Microfluidic DLD Cell Separation for High-Viability Therapeutic Processing
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Solution Overview
Problem
Existing cell preparation methods for therapeutic applications, such as CAR-T cell therapy, are labor-intensive and inefficient, leading to substantial cell losses and reduced viability, particularly due to the use of processes like Ficoll centrifugation.
Innovation Solution
The use of Deterministic Lateral Displacement (DLD) in microfluidic devices for cell separation, which involves flowing a sample through an array of tilted microposts to gently deflect larger cells into a clean buffer stream, allowing for uniform size-based separation while maintaining cell viability and reducing the need for harsh reagents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If traditional cell separation methods (centrifugation, elutriation) are used, then cell separation is achieved, but cell viability and yield are substantially reduced
Solution Approach 1:
The patent replaces traditional mechanical separation systems (centrifugation, elutriation) with a microfluidic device that uses deterministic lateral displacement (DLD). This substitution eliminates the need for harsh mechanical forces that damage cells, achieving separation based on size through controlled fluid flow and micropost arrays, thereby maintaining high cell viability while achieving effective separation.
Solution Approach 2:
The invention changes the separation parameter from density-based (centrifugation) or size-based under harsh conditions (elutriation) to precise size-based separation under gentle flow conditions. By controlling flow rate, micropost geometry, and channel dimensions, the system achieves high-resolution cell separation without the mechanical stress that causes cell loss.
2Ease of manufacture
If traditional cell processing procedures are used, then cell processing is completed, but processing time is extended and cell viability is reduced
Solution Approach 1:
The microfluidic device enables continuous flow processing of cell samples, eliminating the batch processing interruptions inherent in traditional methods. Cells continuously flow through the separation channel, allowing uninterrupted separation and collection, which significantly reduces total processing time while maintaining high cell viability through gentle, continuous handling.
Solution Approach 2:
The patent segments the cell processing workflow into distinct microfluidic modules (sample introduction, separation, collection) that can be integrated into a single device. This segmentation eliminates transfer steps between different equipment, reducing both time and potential cell loss during transfers.
3Manufacturing precision
If size-based cell separation is performed using conventional methods, then cell separation is achieved, but cell damage occurs due to harsh processing conditions
Solution Approach 1:
The patent replaces harsh mechanical separation systems with a microfluidic system that uses controlled laminar flow and geometric constraints (micropost arrays) to achieve separation. This substitution eliminates high g-forces, shear stress, and turbulent flow that cause cell damage, while maintaining precise size-based separation through deterministic lateral displacement.
Solution Approach 2:
The micropost array acts as an intermediary structure that mediates the separation process. Instead of directly applying harsh forces to cells, the microposts create a geometric constraint field that gently guides cells of different sizes into different flow paths, achieving separation without direct mechanical damage to the cells.
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
DLD achieves high-efficiency cell separation with over 99.9% purity and viability, enabling at least 10-50% greater yield of recombinantly engineered target cells compared to traditional methods, and allows for rapid processing without freezing, reducing processing time to under four hours.
Implementation Method 1
Many of the methods rely on Deterministic Lateral Displacement (DLD), a process that involves flowing a sample through a microfluidic device containing a specifically designed array of microposts that are tilted at a small angle from the direction of fluid flow
Implementation Method 2
Cells larger than the target size of the micropost array may be gently deflected ('bumped') by the microposts into a stream of clean buffer, effectively separating them from smaller, non-deflected cells and particles
Data Source
AI summary
The present invention is directed to the use of microfluidics in the preparation of cells and compositions for therapeutic uses.