Inverted Light-Sheet Microscope for Tissue Imaging
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current microscopic inspection methods for fresh tissues are limited by insufficient resolution, contrast, field of view, and imaging speed, making them unsuitable for rapid and comprehensive analysis of large, irregular tissue surfaces, which is crucial for intraoperative guidance and triaging in surgical pathology.
Innovation Solution
The development of a wide-area inverted light-sheet microscope (LSM) that uses a motorized movable stage and optically clear glass plate with oblique illumination and collection beams to achieve high-resolution, three-dimensional imaging over an extended depth of focus, allowing for rapid imaging of fresh tissue surfaces with high contrast and resolution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional single-axis microscope configurations are used, then the system structure is simple, but the resolution and depth of focus must trade off
Solution Approach 1:
The patent transitions from traditional single-axis microscopy to a dual-axis light sheet microscopy configuration. The illumination axis and detection axis are separated and oriented orthogonally, allowing independent optimization of each axis. This dimensional separation enables simultaneous achievement of high resolution (through optimized detection NA) and extended depth of focus (through optimized illumination sheet thickness) without the trade-offs inherent in single-axis systems.
2Productivity
If conventional microscopy methods are used for fresh tissues, then the imaging process is simple, but the imaging speed is insufficient
Solution Approach 1:
The patent replaces traditional mechanical scanning microscopy with a light sheet illumination approach combined with sCMOS camera detection. Instead of mechanically scanning a focused beam across the sample, a thin sheet of light illuminates the entire field of view simultaneously, and the camera captures the emitted or scattered light from the entire illuminated volume in a single exposure. This substitution of mechanical scanning with optical sectioning enables imaging speeds of 10-100 frames per second while maintaining high resolution and contrast.
3Ease of operation
If traditional microscopy is used for irregular tissue surfaces, then no special preparation is needed, but elaborate tissue flattening and alignment procedures are required
Solution Approach 1:
The patent uses the orthogonal dual-axis configuration where the illumination sheet travels in one direction (e.g., vertically through the tissue) while the detection objective collects light from a different direction (e.g., horizontally). This geometric arrangement allows the light sheet to penetrate and illuminate irregular tissue surfaces from below without requiring the tissue to be flattened or aligned with the detection axis. The separation of illumination and detection paths eliminates the need for elaborate tissue preparation procedures.
4Area of stationary object
If wide-area imaging is attempted with traditional microscopes, then the field of view is limited, but the resolution decreases
Solution Approach 1:
The patent segments the imaging task into two independent functions: the illumination system defines the optical section thickness and field of view in the illumination direction, while the detection system determines the resolution in the detection direction. This segmentation allows each subsystem to be optimized independently - the light sheet can be made thin for high axial resolution and extended in length for large field of view, while the detection objective can be optimized for high lateral resolution across the entire illuminated area. The orthogonal geometry ensures that the illumination sheet length directly determines the imaged field of view without compromising detection resolution.
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 rapid, high-resolution, and high-contrast imaging of fresh tissue surfaces, overcoming the limitations of traditional microscopy by providing a large depth of focus and subcellular resolution without the need for elaborate tissue flattening and alignment, facilitating accurate intraoperative guidance and triaging.
Implementation Method 1
an illumination objective disposed on a first side of the optically clear glass plate... generate a light sheet
Implementation Method 2
a wavefront- and index-matching element disposed on the first side of the optically clear plate... an oil layer disposed between the wavefront- and index-matching element and the optically clear plate
Implementation Method 3
a collection objective disposed on the first side of the optically clear glass plate... for detecting light emitted or scattered from an illuminated region of the sample
Data Source
AI summary
Devices and techniques for a light sheet microscope device are generally described. In some examples, the light sheet microscope may comprise a motorized movable stage comprising an optically clear glass plate. In some further examples, the light sheet microscope may comprise an illumination objective and a collection objective disposed on a first side of the optically clear glass plate. In some further examples, the light sheet microscope may comprise a wavefront- and index-matching element disposed on the first side of the optically clear glass plate. An oil layer may be disposed between the optically clear glass plate and the wavefront- and index-matching element. The oil layer, the wavefront- and index-matching element and the glass plate may have matching refractive indexes.