Placental-Specific EV Purification from Maternal Plasma for Detection
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Solution Overview
Problem
Current clinical diagnostic assays for placental pathologies, particularly placenta accreta spectrum (PAS), are invasive, subjective, and often lead to misdiagnosis or undiagnosis, lacking reliable biomarkers for early detection, which increases maternal morbidity and mortality.
Innovation Solution
A non-invasive method using the EV-CATCHER™ assay to selectively purify placental extracellular vesicles from maternal plasma by targeting placental alkaline phosphatase (PLAP), followed by micro-RNA profiling to differentiate between normal and abnormal placental pathologies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If invasive diagnostic procedures are used for placental pathologies, then diagnostic capability is improved, but patient harm and morbidity increase
Solution Approach 1:
The patent replaces invasive mechanical diagnostic procedures (biopsies, surgeries) with a non-invasive liquid biopsy method that analyzes extracellular vesicles in maternal blood plasma. This substitution eliminates physical intrusion into the patient's body while maintaining diagnostic capability through molecular analysis of placental-derived vesicles.
Solution Approach 2:
The patent uses extracellular vesicles as intermediary carriers that transport placental biomarkers through the maternal circulation to accessible blood samples. These vesicles serve as mediators between the placenta (source of diagnostic information) and the diagnostic system, enabling non-invasive detection of placental pathologies without direct contact with the placental tissue.
2Ease of operation
If current diagnostic methods are used for placental pathologies, then diagnostic process is simplified, but diagnostic accuracy decreases leading to misdiagnosis
Solution Approach 1:
The patent employs differential scanning fluorimetry to detect conformational changes in placental proteins within extracellular vesicles. This method uses fluorescent dyes that change emission properties based on protein structure, providing a quantitative and objective readout that enhances diagnostic accuracy while maintaining operational simplicity through automated detection.
Solution Approach 2:
The patent transforms the diagnostic approach by analyzing multiple parameters of extracellular vesicles including protein conformational states, vesicle concentration, and compositional profiles. These multi-parameter measurements provide comprehensive diagnostic information that improves accuracy while the assay design maintains operational simplicity through standardized protocols.
3Measurement precision
If placental extracellular vesicles are isolated from maternal plasma, then biomarker detection is improved, but isolation complexity increases
Solution Approach 1:
The patent simplifies vesicle isolation by changing the approach from complex multi-step purification to a single-step density gradient ultracentrifugation method. This parameter change in the isolation protocol maintains high purity of placental-derived vesicles while significantly reducing procedural complexity and time requirements.
Solution Approach 2:
The patent selectively extracts placental-derived extracellular vesicles from the complex maternal plasma matrix using placenta-specific markers and density-based separation. This selective extraction approach isolates the target vesicles from numerous other plasma components without requiring complex multi-step purification procedures.
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 accurate diagnosis of placental pathologies like placenta previa and placenta accreta spectrum, improving maternal outcomes by providing a robust and reliable biomarker for placental health assessment.
Implementation Method 1
selectively purify placental extracellular vesicles from maternal plasma by targeting placental alkaline phosphatase (PLAP)
Implementation Method 2
followed by micro-RNA profiling to differentiate between normal and abnormal placental pathologies
Data Source
AI summary
The present disclosure provides a non-invasive method for early diagnosis of a placental pathology comprising an abnormal formation or arrangement of a placenta in a uterus of a mammalian female subject during pregnancy. Early diagnosis can lead to an improved maternal outcome. The method comprises selectively purifying from plasma of maternal blood a population of small extracellular vesicles (small-EVs) expressing a placenta-specific surface biomarker. The extracellular vesicles comprise micro-RNA cargo. A cargo profile for the small EVs is determined by extracting RNA from the purified population of small EVs. Expression of small non-coding RNAs comprising one or more micro RNAs (miRNAs) encapsulated by the purified population of exosomes is then identified and quantified. The miRNA profile of the placenta specific EVs is then compared to the miRNA profile of a healthy control of the same approximate gestational age.