Non-Orthogonal OTLS Microscopy for Deep High-Resolution Imaging
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Solution Overview
Problem
Existing open-top light-sheet (OTLS) microscopes face limitations in resolution and imaging depth due to orthogonal geometry between illumination and collection objectives, which restricts high-resolution imaging in thicker specimens and imposes strict refractive index matching requirements.
Innovation Solution
A non-orthogonal arrangement of illumination and collection objectives, allowing for higher numerical aperture collection objectives and reduced index matching constraints, with dual collection paths for high and low magnification modes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If orthogonal geometry is used between illumination and collection objectives in OTLS microscopy, then the system maintains simple open-top configuration, but imaging resolution and depth are limited
Solution Approach 1:
The patent applies asymmetry by changing from orthogonal geometry to non-orthogonal geometry between illumination and collection objectives. This asymmetric arrangement allows higher numerical aperture objectives to be used, improving imaging resolution and depth while maintaining the open-top configuration advantage.
2Length of stationary object
If orthogonal arrangement is used, then index of refraction matching requirements are simplified, but imaging depth in thicker specimens is restricted
Solution Approach 1:
The patent changes the geometric parameter from orthogonal to non-orthogonal arrangement, which simultaneously increases imaging depth and reduces the strictness of index of refraction matching requirements. This parameter change allows the system to image thicker specimens with greater tolerance.
3Measurement precision
If higher numerical aperture objectives are used, then imaging resolution improves, but working distance decreases limiting imaging depth
Solution Approach 1:
The patent uses non-orthogonal geometry to effectively increase the working distance in the imaging direction while maintaining high numerical aperture. By changing the spatial dimension of objective arrangement, the system achieves both high resolution and increased imaging depth in thicker specimens.
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 imaging of thicker specimens with reduced refractive index matching requirements and increased imaging depth, facilitating both screening and detailed analysis without lateral constraints.
Implementation Method 1
The illumination objective directs an illumination light sheet along an illumination axis into a sample
Implementation Method 2
The collection objective receive light from an imaging plane of the sample along a collection axis
Implementation Method 3
OTLS microscope geometries may introduce various limitations to the resolution of the image, the depth of imaging in the sample, and/or impose relatively strict index of refraction tolerances on the system
Data Source
Figure 1
Figure 2A~2B
Figure 2C~2D
AI summary
Apparatuses, systems, and methods for an open-top light-sheet (OTLS) microscope which includes an illumination objective and a collection objective which have optical axes which are non-orthogonal to each other. The optical axis of the collection objective may be orthogonal to a plane of the sample holder. The illumination and collection objective may be located below the sample holder. The OTLS microscope may optionally include a second collection objective which has an optical axis orthogonal to the optical axis of the illumination objective. The illumination objective may be an air objective, and the collection objective may be an immersion objective.