TREML2 Antibody Fetal Cell Isolation from Maternal Blood
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Solution Overview
Problem
Current non-invasive prenatal diagnostic methods, such as cell-free DNA-based screening, are not adequately sensitive or specific for detecting subchromosomal deletions and duplications, and invasive procedures like amniocentesis and CVS carry risks, necessitating a reliable method for isolating fetal cells from maternal blood for accurate prenatal testing.
Innovation Solution
A method involving antibodies that bind to the Triggering Receptor Expressed on Myeloid Cells Like 2 (TREML2) protein, using magnetic particles and exogenous aggregation enhancing factors, to enrich and identify fetal cells, allowing for genetic analysis and detection of abnormalities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If cell-free DNA-based screening (NIPT) is used for prenatal diagnosis, then non-invasive testing is achieved, but detection accuracy for subchromosomal deletions and duplications is insufficient
Solution Approach 1:
The patent uses TREML2 protein as an intermediary marker to bridge the gap between non-invasive sampling and accurate fetal cell identification. By detecting this specific protein marker on fetal cell surfaces, the method enables accurate prenatal diagnosis without requiring invasive procedures, thus resolving the contradiction between safety and detection accuracy.
Solution Approach 2:
The patent changes the detection parameter from cell-free DNA to intact fetal cells marked by TREML2 protein expression. This parameter change allows for both non-invasive sampling (maternal blood) and high-accuracy detection (cell-based), overcoming the limitations of traditional NIPT for subchromosomal abnormalities.
2Quantity of substance
If traditional enrichment methods (filters, density gradients, FACS, microfluidics, immuno-magnetic beads) are used to isolate fetal cells, then fetal cell recovery is achieved, but consistency and reproducibility are lacking
Solution Approach 1:
The patent changes the enrichment approach from physical/chemical methods to a targeted immunological method based on TREML2 protein expression. This parameter change enables consistent and reproducible fetal cell isolation by leveraging the specific presence of TREML2 on fetal cell surfaces, which provides a reliable target for antibody-based enrichment.
Solution Approach 2:
TREML2 protein serves as a reliable intermediary marker that enables consistent fetal cell identification across different samples and laboratories. The antibody-based enrichment method using this specific protein target provides reproducibility that traditional methods cannot achieve, as the marker is specifically expressed on fetal cells and not maternal cells.
3Measurement precision
If invasive procedures (amniocentesis, CVS) are used for prenatal diagnosis, then diagnostic accuracy is high, but pregnancy loss risk is introduced
Solution Approach 1:
The patent uses TREML2 protein as an intermediary marker that enables accurate fetal cell identification through non-invasive maternal blood sampling. This intermediary approach provides diagnostic accuracy comparable to invasive procedures while eliminating the associated pregnancy loss risk, as no penetration of the amniotic sac or placenta is required.
Solution Approach 2:
The patent replaces the mechanical invasive procedures (amniocentesis, CVS) with an immunological method based on TREML2 protein detection. This substitution maintains diagnostic accuracy while eliminating the mechanical trauma and associated risks of pregnancy loss, transitioning from physical intervention to molecular detection.
4Object-affected harmful factors
If the extremely low number of circulating fetal cells (0.1-10 cells in 1 ml) is accounted for, then non-invasive sampling is enabled, but elimination of contaminating nucleated blood cells becomes challenging
Solution Approach 1:
The patent changes the separation approach from generic cell removal to targeted enrichment based on TREML2 protein expression. This parameter change enables high-purity fetal cell isolation from the background of maternal cells by exploiting the specific presence of TREML2 on fetal cell surfaces, achieving the necessary separation precision to work with such low cell numbers.
Solution Approach 2:
TREML2 protein acts as a specific intermediary marker that enables selective identification and enrichment of fetal cells among the vast number of maternal cells. This intermediary approach provides the specificity needed to achieve high purity separation, allowing accurate detection even when fetal cells are present at extremely low concentrations.
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 approach enables the reliable isolation and analysis of fetal cells from maternal blood, improving the accuracy of prenatal diagnostics for chromosomal abnormalities without the risks associated with invasive procedures.
Implementation Method 1
contacting the sample with a first antibody, wherein the sample comprises a plurality of cells; isolating cells bound to the first antibody
Implementation Method 2
the first antibody is conjugated to one or more magnetic particles... step (b) comprises subjecting the sample to a magnetic field
Implementation Method 3
the magnetic particles are coupled to a first exogenous aggregation enhancing factor (EAEF)... adding a second EAEF to induce aggregation of the magnetic particles
Data Source
AI summary
Compositions, kits, and methods for isolating, detecting, and analyzing fetal cells are provided. Methods for preparing a fetal cell sample and for performing fetal genetic testing are also provided herein. The compositions, kits, and methods may comprise use an anti-TREML2 antibody. Alternatively, or additionally, the compositions, kits, and methods comprise or use an antibody conjugated to a colloidal magnetic particle and/or an exogenous aggregation enhancing factor.