Tissue Analysis via Transmitted Light and Fluorescence Merging
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Solution Overview
Problem
Current multicolor fluorescence technologies in pathology lack wide market acceptance and do not fully address the need to understand systemic or cellular systems biology, particularly in tissue-based applications, as they are limited in their ability to analyze complex interactions within cellular systems.
Innovation Solution
A method combining traditional histological staining with multiplexed fluorescent labeling of biomarkers, using transmitted light images as a reference to enhance the interpretation of fluorescence-based reagents, allowing for the creation of cellular systems biology profiles that characterize the interactions and relationships within tissue samples.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If multicolor fluorescence technology is used for tissue analysis, then measurement precision of biomarkers is improved, but device complexity and ease of operation deteriorate due to lack of automation
Solution Approach 1:
The patent combines multiple imaging modes (transmitted light and fluorescence) into a single integrated system that processes tissue sections simultaneously. The imaging system captures both H&E stain patterns and fluorescent biomarker signals from the same tissue section, merging morphological context with molecular information to improve measurement precision while managing system complexity through integration
Solution Approach 2:
The patent introduces transmitted light images as an intermediary reference that bridges the gap between traditional histology and fluorescent biomarker analysis. Pathologists use the transmitted light images to navigate and interpret fluorescent signals, providing a familiar visual framework that simplifies operation while maintaining high measurement precision
2Measurement precision
If multicolor fluorescence technology is used for tissue analysis, then measurement precision of biomarkers is improved, but ease of operation deteriorates due to lack of automation
Solution Approach 1:
The patent implements automated image analysis software that processes fluorescent images and provides quantitative feedback on biomarker expression. The system automatically detects, segments, and quantifies fluorescent signals, reducing manual analysis burden while maintaining high measurement precision through consistent algorithmic evaluation
Solution Approach 2:
The patent creates digital copies of tissue sections through high-resolution imaging that can be analyzed computationally without requiring continuous manual microscopic examination. The digital images serve as replicable copies that can be processed automatically, reducing the operational burden on pathologists while preserving measurement precision
3Loss of information
If traditional histological staining is combined with fluorescent staining, then information completeness is improved, but loss of information increases due to potential signal interference
Solution Approach 1:
The patent segments the analysis process into distinct imaging modes that capture different information types from the same tissue section. Transmitted light imaging captures morphological and staining information, while fluorescence imaging captures biomarker-specific signals. This segmentation allows information from both modalities to be preserved and integrated without interference, as each mode operates independently
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 increases the acceptance of systems biology by pathologists, enabling the selection of specific biomarkers for fluorescence analysis and providing a detailed understanding of cellular functions, disease mechanisms, and treatment responses at the tissue level.
Implementation Method 1
At least one other section is labeled with a panel of fluorescently labeled reagents to produce a fluorescently labeled section
Implementation Method 2
At least one section is labeled with a histological stain, to produce a histologically stained section
Data Source
AI summary
The invention provides an improved method for identifying and interpreting tissue specimens and/or cells derived from tissue specimens. A panel of cell-based reagents provides a number of readouts of cellular states or biomarkers that together define a profile of a diversity of cellular states or biomarkers in a tissue specimen representing the ‘systems” nature of biology. This cellular profile is interpreted using informatics tools, to identify similarities between specimens, in vivo medical conditions, and suggest options for treating medical conditions.