Microfluidic Obstacle Array for Leukocyte Purification

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Solution Overview

Problem

There is a need for improved methods to efficiently isolate and purify leukocytes and stem cells from blood samples, particularly for hematopoietic stem cell transplants, as incomplete erythrocyte removal can lead to harmful side effects and poor recovery of viable leukocytes and CD34+ cells can reduce engraftment success.

Innovation Solution

A method using a microfluidic device with an array of obstacles arranged in rows, where each subsequent row is shifted laterally, differentially deflects particles of a predetermined size to separate leukocytes and stem cells from erythrocytes, achieving high purity and viability, and can process large volumes of blood without significant clogging by using EDTA and PPACK to inhibit coagulation and platelet activation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If traditional methods are used to isolate leukocytes and stem cells from blood samples, then the process is simpler, but the purity and recovery rate are insufficient leading to harmful side effects and reduced engraftment success

Engineering Contradiction:

Improvepurity of leukocyte and stem cell isolationVSAvoidcomplexity of microfluidic device with obstacle array

Core Design Contradiction:

Manufacturing precisionVSDevice complexity

Solution Approach 1:

The microfluidic device segments the blood sample into individual cell trajectories as they pass through the obstacle array. Each cell type follows a distinct path based on its size, enabling separation of leukocytes, stem cells, and erythrocytes without complex mechanical manipulation or chemical processing

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention replaces traditional mechanical separation methods (centrifugation, filtration) with a passive microfluidic obstacle array system. The deterministic lateral displacement mechanism uses fluid flow dynamics and geometric constraints to achieve cell separation based solely on size differences, eliminating the need for complex mechanical moving parts

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Productivity

If large volumes of blood are processed quickly, then productivity increases, but clogging of the device occurs

Engineering Contradiction:

Improveprocessing rate of blood samplesVSAvoidclogging of microfluidic device

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The system applies anticoagulant (EDTA) and platelet activation inhibitor (PPACK) to the blood sample before it enters the microfluidic device. This preliminary treatment prevents coagulation and platelet clumping during processing, ensuring smooth flow through the obstacle array and eliminating clogging even at high processing rates

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The microfluidic device is designed with dynamic flow characteristics that adapt to different cell concentrations. The obstacle array geometry and channel dimensions are optimized to maintain laminar flow and prevent cell aggregation, allowing continuous processing of large blood volumes without clogging

Inventive Principle:

Principle #15Dynamics

3Object-affected harmful factors

If erythrocytes are not completely removed, then the process is faster and simpler, but harmful side effects occur in hematopoietic stem cell transplants

Engineering Contradiction:

Improveharmful side effects from residual erythrocytesVSAvoidtime required for complete erythrocyte removal

Core Design Contradiction:

Object-affected harmful factorsVSLoss of time

Solution Approach 1:

The obstacle array is designed with locally optimized geometries that create size-selective flow paths. Erythrocytes, being smaller than leukocytes and stem cells, are deflected into specific channels and concentrated in a separate outlet stream, achieving complete removal while maintaining efficient processing speed

Inventive Principle:

Principle #3Local quality

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

The method achieves high-purity leukocyte and stem cell isolation with at least 90% purity and viability, significantly improving patient outcomes by reducing harmful side effects and enhancing engraftment success, while allowing for efficient processing of large blood volumes.

Implementation Method 1

the device comprises an array of obstacles arranged in rows, wherein each subsequent row of obstacles is shifted laterally with respect to a previous row, wherein the obstacles differentially deflect the first particles of at least the first predetermined size to a first outlet and second particles in the sample of less than the predetermined size to a second outlet

Methodology Applied

Scientific EffectDeterministic lateral displacement:

Data Source

PatentUS11486802B2Methods and devices for high throughput purification

Publication Date: 2022.11.01 THE TRUSTEES OF PRINCETON UNIV

AI summary

Described herein are devices and methods for high throughput purification of particles. In some cases, methods and devices described herein can be used to remove erythrocytes and purify leukocytes and raise the quality of umbilical cord blood and other transplant grafts, thereby significantly improving patient outcomes.