while enabling damage-free removal through controlled disruption of the interaction, eliminating cell damage associated with conventional adhesion-based capture methods
Solution Approach 2:
The system changes the binding parameters of cell-surface interactions by using antibodies with adjustable affinity and controlling retention forces. This allows specific cell capture through high-affinity binding while enabling gentle release by reducing retention forces below the binding threshold, thereby achieving specific cell selection without cell damage
3Object-affected harmful factors
If cellular filters are used to separate sample components by size, then separation without cell damage can be achieved, but specific cell identification and individual cell retrieval are not possible
Solution Approach 1:
The system segments cells into individual wells rather than using bulk filtration, placing each cell in an isolated compartment. This segmentation enables both gentle handling (avoiding damage) and precise optical interrogation of individual cells for specific identification, while maintaining the ability to retrieve individual cells based on identification results
Solution Approach 2:
The system transitions from one-dimensional size-based filtration to a two-dimensional approach combining spatial confinement in wells with optical dimension analysis. This dimensional change enables specific cell identification through optical properties while maintaining gentle handling, and allows selective retrieval based on identified characteristics rather than just size
4Productivity
If existing technologies are used for cell sorting, then cell isolation can be achieved, but multiplex assays on individual cells cannot be performed with minimal sample preparation
Solution Approach 1:
The system employs universal well structures and reagent delivery mechanisms that can accommodate multiple different assay types on the same captured cells. The same cell capture and retention platform supports various optical analyses and downstream assays without requiring different capture mechanisms or extensive re-preparation, thereby enabling multiplex assays with minimal sample preparation while maintaining high productivity
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
Enables efficient isolation, retention, and analysis of individual cells or clusters, facilitating multiple assays and maintaining cell viability, thereby addressing the limitations of existing technologies in cell sorting and analysis.
Implementation Method 1
facilitating diffusive delivery of a process reagent to the cell population
Implementation Method 2
transmitting heat, through the substrate, to the cell population
Data Source
AI summary
A system and method for isolating cells, comprising: a substrate having a broad surface; an array comprising a set of wells defined at the broad surface of the substrate, each well including: a base surface, an open surface directly opposing the base surface, defined at the broad surface of the substrate, and configured to receive one of a single cell and a single cluster of cells from a direction perpendicular to the broad surface of the substrate, and a set of channels that fluidly couple each well to at least one adjacent well; wherein the set of wells includes an interior subset and an exterior subset fluidly coupled to and surrounding the interior subset by way of the set of channels; and a fluid delivery module surrounding the array and fluidly coupled to each well in the set of wells.