Stabilizing Phycobiliprotein Tandem Dyes with Unconjugated Mediators

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Solution Overview

Problem

Phycobiliprotein-containing tandem dyes in multicolor reagent formulations experience degradation and instability, leading to difficulties in discriminating fluorescence signals in flow cytometry due to subunit exchange between ligand-tandem dye conjugates and directly conjugated phycobiliproteins.

Innovation Solution

Incorporating unconjugated phycobiliproteins from the same bacterial or eukaryotic species into the reagent composition to stabilize the phycobiliprotein-containing tandem dyes, preventing subunit exchange and maintaining fluorescence properties over time.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If phycobiliprotein-containing tandem dyes are used in multicolor reagent formulations, then expanded multi-color analysis capability is improved, but dye instability and degradation occur over time

Engineering Contradiction:
Improvemulti-color analysis capabilityVSAvoiddye stability
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent introduces unconjugated phycobiliprotein as an intermediary substance that mediates between the ligand-tandem dye conjugates and directly conjugated phycobiliproteins. This unconjugated phycobiliprotein acts as a stabilizing agent that prevents degradation of the tandem dyes by forming a protective environment, thereby maintaining dye stability while preserving the expanded multi-color analysis capability.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If multiple tandem dyes are combined in multicolor formulations, then fluorescence signal discrimination capability is improved, but subunit exchange between conjugates occurs leading to signal interference

Engineering Contradiction:
Improvefluorescence signal discriminationVSAvoidconjugate composition stability
Core Design Contradiction:
Measurement precisionVSStability of the object's composition

Solution Approach 1:

The unconjugated phycobiliprotein serves as a mediator that stabilizes the conjugate composition by preventing subunit exchange between different tandem dye complexes. It creates a protective environment that maintains the integrity of each conjugate, thereby preserving fluorescence signal discrimination capability while preventing compositional instability.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent utilizes parameter changes by adjusting the concentration and properties of the unconjugated phycobiliprotein to optimize stability. By controlling the ratio and characteristics of the unconjugated phycobiliprotein added to the formulation, the patent achieves optimal prevention of subunit exchange while maintaining measurement precision.

Inventive Principle:
Principle #35Parameter changes

3Ease of operation

If tandem dyes are stored in reagent formulations, then reagent availability is improved, but degradation over time occurs requiring frequent fresh preparation

Engineering Contradiction:
Improvereagent availabilityVSAvoidshelf life
Core Design Contradiction:
Ease of operationVSDuration of action of stationary object

Solution Approach 1:

The patent applies preliminary action by pre-formulating reagent compositions that include unconjugated phycobiliprotein as a stabilizing agent. This preliminary preparation ensures that the tandem dyes are protected from degradation before use, extending shelf life while maintaining ease of operation through ready-to-use formulations.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The unconjugated phycobiliprotein acts as a protective intermediary in the stored reagent formulation, preventing degradation of the tandem dyes during storage. This intermediary substance maintains reagent availability while significantly extending shelf life by creating a stable environment that prevents time-dependent degradation.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 addition of unconjugated phycobiliproteins results in stable reagent compositions that reduce bleed-over and erroneous data in flow cytometry analysis, extending the shelf life of the reagents and reducing the need for frequent preparation of fresh dye compositions.

Implementation Method 1

Incorporating unconjugated phycobiliproteins from the same bacterial or eukaryotic species into the reagent composition to stabilize the phycobiliprotein-containing tandem dyes, preventing subunit exchange and maintaining fluorescence properties over time.

Methodology Applied
Scientific EffectSubunit exchange prevention:

Implementation Method 2

Phycobiliproteins and their tandem dyes are important fluorochromes that are widely used as fluorescent labels in flow cytometry.

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentEP2356456B1Multicolor flow cytometry compositions containing unconjugated phycobiliproteins
Publication Date: 2016.05.18 BECKMAN COULTER INC
  • EP2356456B1 patent drawingFigure 1A~1B
  • EP2356456B1 patent drawingFigure 1C~1D
  • EP2356456B1 patent drawingFigure 2A~2B

AI summary

Novel compositions containing (i) ligand conjugated phycobiliprotein tandem dyes and (ii) unconjugated phycobiliproteins are provided wherein the phycobiliproteins are derived from the same bacterial or eukaryotic algae species. The phycobiliproteins must be the same or different, but must contain some non-crosslinked subunits which exchange. Also provided are methods for preparing these compositions, kits containing these compositions or components of the same, and methods of using these compositions for cellular and non- cellular analysis.