Genomic Nucleic Acid Anchoring for Genetic Abnormality Detection
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for detecting genomic nucleic acid require amplification and intact cells or nuclei, limiting their applicability for detecting genetic abnormalities such as point mutations, duplications, and translocations without the need for these conditions.
Innovation Solution
A method that hybridizes genomic nucleic acid to a labeled probe and anchors it to a solid support through means other than nucleic acid hybridization, allowing for the detection of genetic abnormalities without amplification or intact cells, using biotin and avidin interaction or covalent linking for anchoring.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If nucleic acid hybridization is used to capture genomic nucleic acid on solid support, then detection sensitivity is improved, but the method requires intact cells or nuclei which limits sample applicability
Solution Approach 1:
The method separates the capture function from the detection function. Genomic nucleic acid is captured on solid support through non-hybridization means (chemical binding, adsorption, or precipitation), while detection is performed using labeled probes that hybridize to specific target sequences. This segmentation allows the use of fragmented or degraded nucleic acid samples without requiring intact cells or nuclei.
Solution Approach 2:
The patent introduces an intermediary capture mechanism that does not rely on nucleic acid hybridization. Instead of using probe-target hybridization for both capture and detection, the method uses a separate capture step (via chemical binding to solid support) followed by hybridization-based detection, allowing degraded nucleic acid to be effectively captured and detected.
2Measurement precision
If genomic nucleic acid amplification is performed before detection, then detection sensitivity is improved, but the detection time and process complexity increase
Solution Approach 1:
The patent extracts the amplification step from the detection process. By using highly sensitive labeled probes that can detect low abundances of target sequences directly in unamplified genomic nucleic acid, the method eliminates the time-consuming amplification steps while maintaining detection sensitivity through the use of detectable labels and optimized hybridization conditions.
3Measurement precision
If multiple detection steps are used to identify different genetic abnormalities, then detection accuracy is improved, but the device complexity and ease of operation deteriorate
Solution Approach 1:
The patent creates a universal detection platform where a single solid support-based capture method can be used with multiple different labeled probes to detect various types of genetic abnormalities (point mutations, insertions, deletions, rearrangements). The same basic assay architecture captures genomic nucleic acid and then uses probe-specific hybridization to identify different targets, eliminating the need for separate assays for each abnormality type.
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 of genetic abnormalities like point mutations, duplications, and translocations directly from unamplified genomic nucleic acid, facilitating diagnosis and prognosis without the need for intact cells or nuclei, with high sensitivity and specificity.
Implementation Method 1
contacting a sample of genomic nucleic acid containing the target sequence with a probe specific for the target sequence and forming on a solid support a complex consisting of the genomic nucleic acid and the probe hybridized to the target sequence
Implementation Method 2
The genomic nucleic acid is anchored to the solid support through means other than nucleic acid hybridization. The method may use biotin and avidin interaction or covalent linking for anchoring.
Data Source
AI summary
The present invention provides methods of detecting unamplifed genomic nucleic acid anchored to a solid support. The methods are useful for the detecting genetic abnormalities associated with various diseases, diagnosis, and prognosis.