Microfluidic Chip Isolates Fetal Cells via Pulsative Flow
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Solution Overview
Problem
Current methods for isolating fetal cells from maternal blood for non-invasive prenatal screening are inefficient, requiring initial removal of maternal cells and resulting in low yields of fetal cells, which limits downstream analysis for genetic abnormalities.
Innovation Solution
A method using microfluidic chips with sinusoidal microchannels coated with binding moieties like EpCAM, CD105, and CD141 antibodies, combined with a liquid handling system and pulsative flow, to isolate fetal cells directly from maternal whole blood without prior removal of maternal cells, enhancing fetal cell recovery and purity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If traditional methods are used to isolate fetal cells from maternal blood, then maternal cells must be removed first, but this results in low yields of fetal cells and reduced efficiency
Solution Approach 1:
The isolation process is segmented into parallel processing streams: one stream removes maternal cells while another stream simultaneously isolates fetal cells using binding moieties. This segmentation allows both functions to occur concurrently rather than sequentially, improving fetal cell yield while managing process complexity through parallelization.
Solution Approach 2:
Binding moieties (such as antibodies against EpCAM, CD105, or CD141) serve as intermediaries that selectively capture fetal cells from maternal blood. These intermediaries enable direct fetal cell isolation without requiring prior maternal cell removal, thereby improving efficiency and yield while simplifying the overall process.
2Reliability
If maternal cells are removed prior to fetal cell isolation, then fetal cell purity is improved, but the process time and complexity increase
Solution Approach 1:
The method merges the maternal cell removal step and fetal cell isolation step into a single simultaneous process. Binding moieties capture fetal cells while maternal cells are removed through density gradient centrifugation in parallel, achieving both high purity and reduced time without requiring sequential processing.
Solution Approach 2:
Binding moieties are pre-coated on microfluidic chips before sample introduction. This preliminary preparation enables immediate selective capture of fetal cells upon blood sample introduction, eliminating the need for time-consuming sequential processing steps and reducing overall isolation time while maintaining high purity.
3Productivity
If conventional isolation methods are used, then the process is simpler, but fetal cell recovery is insufficient for robust downstream analysis
Solution Approach 1:
The method replaces complex mechanical cell removal procedures with a biochemical approach using binding moieties that selectively interact with fetal cell surface markers. This substitution improves recovery efficiency through specific molecular recognition while maintaining operational simplicity through automated microfluidic handling.
Solution Approach 2:
The invention changes the isolation parameter from physical removal methods to affinity-based capture using binding moieties. By exploiting specific antigen-antibody interactions (e.g., EpCAM, CD105, CD141), the method achieves superior fetal cell recovery while keeping the procedure simple and adaptable to existing microfluidic platforms.
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 effectively isolates fetal cells at higher yields and purities compared to traditional methods, enabling more robust downstream analysis for genetic screening without the need for initial maternal cell depletion, improving the efficiency of non-invasive prenatal diagnostics.
Implementation Method 1
sinusoidal microchannels comprise binding moieties that selectively bind to EpCAM, binding moieties that selectively bind to CD105, and/or binding moieties that selectively bind to CD141
Implementation Method 2
hydrodynamically processing the sample through said one or more microfluidic chips
Data Source
AI summary
The presently disclosed subject matter provides methods of isolating fetal cells from a sample from a pregnant subject, methods of isolating multinucleated fetal giant cells from a sample from a pregnant subject, and related compositions and methods.