Lateral Flow Membrane Thickness Variation for Immunoassay Sensitivity

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Solution Overview

Problem

Lateral flow immunoassays typically suffer from low sensitivity and signal intensity, which is five to ten times less than Enzyme-Linked Immuno Sorbent Assay (ELISA), necessitating improvements in signal amplification strategies.

Innovation Solution

A lateral flow membrane arrangement with a microporous membrane layer supported on a liquid-impermeable layer, featuring detection zones with a thickness of 100 to 150 μm and non-detection zones with a thickness of up to 300 μm, oriented orthogonally to the flow direction, enhancing the interaction of the liquid with immobilized binding agents and thereby increasing assay sensitivity and signal intensity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If a uniform thickness microporous membrane layer is used, then the membrane structure is simple and easy to manufacture, but the assay sensitivity and signal intensity are low

Engineering Contradiction:
Improveassay sensitivityVSAvoidmembrane structure complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent applies local quality by creating a microporous membrane layer with non-uniform thickness, where the detection zone has a reduced thickness (50-150 μm) compared to the rest of the membrane (100-300 μm). This localized thickness variation in the detection zone enhances assay sensitivity and signal intensity without requiring complexity throughout the entire membrane structure, thus resolving the contradiction between sensitivity improvement and structural simplicity.

Inventive Principle:
Principle #3Local quality

2Measurement precision

If a thicker microporous membrane layer is used, then the membrane has sufficient rigidity and mechanical strength, but the assay sensitivity and signal intensity are reduced

Engineering Contradiction:
Improvesignal intensityVSAvoidmembrane rigidity
Core Design Contradiction:
Measurement precisionVSStrength

Solution Approach 1:

The patent implements local quality by reducing the membrane thickness specifically in the detection zone (50-150 μm) while maintaining a larger thickness (100-300 μm) in the non-detection zones. This localized thinning enhances signal intensity and assay sensitivity where needed, while the thicker portions maintain the overall mechanical strength and rigidity of the membrane structure, thus resolving the contradiction between signal intensity and membrane strength.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent resolves the contradiction by introducing thickness variation as an additional dimensional parameter within the membrane structure. By creating zones of different thicknesses (50-150 μm vs. 100-300 μm) within the same membrane layer, the invention optimizes both signal intensity in detection zones and mechanical strength in non-detection zones, effectively using dimensional variation to balance conflicting requirements.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

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 structured membrane arrangement significantly enhances the sensitivity and signal intensity of lateral flow immunoassays, allowing for earlier detection of antigens at lower concentrations and reducing the risk of false positives, while also potentially using less antibodies, thus improving assay performance and reliability.

Implementation Method 1

a fluid to be tested for the presence of a ligand is applied to one end of a porous membrane layer and flows in lateral direction through the membrane under the action of capillary forces

Methodology Applied
Scientific EffectCapillary forces: Capillary Action

Implementation Method 2

The porous membrane comprises an immobilized binding agent that is capable of binding the ligand to be detected

Methodology Applied
Scientific EffectBinding interaction: Adsorption

Data Source

PatentUS10345314B2Lateral flow membrane arrangement and lateral flow immunoassay device comprising the same
Publication Date: 2019.07.09 SARTORIUS STEDIM BIOTECH GMBH
  • US10345314B2 patent drawing
  • US10345314B2 patent drawing
  • US10345314B2 patent drawing

AI summary

The present invention relates to a lateral flow membrane arrangement (1), comprising a microporous membrane layer (2) and a liquid-impermeable support layer (3), for lateral flow of a liquid through the microporous membrane layer (2), wherein the microporous membrane layer (2) is supported on the liquid-impermeable support layer (3) and has at least one detection zone (5) and at least one non-detection zone, wherein binding agents are immobilized in the at least one detection zone (5), the liquid-impermeable support layer (3) has at least one zone having a large thickness and at least one zone having a small thickness, the microporous membrane layer (2) is supported on the liquid-impermeable support layer (3) such that said at least one detection zone is provided above said at least one zone of the support layer having a large thickness and said at least one non-detection zone is provided above said at least one zone of the support layer having a small thickness, the zones are oriented in a direction orthogonally to the lateral flow direction (a) of said liquid, the detection zone (5) has a thickness (7) of 100 to 150 μm over the entire width of the membrane, the non-detection zone has a thickness (8) of at most 300 μm over the entire width of the membrane, and the lateral flow membrane arrangement (1) has a constant thickness (9), as well as to a lateral flow immunoassay device comprising said membrane arrangement (1).