Immunochromatographic Test Strip Buffer Solution Suppresses Colloidal Gold Aggregation

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Solution Overview

Problem

Immunochromatographic test strips using whole blood as a sample with polybrene as a blood-agglutinating agent and colloidal gold conjugates as detection reagents face issues with aggregation of colloidal gold conjugates, despite attempts to neutralize polybrene's positive electric charge with polyanions.

Innovation Solution

Incorporating a buffer solution, such as Bis-Tris, MES, or citric acid, in the test strip to suppress aggregation of colloidal gold conjugates due to polybrene, eliminating the need for polyanion neutralization and allowing for effective agglutination and separation of red blood cells without colloidal gold aggregation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If polybrene is used as a blood-agglutinating agent to separate red blood cells, then red blood cell separation is improved, but colloidal gold conjugate aggregation occurs

Engineering Contradiction:
Improvered blood cell separationVSAvoidcolloidal gold conjugate aggregation
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent introduces a polyanion as an intermediary substance that mediates between polybrene and colloidal gold conjugates. The polyanion binds to the positively charged polybrene, forming a complex that prevents direct interaction between polybrene and the negatively charged colloidal gold conjugates, thereby eliminating aggregation while preserving red blood cell separation functionality

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the electrical charge parameter of the system by adding polyanions that neutralize the positive charge of polybrene. This parameter change transforms polybrene from a charge-causing aggregation state to a charge-neutral state that no longer induces colloidal gold conjugate aggregation, while maintaining its blood-agglutinating function

Inventive Principle:
Principle #35Parameter changes

2Object-generated harmful factors

If polyanions are added to neutralize polybrene's positive electric charge, then colloidal gold aggregation is prevented, but red blood cell agglutination efficiency decreases

Engineering Contradiction:
Improvecolloidal gold conjugate aggregationVSAvoidred blood cell agglutination
Core Design Contradiction:
Object-generated harmful factorsVSReliability

Solution Approach 1:

The patent applies preliminary action by adding the polyanion to the reagent composition before it contacts the blood sample. The polyanion pre-neutralizes the polybrene charge in advance, creating a modified reagent environment that simultaneously achieves both red blood cell agglutination and prevention of colloidal gold aggregation, rather than adding polyanion after the problem occurs

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent creates a composite reagent system combining polybrene, polyanion, and colloidal gold conjugates in specific proportions. This composite formulation allows the components to work together synergistically, where the polyanion-modified polybrene maintains blood-agglutinating capability while the overall composite prevents colloidal gold aggregation through charge neutralization

Inventive Principle:
Principle #40Composite materials

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 enables accurate detection and measurement of analytes in whole blood samples by preventing colloidal gold conjugate aggregation, simplifying the reagent configuration and reducing unpredictable effects on immune reactions and analyte spread.

Implementation Method 1

polybrene which is a polycation... agglutinating red blood cells

Methodology Applied
Scientific EffectElectrostatic interaction: Electrostatics

Implementation Method 2

a buffer solution having ability to suppress aggregation of the conjugate due to polybrene

Methodology Applied
Scientific EffectBuffer solution effect:

Implementation Method 3

An example of a label constituting a detection reagent (conjugate) such as the labeled antibody is colloidal gold particles and a color reaction of the colloidal gold particles enables qualitative detection

Methodology Applied
Scientific EffectColor reaction:

Implementation Method 4

the analyte in the sample specifically binds to the labeled antibody to form a complex

Methodology Applied
Scientific EffectSpecific binding:

Data Source

PatentUS10422790B2Immunochromatographic test strip and detection method using immunochromatography for detecting target in red blood cell-containing sample
Publication Date: 2019.09.24 SEKISUI MEDICAL CO LTD
  • US10422790B2 patent drawing

AI summary

A problem to be solved by the present invention is to provide an immunochromatographic test strip and a detection method using immunochromatography avoiding aggregation of colloidal gold conjugates while red blood cells in whole blood are agglutinated and then separated and removed in the case of using polybrene as a blood-agglutinating agent and the colloidal gold conjugates as a detection reagent. To solve the problem, the present inventors reviewed a past reagent configuration itself from a completely different viewpoint rather than selecting type and amount of polyanions and, as a result of extensive study on each element, the inventors surprisingly found that aggregation of colloidal gold can be suppressed by using a certain buffer solution without using neutralization by polyanions.