Microfluidic Device with Dissolvable Matrix for Blood Cell Detection

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Solution Overview

Problem

Current assays for detecting analytes in liquid samples are limited in their ability to efficiently process and analyze bodily fluids, particularly in detecting specific cells like CD4+ and CD3+ cells, due to challenges in lysing red blood cells and stabilizing antibodies within microfluidic systems.

Innovation Solution

A microfluidic device with a capillary inlet containing a matrix that is partially dissolvable in the sample, comprising anti-CD4+ and anti-CD3+ antibodies labeled with fluorescent dyes, and a lyoprotectant, which allows for the lysing of red blood cells and stabilization of antibodies, enabling efficient detection of analytes by forming complexes with optical labels and differential pressure manipulation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a matrix is used to stabilize antibodies and lyse red blood cells in the capillary inlet, then the detection reliability is improved, but the device complexity increases due to the need for partial dissolvability and lyoprotectant incorporation

Engineering Contradiction:
Improvedetection reliabilityVSAvoiddevice complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The matrix is prepared in advance as a lyophilisate containing pre-formulated reagents for red blood cell lysis and antibody stabilization. This preliminary preparation allows the matrix to be stored in a stable dry state and only activated when needed, resolving the contradiction by enabling reliable detection functionality while maintaining device simplicity through pre-packaged solutions.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The matrix transitions from a dry, stable lyophilisate state to a dissolved, active state upon contact with the liquid sample. This parameter change (from solid to dissolved) enables the matrix to perform its detection functions while allowing for controlled activation, thereby improving reliability without permanently increasing device complexity.

Inventive Principle:
Principle #35Parameter changes

2Ease of operation

If the matrix is made partially dissolvable in the sample, then the ease of operation is improved by enabling automatic activation, but the manufacturing precision requirements increase

Engineering Contradiction:
Improveease of operationVSAvoidmanufacturing precision
Core Design Contradiction:
Ease of operationVSManufacturing precision

Solution Approach 1:

The matrix is designed to automatically dissolve and activate upon contact with the liquid sample without requiring external intervention. The partial dissolvability enables the matrix to self-activate, improving ease of operation while the standardized lyophilisate formulation maintains manufacturing precision through controlled material composition.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The matrix employs a porous or particulate structure that facilitates controlled dissolution in the liquid sample. This structure allows the matrix to maintain structural integrity during manufacturing while enabling predictable dissolution behavior in use, thereby balancing ease of operation with manufacturing precision requirements.

Inventive Principle:
Principle #31Porous materials

3Productivity

If differential pressure manipulation is applied to move the liquid sample through the microfluidic channel, then the productivity is improved, but the device complexity increases due to the deformable wall mechanism

Engineering Contradiction:
ImproveproductivityVSAvoiddevice complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The microfluidic channel incorporates a deformable wall that can dynamically change its shape or position in response to pressure changes. This dynamic feature enables efficient liquid sample transport through differential pressure manipulation, improving productivity while the deformable wall design itself remains relatively simple, thus minimizing the increase in device complexity.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The device uses differential pressure (pneumatic/hydraulic principle) to drive the liquid sample through the microfluidic channel. This approach improves productivity by enabling controlled fluid transport without complex mechanical pumps, and the deformable wall serves as a simple pressure-responsive element rather than a complex mechanism.

Inventive Principle:
Principle #29Pneumatics and hydraulics

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 device effectively detects analytes by forming complexes with optical labels and applying differential pressure, enhancing the analysis of bodily fluids and improving the detection of specific cells like CD4+ and CD3+ cells within the microfluidic system.

Implementation Method 1

a matrix covering at least a sub-section of the cross-sectional area of the capillary inlet and not filling the entire length of the capillary structure and allowing a flow through of liquid sample, wherein said matrix is at least partially dissolvable in the sample and is a lyophilisate comprising an anti-CD4+-antibody labelled with a first fluorescent dye and an anti-CD3+-antibody labelled with a second fluorescent dye

Methodology Applied
Scientific EffectAntibody-antigen binding:

Implementation Method 2

an anti-CD4+-antibody labelled with a first fluorescent dye and an anti-CD3+-antibody labelled with a second fluorescent dye

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 3

wherein the matrix comprises means for lysing red blood cells, and a lyoprotectant

Methodology Applied
Scientific EffectCell lysis:

Implementation Method 4

introducing at least a portion of the liquid sample into the microfluidic flow path of the device by reducing a pressure acting on a liquid sample-gas interface of the liquid sample, wherein the reducing a pressure is performed by compressing at least a portion of the microfluidic flow path to displace gas therefrom and subsequently decompressing the at least a portion of the microfluidic flow path

Methodology Applied
Scientific EffectCompression and decompression: Compression

Implementation Method 5

a microfluidic channel including a capillary inlet

Methodology Applied
Scientific EffectCapillary action: Capillary Action

Data Source

PatentEP3636341B1Assays and devices
Publication Date: 2021.12.08 ABBOTT RAPID DIAGNOSTICS JENA GMBH
  • EP3636341B1 patent drawingFigure 1~2
  • EP3636341B1 patent drawingFigure 3a
  • EP3636341B1 patent drawingFigure 3b~3g

AI summary

A method for assaying a sample for each of multiple analytes is described. The method includes contacting an array of spaced-apart test zones with a liquid sample (e.g., whole blood). The test zones disposed within a channel of a microfluidic device. The channel is defined by at least one flexible wall and a second wall which may or may not be flexible. Each test zone comprising a probe compound specific for a respective target analyte. The microfluidic device is compressed to reduce the thickness of the channel, which is the distance between the inner surfaces of the walls within the channel. The presence of each analyte is determined by optically detecting an interaction at each of multiple test zones for which the distance between the inner surfaces at the corresponding location is reduced. The interaction at each test zone is indicative of the presence in the sample of a target analyte. Capillary structures of the devices or used in the methods may comprise a matrix and the devices may comprise control elements and methods for assaying of sample may use corresponding controlling activities.