Collective Cell Tomography for High-Throughput 3D Analysis

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Solution Overview

Problem

Existing tomographic methods for biological samples require tedious and subjective manual analysis of individual cells to obtain averaged features, which is time-consuming and inefficient for large populations.

Innovation Solution

A novel tomographic approach that enables simultaneous analysis of a population of biological cells by generating a collective 3D refractive index model using multiple cell projections, without the need for cell rotation or staining, through angular tomography and processing cell complex wavefronts to create a single 3D model representing the entire cell population.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If manual analysis of individual cells is performed to obtain averaged features, then measurement precision is improved, but productivity deteriorates due to time-consuming analysis of large cell populations

Engineering Contradiction:
Improvefeature extraction accuracyVSAvoidanalysis speed
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent merges the analysis of multiple individual cells into a single collective 3D refractive index model. By combining projections from multiple cells and processing them together through tomographic reconstruction, the system generates one averaged 3D model representing the entire cell population, thereby maintaining measurement precision while dramatically improving productivity through high-throughput batch processing

Inventive Principle:
Principle #5Merging (Combining)

2Manufacturing precision

If traditional tomography views a single cell from multiple angles through rotation, then manufacturing precision of the 3D model is improved, but device complexity increases due to rotation mechanisms

Engineering Contradiction:
Improve3D model accuracyVSAvoidrotation mechanism complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

Instead of rotating the sample to achieve multiple viewing angles, the patent inverts the approach by keeping cells stationary and acquiring projections from multiple fixed angular positions around the sample. This eliminates the need for rotation mechanisms while maintaining the ability to reconstruct accurate 3D models through computational tomography

Inventive Principle:
Principle #13The other way round (Inversion)

Solution Approach 2:

The patent replaces mechanical rotation systems with a stationary acquisition system that captures projections at multiple fixed angles. The tomographic reconstruction algorithm then computationally synthesizes the 3D model from these stationary multi-angle projections, substituting mechanical complexity with computational processing

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Measurement precision

If multiple projections from individual cells are collected and averaged, then measurement precision is improved, but loss of time increases due to the tedious manual process

Engineering Contradiction:
Improveaveraged feature accuracyVSAvoiddata processing time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The system performs automated tomographic reconstruction and averaging of multiple cell projections without manual intervention. The processing unit automatically collects projections from multiple cells, reconstructs individual 3D models, averages them to generate a collective 3D refractive index model, and produces the final result through fully automated computational processing, eliminating tedious manual analysis

Inventive Principle:
Principle #25Self-service

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 rapid and objective analysis of large cell populations, providing a comprehensive 3D model for quick evaluation and high-throughput processing, suitable for applications like blood and sperm tests.

Implementation Method 1

The presently disclosed subject matter relates to tomography, and more specifically, to a tomography system and method for measuring biological samples or other samples

Methodology Applied
Scientific EffectTomography: Tomography

Implementation Method 2

This approach provides rapid capturing of the 3D refractive-index distribution of single cells in suspension

Methodology Applied
Scientific EffectInterferometry: Interference

Data Source

PatentEP4158314B1A tomography system and a method for analysis of biological cells
Publication Date: 2025.10.01 RAMOT AT TEL AVIV UNIVERSITY LTD
  • EP4158314B1 patent drawingFigure 1
  • EP4158314B1 patent drawingFigure 2
  • EP4158314B1 patent drawingFigure 3A~3C

AI summary

The present invention provides a novel technique for collective tomography (i.e. analyzing many cells at once), without staining, using one 3D model representing the entire cell population, enabling high-throughput tomography. There is provided a tomographic technique for analyzing a sample containing a population of biological cells. In this technique, at least one tomographic projection may come from another cell in the cell population, and each cell in the population may contribute one or more projections to the final 3D refractive-index map.