Microscopy Imaging Resolution Correction via Structured Illumination

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Solution Overview

Problem

Traditional optical microscopes are limited by the diffraction limit, making it difficult to achieve high resolution for structures smaller than 200 nm, such as microtubules and subcellular organelles, which hinders research in life sciences.

Innovation Solution

The method combines super-resolution fluorescence microscopy techniques like Structured Illumination Microscopy and Stimulated Emission Depletion Microscopy with correction algorithms to enhance image resolution beyond the diffraction limit, using structured light illumination and radial fluctuation positioning to reconstruct images with resolutions down to 30 nm.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional optical microscopy is used, then the imaging system is simple and easy to operate, but the resolution is limited to 200-350 nm due to the diffraction limit

Engineering Contradiction:
ImproveresolutionVSAvoidimaging system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent uses structured illumination light as an intermediary to encode high-frequency spatial information into the sample. By modulating the illumination pattern and using computational algorithms to decode the encoded information, the system achieves super-resolution without requiring complex hardware modifications to the basic microscopy setup

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent transitions from direct spatial resolution to a combination of lower spatial resolution with temporal and computational dimensions. By capturing multiple images with different structured illumination patterns and using computational reconstruction algorithms, the system achieves effective super-resolution through adding temporal and computational dimensions rather than purely spatial hardware complexity

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

2Measurement precision

If super-resolution techniques are used to achieve resolution beyond diffraction limit, then the imaging resolution improves, but phototoxicity and artifacts increase

Engineering Contradiction:
ImproveresolutionVSAvoidphototoxicity
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent uses periodic structured illumination patterns that cycle through different phases and orientations. By acquiring multiple images during one illumination cycle and combining them computationally, the system achieves super-resolution with reduced phototoxicity compared to continuous high-intensity illumination methods, as the periodic cycling allows for dose distribution and computational reconstruction

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The patent creates multiple copies of the sample information through structured illumination at different phases and orientations. Instead of relying on a single high-intensity exposure, the system captures multiple lower-intensity images that are computationally combined to reconstruct the super-resolution image, thereby reducing phototoxicity while maintaining resolution

Inventive Principle:
Principle #26Copying

3Measurement precision

If super-resolution microscopy is used to observe subcellular structures smaller than 200 nm, then the imaging resolution improves, but the imaging speed decreases due to multiple image acquisitions

Engineering Contradiction:
ImproveresolutionVSAvoidimaging speed
Core Design Contradiction:
Measurement precisionVSSpeed

Solution Approach 1:

The patent performs preliminary actions by capturing multiple images with different structured illumination patterns in rapid succession before computational reconstruction. By pre-acquiring all necessary raw data frames during a single illumination cycle and then performing computationally intensive reconstruction afterward, the system separates the fast data acquisition phase from the slower processing phase, enabling dynamic imaging of subcellular structures

Inventive Principle:
Principle #10Preliminary action

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

This approach allows for rapid acquisition of high-resolution images with reduced phototoxicity and artifacts, enabling dynamic observation of subcellular processes without the need for extensive hardware modifications, thus improving imaging quality and resolution.

Implementation Method 1

the detection radiation includes an optical signal, especially a fluorescent signal

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS11768363B2Method and apparatus for microscopy imaging with resolution correction
Publication Date: 2023.09.26 FUDAN UNIVERSITY
  • US11768363B2 patent drawing
  • US11768363B2 patent drawing
  • US11768363B2 patent drawing

AI summary

A method and apparatus for microscopic imaging is provided. The method includes: illuminating the sample with illumination radiation to stimulate the detection radiation; capturing the detection radiation from the sample; with the intensity data of the detection radiation from the sample; applying the calibration algorithm to the captured image(s) to acquire the processed second image; the resolution of the processed second image is higher than the acquired first image.