Up-converting Phosphor DNA Linker for Covalent Binding

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Solution Overview

Problem

Current methods lack the ability to covalently bind up-converting phosphor particles to DNA molecules of detectable sequences, limiting their use for labeling and identification of DNA and further analysis techniques such as PCR or sequence analysis.

Innovation Solution

Development of compositions that link coated optical reporter particles, specifically up-converting phosphor particles, to nucleic acid oligomers through a linking group, enabling covalent binding and subsequent detection and analysis of DNA molecules.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If up-converting phosphor particles are used to detect biomolecules, then detection capability is improved, but the ability to perform further analysis (PCR, sequence analysis) deteriorates because covalent binding to DNA is not achieved

Engineering Contradiction:
Improvedetection capabilityVSAvoidability to perform further analysis
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

A linker molecule serves as an intermediary between the up-converting phosphor particle and the DNA molecule. The linker has a first end that covalently binds to the phosphor particle surface and a second end that covalently binds to the DNA molecule, enabling both detection and subsequent analysis capabilities

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention creates a composite structure consisting of three components: the up-converting phosphor particle, the linker molecule, and the DNA molecule. This composite material integrates the optical detection properties of the phosphor with the analytical utility of DNA, resolving the contradiction between detection capability and adaptability for further analysis

Inventive Principle:
Principle #40Composite materials

2Measurement precision

If covalent binding of UCP particles to DNA molecules is achieved, then labeling and identification capability is improved, but device complexity increases due to the need for linker molecules and coating layers

Engineering Contradiction:
Improvelabeling and identification capabilityVSAvoidstructure complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The phosphor particle surface is preliminarily prepared by coating with a layer (such as silica) that contains functional groups capable of covalent bonding. This preliminary action simplifies the subsequent coupling process and makes the overall system more manageable despite the added complexity of the coating layer

Inventive Principle:
Principle #10Preliminary action

3Reliability

If linker molecules are used to connect phosphor particles to DNA, then covalent binding is achieved, but manufacturing precision requirements increase

Engineering Contradiction:
Improvecovalent binding stabilityVSAvoidlinker attachment precision
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

The invention changes the chemical parameters of the phosphor particle surface by applying a coating layer with specific functional groups. This parameter change enables reliable covalent bonding while providing a standardized interface that simplifies the manufacturing process and reduces precision requirements for linker attachment

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

Enables the detection and analysis of DNA molecules by using the linked up-converting phosphor particles, which can be excited with a high-energy light source, facilitating visualization and analysis through techniques like PCR or sequence analysis.

Implementation Method 1

up-converting phosphor particles (UCP) have been encapsulated in transparent polyacrylate micro-carriers

Methodology Applied
Scientific EffectUp-conversion phosphorescence: Phosphorescence

Implementation Method 2

Reporters can be easily detected by using a high energy light source for excitation, and the location of labeled biomolecules is identified by the presence of a reporter

Methodology Applied
Scientific EffectLight absorption and emission: Absorption (EM radiation)

Data Source

PatentUS8372648B2Optical reporter compositions
Publication Date: 2013.02.12 APDN (BVI) INC
  • US8372648B2 patent drawing
  • US8372648B2 patent drawing
  • US8372648B2 patent drawing

AI summary

This invention provides compositions that have a light emitting reporter linked to biomolecules, preferably, nucleotide oligomers. The light reporter particles are silylated and functionalized to produce a coated light reporter particle, prior to covalently linking the biomolecules to the light reporter particle. The light reporter particles of the invention can be excited by a light excitation source such as UV or IR light, and when the biomolecule is DNA, the attached DNA molecule(s) are detectable by amplification techniques such as PCR.