Fetal Cell Isolation from Cervical Mucus for Non-Invasive Diagnosis
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Solution Overview
Problem
Current methods for prenatal diagnosis of chromosomal abnormalities and genetic disorders are invasive, carry risks of fetal loss, and have high false positive and negative rates, with existing non-invasive methods like fetal DNA analysis in maternal plasma being unreliable due to the fragmented nature of circulating cell-free DNA.
Innovation Solution
A method for non-invasive retrieval and isolation of fetal cells from the endocervical sample using acidification to dissociate fetal cells from maternal cells, followed by treatment with fetal-specific antibodies to identify and isolate fetal cells, allowing for genetic analysis and prediction of pregnancy outcomes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If invasive diagnostic tests like amniocentesis and chorionic villous sampling are used to obtain fetal genetic material, then diagnostic accuracy is improved, but the risk of fetal loss increases
Solution Approach 1:
The invention extracts fetal cells from maternal cervical mucus, separating the fetal genetic material source from invasive procedures. By isolating fetal cells that naturally shed into the cervical canal, the method obtains diagnostic material without penetrating the uterus or amniotic sac, thereby eliminating the procedural risks of fetal loss while maintaining diagnostic capability
Solution Approach 2:
The invention uses cervical mucus as an intermediary medium to access fetal cells. Instead of directly accessing the fetus through invasive procedures, the method captures fetal cells that have naturally migrated into the cervical canal, using the mucus as a transport medium. This intermediary approach provides indirect access to fetal genetic material without the harmful effects of direct invasive intervention
2Object-affected harmful factors
If fetal cells are isolated from maternal plasma, then non-invasive sampling is achieved, but the rarity of fetal cells (1 per 10^6-10^7 maternal cells) reduces diagnostic reliability
Solution Approach 1:
The invention targets a specific local environment (cervical mucus) where fetal cells are concentrated rather than searching through the entire maternal blood volume. By focusing on the cervical canal where fetal cells naturally accumulate during early pregnancy, the method achieves local enrichment of fetal cells, dramatically improving the fetal-to-maternal cell ratio compared to plasma-based approaches
Solution Approach 2:
The invention shifts from searching for fetal cells in the three-dimensional volume of maternal blood plasma to sampling the two-dimensional surface layer of cervical mucus. This dimensional change allows for more efficient capture of fetal cells that are shed into the cervical canal, increasing the probability of obtaining sufficient fetal genetic material for diagnosis
3Loss of time
If fetal cells are retrieved from cervical mucus, then early non-invasive diagnosis is enabled, but the complexity of isolating fetal cells from maternal cells increases
Solution Approach 1:
The invention uses fluorescently labeled antibodies that bind to fetal cell surface markers, causing fetal cells to emit fluorescent signals distinguishable from maternal cells. This optical differentiation method allows for rapid identification and isolation of fetal cells based on their fluorescent properties, simplifying the separation process despite the complexity of dealing with mixed cell populations
Solution Approach 2:
The invention replaces complex mechanical separation methods with immunological recognition systems. Instead of using physical properties like size or density for cell separation, the method uses antibody-antigen specificity to automatically distinguish fetal from maternal cells, reducing the mechanical complexity of the isolation process while enabling early diagnosis
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 early and reliable non-invasive prenatal diagnosis by isolating fetal cells from the cervix, providing vital genetic information for predicting chromosomal abnormalities and obstetrical disorders, reducing the risk of invasive procedures and improving diagnostic accuracy.
Implementation Method 1
removing the mucus from the endocervical sample by disassociating fetal cells and maternal cells in the endocervical sample
Implementation Method 2
treating the cells with a fetal-specific antibody, identifying cells that have bound to the fetal-specific antibody
Data Source
AI summary
A method of retrieving fetal cells from an endocervical sample by removing the mucus from the endocervical sample by disassociating fetal cells and maternal cells in the endocervical sample; and isolating disassociated fetal cells from other cells in the endocervical sample. Also provided is a method of retrieving fetal cells from an endocervical sample, by obtaining a mixture of disassociated cells prepared by the above method, treating the cells with a fetal-specific antibody, identifying cells that have bound to the fetal-specific antibody, and isolating the identified cells. The disassociated cell prepared by the above method can be analyzed and used for a variety of purposes including, but not limited to, the identification of fetal cells among cervical cells, determination of fetal cell density to predict high risk pregnancy, genetic analysis of fetal cells, and determination of growth factor or other biomarker expression to predict obstetrical disorders.
