Closed-Loop Microfluidics for Leukemia Blast Cell Enrichment

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Solution Overview

Problem

Current methods for detecting blast cells in leukemia patients, such as flow cytometry and bone marrow biopsies, are invasive, costly, and inefficient, especially for patients with low blast cell counts, leading to false negatives and increased mortality risks.

Innovation Solution

A continuous closed-loop microfluidic device with a curvilinear microchannel is used to separate and enrich blast cells from blood samples, allowing for a non-invasive and cost-effective method that recirculates the sample for repeated separation and concentration, maximizing purity and concentration of blast cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If flow cytometry is used to detect blast cells, then detection can be performed, but false negatives occur in patients with low blast cell counts

Engineering Contradiction:

Improvedetection sensitivityVSAvoidfalse negative rate

Core Design Contradiction:

Measurement precisionVSReliability

Solution Approach 1:

The device segments the blood sample into different flow streams, allowing rare blast cells to be isolated from the majority of normal blood cells through size-based inertial separation in curvilinear microchannels

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent replaces the mechanical dilution and random sampling approach of flow cytometry with a deterministic inertial microfluidic system that uses curved channel geometry to systematically separate cells by size, providing reliable detection without false negatives

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Measurement precision

If bone marrow biopsy is performed for leukemia detection, then accurate diagnosis is achieved, but the procedure is invasive and carries increased mortality risk

Engineering Contradiction:

Improvediagnostic accuracyVSAvoidinvasiveness and mortality risk

Core Design Contradiction:

Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The device uses peripheral blood as an intermediary sample type instead of requiring direct bone marrow access, while still achieving accurate leukemia detection through enriched blast cell analysis from the blood sample

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the invasive surgical biopsy procedure with a non-invasive blood draw followed by microfluidic processing, eliminating surgical risks while maintaining diagnostic capability

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Quantity of substance

If conventional cell sorting microfluidics is used, then cell separation is achieved, but large output volumes are generated requiring subsequent concentration steps

Engineering Contradiction:

Improveseparation capabilityVSAvoidtarget cell loss during concentration

Core Design Contradiction:

Quantity of substanceVSLoss of substance

Solution Approach 1:

The closed-loop system continuously recirculates the sample through the separation channel, progressively enriching blast cells with each pass while maintaining a constant small sample volume, eliminating the need for concentration steps that cause cell loss

Inventive Principle:

Principle #20Continuity of useful action

4Productivity

If high dilution factors are used in cell sorting, then processing speed is improved, but large output volumes are generated

Engineering Contradiction:

Improveprocessing speedVSAvoidoutput volume

Core Design Contradiction:

ProductivityVSQuantity of substance

Solution Approach 1:

The continuous closed-loop recirculation allows the device to process large effective sample volumes over time while maintaining a small physical output volume at any given moment, achieving both high productivity and compact sample concentration

Inventive Principle:

Principle #20Continuity of useful action

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 enables robust detection of blast cells even at low concentrations, reducing cell loss and maintaining the original cell phenotype, thus providing a sensitive and reliable tool for leukemia monitoring and early detection.

Implementation Method 1

We previously demonstrated the use of inertial-based microfluidics for sorting circulating tumor cells from peripheral blood of patients with solid tumors

Methodology Applied

Scientific EffectInertial microfluidics: Inertia

Data Source

PatentUS10697964B2Liquid biopsy detection of leukemia using closed-loop microfluidics

Publication Date: 2020.06.30 MASSACHUSETTS INST OF TECH

AI summary

This invention describes a one-step technique for the simultaneous label-free detection and concentration of blast cells from a blood sample. Enrichment of blast cells is achieved using a closed loop microfluidics system, allowing continuous removal of waste and non-target cells to generate concentrated samples of high purity without the need for specific targeting of proteins by antibodies. The technique is highly effective for samples which cannot be purified in a single run. The application of detecting rare blast cells for monitoring minimal residual disease in leukemia patients is demonstrated. The sensitivity of the invention promotes the detection of blast cells in blood samples of early-stage patients.