Wavefront Encoding Element for Extended Depth of Field in Light Sheet Microscopy

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Light sheet microscopy (LSM) techniques face challenges in achieving precise alignment, maintaining image clarity due to changes in refractive index, and facilitating fast 3D imaging without mechanical disturbances, which limits their application for biological specimens and in-vivo imaging.

Innovation Solution

The integration of a Wavefront Encoding (WFE) element or system at the exit pupil of the objective lens in the collection arm of an LSM extends the depth of field, allowing for relaxed alignment requirements, compensation for refractive index changes, and enabling 3D imaging without moving the specimen or objective, by scanning the light sheet within the extended depth of field.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If the objective lens is placed at a fixed distance equal to its focal length from the light sheet to obtain clear 2D images, then image clarity is improved, but the alignment requirements become critical and the system lacks adaptability to refractive index changes

Engineering Contradiction:
Improveimage clarityVSAvoidalignment requirements
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent segments the imaging function by placing a wavefront encoding element in the exit pupil plane of the objective lens, separating the focusing function from the depth encoding function. This allows the objective to maintain a fixed distance from the light sheet while the WFE element handles depth discrimination, reducing alignment sensitivity.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The wavefront encoding element acts as an intermediary between the objective lens and the detector, modifying the wavefront to extend depth of field and encode axial position information. This intermediary component enables the system to tolerate variations in objective-to-sheet distance while maintaining image quality and depth discrimination.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If the objective distance is adjusted to compensate for refractive index changes, then image quality is maintained, but the system complexity and adjustment requirements increase

Engineering Contradiction:
Improveimage quality consistencyVSAvoidadjustment requirements
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent replaces the mechanical adjustment of objective distance with an optical solution using a wavefront encoding element in the exit pupil plane. This element optically compensates for refractive index changes by encoding depth information in the wavefront, eliminating the need for mechanical repositioning and reducing system complexity.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Adaptability or versatility

If the light sheet and objective are scanned in the z direction to obtain 3D images, then 3D imaging capability is achieved, but mechanical movements and pressure waves interfere with the specimen

Engineering Contradiction:
Improve3D imaging capabilityVSAvoidmechanical disturbances
Core Design Contradiction:
Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The patent replaces mechanical scanning of the objective and specimen with a stationary configuration where the light sheet is scanned. The wavefront encoding element enables depth discrimination without moving the objective, and the scanned light sheet positions are determined by optical scanning rather than mechanical stage movement, reducing disturbances to the specimen.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

4Ease of operation

If the depth of field is extended using wavefront encoding to allow relaxed alignment, then ease of operation is improved, but additional optical elements and processing complexity are introduced

Engineering Contradiction:
Improvealignment toleranceVSAvoidoptical elements and processing
Core Design Contradiction:
Ease of operationVSDevice complexity

Solution Approach 1:

The wavefront encoding element in the exit pupil plane serves multiple functions simultaneously: it extends the depth of field to relax alignment requirements, encodes axial position information for depth discrimination, and maintains compatibility with standard microscopy objectives and detectors. This multi-functionality justifies the addition of the WFE element.

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

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 non-invasive, fast, and stable 3D imaging with improved depth discrimination, reduced artifacts, and the ability to calibrate lateral shifts and magnification, while maintaining image quality across the extended depth of field, thus overcoming limitations of traditional LSM and WFE systems.

Implementation Method 1

a wavefront encoder element or system placed at the exit pupil of the objective lens in the collection arm of a light sheet microscope

Methodology Applied
Scientific EffectWavefront encoding: Phase Modulation

Implementation Method 2

the fluorescence emitted from the specimen is recorded in the orthogonal direction with an image detector

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentEP2829903B1Light sheet-based imaging device with extended depth of field
Publication Date: 2021.09.15 FUNDACIO INST DE CIENCIES FOT NIQUES
  • EP2829903B1 patent drawingFigure 1
  • EP2829903B1 patent drawingFigure 2
  • EP2829903B1 patent drawingFigure 3

AI summary

Light sheet microscope for recording 3D images of a specimen, comprising a light sheet generator, an objective lens, an image detector and a wavefront encoder element or system positioned between the objective lens and the image detector for extending the depth of field of the objective lens. By doing so, the restriction on the distance between the collecting objective and the light sheet is relaxed, allowing the use of a light sheet scanning unit. The resulting light sheet microscope allows for a robust, aberration insensitive, fast 3D imaging without the need to move or perturb the specimen.