3D Refractive Index Tomography Using Wavefront Shaper

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Solution Overview

Problem

Current methods for measuring the inner structure of cells, such as fluorescence imaging and 3D refractive index tomography, face challenges in achieving high resolution and long-term measurement without invasive processes, with fluorescence imaging suffering from photobleaching and 3D refractive index tomography lacking specificity at the molecular level.

Innovation Solution

An ultra-high-speed 3D refractive index tomography and structured illumination microscopy system using a wavefront shaper that simultaneously measures 3D high-resolution fluorescence and refractive index images by adjusting the irradiation angle and phase of a plane wave, allowing for non-invasive, long-term observation of cellular structures.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If fluorescence imaging is used to measure cellular structures, then molecular specificity is improved, but photobleaching occurs limiting long-term measurement

Engineering Contradiction:
Improvemolecular specificityVSAvoidmeasurement duration
Core Design Contradiction:
Measurement precisionVSDuration of action of stationary object

Solution Approach 1:

The patent combines fluorescence imaging and 3D refractive index tomography into a single integrated system that uses a single objective lens and shared optical path. This merging allows simultaneous acquisition of both molecularly specific fluorescence data and long-term viable refractive index data, resolving the contradiction between specificity and measurement duration.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The system implements multi-functionality by enabling the same hardware platform to perform both fluorescence imaging (for molecular specificity) and refractive index tomography (for long-term non-invasive measurement). The wavefront shaper and spatial light modulator allow the system to switch between different imaging modes, providing universal capability that addresses both requirements.

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

2Duration of action of stationary object

If 3D refractive index tomography is used to measure cellular structures, then long-term non-invasive measurement is improved, but molecular specificity is lost

Engineering Contradiction:
Improvemeasurement durationVSAvoidmolecular specificity
Core Design Contradiction:
Duration of action of stationary objectVSMeasurement precision

Solution Approach 1:

The patent combines fluorescence imaging and 3D refractive index tomography into a single integrated system that uses a single objective lens and shared optical path. This merging allows simultaneous acquisition of both molecularly specific fluorescence data and long-term viable refractive index data, resolving the contradiction between specificity and measurement duration.

Inventive Principle:
Principle #5Merging (Combining)

3Adaptability or versatility

If multiple wavefront shapers are used to achieve both fluorescence and refractive index imaging, then imaging capability is improved, but system complexity increases

Engineering Contradiction:
Improveimaging capabilityVSAvoidsystem complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The system implements multi-functionality by enabling the same hardware platform to perform both fluorescence imaging (for molecular specificity) and refractive index tomography (for long-term non-invasive measurement). The wavefront shaper and spatial light modulator allow the system to switch between different imaging modes, providing universal capability that addresses both requirements.

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

Solution Approach 2:

The patent combines fluorescence imaging and 3D refractive index tomography into a single integrated system that uses a single objective lens and shared optical path. This merging allows simultaneous acquisition of both molecularly specific fluorescence data and long-term viable refractive index data, resolving the contradiction between specificity and measurement duration.

Inventive Principle:
Principle #5Merging (Combining)

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 high-resolution, non-invasive measurement of cellular structures and biochemical properties over time, improving the specificity and longevity of imaging without the need for fluorescent labels, contributing to advanced biological and pathological studies.

Implementation Method 1

adjusting an irradiation angle of a plane wave incident on a sample by using the wavefront shaper

Methodology Applied
Scientific EffectWavefront shaping:

Implementation Method 2

measuring a 2D optical field, which passes through the sample, based on the irradiation angle of the plane wave

Methodology Applied
Scientific EffectOptical diffraction: Diffraction

Implementation Method 3

measuring a 2D optical field, which passes through the sample, based on the irradiation angle of the plane wave

Methodology Applied
Scientific EffectInterference: Interference

Implementation Method 4

adjusting a phase and a pattern of a wavefront of the plane wave to obtain a 3D high resolution fluorescence image

Methodology Applied
Scientific EffectStructured illumination:

Implementation Method 5

obtain a 3D high resolution fluorescence image

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS10082662B23D refractive index tomography and structured illumination microscopy system using wavefront shaper and method thereof
Publication Date: 2018.09.25 TOMOCUBE INC
  • US10082662B2 patent drawing
  • US10082662B2 patent drawing
  • US10082662B2 patent drawing

AI summary

An ultra-high-speed 3D refractive index tomography and structured illumination microscopy system using a wavefront shaper and a method using the same are provided. A method of using an ultra-high-speed 3D refractive index tomography and structured illumination microscopy system that utilizes a wavefront shaper includes adjusting an irradiation angle of a plane wave incident on a sample by using the wavefront shaper, measuring a 2D optical field, which passes through the sample, based on the irradiation angle of the plane wave, and obtaining a 3D refractive index image from information of the measured 2D optical field by using an optical diffraction tomography or a filtered back projection algorithm.