Biochip Marker Sites for Quantitative Hybridization Efficiency

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Solution Overview

Problem

Conventional biochips cannot quantitatively measure hybridization efficiency due to unknown quantities of probe DNA, and existing methods like the Code Link Expression Bioarray System fail to account for probe DNA loss during hybridization processing.

Innovation Solution

A biochip with probe sites and marker sites, where the number of fluorophore-modified molecules at marker sites is known, allowing for quantitative assessment of hybridization efficiency by comparing fluorescent light intensities between probe and marker sites, ensuring accurate measurements regardless of processing conditions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional biochip methods are used to measure hybridization, then fluorescent intensity can be detected, but the number of probe DNA at probe sites is unknown making quantitative measurement impossible

Engineering Contradiction:
Improvehybridization efficiency measurementVSAvoidprobe DNA quantity information
Core Design Contradiction:
Measurement precisionVSLoss of information

Solution Approach 1:

The patent introduces marker sites with known quantities of fluorophore-modified molecules as intermediary reference elements. These marker sites serve as a bridge between the unknown probe DNA quantities and the measurable fluorescent intensity, enabling quantitative calculation of hybridization efficiency through comparison.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the parameter of fluorescent intensity measurement from absolute to relative by introducing marker sites with known fluorophore quantities. This allows the system to work with intensity ratios rather than absolute values, resolving the measurement quantification problem.

Inventive Principle:
Principle #35Parameter changes

2Quantity of substance

If Code Link Expression Bioarray System method is used to measure probe quantity by fluorescent intensity, then spotted quantity can be grasped, but the ratio of probe DNA washed away during hybridization processing remains unknown

Engineering Contradiction:
Improveprobe DNA quantityVSAvoidhybridization efficiency accuracy
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

Marker sites act as intermediary reference elements that experience the same washing and processing conditions as probe sites. By comparing fluorescent intensities between marker and probe sites, the system compensates for DNA loss during processing without needing to know the exact loss ratio.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent creates homogeneous treatment conditions for both marker sites and probe sites during hybridization processing. Both types of sites are subjected to identical washing and processing steps, ensuring that any DNA loss affects both equally, thus maintaining the reliability of comparative measurements.

Inventive Principle:
Principle #33Homogeneity

3Manufacturing precision

If marker sites are formed by use of biopolymer of the same species as probe sites, then biopolymer amount can be equalized, but additional processing steps are required

Engineering Contradiction:
Improvebiopolymer amount uniformityVSAvoidbiochip structure
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The marker sites use biopolymers of the same species as probe sites, allowing the same spotting and processing procedures to be applied universally to both types of sites. This multi-functionality simplifies the overall manufacturing process despite the added reference functionality.

Inventive Principle:
Principle #6Universality (Multi-functionality)

4Adaptability or versatility

If multiple marker sites with different fluorophore quantities are disposed, then hybridization efficiency can be grasped over wide range, but device complexity increases

Engineering Contradiction:
Improvemeasurement rangeVSAvoidmarker sites configuration
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent segments the reference measurement function into multiple marker sites with different fluorophore quantities. This segmentation allows the system to handle a wide range of hybridization efficiencies by selecting appropriate marker sites for comparison, with each segment covering a specific intensity range.

Inventive Principle:
Principle #1Segmentation

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 stable and accurate quantification of hybridization efficiency across a wide range by equalizing biopolymer amounts and minimizing the impact of processing variations, providing reliable hybridization efficiency measurements.

Implementation Method 1

a quantity of the target DNA as bonded can be measured by use of a fluorescent marker

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS7781204B2Method for analyzing a biochip
Publication Date: 2010.08.24 YOKOGAWA ELECTRIC CORP
  • US7781204B2 patent drawing
  • US7781204B2 patent drawing
  • US7781204B2 patent drawing

AI summary

There is provided a biochip capable of quantitatively grasping hybridization efficiency. In the biochip comprising a plurality of probe sites with target molecules bonded thereto, respectively, the probe sites disposed thereon, the marker sites with a known number of fluorescent molecules bonded thereto, respectively, are disposed. With the biochip, the number of the fluorescent molecules bonded to the respective marker sites is already known, so that respective hybridization efficiencies at the probe sites can be quantitatively grasped by comparing respective intensity of fluorescent light of the probe sites with an intensity of fluorescent light of the marker sites. The fluorescent molecule may be bonded to the respective marker sites when the biochip is formed, or the respective marker sites may be made up such that the fluorescent molecule of a predetermined molecular weight is bonded thereto by a predetermined processing applied to the biochip. The respective marker sites may be formed by use of a biopolymer of the same species as that for the respective probe sites.