Grid-Shaped Light Sheet Microscopy for Gentle Sample Imaging

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Solution Overview

Problem

Existing light sheet microscopy methods require high light power and lengthy scanning times to generate an image of a sample, leading to potential sample damage and inefficiency.

Innovation Solution

A method using a grid-shaped light sheet of a specific wavelength range to inhomogeneously illuminate the sample, combined with a machine learning system to reconstruct non-illuminated or weakly illuminated areas based on captured light from more strongly illuminated areas.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If the sample is irradiated intensively using high light power to ensure sufficient signal, then the image quality is improved, but the sample may be damaged and the imaging time increases

Engineering Contradiction:
Improveimage qualityVSAvoidsample damage
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent divides the sample into multiple planes and irradiates them sequentially using a grid-shaped light sheet that scans through the sample. This segmentation allows low light power to be used for each individual plane while still achieving complete image coverage through sequential scanning, thereby preventing sample damage.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent employs periodic scanning of the light sheet through the sample planes in a systematic sequence. This periodic action enables the sample to be irradiated repeatedly at low power across multiple cycles, accumulating sufficient signal for image reconstruction without causing damage from continuous high power irradiation.

Inventive Principle:
Principle #19Periodic action

2Measurement precision

If the sample is scanned plane by plane using a movable mirror to achieve homogeneous illumination, then the imaging completeness is improved, but the imaging time increases significantly

Engineering Contradiction:
Improveimaging completenessVSAvoidimaging time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent pre-defines a grid-shaped light sheet pattern that systematically covers the entire sample plane before actual imaging begins. This preliminary arrangement of illumination zones allows for rapid sequential scanning without requiring time-consuming adaptive adjustments during the imaging process, thus reducing total imaging time while maintaining completeness.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent uses a dynamic scanning approach where the grid-shaped light sheet moves systematically through the sample planes in a controlled sequence. This dynamic scanning enables efficient coverage of all planes without redundant movements, achieving complete imaging in reduced time compared to static or random scanning methods.

Inventive Principle:
Principle #15Dynamics

3Stability of the object's composition

If the light sheet position is changed using dithering method to homogeneously illuminate the sample plane, then the illumination uniformity is improved, but the imaging speed decreases

Engineering Contradiction:
Improveillumination uniformityVSAvoidimaging speed
Core Design Contradiction:
Stability of the object's compositionVSSpeed

Solution Approach 1:

The patent segments the illumination process into a grid pattern where specific zones are illuminated in a systematic sequence. This segmentation allows the light sheet to cover the entire sample plane efficiently without requiring slow dithering movements, achieving both uniformity and speed by planning the illumination paths in advance.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent changes the illumination parameters by using a grid-shaped light sheet with specific spatial frequencies and patterns rather than continuous scanning. This parameter change enables rapid illumination of multiple zones simultaneously while maintaining uniformity through the structured grid pattern, significantly increasing imaging speed compared to traditional dithering methods.

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

This approach reduces light power usage and shortens imaging time, allowing for quick and gentle image generation of samples while maintaining high reconstruction accuracy.

Implementation Method 1

capturing the light emitted from the sample due to the radiating of the first light sheet of the first wavelength range onto the sample

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS20250076630A1Method for generating an image of a sample
Publication Date: 2025.03.06 CARL ZEISS MICROSCOPY GMBH
  • US20250076630A1 patent drawing
  • US20250076630A1 patent drawing
  • US20250076630A1 patent drawing

AI summary

A method for generating an image of a sample includes radiating a first grid-shaped light sheet of a first wavelength range onto the sample in such a way that the sample is inhomogeneously illuminated by the first light sheet, capturing the light emitted by the sample due to the radiating of the first light sheet of the first wavelength range onto the sample; and reconstructing first areas of the sample, which are not illuminated or are more weakly illuminated using the first light sheet of the first wavelength range, on the basis of the captured light of the second areas of the sample, which are more strongly illuminated using the light sheet of the first wavelength range, by means of a machine learning system.