Degradable Hydrogel Cell Sorting for High-Throughput Imaging
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Solution Overview
Problem
Existing image-based cell sorting systems face trade-offs between throughput, scalability, and flexibility, with microfluidic capture reducing throughput and microwell arrays having low throughput.
Innovation Solution
A method using degradable gel structures for cell selection and sorting, involving a fluidics device with a channel, spatial energy modulation, and a detector to immobilize cells in gel structures based on optical signals, allowing flexible containment and scalable sorting.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If microfluidic capture and containment is used to avoid imaging challenges, then imaging capability is improved, but throughput is reduced
Solution Approach 1:
The system segments the cell sorting process into discrete steps: cells flow through a microfluidic channel one by one, are imaged by a detector, and selected cells are captured in individual microwell array positions. This segmentation allows high-speed imaging during flow while maintaining the ability to sort cells at high throughput through the array format.
Solution Approach 2:
The invention transitions from two-dimensional flow-based sorting to a three-dimensional system where cells are sorted both temporally (during flow) and spatially (into microwell array positions). This dimensional addition resolves the contradiction by allowing imaging during flow while achieving high throughput through the array format.
2Measurement precision
If microwell array systems are used to permit excellent image collection, then measurement precision is improved, but throughput is reduced
Solution Approach 1:
The system performs preliminary imaging of cells during their flow through the microfluidic channel before they are sorted into the micrawell array. This preliminary action allows the system to identify which cells to sort based on imaging data while maintaining high throughput by not requiring post-sorting imaging analysis.
Solution Approach 2:
The system maintains continuous cell flow through the microfluidic channel while simultaneously performing imaging and sorting operations. This continuity eliminates idle time between imaging and sorting, thereby maintaining high throughput while achieving excellent image collection capability.
3Productivity
If image-based sorting during flow is implemented, then throughput is improved, but device complexity increases
Solution Approach 1:
The detector system serves multiple functions: it images cells during flow, determines cell characteristics for sorting decisions, and provides feedback for real-time sorting control. This multi-functionality reduces the need for separate specialized systems, thereby managing device complexity while maintaining high throughput.
Solution Approach 2:
The microfluidic channel acts as an intermediary that brings cells into close proximity with the detector, enabling high-speed imaging during flow without requiring complex high-speed optical systems. The channel geometry and flow control serve as intermediaries that simplify the optical requirements while maintaining throughput.
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 scalable and flexible image-based cell sorting and selection with high throughput, capable of immobilizing and degrading cells based on various characteristics, including size, morphology, and protein expression.
Implementation Method 1
projecting light into the channel with the spatial energy modulating element such that the projected light causes cross-linking of the one or more polymer precursors to form gel structures
Implementation Method 2
a detector in optical communication with the surface and in operable association with the spatial energy modulating element, the detector identifying cells and determining positions thereof on the surface
Implementation Method 3
the method further comprises degrading the gel structures of the immobilized cells and eluting the selected cells from the channel
Data Source
AI summary
Described herein are systems and methods for sorting and selecting cells by immobilizing or enclosing cells in degradable hydrogel chambers, including a method of sorting cells comprising: (a) providing a fluidics device comprising: (i) a channel comprising a surface, (ii) a spatial energy modulation element in optical communication with the surface, and (iii) a detector in optical communication with the surface and in operable association with the spatial energy modulating element, the detector identifying cells and determining positions thereof on the surface; (b) loading the channel with cells and one or more polymer precursors so that the cells are disposed on or adjacent to the surface; (c) immobilizing one or more cells selected based on one or more optical signals therefrom by synthesizing one or more gel structures enclosing each of the one or more cells by projecting light into the channel with the spatial energy modulating element such that the projected light causes cross-linking of the one or more polymer precursors to form gel structures, wherein the positions of the gel structures in the channel are determined by the positions of the cells enclosed thereby identified by the detector; and (d) removing from the channel unselected cells.