Single Label Comparative Hybridization for Genetic Abnormality Detection
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Solution Overview
Problem
Comparative genomic hybridization methods face limitations due to the need for different labels that must be read at distinct wavelengths, complicating sample processing and standardization, particularly in detecting chromosomal or genetic abnormalities.
Innovation Solution
A method using a single detectable label for both test and reference nucleic acids, allowing for the determination of their relative amounts hybridized to an array through selective degradation and subtraction, enabling the detection of chromosomal or genetic abnormalities without the need for multiple wavelength readings.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If different labels are used for test and reference nucleic acids, then the amounts of hybridized nucleic acids can be determined by detecting signals at distinct wavelengths, but the sample processing and standardization become complicated
Solution Approach 1:
The patent merges the labeling approach by using a single detectable label for both test and reference nucleic acids instead of different labels. This combining of labeling strategies simplifies the detection system while maintaining the ability to distinguish between test and reference samples through selective degradation and subtraction methods
Solution Approach 2:
The patent changes the detection parameter from wavelength discrimination (multiple labels) to signal intensity comparison (single label with selective degradation). By altering the detection approach from spectral differentiation to quantitative subtraction, the system reduces complexity while preserving measurement precision
2Device complexity
If a single detectable label is used for both test and reference nucleic acids, then the detection process is simplified and sensitivity is enhanced, but the ability to distinguish between samples must be achieved through alternative methods
Solution Approach 1:
The patent applies preliminary action by selectively degrading either test or reference nucleic acids before detection. By pre-modifying one sample type with degradation-prone markers (such as uracil incorporation), the system enables clear distinction between samples during the detection phase without requiring complex multi-wavelength reading
Solution Approach 2:
The patent introduces an intermediary degradation step as a mediator between hybridization and detection. This intermediate processing stage, where selective nucleic acid degradation occurs, serves as a bridge that allows single-label detection to distinguish between test and reference samples through subtraction of signal intensities
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 simplifies the detection process, enhances sensitivity, and improves the accuracy of identifying genetic abnormalities by allowing the use of a single label for both samples, reducing complexity and increasing the resolution of chromosomal analysis.
Implementation Method 1
comparing the amount of test and reference nucleic acids hybridized to a nucleic acid array
Implementation Method 2
labeled with a first tag; and the reference sample nucleic acids comprise a second tag
Data Source
AI summary
Provided are methods of determining differences between nucleic acids in a test sample and a reference sample. In certain embodiments the methods are used for detecting and mapping chromosomal or genetic abnormalities associated with various diseases or with predisposition to various diseases, or to detecting the phenomena of large scale copy number variants. In particular, provided are advanced methods of performing array-based comparative hybridization that allow reproducibility between samples and enhanced sensitivity by using the same detectable label for both test sample and reference sample nucleic acids. Invention methods are useful for the detection or diagnosis of particular disease conditions such as cancer, and detecting predisposition to cancer based on detection of chromosomal or genetic abnormalities and gene expression level. Invention methods are also useful for the detection or diagnosis of hereditary genetic disorders or predisposition thereto, especially in prenatal samples. Moreover, invention methods are also useful for the detection or diagnosis of de novo genetic aberrations associated with post-natal developmental abnormalities.