Microfluidic Device for Post-Centrifugation Sample Extraction
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Solution Overview
Problem
Current microfluidic cytometry systems face challenges in maintaining sample purity and sterility during centrifugation and transfer, leading to potential layer mixing and cell loss, especially when dealing with low cell numbers, and they are not biosafe for clinical environments.
Innovation Solution
A microfluidic device adapted for post-centrifugation use with selective sample extraction, employing dye-selective and geographically-selective methods, where the device itself contains the sample during centrifugation, allowing for precise extraction of desired cell populations using Ficoll-Hypaque gradients and strategically positioned ports for efficient separation and analysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If sample transfer and centrifugation are performed using conventional methods, then cell separation can be achieved, but sample purity is compromised due to layer mixing and cell loss
Solution Approach 1:
The patent combines multiple functions (centrifugation, separation, and analysis) into a single integrated microfluidic device. The device includes a centrifugal separation chamber that performs density gradient centrifugation directly within the microfluidic system, eliminating the need for external transfer steps that cause layer mixing and cell loss.
Solution Approach 2:
The microfluidic device is segmented into distinct functional zones including a centrifugal separation chamber, extraction channels, and analysis chambers. This segmentation allows different operations to occur in isolated regions, maintaining layer integrity during centrifugation and enabling precise extraction of separated components without cross-contamination.
2Reliability
If conventional open systems are used for centrifugation and sample transfer, then processing can be performed, but sterility is compromised leading to potential contamination
Solution Approach 1:
The device merges sample preparation, centrifugation, separation, and analysis functions into a single closed microfluidic system. This integration eliminates multiple transfer steps between open containers, maintaining sterility throughout the entire process while the compact microfluidic structure keeps overall system complexity manageable.
3Quantity of substance
If low cell numbers are processed using conventional methods, then analysis can be performed, but cell loss increases due to layer mixing during transfer
Solution Approach 1:
The device segments the sample processing into distinct functional zones with controlled fluid flow paths. The centrifugal separation chamber isolates rare cells during density gradient centrifugation, and the extraction channels provide controlled access to separated layers, minimizing cell loss that would occur during conventional transfer operations.
Solution Approach 2:
The microfluidic device performs self-contained processing where sample loading, centrifugation, separation, and extraction occur within the same integrated system without requiring external intervention or transfer steps. This self-service capability preserves rare cell populations throughout the entire processing sequence.
4Manufacturing precision
If selective sample extraction is implemented, then target cell purity is improved, but device complexity increases due to additional ports and extraction mechanisms
Solution Approach 1:
The device implements local quality by providing different extraction capabilities at different locations. The side wall of the centrifugal separation chamber includes multiple extraction ports positioned at specific heights to access different density layers, allowing selective extraction of target cells while maintaining a relatively simple overall device structure.
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 reduces the risk of layer mixing, minimizes cell loss, and enables sterile, efficient separation and analysis of biological samples within a closed environment, suitable for clinical applications, while maintaining high purity and concentration of target cells.
Implementation Method 1
centrifuging the microfluidic device to create a first sample layer and a second sample layer within the sample well
Implementation Method 2
allowing for precise extraction of desired cell populations using Ficoll-Hypaque gradients
Data Source
AI summary
The present disclosure relates to microfluidic devices adapted for post-centrifugation use with selective sample extraction, and methods for their use. Certain embodiments make use of a dye-selective sample extraction. Other embodiments make use of a geographically-selective sample extraction. Other embodiments are also disclosed.