Cell Lysis for Target Molecule Detection in Whole Blood

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current methods for detecting target molecules in body fluids, such as blood, face challenges due to optical interferences from red blood cells and the need for centrifugation or filters, which can lead to high costs, power consumption, and adsorption issues, making them unsuitable for point-of-care devices.

Innovation Solution

A method involving cell lysis in a cartridge with detergent, followed by mixing with specific binding particles and substrates, allowing direct detection of target molecules using FTIR or magnetic label assays without removing blood cells, enabling analysis in a handheld device.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If centrifugation is used to remove blood cells, then measurement precision is improved, but device complexity and power consumption increase

Engineering Contradiction:
Improvedetection accuracyVSAvoiddevice complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent extracts and removes the harmful component (blood cells) from the sample through lysis, separating the interference source from the analyte of interest. This eliminates the need for complex centrifugation equipment while maintaining detection precision by working with a cell-free lysate matrix.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent replaces the mechanical centrifugation system with a chemical lysis approach. Instead of using motors and moving parts to separate cells, the invention uses detergent-based lysis to break down cell membranes, achieving cell removal through chemical means that are compatible with simple, portable devices.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Device complexity

If filters are used to remove blood cells, then device complexity is reduced, but measurement precision deteriorates due to adsorption of target molecules

Engineering Contradiction:
Improvedevice complexityVSAvoiddetection accuracy
Core Design Contradiction:
Device complexityVSMeasurement precision

Solution Approach 1:

The patent introduces an intermediary substance (detergent/lysis buffer) that mediates between the blood sample and the detection system. The lysis buffer solubilizes cell membranes and proteins, creating a homogeneous liquid matrix that prevents target molecule adsorption onto filter surfaces while maintaining molecule availability for detection.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If magnetic particles are used for detection, then measurement precision is improved, but reliability deteriorates due to irreversible attachment to blood cells

Engineering Contradiction:
Improvedetection accuracyVSAvoidassay reliability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent performs preliminary lysis of blood cells before introducing magnetic particles to the sample. By breaking down cell structures in advance, the magnetic particles are prevented from irreversibly attaching to intact cells, ensuring they remain available for specific binding to target molecules and maintaining assay reliability.

Inventive Principle:
Principle #10Preliminary 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

This approach allows for accurate, cost-effective, and sensitive detection of target molecules in whole blood samples, reducing interference and maintaining high precision, similar to central lab standards, without the need for centrifugation or expensive components.

Implementation Method 1

lysing agent for lysing cells in a body fluid sample

Methodology Applied
Scientific EffectLysis:

Implementation Method 2

The cartridge comprises a detergent for lysing cells

Methodology Applied
Scientific EffectSolubilization: Solvation

Implementation Method 3

a magnet below the cartridge body fluid chamber adapted to move the magnetic particles towards a substrate surface

Methodology Applied
Scientific EffectMagnetic force: Magnetic Field

Implementation Method 4

Near field optical techniques like the FTIR (frustrated total internal reflection) technique

Methodology Applied
Scientific EffectFTIR (frustrated total internal reflection): Total Internal Reflection

Data Source

PatentEP2805164B1Determining a presence of target molecules in a body fluid comprising cells
Publication Date: 2017.11.08 KONINKLIJKE PHILIPS NV
  • EP2805164B1 patent drawingFigure 1~2
  • EP2805164B1 patent drawingFigure 3~4
  • EP2805164B1 patent drawingFigure 5~6

AI summary

A method of determining a presence of target molecules in a body fluid (16) with cells comprises the steps of: lysing cells in the body fluid (16) for generating a lysate (17); mixing the lysate (16) with particles (36) with first detector molecules; binding target molecule to the particles through first detector molecules; exposing a substrate (38) with second detector molecules to the lysate (17); binding target molecules to the substrate through second detector molecules; detecting particles (36) attached to the substrate (36).