Photostable Detectable Compounds for Fluorescence Stability

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Solution Overview

Problem

Fluorescent dyes used in biological applications face limitations due to photobleaching and phototoxicity when exposed to illumination sources, affecting their performance in microscopy, cytometry, and DNA sequencing.

Innovation Solution

Development of photostable detectable compounds with specific fluorescent dye moieties and bioconjugate reactive groups, covalently linked to biomolecules, which maintain fluorescence intensity over time and reduce toxicity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If fluorescent dyes are used for extended illumination in biological applications, then imaging and detection capabilities are achieved, but photobleaching occurs reducing fluorescence intensity over time

Engineering Contradiction:
Improvefluorescence durationVSAvoidfluorescence stability
Core Design Contradiction:
Duration of action of moving objectVSReliability

Solution Approach 1:

The patent modifies the chemical structure of fluorescent dyes by introducing specific substituent groups (e.g., fluorinated alkyl groups, sulfonate groups) and adjusting molecular parameters to enhance photostability. These parameter changes in the dye structure directly address the photobleaching issue while maintaining fluorescence properties.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention creates composite fluorescent probe structures by combining fluorescent dye moieties with bioconjugate reactive groups and linker moieties. This composite approach integrates multiple functional components into a single molecule that simultaneously provides fluorescence, target binding, and enhanced stability against photobleaching.

Inventive Principle:
Principle #40Composite materials

2Duration of action of moving object

If fluorescent dyes are used for extended illumination, then imaging capability is maintained, but phototoxicity increases causing damage to biological samples

Engineering Contradiction:
Improveimaging durationVSAvoidphototoxicity
Core Design Contradiction:
Duration of action of moving objectVSObject-affected harmful factors

Solution Approach 1:

The patent optimizes the chemical parameters of fluorescent dyes by incorporating specific substituent groups that reduce reactive oxygen species generation and minimize phototoxic effects on biological samples, allowing longer imaging durations without sample damage.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention introduces intermediary protective groups and linker moieties that act as buffers between the fluorescent dye and the biological sample, reducing direct phototoxic interactions while maintaining the imaging function.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Illumination intensity

If conventional fluorescent dyes are used, then initial fluorescence intensity is achieved, but signal stability deteriorates over time due to photobleaching

Engineering Contradiction:
Improvefluorescence intensityVSAvoidfluorescence stability
Core Design Contradiction:
Illumination intensityVSStability of the object's composition

Solution Approach 1:

The patent systematically modifies molecular parameters including substituent types, linker lengths, and dye core structures to achieve optimal balance between high initial fluorescence intensity and long-term signal stability, preventing photobleaching-induced signal deterioration.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention applies local structural modifications at specific positions within the fluorescent molecule (e.g., adding stabilizing groups at particular locations on the dye core) to enhance overall photostability while preserving the fluorescence-generating regions of the molecule.

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

The compounds exhibit stable fluorescence over extended exposure to illumination, minimizing photobleaching and phototoxicity, thereby enhancing imaging and analysis in biological applications.

Implementation Method 1

R1 is a fluorescent dye moiety... detecting a light emission from the detectable moiety

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS20240410892A1Photostable detectable compounds
Publication Date: 2024.12.12 SINGULAR GENOMICS SYSTEMS INC
  • US20240410892A1 patent drawing
  • US20240410892A1 patent drawing
  • US20240410892A1 patent drawing

AI summary

Disclosed herein, inter alia, are detectable compounds including a triplet state quencher and the method of use thereof.