Addressable Antibody Arrays for Multiplex Autoantibody Detection

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Solution Overview

Problem

Current methods for detecting autoantibodies in clinical laboratories lack universal standards, are not practical for parallel, high-throughput analysis of multiple autoantibodies, and struggle with sensitivity and specificity, especially in detecting low-affinity antibodies.

Innovation Solution

The development of array format assay methods using tagged antigens and mass spectrometric techniques, which allow for multiplex detection, minimize biological sample usage, and enhance sensitivity and specificity by forming immunological pairs with solid supports and releasing cleavable mass tags for detection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If traditional ELISA or Western blotting methods are used to detect autoantibodies, then sensitivity can be maintained, but parallel high-throughput analysis of multiple autoantibodies is not practical and results are not comparable

Engineering Contradiction:
Improvethroughput of autoantibody detectionVSAvoidcomparability of results
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The invention segments the detection process by immobilizing multiple different antigens at specific spatial locations on a solid support surface. Each antigen location can independently detect specific autoantibodies in parallel, enabling high-throughput analysis while maintaining standardized measurement conditions across all detections

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The solid support surface serves as a universal platform that can simultaneously perform multiple detection functions. Different antigens are immobilized on the same support, allowing a single system to detect multiple autoantibodies under identical conditions, ensuring result comparability while achieving parallel high-throughput analysis

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Productivity

If multiple autoantibodies are detected separately using traditional methods, then each measurement can be optimized, but the overall process is not practical for high-throughput analysis

Engineering Contradiction:
Improveparallel detection capabilityVSAvoidassay system complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The invention merges multiple separate detection assays into a single integrated solid support system. Multiple antigens are immobilized on one support surface, allowing simultaneous detection of multiple autoantibodies in a single experiment, achieving parallel high-throughput analysis without proportionally increasing system complexity

Inventive Principle:
Principle #5Merging (Combining)

3Measurement precision

If autoantibodies are detected using conventional methods, then standard procedures can be followed, but sensitivity for low-affinity autoantibodies is insufficient

Engineering Contradiction:
Improvedetection sensitivityVSAvoidassay implementation complexity
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The invention applies local quality by creating distinct functional zones on the solid support surface where different antigens are immobilized at optimized local concentrations and conditions. This allows enhancement of detection sensitivity for low-affinity autoantibodies at specific locations while maintaining overall assay implementability through standardized protocols

Inventive Principle:
Principle #3Local quality

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

These methods provide sensitive and specific detection of autoantibodies, enabling accurate diagnosis of autoimmune diseases and cancer with improved throughput and cost-effectiveness, and can detect low-affinity antibodies effectively.

Implementation Method 1

contacting the immunological pair with a solid support having a binding member specific for the immunological pair to form, or wherein the immunological pair is transform into, a protein complex; separating the protein complex from the sample

Methodology Applied
Scientific EffectSpecific binding: Adsorption

Implementation Method 2

releasing the tag from the isolated protein complex for detection. The detection is preferably by mass spectrometric techniques.

Methodology Applied
Scientific EffectMass spectrometry:

Data Source

PatentEP2409150B1Addressable antibody arrays and methods of use
Publication Date: 2016.09.14 NESTEC SA
  • EP2409150B1 patent drawingFigure 1A
  • EP2409150B1 patent drawingFigure 1B
  • EP2409150B1 patent drawingFigure 2A

AI summary

Systems and assay methods are disclosed for detecting an autoantibody in a sample. In certain instances, the systems and methods employ a mass tag releasably connected to an antigen. The tag is thereafter released for detection. A tag can be detected by mass spectrometry or in certain instances the tag is fluorescent. Methods for diagnosing a disease or disorder in a subject are also disclosed.