Volatile Mounting Medium for High Fidelity Tissue Imaging
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Solution Overview
Problem
Current methods for high fidelity high resolution full color microscopic visualization of tissues, particularly for unstained or chemically stained samples, face challenges such as air refractive index mismatch leading to distorted images, and existing solutions like oil immersion or xylene damage the tissue, preventing downstream molecular analyses.
Innovation Solution
A class of volatile organic compounds with specific properties, including low molecular weight esters, ethers, or formates, is used as a visualization fluid that provides superior imaging and is compatible with both infrared and near-UV laser microdissection systems, avoiding interference with molecular analytes and microdissection processes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If a coverslip is placed on the tissue sample to improve visualization, then image quality is improved, but the sample is compromised and adjacent sections must be used
Solution Approach 1:
The patent introduces a volatile mounting medium as an intermediary substance between the tissue sample and the objective lens. This medium provides the necessary optical properties for high-quality imaging while being volatile enough to evaporate completely after use, leaving no residue that would compromise the sample for subsequent molecular analyses.
Solution Approach 2:
The mounting medium utilizes phase transition from liquid to vapor. The volatile components evaporate during or after imaging, allowing the tissue to be fully accessed by the objective lens without permanent contamination. This phase change enables the medium to fulfill its imaging function temporarily while disappearing completely to preserve sample integrity for downstream applications.
2Measurement precision
If oil immersion or xylene is used to visualize the slide, then image quality is improved, but the tissue is damaged or adhered to, preventing downstream molecular analyses
Solution Approach 1:
The patent changes the physical and chemical parameters of the mounting medium by selecting volatile compounds with specific refractive indices (1.3-1.5) and optical properties. These parameter changes allow the medium to provide superior imaging characteristics while its volatility ensures complete evaporation, preventing tissue damage and residue formation that would interfere with downstream molecular analyses.
3Ease of operation
If air refractive index mismatch is present in unstained tissue, then full access to tissue surface is achieved, but image distortion, darkening and loss of resolution occur
Solution Approach 1:
The volatile mounting medium serves as an optical intermediary between the air and the tissue sample. By providing a refractive index (1.3-1.5) that is closer to that of the objective lens and tissue, this medium reduces the refractive index mismatch and minimizes light scattering, thereby improving image quality while maintaining full access to the tissue surface.
4Ease of manufacture
If infrared laser is used for LCM, then tissue capture is enabled, but the laser spot size expands making microdissection of smaller regions difficult
Solution Approach 1:
The patent changes the laser wavelength parameter from infrared to near-UV (405 nm). This parameter change allows for smaller spot sizes and better optical resolution, enabling microdissection of single cells and small regions while maintaining the ability to capture tissue through the volatile mounting medium.
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
The volatile organic compounds enable high fidelity imaging and tissue capture without damaging the samples, allowing for diagnostic-quality histomorphology and molecular analysis without the need for coverslips, thereby improving the efficiency and accuracy of tissue visualization and microdissection.
Implementation Method 1
LCM tissue capture relies on a thermoplastic polymer, typically an EVA polymer, which contains a compound which absorbs and transfers the laser energy as heat to melt the EVA polymer
Implementation Method 2
a compound which absorbs and transfers the laser energy as heat to melt the EVA polymer
Implementation Method 3
there is a need for a visualization chemistry that is applied on the open face tissue section to permit full color high fidelity histologic and cytologic digital imaging
Implementation Method 4
A class of volatile organic compounds with specific properties, including low molecular weight esters, ethers, or formates, is used as a visualization fluid
Data Source
AI summary
A visualization fluid composition is provided to enhance visualization and analysis of samples. The visualization fluid composition includes a low molecular weight ester, ether, or formate moiety, a volatile organic liquid chemical component, stabilization components, preservation components; and an image color adjusting moiety.