Pathology Slide Scanners Using 2D Sensor Arrays for Fluorescence Imaging
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current microscopic imaging technologies face challenges in efficiently imaging large specimens, particularly in fluorescence microscopy, due to issues like tiling artifacts, fluorophore bleaching, and difficulty in simultaneous imaging of multiple fluorophores with varying signal strengths, which result in noisy or overexposed images.
Innovation Solution
The use of two-dimensional CCD or CMOS sensor arrays instead of linear arrays or TDI arrays allows for simultaneous imaging of multiple fluorophores by adding and contracting exposures on a line-by-line basis, increasing dynamic range and reducing noise, enabling proper exposure estimation and dynamic range contraction for each fluorophore.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Area of stationary object
If tiling microscopes are used to image large specimens, then the field of view is covered completely, but tiling artifacts occur and imaging speed is very slow
Solution Approach 1:
The patent divides the large specimen into multiple smaller fields of view that are captured sequentially by the microscope camera. Each field of view is imaged separately and then computationally stitched together to form a complete high-resolution image of the entire large specimen, enabling both complete coverage and maintained imaging speed
Solution Approach 2:
The patent introduces computational image processing algorithms as an intermediary step between capturing individual field of view images and producing the final complete specimen image. This computational stitching process combines multiple partial images into a unified high-resolution image, resolving the contradiction between complete coverage and imaging speed
2Measurement precision
If exposure time is increased to reduce noise in fluorescence images, then image quality improves, but fluorophore bleaching increases
Solution Approach 1:
The patent employs periodic scanning where the stage moves back and forth across the specimen in a periodic manner, capturing multiple passes over the same region. This periodic action allows accumulation of signal over time while distributing the total exposure, reducing noise through averaging while limiting fluorophore bleaching by not continuously exposing the same area
Solution Approach 2:
The patent performs preliminary scanning at lower resolution or with lower exposure to identify regions of interest before performing high-resolution imaging only on those specific areas. This preliminary action allows the system to concentrate exposure time where needed, reducing overall fluorophore bleaching while maintaining image quality in critical regions
3Adaptability or versatility
If multiple fluorophores are imaged simultaneously with different exposure times, then all fluorophores can be captured, but images become noisy or overexposed
Solution Approach 1:
The patent applies different exposure times and imaging parameters to different regions of the specimen based on the local fluorescence intensity requirements. Each region is analyzed and assigned appropriate exposure parameters, allowing simultaneous imaging of multiple fluorophores with varying signal strengths while maintaining optimal exposure accuracy for each local area
Solution Approach 2:
The patent dynamically adjusts imaging parameters including exposure time, scan speed, and laser power during the imaging process based on real-time feedback from preliminary scans or reference measurements. This dynamic adaptation enables proper exposure for multiple fluorophores with different intensities, preventing both noise and overexposure
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 noise and allows for accurate, simultaneous imaging of multiple fluorophores with varying signal strengths, improving image quality and efficiency by increasing exposure time and dynamic range, while minimizing artifacts and bleaching.
Implementation Method 1
two-dimensional CCD or CMOS sensor arrays
Implementation Method 2
fluorescence imaging
Implementation Method 3
photoluminescence and spectrally-resolved fluorescence
Data Source
Figure 1
Figure 2
Figure 3
AI summary
An instrument for scanning a specimen has a two-dimensional sensor array, the sensor array containing a mosaic colour filter array or a scanning colour filter array. The instrument can be operated in fluorescence or in brightfield. The scanning colour filter array has the same colour throughout each row with adjacent rows having different colours.