Single-Cell Embryo Proteomics for Blastomere Asymmetry Detection

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Solution Overview

Problem

The extent of intra-zygotic and inter-blastomere proteomic asymmetry in mammalian embryos remains unclear, hindering the assessment of embryo development potential and health status in IVF clinics.

Innovation Solution

Single-cell mass-spectrometry methods are employed to analyze the proteomic profiles of individual blastomeres from mammalian embryos at various stages, identifying distinct protein sets in alpha and beta blastomeres, and detecting perturbation-induced changes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If single-cell mass spectrometry is used to analyze proteomic profiles of individual blastomeres, then measurement precision of proteomic asymmetry is improved, but device complexity and difficulty of detecting and measuring increase

Engineering Contradiction:

Improveproteomic asymmetry detectionVSAvoidsingle-cell proteomics analysis

Core Design Contradiction:

Measurement precisionVSDifficulty of detecting and measuring

Solution Approach 1:

The embryo is segmented into individual blastomeres for separate analysis. The method isolates and analyzes proteomes of individual cells rather than bulk tissue, enabling detection of cell-to-cell variability and proteomic asymmetry at the single-cell level, which directly addresses the measurement precision challenge.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

Carrier cells are introduced as an intermediary to facilitate single-cell proteomics analysis. The carrier cells provide a background proteome that enables mass spectrometry detection of low-abundance proteins in single blastomeres, effectively mediating the detection process and improving measurement precision while managing the technical difficulty.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Loss of information

If single-cell mass spectrometry analysis is performed on individual blastomeres, then information completeness about intra-embryo differences is improved, but loss of substance and productivity decrease

Engineering Contradiction:

Improveintra-embryo proteomic differencesVSAvoidsample material

Core Design Contradiction:

Loss of informationVSLoss of substance

Solution Approach 1:

Multiple single-cell proteomics datasets are merged and integrated to reconstruct comprehensive proteomic profiles. By combining information from multiple carrier cells and technical replicates, the method recovers complete proteomic information that would be lost in individual single-cell analyses, thereby reducing information loss.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

Proteomic extraction and labeling are performed on carrier cells beforehand to create a pooled carrier proteome. This preliminary preparation allows the actual single-blastomere analyses to proceed more efficiently with less sample consumption, as the carrier proteome is reused across multiple measurements.

Inventive Principle:

Principle #10Preliminary action

3Reliability

If proteomic profiling of single blastomeres is conducted to identify differentially abundant proteins, then reliability of developmental potential assessment is improved, but device complexity and measurement difficulty increase

Engineering Contradiction:

Improvedevelopmental potential assessmentVSAvoidsingle-cell proteomics system

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The method uses comparative proteomic profiling where each blastomere's proteome is compared against a reference (carrier or sibling blastomeres). This feedback mechanism identifies differentially abundant proteins that serve as biomarkers for developmental potential, improving assessment reliability by using empirical reference data rather than theoretical predictions.

Inventive Principle:

Principle #23Feedback

Solution Approach 2:

Carrier cells serve as a proteomic copy or surrogate that mimics the background proteome of embryonic cells. By using this copied reference proteome, the system reduces complexity of direct single-cell measurements while maintaining reliability of developmental potential assessment through comparative analysis.

Inventive Principle:

Principle #26Copying

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

Reveals the earliest incidence of proteomic asymmetry correlated with developmental potential, enabling the selection of blastomeres with higher potential and understanding embryo health.

Implementation Method 1

subjecting the single blastomeres to single-cell mass-spectrometry to obtain a proteomic profile of each single blastomere

Methodology Applied

Scientific EffectMass spectrometry:

Data Source

PatentUS20260002941A1Single-cell proteomics analysis of embryos

Publication Date: 2026.01.01 CALIFORNIA INST OF TECH

AI summary

Provided herein include methods and compositions for single-cell proteomics analysis of mammalian embryos and uses thereof to screen perturbations and to detect perturbation-induced change in the protein composition of the mammalian embryos.