Polycationic Dextran for Leukocyte Interference Reduction

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Solution Overview

Problem

Immunoassay methods face interference from leukocytes in blood samples, leading to inaccurate results due to incomplete separation during centrifugation, and existing solutions like poly-L-Lysine are costly and may introduce additional interference.

Innovation Solution

The use of a polycationic derivative of dextran, such as DEAE-dextran, is added to the assay system to prevent leukocyte interference by binding to their surface without interacting with polyanion materials, thereby improving assay accuracy without increasing costs.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If poly-L-Lysine is added to the assay system to address leukocyte interference, then leukocyte binding is improved, but additional interference is introduced and cost increases

Engineering Contradiction:
Improveassay accuracyVSAvoidadditional interference
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent introduces polyanion materials as intermediary substances that selectively bind to leukocytes in the plasma layer. These polyanions act as mediators between the leukocytes and the assay system, capturing the interfering cells without disrupting the antibody-antigen binding process. This resolves the contradiction by providing a targeted approach that improves reliability without introducing additional interference.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs cost-effective polyanion materials such as heparin, dextran sulfate, and chondroitin sulfate instead of expensive poly-L-Lysine. These materials are used in disposable test strips or single-use assay systems, providing an economical solution that maintains assay accuracy without the high costs associated with traditional leukocyte-binding agents.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

2Reliability

If poly-L-Lysine is added to bind leukocytes, then separation effectiveness is improved, but reagent aggregation occurs

Engineering Contradiction:
Improveseparation effectivenessVSAvoidreagent aggregation
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

Polyanion materials serve as intermediary agents that selectively interact with leukocytes through electrostatic attraction to their positively charged surfaces. This targeted mediation prevents reagent aggregation by avoiding non-specific binding to other assay components, thereby improving separation effectiveness while maintaining reagent stability.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent applies polyanion materials with specific local properties - their negative charge density and molecular structure are optimized to bind selectively to leukocytes at specific locations in the assay system (plasma layer interface) without affecting the overall composition stability of other reagents. This localized action resolves the contradiction between separation effectiveness and reagent stability.

Inventive Principle:
Principle #3Local quality

3Reliability

If centrifugation is increased to separate leukocytes, then separation completeness is improved, but assay time and complexity increase

Engineering Contradiction:
Improveseparation completenessVSAvoidassay time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent incorporates polyanion materials into the assay system in advance, before the actual measurement process. These pre-added materials immediately begin binding to leukocytes upon contact with the plasma layer, eliminating the need for extended centrifugation or additional separation steps. This preliminary action achieves complete separation while minimizing assay time.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent extracts the leukocyte separation function from the mechanical centrifugation process by using polyanion-based chemical separation. This extraction allows leukocytes to be removed from the plasma layer through selective binding rather than prolonged mechanical separation, thereby achieving complete separation without increasing assay time or complexity.

Inventive Principle:
Principle #2Taking out (Extraction)

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 effectively reduces interference from leukocytes, ensuring accurate detection of target analytes in serum or plasma samples by enhancing the separation and binding processes, thus minimizing false negative diagnostic results.

Implementation Method 1

adding an effective amount of a polycationic derivative of dextran to the specific binding assay... the polycationic derivative of dextran can be, for example, diethylaminoethyl-dextran (DEAE-dextran)

Methodology Applied
Scientific EffectElectrostatic interaction: Electrostatics

Implementation Method 2

These magnetic or paramagnetic microparticles are used to facilitate manipulation of the microparticle within a magnetic field, so that they can be separated from a mixture of soluble reagents and a test sample using the magnetic field

Methodology Applied
Scientific EffectMagnetic field: Magnetic Field

Implementation Method 3

Immunoassays exploit the highly specific binding of an antibody to its corresponding antigen, wherein the antigen is the target analyte

Methodology Applied
Scientific EffectAntigen-antibody binding: Adsorption

Data Source

PatentUS10641768B2Methods and kits for decreasing interferences from leukocytes in specific binding assays
Publication Date: 2020.05.05 ABBOTT JAPAN LLC
  • US10641768B2 patent drawing
  • US10641768B2 patent drawing
  • US10641768B2 patent drawing

AI summary

The present disclosure describes methods and kits for reducing interferences in immunoassays performed on solid phase and on samples containing serum or plasma, by adding an effective amount of a polycationic derivative of dextran to the assay.