GrFFF Isolation of Fetal Erythroblasts for Non-Invasive Prenatal Diagnosis
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Solution Overview
Problem
Current prenatal diagnosis methods for chromosomal and genetic abnormalities are either invasive and risky or non-invasive but unreliable, failing to provide clear and safe outcomes, especially in identifying fetal DNA from maternal blood due to fragmentation and contamination issues.
Innovation Solution
A non-invasive method using gravitational field-flow fractionation (GrFFF) to isolate intact fetal erythroblasts from maternal blood, allowing for the separation and analysis of fetal DNA, RNA, and proteins, enabling precise prenatal diagnosis without risks to the mother or fetus.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If invasive tests (amniocentesis, villocentesis) are used to analyze fetal DNA, then diagnostic accuracy is improved, but risk to fetus and mother increases significantly
Solution Approach 1:
The invention extracts and isolates fetal erythroblasts containing intact fetal DNA from maternal blood, separating the desired diagnostic material (fetal DNA in erythroblasts) from the harmful context (invasive procedures). This extraction approach enables non-invasive diagnosis by obtaining fetal genetic material without penetrating the uterus or amniotic sac.
Solution Approach 2:
The invention uses maternal blood as an intermediary medium to access fetal genetic material. Instead of directly invading fetal tissues, the method leverages the natural presence of fetal erythroblasts in maternal circulation as a safe intermediary source of fetal DNA for diagnostic analysis.
2Object-affected harmful factors
If non-invasive tests (morphological, hematochemical) are used to screen for abnormalities, then risk to fetus and mother is eliminated, but diagnostic accuracy and clarity deteriorate
Solution Approach 1:
The invention replaces traditional mechanical/invasive sampling methods with a biological selection approach. Instead of physically penetrating tissues to obtain samples, the method uses gravitational field-flow fractionation to separate and isolate fetal erythroblasts from maternal blood based on their physical properties, achieving non-invasive acquisition of diagnostic material with high accuracy.
Solution Approach 2:
The invention changes the parameter of sample integrity by isolating intact fetal erythroblasts rather than fragmented fetal DNA or indirect biomarkers. This parameter change from analyzing fragmented molecules to analyzing intact cells enables comprehensive genetic, chromosomal, and epigenetic analysis while maintaining non-invasive status.
3Object-affected harmful factors
If fetal DNA is isolated from maternal blood using conventional methods, then non-invasive sampling is achieved, but DNA fragmentation and contamination with maternal DNA reduce reliability
Solution Approach 1:
The invention segments the maternal blood sample into distinct cellular components using gravitational field-flow fractionation, separating fetal erythroblasts from other blood cells including maternal cells. This segmentation approach isolates the specific cell type containing fetal DNA while excluding contaminating maternal DNA, thereby improving reliability.
Solution Approach 2:
The invention applies local quality by targeting specifically fetal erythroblasts within the heterogeneous maternal blood sample. The gravitational field-flow fractionation process creates distinct zones where cells with specific properties (fetal erythroblasts) are separated and collected, ensuring that only the desired cell type with intact fetal DNA is isolated for analysis.
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 method enables accurate and safe prenatal diagnosis of chromosomal abnormalities and genetic diseases across all gestational ages, providing clear indications without the risks associated with invasive procedures and improving the reliability of non-invasive tests by isolating intact fetal cells for analysis.
Implementation Method 1
applying a laminar flow by gravitational field-flow fractionation (GrFFF) to a blood sample containing isolated intact fetal erythroblasts
Implementation Method 2
applying a laminar flow by gravitational field-flow fractionation (GrFFF) to a blood sample
Data Source
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AI summary
The invention pertains to a method which allows separation of nucleated fetal cells, particularly fetal erythroblasts, from maternal peripheral blood. More specifically the invention relates to a non-invasive method which can isolate and provide intact nucleated fetal cells, and is useful for subsequent chromosome, gene expression and protein investigations, and is feasible at all gestational ages.