Sequential Tissue Section Imaging for Multi-Cell Visualization
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Solution Overview
Problem
Current immunohistochemistry techniques are limited in simultaneously identifying multiple cell types within a single tissue section due to the lack of appropriate antibody combinations, leading to incomplete visualization of cellular interactions and spatial relationships in diseased tissues.
Innovation Solution
A method involving the creation of secondary digital images by evaluating primary digital images based on selection criteria, inserting new image marker areas with unique features, and combining these to generate a new image that visualizes multiple cell types within the same three-dimensional space, using molecular detection means like antibodies and enzymes to stain cell markers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If multiple-chromogen or multiple immunofluorescence techniques are used to detect more cell types in one section, then the number of detectable cell types increases, but the complexity of the detection system and lack of appropriate antibody combinations limits the number of cell markers that can be stained
Solution Approach 1:
The detection process is divided into multiple sequential cycles, each detecting one or more cell markers. In each cycle, specific antibodies are applied to detect particular cell types, then the detection groups are destroyed to prepare for the next cycle. This segmentation allows detection of many more cell types than could be simultaneously detected, while managing system complexity through structured sequential processing
Solution Approach 2:
The method employs continuous sequential detection cycles where each cycle builds upon the previous one. After detecting and destroying specific detection groups, the tissue section is immediately prepared for the next detection cycle without interruption to the overall detection process, maintaining continuous useful action throughout the analysis of multiple cell markers
2Quantity of substance
If tissue-destructive procedures or detection molecule-labeled primary antibodies are used to increase marker detection, then more cell types can be detected, but the number of cell markers that can be stained is limited by the destructive nature of the procedures
Solution Approach 1:
After each detection cycle, the specific detection groups (antibodies and their labels) are deliberately destroyed or discarded. The tissue section itself is preserved and recovered for use in subsequent detection cycles. This allows repeated detection of different cell markers on the same tissue section without permanently damaging the tissue structure
Solution Approach 2:
The tissue section is prepared and preserved in its intact state before the detection process begins. Detection cycles are then performed sequentially on this preserved tissue, with each cycle using preliminary applied antibodies that are subsequently removed. This preliminary preservation of tissue integrity allows multiple detection cycles to be performed
3Quantity of substance
If conventional IHC techniques are used to stain cell types, then spatial relationships between cell types can be visualized, but only up to 4 cell types can be detected simultaneously and often only 2 due to lack of appropriate antibody combinations
Solution Approach 1:
The method creates a universal detection system that can detect any number of cell markers by using sequential cycles with different antibody combinations. Each cycle uses standard IHC techniques with appropriate antibodies, and the system adapts to detect different cell types by changing the antibody panel used in each cycle, providing multi-functionality for detecting up to 10 or more cell markers
Solution Approach 2:
The detection process uses periodic sequential cycles rather than simultaneous detection. Each cycle periodically applies a specific set of antibodies, detects the target cell types, destroys the detection groups, and then proceeds to the next cycle with a different antibody panel. This periodic action allows systematic detection of multiple cell types beyond the simultaneous detection limit
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 the detailed visualization and spatial analysis of multiple cell types and structures within a single tissue section, providing comprehensive information on cell distribution, size, and shape, which is not achievable with existing techniques.
Implementation Method 1
Immunohistochemistry (IHC), whereby a marker (i.e. an antigen) is detected by a antigen-specific antibody
Implementation Method 2
using molecular detection means like antibodies and enzymes to stain cell markers
Data Source
AI summary
A method for differentiating areas in a series of digital images, the method comprising the steps of: providing a series of images comprising undetermined marker areas; evaluating every image 1n for 1≦n≦N according to predetermined selection criteria and defining image marker areas as undetermined marker areas fulfilling the predetermined selection criteria; providing a new image 1new; and inserting new image marker areas in the new image 1new, said new image marker areas having the same shape and location as image marker areas present in image 1n but not in image 1n−1, and said new image marker areas being identifiable in 1new by a unique feature. Further, the application discloses a method for visualizing cell populations in tissue sections of a histological sample. Further, the application discloses a method for visualizing three-dimensional distribution of multiple cell populations in a histological sample.