Optically Isomeric Biotin-Binding Site Reagent for L-biotin Measurement

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Solution Overview

Problem

Current methods for immunological measurements using D-biotin-labeled antibodies are affected by high concentrations of free D-biotin in biological samples, which compete with the target and interfere with measurement results, and there is a lack of methods to measure L-biotin specifically.

Innovation Solution

A reagent containing an optically isomeric biotin-binding site and an azobenzene derivative is used to measure L-biotin, allowing for the determination of L-biotin concentration and the number of L-biotin labels on a molecule, while minimizing interference from D-biotin.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If D-biotin-labeled antibodies are used for immunological measurement, then high sensitivity measurement is achieved, but free D-biotin in biological samples competes with the target and interferes with measurement results

Engineering Contradiction:

Improvemeasurement sensitivityVSAvoidinterference from free D-biotin

Core Design Contradiction:

Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent inverts the conventional approach by using L-biotin (the optical isomer of D-biotin) instead of D-biotin for labeling. Since biological samples contain free D-biotin but not L-biotin, this inversion eliminates the competition problem while maintaining the high affinity binding characteristics of biotin-streptavidin interactions, thus achieving both high sensitivity and freedom from interference.

Inventive Principle:

Principle #13The other way round (Inversion)

2Measurement precision

If conventional biotin measurement methods (HABA method) are used, then D-biotin concentration can be measured, but L-biotin cannot be measured specifically

Engineering Contradiction:

Improvebiotin quantification capabilityVSAvoidability to measure L-biotin

Core Design Contradiction:

Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent applies local quality by using optically isomeric streptavidin (containing D-amino acids) instead of conventional L-amino acid streptavidin. This creates a localized chiral environment that specifically recognizes L-biotin while excluding D-biotin, enabling selective measurement of L-biotin in samples that may contain both isomers.

Inventive Principle:

Principle #3Local quality

3Measurement precision

If the number of D-biotin bound to one antibody molecule is not controlled, then measurement results are affected, but quantifying D-biotin bound to protein is difficult due to lack of specific measurement methods

Engineering Contradiction:

Improvemeasurement result accuracyVSAvoidcomplexity of biotin quantification

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent enables self-service quantification by providing a reagent system where optically isomeric streptavidin and HABA work together to automatically indicate L-biotin concentration through absorbance changes. The system self-regulates and provides direct measurement of L-biotin bound to capture bodies, eliminating the need for complex separate quantification procedures.

Inventive Principle:

Principle #25Self-service

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

Enables accurate measurement of L-biotin in biological samples by utilizing an optically isomeric biotin-binding site that selectively binds to L-biotin, suppressing the effect of D-biotin and allowing for precise quantification of L-biotin and its labels.

Implementation Method 1

an optically isomeric biotin-binding site that does not substantially bind to D-biotin and binds to L-biotin

Methodology Applied

Scientific EffectOptical isomeric binding:

Implementation Method 2

HABA and avidin bind to each other to form a complex having light absorption at a central wavelength of 500 nm

Methodology Applied

Scientific EffectLight absorption: Absorption (EM radiation)

Data Source

PatentUS20230288426A1Reagent for measuring l-biotin, method for measuring sample containing l-biotin, method for determining number of labels of l-biotin-labeled substance, and method for producing solid phase on which optically isomeric biotin-binding site is immobilized

Publication Date: 2023.09.14 SYSMEX CORP

AI summary

Disclosed is a reagent for measuring L-biotin, comprising an optically isomeric biotin-binding site and an azobenzene derivative represented by following formula (I):wherein R1 to R10 are each independently a group selected from the group consisting of a hydrogen atom, a hydroxy group, a carboxy group, C1 to C6 dialkylamino groups having no substituent or a substituted group, C1 to C6 alkyl groups having no substituent or a substituted group, and C1 to C6 alkoxy groups having no substituent or a substituted group, provided that at least one of R1 to R5 is a hydroxy group or a C1 to C6 dialkylamino group having no substituent or a substituted group, and at least one of R6 to R10 is a carboxy group.