Coumarin-Based Cell Tracking Reagents for Blue Spectrum Fluorescence

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Solution Overview

Problem

Current cell-tracking reagents lack alternatives that fluoresce in the blue portion of the UV/VIS spectrum, limiting their use for long-term monitoring of cell proliferation, differentiation, migration, and function in mixed cell cultures using flow cytometry and fluorescence microscopy.

Innovation Solution

Development of coumarin-based cell-tracking reagents that fluoresce in the blue portion of the UV/VIS spectrum, providing bright fluorescence intensity, uniform cell staining, and low toxicity, allowing for their use in place of or in combination with existing reagents like GFP and allophycocyanine for tracking cell populations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If CFDA-SE is used as a cell-tracking reagent, then bright green fluorescence and homogeneous staining are achieved, but spectral overlap with other commonly used reagents (GFP, APC, ALEXA FLUOR 633) limits multi-color applications

Engineering Contradiction:
Improvemulti-color application capabilityVSAvoidspectral overlap with existing reagents
Core Design Contradiction:
Adaptability or versatilityVSIllumination intensity

Solution Approach 1:

The patent applies color changes by developing coumarin-based fluorophores that emit in the blue region (400-480 nm), which is distinct from the green (CFDA-SE), red (APC, ALEXA FLUOR 633), and yellow-green (GFP) regions. This spectral separation enables simultaneous use with other reagents without overlap, directly resolving the contradiction between versatility and spectral overlap.

Inventive Principle:
Principle #32Color changes

2Adaptability or versatility

If blue-fluorescing cell-tracking reagents are developed, then spectral compatibility with existing reagents is improved, but such reagents have not been successfully realized for long-term monitoring

Engineering Contradiction:
Improvespectral compatibilityVSAvoidlong-term monitoring reliability
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent applies parameter changes by optimizing the coumarin fluorophore structure with specific substituents (R1, R2, R3, R4, R5, R6, R7, R8) to achieve the desired balance. The chemical structure modifications enable the fluorophore to maintain stability and low toxicity over time while fluorescing in the blue region, thus achieving both spectral compatibility and long-term monitoring reliability.

Inventive Principle:
Principle #35Parameter changes

3Adaptability or versatility

If alternative fluorescent dyes are developed for blue spectrum, then multi-color flow cytometry applications are enabled, but no such dyes with bright fluorescence and low toxicity have been successfully created

Engineering Contradiction:
Improvemulti-color flow cytometry capabilityVSAvoidtoxicity to cells
Core Design Contradiction:
Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies composite materials by creating coumarin-based fluorophores with specific chemical structures that combine multiple properties: blue emission spectrum, high brightness, and low toxicity. The molecular design incorporates electron-donating and electron-withdrawing groups at specific positions to optimize these properties simultaneously, enabling multi-color flow cytometry without compromising cell viability.

Inventive Principle:
Principle #40Composite materials

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

Enables effective short- and long-term tracking of cell proliferation with improved spectral properties, enabling multi-color applications and better differentiation of cell populations in mixed cultures through enhanced fluorescence intensity and retention within cells.

Implementation Method 1

coumarin-based cell-tracking reagents that fluoresce in the blue portion of the UV/VIS spectrum, provide bright fluorescence intensity

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentEP3314257B1Cell tracking reagents and their methods of use
Publication Date: 2021.06.16 LIFE TECHNOLOGIES CORP
  • EP3314257B1 patent drawingFigure 1A~1B
  • EP3314257B1 patent drawingFigure 2A~2B
  • EP3314257B1 patent drawing

AI summary

Described herein are compounds, methods, and kits for short- and long-term tracking of cell proliferation, differentiation, and/or function. The compounds disclosed herein are coumarin- based cell-tracking reagents that fluoresce in the blue portion of the UV/VIS spectrum and provide bright fluorescence intensity, uniform cell staining, good retention within cells and low toxicity toward cells.