Tissue Staining Inverse Dye Concentration for Depth Imaging
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Solution Overview
Problem
Current tissue processing and imaging techniques face challenges in achieving consistent image quality and cost-effectiveness due to the high cost of dyes and variability in dye concentrations, particularly when imaging at depth in tissues with varying protein content.
Innovation Solution
Adopting tissue-specific fluorescent dye concentrations that are inversely related to protein content, using lower concentrations in high-protein tissues and higher concentrations in low-protein tissues to optimize image quality and reduce reagent waste, while maintaining sufficient contrast and signal intensity for diagnostic evaluations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If higher fluorescent protein dye concentration is used in tissue staining, then image contrast at depth is improved for low-protein tissues, but signal absorption increases in high-protein tissues, decreasing contrast and degrading image quality
Solution Approach 1:
The patent applies local quality by tailoring the fluorescent dye concentration to the specific protein content of each tissue type. Low-protein tissues (e.g., renal tissue) receive higher dye concentrations to enhance contrast, while high-protein tissues (e.g., epithelial tissue) receive lower concentrations to minimize signal absorption. This tissue-specific optimization resolves the contradiction by adapting the staining protocol to local tissue characteristics rather than using a uniform concentration for all tissues.
Solution Approach 2:
The patent implements parameter changes by varying the fluorescent dye concentration parameter based on tissue protein content. By adjusting this critical parameter according to tissue type, the method optimizes the balance between achieving sufficient contrast in low-protein tissues and minimizing excessive absorption in high-protein tissues, thereby improving overall image quality at depth across different tissue samples.
2Ease of operation
If standardized fluorescent dye concentrations are used for all tissue types, then processing simplicity is maintained, but image quality consistency at depth deteriorates across different tissue types
Solution Approach 1:
The patent resolves this contradiction by implementing tissue-specific dye concentration protocols that account for variations in protein content across different tissue types. Rather than applying a uniform concentration, the method tailors the staining parameters to local tissue characteristics, ensuring consistent image quality at depth while maintaining relatively simple processing through established protocols for each tissue type.
3Measurement precision
If higher fluorescent dye concentrations are used to improve contrast, then reagent cost increases and waste increases, but image quality at depth improves
Solution Approach 1:
The patent addresses this contradiction by optimizing the fluorescent dye concentration parameter based on tissue protein content. By using higher concentrations only for low-protein tissues that require them and lower concentrations for high-protein tissues, the method achieves necessary image contrast while minimizing reagent waste and cost across the overall processing workflow.
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 enhances image quality at depth, reduces reagent costs, and supports accurate second harmonic generation detection, making the techniques more suitable for everyday clinical use by tailoring dye concentrations to the specific protein content of each tissue type.
Implementation Method 1
treatment with fluorescent dyes and the use of confocal microscopy and multiphoton microscopy provide high-quality images
Implementation Method 2
short-pulse, high-intensity laser light can be used to generate mapping of second-harmonic generation (SHG), which is useful in imaging protein structures such as collagen and amyloid
Implementation Method 3
Increased absorption can affect both nuclear and protein fluorescent signals based on the relative emission and absorption spectra of the specific dyes employed
Data Source
AI summary
The present invention relates to systems and methods for tissue processing and imaging including a counterintuitive inverse relationship between protein dye concentration and tissue sample protein content. Varying dye concentration in such a manner affords higher quality fluorescent imaging at depth in tissue when using optical sectioning microscopy or second harmonic generation (SHG) analysis. Methods of the invention thereby provide more usable histopathology images while reducing waste and reagent costs and are of particular utility in combination assays that include simultaneous protein and nuclear staining and SHG analysis.