Fluorescent Reagent Selection for Flow Cytometry Cross-Reactivity

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Solution Overview

Problem

Current flow cytometry technologies require specialized knowledge to select appropriate fluorescent reagents for multicolor assays, leading to complications in detecting multiple antigens simultaneously due to issues like cross-reactivity and varying fluorescence intensities, which are not user-friendly for non-experts and can result in suboptimal detection of target molecules.

Innovation Solution

A reagent selection support apparatus and method that determines a combination of fluorescent reagents based on the properties of target molecules and stains, including fluorescence intensity and abundance, to ensure accurate detection without expert intervention, using a processing unit to acquire order information and output suitable reagent combinations, considering factors like remaining reagent amounts and expiration dates.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If multiple fluorescent stains are used to detect multiple target molecules in one assay, then the productivity and efficiency of antigen detection is improved, but the complexity of reagent selection and the risk of cross-reactivity and fluorescence intensity interference increases

Engineering Contradiction:
Improveefficiency of antigen detectionVSAvoidcomplexity of reagent selection
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The system performs self-service by automatically selecting appropriate fluorescent reagent combinations based on input measurement items, eliminating the need for expert intervention. The processing unit autonomously evaluates multiple factors including cross-reactivity, fluorescence intensity ratios, and reagent availability to determine optimal reagent sets for multicolor flow cytometry assays.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The reagent selection support apparatus acts as an intermediary between the user's measurement requirements and the complex world of fluorescent reagents. It translates measurement items into appropriate reagent combinations by considering numerous parameters such as antibody cross-reactivity, fluorescence intensity relationships, and instrument compatibility, thereby simplifying the user's task while ensuring optimal assay conditions.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If fluorescent stains with different fluorescence intensities are used to detect target molecules with different abundance levels, then the measurement precision is improved, but the difficulty of selecting appropriate reagent combinations increases

Engineering Contradiction:
Improvedetection accuracy of target moleculesVSAvoiddifficulty of reagent combination selection
Core Design Contradiction:
Measurement precisionVSDifficulty of detecting and measuring

Solution Approach 1:

The system applies parameter changes by evaluating and matching fluorescence intensity parameters of stains with abundance parameters of target molecules. It automatically adjusts the selection based on the relationship between these parameters, ensuring that high-abundance targets are paired with appropriate fluorescence intensities while avoiding saturation or signal loss, thereby optimizing measurement precision without requiring manual parameter analysis.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent replaces the mechanical/expert system of manual reagent selection with an automated information processing system. The processing unit substitutes human expertise by computationally evaluating fluorescence intensity relationships, cross-reactivity data, and abundance levels to determine optimal reagent combinations, thereby eliminating the need for specialized knowledge while maintaining high measurement precision.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Reliability

If a plurality of detection antibodies are used to detect multiple surface markers, then the reliability of disease diagnosis is improved, but the risk of cross-reactivity between antibodies increases

Engineering Contradiction:
Improveaccuracy of disease diagnosisVSAvoidcross-reactivity of detection antibodies
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The system applies preliminary anti-action by proactively identifying and preventing cross-reactivity issues before the assay is performed. The processing unit evaluates cross-reactivity data for all candidate antibody combinations and eliminates combinations where cross-reactivity would compromise diagnostic reliability, thereby preventing harmful effects rather than addressing them after they occur.

Inventive Principle:
Principle #9Preliminary anti-action

Solution Approach 2:

The system incorporates feedback mechanisms by evaluating cross-reactivity information and fluorescence intensity relationships to refine reagent selection. It uses stored data on antibody specificities and fluorescence properties to provide feedback on suitable combinations, ensuring that selected reagents will not interfere with each other's detection while maintaining high diagnostic reliability across multiple target markers.

Inventive Principle:
Principle #23Feedback

Data Source

PatentUS11754568B2Reagent selection support apparatus, cell analysis system, reagent selection support method, and storage medium storing computer program
Publication Date: 2023.09.12 SYSMEX CORP
  • US11754568B2 patent drawing
  • US11754568B2 patent drawing
  • US11754568B2 patent drawing

AI summary

A reagent selection support apparatus for supporting selection of a reagent used for cell measurement is provided. The apparatus includes a processing unit configured to acquire order information including a first measurement item and a second measurement item different from the first measurement item, and determine a combination of a first fluorescence reagent used to measure a first target molecule corresponding to the first measurement item and a second fluorescence reagent used to measure a second target molecule corresponding to the second measurement item, based on information on a property of the first target molecule and a property of a first fluorescent stain contained in the first fluorescent reagent, and information on a property the second target molecule and a property of a second fluorescent stain contained in the second fluorescent reagent; and an output unit configured to output the determined combination of the first fluorescence reagent and the second fluorescence reagent.