Receptor Stabilization in Liquid Assays Using Polyols and Chelators

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Solution Overview

Problem

Receptor reagents used in clinical diagnostics are unstable in liquid form, leading to short half-life and increased manufacturing costs, making it difficult to detect low concentrations of analytes like antibodies in biological fluids.

Innovation Solution

Combining a receptor with a chelating agent and a C2-C6 polyol in a liquid medium to create a stable and sensitive solution that maintains stability at temperatures from 2°C to 40°C, enhancing the sensitivity and stability of receptor-based assays.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If receptors are stored in liquid form, then convenience of use is improved, but stability and half-life deteriorate

Engineering Contradiction:
Improveconvenience of useVSAvoidstability
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent introduces stabilizing agents (polyols such as glycerol, propylene glycol, or ethylene glycol at concentrations of 5-50% w/v, and chelating agents such as EDTA at concentrations of 0.1-20 mM) as intermediary substances that mediate between the liquid storage medium and the receptor, preventing direct degradation while maintaining solubility and biological activity. This allows the receptor to remain stable in liquid form without requiring freezing or drying.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If receptors are dried or lyophilized to improve stability, then stability is improved, but manufacturing cost and complexity increase

Engineering Contradiction:
ImprovestabilityVSAvoidmanufacturing complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent changes the chemical parameters of the storage medium by adding specific stabilizing agents (polyols and chelating agents) to create an optimized liquid environment. This parameter modification allows the receptor to maintain stability in liquid form without undergoing phase transitions to dried or lyophilized states, thereby eliminating the complexity of drying equipment and processes while maintaining reliability.

Inventive Principle:
Principle #35Parameter changes

3Ease of operation

If conventional liquid storage is used, then ease of operation is improved, but sensitivity in detection deteriorates

Engineering Contradiction:
Improveease of operationVSAvoidsensitivity
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The stabilizing agents (polyols and chelating agents) serve as intermediaries that not only protect the receptor from degradation but also maintain its conformational integrity and binding affinity. This dual function allows the receptor to remain both stable and sensitive in liquid form, enabling detection of low concentrations of analytes without requiring complex drying or concentration procedures.

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 provides a stable receptor solution that maintains activity for extended periods, enhancing sensitivity in assays for detecting analytes such as thyroid-stimulating hormone receptor antibodies, allowing for accurate detection of low concentrations in biological samples.

Implementation Method 1

combining in a liquid medium the receptor, a chelating agent and a C2-C6 polyol

Methodology Applied
Scientific EffectChelation:

Implementation Method 2

combining in a liquid medium the receptor, a chelating agent and a C2-C6 polyol

Methodology Applied
Scientific EffectHydrogen bonding:

Implementation Method 3

combining in a liquid medium the receptor, a chelating agent and a C2-C6 polyol

Methodology Applied
Scientific EffectHydrophobic interaction:

Data Source

PatentUS11119108B2Stabilized liquid formulations containing receptors
Publication Date: 2021.09.14 SIEMENS HEALTHCARE DIAGNOSTICS INC
  • US11119108B2 patent drawing
  • US11119108B2 patent drawing

AI summary

Methods and reagents are disclosed for preparing a liquid solution of a receptor. The methods comprise combining in a liquid medium the receptor, a chelating agent and a C2-C6 polyol. An amount of the chelating agent and the C2-C6 polyol is sufficient to achieve a stable and active receptor in the liquid solution, which is maintained at a temperature of about 2° C. to about 40° C. The compositions may be employed in assays for the determination of analytes that include receptor-binding analytes.