Histamine Detection Polypeptides via Modified Immunogen Linkers

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Solution Overview

Problem

Current methods for detecting histamine suffer from low analytical sensitivity and complex sample processing, particularly for free histamine, due to the limitations of antibody-based diagnostic methods that recognize protein-bound histamine with limited affinity and sensitivity.

Innovation Solution

Development of novel polypeptides with specific variable heavy and light chain domains that enhance binding to free histamine and histidine, allowing for improved detection in test samples.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If antibody-based diagnostic methods are used to detect histamine, then detection capability is provided, but analytical sensitivity and affinity for free histamine are limited

Engineering Contradiction:
Improveanalytical sensitivityVSAvoidaffinity for free histamine
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent modifies the immunogen structure by using small molecule haptens (free histamine or histidine) coupled to carrier proteins through multiple different chemical linkers and at various positions, rather than using conventional protein-bound histamine. This parameter change in the immunogen structure enables the generation of antibodies with high affinity and sensitivity for free histamine, resolving the contradiction between measurement precision and reliability.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent performs preliminary conjugation of histamine to carrier proteins using multiple different chemical linkers and coupling positions before immunization. This preliminary action creates a diverse library of immunogens that pre-program the immune system to recognize free histamine in various forms, thereby improving both analytical sensitivity and affinity for free histamine detection.

Inventive Principle:
Principle #10Preliminary action

2Reliability

If conventional immunization methods with protein-bound histamine are used, then antibody production is achieved, but the antibodies recognize only protein-bound histamine with limited affinity

Engineering Contradiction:
Improveantibody recognition capabilityVSAvoidaffinity for free histamine
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

Instead of conjugating histamine to protein and expecting antibodies to recognize free histamine (conventional approach), the patent inverts the approach by using small molecule haptens coupled to carriers through multiple different linkers to generate antibodies that specifically recognize free histamine. This inversion of the conventional immunization strategy resolves the contradiction between antibody recognition capability and affinity for free histamine.

Inventive Principle:
Principle #13The other way round (Inversion)

3Measurement precision

If chromatography-based methods are used for histamine detection, then analytical determination is achieved, but cost, analysis time, and portability are compromised

Engineering Contradiction:
Improveanalytical determination capabilityVSAvoidanalysis time and portability
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent extracts the detection capability from complex chromatography systems and concentrates it into a simplified antibody-based immunoassay format. By using highly specific antibodies generated through the novel immunization method, the patent eliminates the need for complex chromatography instrumentation, thereby reducing analysis time and enabling portability while maintaining analytical determination capability.

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

The novel polypeptides provide enhanced sensitivity and specificity for detecting free histamine and histidine, addressing the limitations of existing methods and enabling more effective medical diagnostics and food safety applications.

Implementation Method 1

novel polypeptides with specific variable heavy and light chain domains that enhance binding to free histamine and histidine

Methodology Applied
Scientific EffectAntigen-antibody binding:

Data Source

PatentUS20230287142A1Histamine binding polypeptides and uses thereof
Publication Date: 2023.09.14 PRESIDENT & FELLOWS OF HARVARD COLLEGE
  • US20230287142A1 patent drawing
  • US20230287142A1 patent drawing
  • US20230287142A1 patent drawing

AI summary

Described herein are polypeptides, compositions, kits, and analyte detection systems for the detection of the presence or absence of small molecules (e.g. histamine and/or histidine) in a test sample.