Hybridization Array Detection of Fetal Aneuploidy

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Solution Overview

Problem

Current methods for detecting genetic abnormalities such as copy number variations (CNVs) are inefficient and lack reproducibility, particularly in identifying fetal aneuploidy and other genetic disorders.

Innovation Solution

The method involves interrogating loci from target genomic regions using fixed sequence oligonucleotides that hybridize and ligate, with ligation products captured on a solid support, allowing for the detection of copy number variations, insertions, deletions, translocations, and polymorphisms through hybridization and quantification of labeled oligonucleotides on an array.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If current methods are used for detecting genetic abnormalities, then detection can be performed, but the methods are inefficient and lack reproducibility

Engineering Contradiction:

Improvedetection efficiencyVSAvoidreproducibility

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The method segments the detection process into distinct steps: hybridization of fixed sequence oligonucleotides to target loci, ligation to form capture products, capture on solid support, and quantification. This segmentation enables standardized protocols that improve both efficiency and reproducibility across different laboratories and samples.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention changes key parameters of the detection method by using fixed sequence oligonucleotides with specific hybridization conditions and ligation efficiency optimizations. These parameter changes create a more reliable and reproducible assay that maintains high detection efficiency while improving consistency across experiments.

Inventive Principle:

Principle #35Parameter changes

2Loss of information

If sequencing is used to detect genetic abnormalities, then comprehensive genetic information can be obtained, but the process is time-consuming and complex

Engineering Contradiction:

Improvegenetic information completenessVSAvoiddetection time

Core Design Contradiction:

Loss of informationVSLoss of time

Solution Approach 1:

The method extracts only the specific genetic information needed for detecting copy number variations and aneuploidy through targeted hybridization of fixed sequence oligonucleotides to specific loci. This extraction approach avoids the time-consuming full sequencing process while maintaining the ability to detect relevant genetic abnormalities with high accuracy.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

Instead of performing complete sequencing, the method applies partial action by targeting specific genomic regions with fixed sequence oligonucleotides. This partial approach is sufficient for detecting copy number variations and aneuploidy, significantly reducing detection time while maintaining diagnostic value.

Inventive Principle:

Principle #16Partial or excessive action

3Adaptability or versatility

If multiple target genomic regions are interrogated simultaneously, then comprehensive screening is achieved, but the assay complexity increases

Engineering Contradiction:

Improvescreening coverageVSAvoidassay complexity

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The method employs universal fixed sequence oligonucleotides that can hybridize to multiple different target loci across various genomic regions. This universality allows simultaneous interrogation of multiple target genomic regions using the same assay platform, achieving comprehensive screening without proportionally increasing assay complexity.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The fixed sequence oligonucleotides serve as intermediaries that bridge the sample DNA and the detection system. These intermediaries enable simultaneous targeting of multiple genomic regions through a unified approach, simplifying the overall assay design while maintaining comprehensive screening capability.

Inventive Principle:

Principle #24Intermediary (Mediator)

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

This approach provides a statistically reliable and efficient method for detecting genetic abnormalities, including fetal aneuploidy, by quantifying relative frequencies of target genomic regions without the need for sequencing, enhancing diagnostic accuracy and reproducibility.

Implementation Method 1

introducing a first set of first and second fixed sequence oligonucleotides to a sample under conditions that allow the first and second fixed sequence oligonucleotides to hybridize specifically to complementary regions in loci from a first target genomic region

Methodology Applied

Scientific EffectHybridization:

Data Source

PatentUS9567639B2Detection of target nucleic acids using hybridization

Publication Date: 2017.02.14 ROCHE MOLECULAR SYSTEMS INC

AI summary

The present invention provides detection systems and methods for detection of loci and genomic regions in a sample, including mixed samples, using hybridization to an array.