3D Phase Imaging for Cell Tissues Under Multiple Scattering

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Solution Overview

Problem

Conventional optical diffraction tomography (ODT) struggles to effectively image three-dimensional cell tissues due to the overwhelming influence of multiple scattered light, which causes speckle generation and deteriorates the single-to-multi-scattering ratio (SMR), making it difficult to extract structural information.

Innovation Solution

An observation apparatus and method that utilizes an interference intensity image acquisition unit, complex amplitude image generation units, phase conjugate operations, and three-dimensional phase image generation to reduce the impact of multiple scattered light by selectively detecting single-scattered light, employing phase conjugate operations to enhance image clarity and structural information retrieval.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional optical diffraction tomography is applied to image three-dimensional cell tissues, then three-dimensional structural information can be obtained, but multiple scattered light causes speckle generation and deteriorates image quality

Engineering Contradiction:
Improveimage qualityVSAvoidmultiple scattered light
Core Design Contradiction:
Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

The patent extracts and processes different scattering components separately using migration operator decomposition. The multiple scattered light component is isolated and processed independently from the single scattered light component, allowing selective suppression of harmful multiple scattering effects while preserving useful single scattering information for high-quality 3D imaging

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the scattering order parameter to separate and process single-scattered light and multiple-scattered light components differently. By adjusting the scattering order in the migration operator decomposition, the system can selectively enhance or suppress specific scattering components to optimize image quality for different observation depths and conditions

Inventive Principle:
Principle #35Parameter changes

2Volume of moving object

If observation depth is increased to capture more of the three-dimensional cell tissue, then more structural information is obtained, but multiple scattered light influence increases significantly

Engineering Contradiction:
Improveobservation volumeVSAvoidmultiple scattered light
Core Design Contradiction:
Volume of moving objectVSObject-generated harmful factors

Solution Approach 1:

The patent introduces a migration operator decomposition mechanism as an intermediary that mediates between the observation volume and multiple scattered light. This intermediary process separates different scattering components and applies appropriate processing to each, enabling deep tissue observation while controlling multiple scattering effects through selective component processing

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If fluorescent probes are used to improve imaging resolution and information quality, then detailed structural information can be obtained, but the method becomes invasive and requires staining

Engineering Contradiction:
Improveinformation qualityVSAvoidinvasive staining
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent changes the detection parameter from intensity-only measurement to complex amplitude measurement, capturing both amplitude and phase information. This parameter change enables non-invasive quantitative phase imaging that provides high-quality structural information without requiring fluorescent probes or staining, avoiding the harmful effects of invasive labeling

Inventive Principle:
Principle #35Parameter changes

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 clear three-dimensional imaging of multiple scattering objects like three-dimensional cell tissues by minimizing speckle generation and preserving the single-scattered light component, thereby improving the accuracy of structural analysis.

Implementation Method 1

an interference intensity image at a reference position from an imaging unit for imaging the interference intensity image at the reference position generated by interference between light irradiating an observation object

Methodology Applied
Scientific EffectInterference: Interference

Implementation Method 2

a phase conjugate operation unit for performing, before, during, or after a processing step by the second complex amplitude image generation unit, a phase conjugate operation on the complex amplitude image of each of the plurality of light irradiation directions

Methodology Applied
Scientific EffectPhase conjugation:

Implementation Method 3

Light scattering refers to a phenomenon in which light interacts with an object to change a traveling direction of the light. In particular, when spatial non-uniformity of a refractive index in the object increases, the light interacts with the object many times in passing through the object.

Methodology Applied
Scientific EffectLight scattering: Scattering

Data Source

PatentUS12504370B2Observation device and observation method
Publication Date: 2025.12.23 HAMAMATSU PHOTONICS KK
  • US12504370B2 patent drawing
  • US12504370B2 patent drawing
  • US12504370B2 patent drawing

AI summary

An observation apparatus includes a light source, a mirror, a condenser lens, an objective lens, a beam splitter, an imaging unit, and an analysis unit. The analysis unit includes an interference intensity image acquisition unit, a first complex amplitude image generation unit, a second complex amplitude image generation unit, a phase conjugate operation unit, a two-dimensional phase image generation unit, a three-dimensional phase image generation unit, and a refractive index distribution calculation unit. The analysis unit irradiates an observation object with light along each of a plurality of light irradiation directions by changing an orientation of a reflection surface of the mirror, acquires an interference intensity image at a reference position for each of the plurality of light irradiation directions from the imaging unit, and performs necessary processing based on the interference intensity images to obtain a three-dimensional phase image of the observation object.