Multisort Valve with Out-of-Plane Channels for Cell Sorting
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Solution Overview
Problem
Current cell sorting technologies, such as FACS and magnetic cell sorting, face limitations in processing large volumes of cells efficiently and accurately, particularly in terms of speed and precision, especially when dealing with small numbers of target cells.
Innovation Solution
A microfabricated particle sorting system that combines MEMS-based cell sorting with magnetic sorting and centrifugation in a closed system, featuring a novel valve architecture with out-of-plane channels and hydrodynamic focusing, allowing for faster actuation and more precise control over fluid flow, enabling efficient sorting of cells based on both magnetic and fluorescent markers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional FACS or magnetic cell sorting is used, then cells can be sorted by fluorescence or magnetic markers, but the processing speed is slow and the system cannot efficiently handle large volumes of cells to obtain small numbers of target cells
Solution Approach 1:
The sorting system is divided into multiple independent sorting magnets arranged in series, each handling a specific sorting task. This segmentation allows parallel processing of different cell populations while maintaining high sorting accuracy for each stage, thereby increasing overall productivity without sacrificing precision
Solution Approach 2:
Magnetic sorting is performed as a preliminary enrichment step before FACS to pre-concentrate target cells. This preliminary action reduces the volume and complexity of the sample entering the FACS system, enabling faster processing while maintaining high sorting accuracy for the final target cell population
2Quantity of substance
If magnetic cell sorting is used to enrich target cells, then large volumes can be processed, but the system requires complex automated centrifugation steps and multiple processing stages
Solution Approach 1:
Multiple sorting magnets are combined into a single integrated device that performs multiple sorting operations simultaneously. This merging eliminates the need for separate automated centrifugation steps and multiple processing stages, reducing system complexity while maintaining the ability to process large volumes of cells
Solution Approach 2:
Each sorting magnet is designed to perform multiple functions: magnetic separation, cell enrichment, and direct sorting to collection tubes. This multi-functionality eliminates the need for separate centrifugation steps and intermediate processing stages, simplifying the overall system while maintaining high processing capacity
3Measurement precision
If conventional cell sorting systems are used, then they can distinguish target from non-target cells, but they experience fluid resistance that limits actuation speed and reduces sorting efficiency
Solution Approach 1:
The valve design transitions from planar in-plane channels to three-dimensional out-of-plane channels. This dimensional change allows fluid to bypass the moving valve leaflet through vertical pathways, dramatically reducing fluid resistance and enabling faster actuation speeds while maintaining precise cell identification and sorting accuracy
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 system significantly improves sorting speed and accuracy by minimizing fluid resistance and allowing for faster actuation, enabling the processing of large volumes of cells to obtain small numbers of target cells with high precision and minimal yield loss.
Implementation Method 1
magnetic labeling of first target cells and removal of the non-target cells by applying magnetic fields
Implementation Method 2
Magnetic cell sorting uses relays on labeling target cells with a magnetic bead
Implementation Method 3
The particle manipulation device, sorting magnet and optionally centrifugation device may be connected to each other to allow fluidic communication
Implementation Method 4
fluorescence-activated labeling of second target cells present in the second cell suspension and separating the fluorescence-activated second target cells
Data Source
AI summary
A cell sorting device is disclosed, wherein the device includes a sorting magnet and at least one particle manipulation device, wherein the particle manipulation device is formed on a surface of a fabrication substrate. The device may include at least one fluid channel, wherein the sorting magnet and the particle manipulation device are in fluid communication with one another through at least one fluid channel. A method of sorting cells from a first cell suspension is also disclosed, The method may include a) magnetic labeling of first target cells and removal of the non-target cells by applying magnetic fields to obtain a second cell suspension; b) fluorescence-activated labeling of second target cells present in the second cell suspension and separating the fluorescence-activated second target cells from the not labeled cells to obtain a third cell suspension.