Label-Free 3D Density and Anisotropy Imaging via Polarization

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Solution Overview

Problem

Current methods for biological imaging lack the capability for quantitative, label-free measurement of three-dimensional density, anisotropy, and orientation, which is essential for understanding tissue and cellular structures and interactions.

Innovation Solution

The development of a system and method that uses polarization and illumination diversity to perform quantitative imaging of 3D density, anisotropy, and orientation without the need for labels, employing a programmable illumination unit, a polarization-state analyzer, and advanced image processing techniques.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If labels are used for biological imaging, then measurement precision of cellular structures is improved, but the dynamic properties of the structure are modified and the function of the protein, organelle, cell, or tissue may be obstructed

Engineering Contradiction:
Improvemeasurement precisionVSAvoiddynamic properties
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent extracts and removes the labeling step from the imaging process entirely. By using label-free optical microscopy with quantitative phase imaging and polarization-resolved imaging, the system measures cellular structures without introducing any external labels, thereby preserving the natural dynamic properties and functions of the biological specimens while maintaining measurement precision.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent enables biological specimens to serve themselves as imaging targets without external assistance. By exploiting the intrinsic optical properties of cells and tissues (such as refractive index variations, birefringence, and optical path length differences), the system allows the specimens to provide their own contrast and structural information, eliminating the need for labels that could interfere with their natural functions.

Inventive Principle:
Principle #25Self-service

2Measurement precision

If genetic labeling is used to preserve dynamic properties, then the ability to measure structure is improved, but applicability to primary samples is limited

Engineering Contradiction:
Improvestructure measurementVSAvoidapplicability to primary samples
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent creates a universal imaging system that can measure structural properties across diverse sample types without requiring sample-specific preparation or labeling. The label-free quantitative optical microscopy approach works equally well for primary cells, tissue sections, organoids, and other biological specimens, making the system universally applicable while maintaining structural measurement precision.

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Ease of operation

If conventional microscopy is used, then imaging capability is provided, but the ability to perform quantitative imaging of 3D density, anisotropy, and orientation without labels is insufficient

Engineering Contradiction:
Improveimaging capabilityVSAvoidquantitative imaging capability
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent transitions from conventional 2D optical microscopy to 3D quantitative imaging by incorporating optical sectioning capabilities and three-dimensional reconstruction algorithms. This dimensional enhancement allows the system to measure not only intensity but also quantitative parameters such as 3D density, anisotropy, and orientation, providing comprehensive structural information while maintaining ease of operation through automated processing.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

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 comprehensive, reproducible, and consistent measurements of density and anisotropy with high spatial and angular resolution, applicable to various biological samples and materials, including clinical tissues and liquid crystals.

Implementation Method 1

converting the array of multiple sets of polarization channels into Stokes parameter maps

Methodology Applied
Scientific EffectPolarization: Polarisation

Implementation Method 2

a condenser lens or a spatial light modulator to generate the illumination patterns

Methodology Applied
Scientific EffectRefraction: Refraction

Implementation Method 3

The permittivity tensor reports the architectural symmetries at the scale of cells and tissues

Methodology Applied
Scientific EffectScattering: Scattering

Data Source

PatentUS12306102B2Method and system for quantitative three dimensional measurement of density, anisotropy, and orientation without label
Publication Date: 2025.05.20 CZ BIOHUB SF LLC
  • US12306102B2 patent drawing
  • US12306102B2 patent drawing
  • US12306102B2 patent drawing

AI summary

A method of measuring optical properties of a specimen, for example, a uniaxial specimen, includes generating a plurality of illumination patterns incident on the specimen and, for each of the plurality of illumination patterns, collecting sample light passing through the specimen and detecting the collected sample light using a polarization state analyzer to form a set of polarization channels. The method also includes receiving a calibration tensor, converting the set of polarization channels for each of the illumination patterns into Stokes parameter maps using the calibration tensor, and deconvolving the Stokes parameter maps to provide volumetric measurement of permittivity tensor of the specimen, specifically, absorption, optical path length, optical anisotropy, and 3D orientation of the specimen.