Amniotic Cell Chromosome Analysis via Direct DNA Sequencing
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Solution Overview
Problem
Current methods for detecting fetal chromosomal aneuploidy, such as amniocentesis and non-invasive prenatal testing using maternal plasma DNA, face challenges like high failure rates, time-consuming results, and limited accuracy in detecting chromosomal abnormalities beyond chromosomes 21, 18, and 13.
Innovation Solution
A method involving high-throughput sequencing of amniotic cells, where genomic DNA is isolated, broken into fragments, and sequenced to determine chromosomal ratios (ChrN%) for each chromosome, allowing for the detection of aneuploidy by comparing these ratios to standard cells, without the need for culturing amniotic cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If amniotic cells are cultured to obtain chromosomal specimens, then chromosomal analysis can be performed, but the process is time-consuming (10 days to 3 weeks) and has high failure rate (about 1.00%)
Solution Approach 1:
The patent extracts the essential genetic information (DNA) from amniotic cells without requiring full cell culture. By isolating and sequencing DNA directly, the method obtains chromosomal information while avoiding the time-consuming culture process, thus resolving the contradiction between analysis reliability and time consumption.
Solution Approach 2:
The patent replaces the mechanical cell culture system with a direct DNA extraction and sequencing system. Instead of relying on cell division and growth (mechanical/biological process), the method uses molecular biology techniques to directly obtain and analyze chromosomal DNA, significantly reducing time while maintaining accuracy.
2Quantity of substance
If amniotic cells are cultured to obtain sufficient viable cells, then chromosomal counting and analysis can be performed, but the culturing failure rate is high (about 1.00%) due to cell aging and pyknosis
Solution Approach 1:
The patent extracts DNA directly from amniotic cells without requiring the cells to be cultured to viability. This extraction approach bypasses the culturing step entirely, eliminating the high failure rate associated with cell aging and pyknosis while still obtaining sufficient genetic material for analysis.
Solution Approach 2:
The patent creates copies of the chromosomal information through DNA sequencing rather than relying on physical cell copies. By sequencing DNA directly, the method obtains multiple copies of chromosomal data without needing to culture and divide the original cells, thus avoiding culturing failures.
3Measurement precision
If traditional karyotype analysis is performed on cultured amniotic cells, then chromosomal abnormalities can be detected, but the process requires significant labor and costs that many hospitals cannot afford
Solution Approach 1:
The patent replaces the labor-intensive manual karyotype analysis system with an automated DNA sequencing and bioinformatics analysis system. This substitution maintains high detection accuracy while significantly reducing manual labor requirements and associated costs, making the procedure more accessible to hospitals with limited resources.
Solution Approach 2:
The patent changes the measurement parameters from visual chromosomal inspection to molecular DNA sequencing. This parameter change enables automated analysis through computational methods, reducing the need for skilled manual interpretation and lowering operational costs while maintaining or improving detection precision.
4Object-affected harmful factors
If non-invasive prenatal testing using maternal plasma DNA is performed, then chromosomal abnormalities can be detected without amniocentesis, but the method cannot completely replace amniocentesis due to limitations in detecting aneuploidy, translocation, and mosaicism
Solution Approach 1:
The patent creates a hybrid approach by using amniotic cell DNA sequencing that copies the direct fetal genetic material rather than relying on cell-free DNA fragments in maternal plasma. This provides more complete genomic information for detecting aneuploidy, translocation, and mosaicism while avoiding the invasive risks of repeated amniocentesis procedures.
Solution Approach 2:
The patent combines the advantages of both invasive and non-invasive approaches by using direct amniotic cell DNA analysis. This composite method integrates the completeness of direct fetal DNA access with reduced procedural risk, achieving high detection accuracy without the limitations of plasma-based testing.
Data Source
Figure 1A~1B
Figure 1C~1D
AI summary
The present invention involves an analysis method of cellular chromosomes, particularly involves a method of analyzing whether a difference exists in the chromosome number between amniotic cells and standard cells by a sequencing method.