Fetal Cell Isolation via Binding Agents and Microfluidic Sorting
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Solution Overview
Problem
Current methods for non-invasive prenatal testing (NIPT) face challenges in accurately and safely isolating fetal cells from maternal blood, particularly due to the rarity of fetal cells and the difficulty in distinguishing them from maternal cells, which limits the accuracy and safety of early gestational age testing.
Innovation Solution
A method involving the use of binding agents directed against fetal or maternal cell markers, followed by sorting using microfluidic, microbubble-based, or fluorescence-activated cell sorting devices to isolate fetal cells from biological samples, allowing for early gestational age testing with increased accuracy and safety.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If invasive methods like amniocentesis or CVS are used to obtain fetal cells, then definitive fetal DNA can be obtained for genetic testing, but the risk of miscarriage and complications increases
Solution Approach 1:
The patent uses cell markers (proteins or nucleic acids) as intermediaries to indirectly identify and isolate fetal cells from maternal blood without direct invasive access to fetal tissues. These markers serve as mediators that enable specific recognition of fetal cells through their unique expression patterns, allowing non-invasive sampling while maintaining diagnostic accuracy
Solution Approach 2:
The patent replaces the mechanical invasive procedures of amniocentesis and CVS with a non-invasive blood draw approach. Instead of physically accessing fetal cells through needle puncture or tissue sampling, the method uses biochemical detection of fetal cell markers in maternal circulation to identify and isolate fetal cells, substituting mechanical intrusion with molecular recognition
2Object-affected harmful factors
If cell-free fetal DNA (cffDNA) is used for non-invasive prenatal testing, then the procedure is safe with no risk of complications, but the accuracy and utility are limited due to fragmented DNA of about 200 base pairs
Solution Approach 1:
The patent extracts intact fetal cells from maternal blood by targeting specific cell markers, rather than relying on fragmented cell-free DNA. This extraction approach isolates complete cellular structures containing full genomic DNA, thereby obtaining sufficient high-quality material for comprehensive genetic analysis while maintaining the non-invasive safety profile
Solution Approach 2:
The patent changes the parameter of DNA integrity by isolating intact fetal cells rather than using fragmented cell-free DNA. By targeting cellular structures that preserve complete genomic material, the method transforms the DNA state from fragmented (200 bp) to intact, enabling more accurate and comprehensive genetic testing
3Loss of time
If cell-based NIPT is performed to isolate fetal cells from maternal blood, then early gestational age testing becomes possible, but the rarity of fetal cells (1-2 cells/mL) makes isolation difficult and inaccurate
Solution Approach 1:
The patent applies local quality by targeting specific cell markers that are uniquely or preferentially expressed on fetal cells. Rather than attempting to isolate cells based on general characteristics, the method focuses detection on specific molecular features (such as fetal-specific proteins or nucleic acid sequences) that distinguish fetal cells from the overwhelming majority of maternal cells, enabling accurate identification despite low abundance
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 the safe and accurate isolation of fetal cells from maternal blood, facilitating earlier and more reliable genetic testing by enriching fetal cells, thereby improving the detection of genetic abnormalities.
Implementation Method 1
contacting the biological sample with one or more binding agents directed against at least one of the group consisting of a fetal cell marker, a maternal cell marker, and a nuclear marker
Implementation Method 2
The one or more binding agents may be a nucleotide probe. The nucleotide probe may be an RNA probe, a DNA probe, a GNA probe or an LNA probe
Implementation Method 3
magnetic activated cell sorting (MACS) device
Implementation Method 4
fluorescence activated cell sorting (FACS) device
Data Source
AI summary
This disclosure generally relates to isolation of fetal cells from biological samples. Methods of using the enriched fetal cells for detecting genetic or epigenetic abnormalities or variations are also provided herein.