Aromatic Tertiary Amine Fluorophore for High SNR Biomolecule Detection

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Solution Overview

Problem

Current fluorescent labeling techniques face challenges in achieving high sensitivity and signal-to-noise ratio (SNR) for detecting biomolecules due to issues with stray light interference and photodegradation, especially when using fluorescent dyes with small Stokes shifts and low light resistance.

Innovation Solution

A labeled compound with an aromatic tertiary amine structure, designed to have a high Stokes shift and increased light resistance, is developed. This compound is capable of binding with biomolecules and features a molecular chain or reactive group that enhances fluorescence yield and reduces quenching, allowing for high sensitivity and SNR detection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional fluorescent dyes are used for labeling biomolecules, then the labeling process is simple and well-established, but the detection sensitivity and signal-to-noise ratio are limited due to small Stokes shifts and stray light interference

Engineering Contradiction:
Improvedetection sensitivityVSAvoidstray light interference
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent changes the fundamental optical parameter of the fluorescent label by using aromatic tertiary amine compounds with large Stokes shifts (greater than 50 nm, preferably greater than 100 nm). This parameter change directly addresses the stray light interference problem by separating the excitation and emission wavelengths more effectively, thereby improving detection sensitivity and signal-to-noise ratio without complicating the labeling process

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs composite fluorescent labels combining aromatic tertiary amine compounds with specific molecular chains or reactive groups. This composite structure integrates the optical benefits of large Stokes shift compounds with the functional capabilities of biomolecule-targeting moieties, achieving both high detection sensitivity and effective biomolecule labeling

Inventive Principle:
Principle #40Composite materials

2Reliability

If conventional fluorescent dyes are used, then the labeling technique isๆˆ็†Ÿ and easy to operate, but photodegradation occurs leading to data variation and reduced reliability

Engineering Contradiction:
Improvemeasurement stabilityVSAvoidlight resistance
Core Design Contradiction:
ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent selects aromatic tertiary amine compounds as the fluorophore base, which inherently possess superior photostability and light resistance compared to conventional fluorescent dyes. This material parameter change reduces photodegradation during detection, ensuring more stable and reliable measurements over time without requiring complex protective measures

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces molecular chains or reactive groups as intermediaries between the aromatic tertiary amine fluorophore and the biomolecule. These intermediaries protect the fluorophore from direct interaction with the biomolecule environment that could cause degradation, while still enabling effective labeling and detection, thereby improving measurement stability

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If fluorescent dyes with small Stokes shifts are used, then the labeling is straightforward, but the signal-to-noise ratio is poor due to difficulty in separating excitation light from fluorescence

Engineering Contradiction:
Improvesignal-to-noise ratioVSAvoidfilter requirements
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent fundamentally changes the Stokes shift parameter of the fluorescent label to be greater than 50 nm (preferably greater than 100 nm). This parameter change creates a larger wavelength gap between excitation and emission, making it easier to separate the two using standard optical filters. Consequently, the signal-to-noise ratio improves without significantly increasing device complexity, as conventional filter technology suffices

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

The labeled compound enables detection of biomolecules at high sensitivity and SNR, with improved light resistance, reducing data variation from photodegradation and allowing for stable, reproducible measurements.

Implementation Method 1

a labeled compound which has a skeletal structure ensuring a high Stokes shift and a high fluorescence yield and is able to detect a sample molecule at high sensitivity and a high SN ratio

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

The labeled compound contains either a molecular chain-bound group wherein a molecular chain capable of binding with a sample molecule is bound to a divalent spacer

Methodology Applied
Scientific EffectStokes shift:

Implementation Method 3

one of S1 and S2 represents a molecular chain-bound group wherein a molecular chain capable of binding with a sample molecule is bound to a divalent spacer

Methodology Applied
Scientific EffectMolecular binding: Chemical Bonding

Data Source

PatentUS8063200B2Labeled compound and detection method using the same
Publication Date: 2011.11.22 SONY GROUP CORP
  • US8063200B2 patent drawing
  • US8063200B2 patent drawing
  • US8063200B2 patent drawing

AI summary

A labeled compound is so designed that an aromatic tertiary amine compound is bondable with a biomolecule. One of S1 and S2 contains a group bound with a molecular chain 10 (e.g. an oligonucleotide) capable of binding with a biomolecule or a reactive group covalently binding with a reactive group present in the biomolecule, n is 0 or 1, R3 is a phenyl group or a naphthyl group, Ar1 is a phenylene group or a naphthylene group, and Ar2 is any of a phenylene group, a naphthylene group, an anthrylene group, and a phenanthrene group. The detection of a fluorescence emitted by excitation of the labeled compound bound to a biomolecule ensures the biomolecule being detected at high sensitivity and a high SN ratio.