Microscopy-Based Particle Capture Using Selective Hydrogel Fixation
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Solution Overview
Problem
Existing methods struggle to sort heterogeneous biological compositions into enriched subpopulations while maintaining individual cell information and without relying on target-specific fluidics-driven sorting.
Innovation Solution
The method involves introducing a population of particles into a flow cell, capturing images, selectively polymerizing a hydrogel over target particles to fix them at a position, and optionally barcoding microcapsules to preserve positional information, allowing for downstream analysis without changing flow pressure or direction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If fluidics-driven cell sorting is used to separate heterogeneous cell populations, then sorting capability is improved, but device complexity and operational complexity increase due to requirements for flow pressure control, microvalves, and complex microfluidic channels
Solution Approach 1:
The patent extracts the sorting function from complex fluidics-driven systems and relocates it to a simpler platform where cells are passed through a linear flow cell and sorted based on imaging identification without requiring flow pressure changes or microvalves. This separates the sorting decision-making process from the physical sorting mechanism, dramatically simplifying the device while maintaining sorting capability.
Solution Approach 2:
The patent replaces the mechanical fluidics-based sorting system with an imaging-based identification system combined with a simpler deposition mechanism. Instead of using flow dynamics, pressure control, and microvalves to sort cells, the system uses optical imaging to identify target cells and then deposits them onto a substrate based on their identified positions, substituting complex mechanical control with optical detection and controlled deposition.
2Productivity
If bulk analysis is used to analyze heterogeneous cell populations, then analysis throughput is improved, but loss of individual cell information occurs
Solution Approach 1:
The patent performs preliminary imaging and identification of individual cells before bulk processing. By capturing images of cells at their specific positions in the flow cell and recording this positional information before deposition and bulk analysis, the system preserves individual cell information that can be correlated with downstream bulk analysis results, enabling both high throughput and individual cell resolution.
3Device complexity
If microscopy-based particle capture is used to sort particles, then device complexity is reduced, but sorting speed may be limited by imaging and processing time
Solution Approach 1:
The patent employs periodic action by passing the cell suspension through the flow cell in discrete passes or cycles. Cells are imaged, identified, and deposited during each pass, allowing the system to maintain simple device architecture while achieving sorting through repeated periodic processing rather than requiring complex real-time sorting mechanisms.
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 the sorting of diverse particle populations using simpler microfluidics systems, maintaining cell viability and facilitating bulk analysis by correlating image data with positional information for accurate sequencing.
Implementation Method 1
selectively polymerizing a hydrogel over at least part of the at least one imaged target particle so as to fix, or thereby fixing the at least one imaged target particle at a position on the flow cell
Data Source
AI summary
A method of sorting particles, the method comprising: introducing a population of particles into a flow cell; identifying at least one target particle among at least some particles of the population of particles; selectively polymerizing a hydrogel over at least part of the at least one target particle so as to fix the at least one target particle at a position on the flow cell.