SDMA Immunoassay Solid Matrix Reducing Serum-Plasma Bias

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Solution Overview

Problem

Current methods for detecting symmetrical dimethylarginine (SDMA) in biological samples are not accurate or efficient, particularly in distinguishing between renal and cardiac diseases, and suffer from serum-plasma bias in immunoassays.

Innovation Solution

A device and method using a solid matrix with a capture reagent, including an analog of methylated arginine derivatives covalently or non-covalently attached to a protein, which is less affinity-sensitive to anti-SDMA antibodies, allowing for precise detection of SDMA by forming a mixture with a labeled conjugate and washing to measure bound label amounts.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If traditional immunoassay methods are used for SDMA detection, then the assay can be performed with standard reagents, but serum-plasma bias occurs and measurement precision deteriorates

Engineering Contradiction:
Improveassay implementationVSAvoidSDMA detection accuracy
Core Design Contradiction:
Ease of manufactureVSMeasurement precision

Solution Approach 1:

The patent introduces an analog of methylated arginine derivatives as an intermediary substance in the immunoassay. This analog serves as a mediator that reduces the affinity sensitivity of anti-SDMA antibodies, thereby eliminating serum-plasma bias while maintaining assay functionality. The analog acts as a bridge between the antibody and the actual SDMA analyte, improving measurement precision across different sample types.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Device complexity

If common renal markers (creatinine and BUN) are used, then the detection method is simple and widely available, but the ability to distinguish renal from cardiac disease is insufficient

Engineering Contradiction:
Improvedetection method simplicityVSAvoiddisease differentiation capability
Core Design Contradiction:
Device complexityVSLoss of information

Solution Approach 1:

The patent changes the chemical parameter of the detection system by introducing analogs of methylated arginine derivatives. This parameter change enables the assay to detect SDMA with high specificity, providing additional diagnostic information that distinguishes renal from cardiac disease while maintaining relative simplicity in the detection approach.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If high affinity anti-SDMA antibodies are used, then the sensitivity of SDMA detection is high, but cross-reactivity with methylated arginine derivatives increases

Engineering Contradiction:
ImproveSDMA detection sensitivityVSAvoidcross-reactivity
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The analog of methylated arginine derivatives serves as an intermediary that modulates antibody binding. By incorporating this analog into the assay system, the patent reduces the cross-reactivity of high-affinity anti-SDMA antibodies with methylated arginine derivatives, allowing sensitive detection without harmful cross-reactivity interference.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 solution enables accurate and efficient detection of SDMA, reducing serum-plasma bias and improving assay precision, with results correlating well with established assays like LC-MS and EMIT, and demonstrating stability across various conditions.

Implementation Method 1

forming a mixture including the sample and a labeled conjugate including an anti-SDMA antibody conjugated to a label

Methodology Applied
Scientific EffectAntigen-antibody binding:

Implementation Method 2

contacting the mixture with the device including an analog of a methylated arginine derivative and a solid support or solid matrix, washing the solid support or matrix to remove conjugate that is not bound to the solid matrix

Methodology Applied
Scientific EffectAdsorption: Adsorption

Data Source

PatentUS20230102277A1Detection of symmetrical dimethylarginine
Publication Date: 2023.03.30 IDEXX LABORATORIES INC
  • US20230102277A1 patent drawing
  • US20230102277A1 patent drawing
  • US20230102277A1 patent drawing

AI summary

The disclosure generally relates to the detection of symmetrical dimethylarginine (SDMA). More particularly, the disclosure relates to the detection of SDMA using a solid phase. The disclosure provides devices, reagents, kits and methods for detecting symmetrical dimethyl arginine (SDMA) in sample, such as a biological sample from an animal. The method includes detecting the presence or amount of SDMA in the sample by using an immunoassay format, such as a competitive immunoassay. The assay includes the use of antibodies to SDMA that are specific for SDMA and that have less affinity for other arginine derivatives.