Microfluidic DLD Array for Automated Cell Purification
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Solution Overview
Problem
Current methods for isolating and purifying particles, such as cells, from samples are inefficient and labor-intensive, requiring multiple manual steps and often involving centrifugation, which can lead to low cell yields and high contamination.
Innovation Solution
A microfluidic device with a deterministic lateral displacement (DLD) array of obstacles, where each row is shifted laterally, differentially deflects particles of a predetermined size to one outlet and smaller particles to another, combined with a flow-through incubator for further processing with reagents, simplifying the cell preparation process and reducing manual handling.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If manual isolation and purification methods are used, then operators can perform cell preparation steps, but the process becomes labor-intensive and time-consuming
Solution Approach 1:
The microfluidic device performs cell isolation and purification automatically through integrated DLD arrays and flow-through incubators, eliminating the need for manual operator intervention in each processing step while maintaining high throughput
Solution Approach 2:
Multiple cell preparation functions (isolation, purification, incubation with reagents) are merged into a single integrated microfluidic device, allowing continuous processing without manual transfer between separate equipment
2Manufacturing precision
If centrifugation is used for cell separation, then particles can be separated by density, but cell yields become low and contamination increases
Solution Approach 1:
The patent replaces centrifugal separation with deterministic lateral displacement (DLD) based microfluidic separation, which uses geometric obstacle arrays to deflect particles based on size without the mechanical forces of centrifugation, achieving both high purity and high yield
Solution Approach 2:
The DLD obstacle arrays are designed with specific local geometric configurations (obstacle spacing, size, and arrangement) that create size-selective flow paths, allowing precise separation of target cells from contaminants while maintaining cell integrity and yield
3Ease of manufacture
If multiple manual handling steps are performed, then cell preparation can be completed, but handling costs increase and operator dependency increases
Solution Approach 1:
The microfluidic device is designed as a universal platform that can perform multiple cell preparation functions (isolation, purification, incubation with various reagents) through a single integrated system, reducing the need for multiple separate manual operations and equipment
Solution Approach 2:
The flow-through incubator sections automatically mix cells with reagents as they flow through designated channels, eliminating the need for manual mixing steps and reducing operator intervention while maintaining consistent reagent-cell contact
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 automates and simplifies the cell preparation process, achieving high yields of purified cells with low contamination and reducing processing time from hours to less than 20 minutes, while minimizing operator-dependent steps and handling costs.
Implementation Method 1
a first deterministic lateral displacement (DLD) array of obstacles arranged in rows in the channel, wherein each subsequent row of obstacles is shifted laterally with respect to a previous row, wherein the array of obstacles is configured to differentially deflect first particles of at least a predetermined size to a first outlet and second particles of less than the predetermined size in the sample to a second outlet
Data Source
Figure 1
Figure 2A~2C
Figure 3A
AI summary
Described herein are improved microfluidic devices and methods for processing cells that can improve cell quality, streamline workflows, and lower costs. Applications include research and clinical diagnostics in cancer, infectious disease, and inflammatory disease, among other disease areas.