Control Marker for Spot Integrity Verification in Multiplex Analysis

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Solution Overview

Problem

Multiplex analysis methods face challenges in verifying the presence, location, and integrity of spots on solid supports, leading to false negative or false positive results due to spot alterations or deterioration during sample preparation and analysis, which is critical for diagnostic accuracy, especially in detecting viral or bacterial contamination in blood samples.

Innovation Solution

The use of resistant control markers that are deposited alongside capture ligands on solid supports, producing a detectable signal at the end of the analysis method without interfering with analyte detection, allowing for verification of spot quality and optimization of detection sensitivity by defining a reading grid based on the actual spot location.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If spots are deposited on solid support for multiplex analysis, then detection of multiple analytes is enabled, but spots may be altered or deteriorated during preparation and analysis leading to false results

Engineering Contradiction:
Improvemultiplex analysis capabilityVSAvoidspot integrity
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

A control marker is introduced as an intermediary element deposited together with capture ligands on the solid support. This control marker serves as a mediator to monitor spot integrity throughout the analysis process, allowing verification that spots remain intact and functional, thereby resolving the contradiction between maintaining spot integrity and performing multiplex analysis operations.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The control marker provides feedback information about spot presence, location, and integrity at the end of the analysis method. By detecting the control marker signal, the system receives feedback confirming whether spots maintained their integrity during preparation and analysis, enabling identification and exclusion of spots that deteriorated, thus ensuring reliable multiplex analysis results.

Inventive Principle:
Principle #23Feedback

2Manufacturing precision

If quality verification is performed at the end of manufacturing, then spot quality can be checked, but it does not verify spot integrity after sample treatment and analysis

Engineering Contradiction:
Improvespot quality verificationVSAvoidpost-analysis spot integrity confirmation
Core Design Contradiction:
Manufacturing precisionVSReliability

Solution Approach 1:

The control marker is deposited preliminarily together with the capture ligand during spot formation. This preliminary placement ensures the control marker is present from the beginning and remains with the spot throughout all subsequent steps including sample treatment and analysis, enabling verification of spot integrity at the end of the complete process rather than just at manufacturing.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The verification approach changes from checking spot quality parameters during manufacturing to detecting the presence and signal of the control marker at the end of analysis. This parameter change enables confirmation that spots maintained their integrity through all processing steps, not just their initial manufacturing quality.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If control markers are deposited with capture ligands, then spot integrity can be verified, but detection sensitivity may be affected

Engineering Contradiction:
Improvespot integrity verificationVSAvoidanalyte detection sensitivity
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The control marker and capture ligand are deposited together to form spots with local quality differentiation. The control marker provides verification functionality at specific locations (spots) without affecting the overall analyte detection capability. Each spot maintains its specific function while the control marker enables integrity verification, resolving the contradiction between verification and sensitivity.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The system changes the detection parameter from solely measuring analyte signal to also measuring control marker signal. By detecting the control marker's presence and signal characteristics, the system verifies spot integrity while the analyte detection sensitivity is maintained through separate measurement of analyte-specific signals, allowing both objectives to be achieved.

Inventive Principle:
Principle #35Parameter changes

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

This approach ensures reliable results by eliminating false negatives and positives, improving analyte detection sensitivity, and securing the integrity of the analysis method by confirming spot presence, location, and quality, even after sample treatment and analysis.

Implementation Method 1

The fluorophore is used to verify the quality of each spot at the end of the preparation method for the DNA microarray

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS11592442B2Control marker for implementing analysis methods on spots
Publication Date: 2023.02.28 BIO RAD EURO GMBH
  • US11592442B2 patent drawing
  • US11592442B2 patent drawing
  • US11592442B2 patent drawing

AI summary

The present invention relates to the use of a control marker for implementing analysis methods on spots, in particular in the context of multiplex analyses. The present invention thus relates to solid supports containing said control marker, their preparation method and their use in analysis methods. The present invention makes it possible to verify the presence, location and/or integrity of the spots at the end of the analysis method, and thus to secure the obtained results while guaranteeing that the yielded result indeed results from a present, intact and localized spot.