In Vivo Lymphatic Visualization Using Fluorescent Dyes

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Solution Overview

Problem

Current methods for identifying lymphatic vessels, such as conventional immunohistochemistry, are time-consuming, labor-intensive, and cannot provide real-time information on lymphatic morphology or interactions in living tissues, limiting research on dynamic processes like lymphangiogenesis and making it difficult to study cell origins and therapeutic interventions.

Innovation Solution

The use of fluorescently-labeled lymphatic tissue-specific dyes, like FITC or rhodamine-dextran, allows for visualizing lymphatic tissue in living subjects, enabling imaging from a single time point to video over time, facilitating the study of lymphatic vessel development and interaction with other tissues.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional immunohistochemistry method is used to identify lymphatic vessels, then lymphatic vessels can be identified, but the process is time-consuming and labor-intensive

Engineering Contradiction:
Improvelymphatic vessel identificationVSAvoidtime-consuming process
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent replaces the mechanical/chemical process of immunohistochemistry with optical imaging using fluorescent dyes. Instead of using antibodies and complex staining procedures, the invention uses fluorescently-labeled dyes that can be visualized in real-time through imaging systems, eliminating the need for tissue fixation and lengthy staining protocols

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent introduces fluorescent dyes as intermediaries that specifically bind to or are taken up by lymphatic vessels. These dyes act as mediators between the lymphatic vessels and the imaging system, enabling direct visualization without the need for complex immunohistochemical processing

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If conventional immunohistochemistry method is used, then lymphatic vessels can be identified, but real-time information on lymphatic morphology or interactions in living tissues cannot be provided

Engineering Contradiction:
Improvelymphatic vessel identificationVSAvoidreal-time information
Core Design Contradiction:
Measurement precisionVSLoss of information

Solution Approach 1:

The patent replaces the static, post-mortem analysis of immunohistochemistry with dynamic, in vivo optical imaging. The fluorescent dye-based system allows real-time observation of lymphatic vessels in living subjects, capturing temporal changes in morphology and interactions that are impossible with conventional methods

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The invention enables dynamic observation of lymphatic vessels in living subjects over time. By using fluorescent dyes that remain in the vessels, the system captures temporal changes in lymphatic morphology, vessel formation, and interactions with other tissues, transforming static identification into dynamic visualization

Inventive Principle:
Principle #15Dynamics

3Measurement precision

If tissue is excised for fixed time point analysis, then lymphatic vessels can be studied, but longitudinal information on the same tissue cannot be obtained

Engineering Contradiction:
Improvelymphatic vessel studyVSAvoidlongitudinal study capability
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The fluorescent dyes serve as persistent markers that remain in the lymphatic vessels throughout the observation period. This allows repeated imaging of the same tissue in the same subject over time, providing longitudinal data on lymphatic development, regression, or response to treatment without sacrificing the subject at each time point

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The system enables longitudinal studies by allowing multiple imaging sessions of the same living subject. The fluorescent dyes provide persistent labeling that allows tracking of lymphatic changes over days, weeks, or months, capturing dynamic processes like lymphangiogenesis or vessel regression in real-time

Inventive Principle:
Principle #15Dynamics

4Measurement precision

If conventional immunohistochemistry is used on dead tissues, then lymphatic vessels can be identified, but information on lymphatic vessels in their natural morphology and interaction with other components cannot be obtained

Engineering Contradiction:
Improvelymphatic vessel identificationVSAvoidnatural morphology
Core Design Contradiction:
Measurement precisionVSStability of the object's composition

Solution Approach 1:

The patent replaces the requirement for tissue fixation and sectioning with in vivo optical imaging. The fluorescent dyes allow visualization of lymphatic vessels in their native, three-dimensional architecture within living tissue, preserving natural morphology and spatial relationships with other tissue components that are disrupted in fixed, sectioned samples

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

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 provides real-time, dynamic visualization of lymphatic tissue in its natural state, enabling longitudinal studies and effective evaluation of therapeutic agents, improving understanding and treatment of lymphatic disorders.

Implementation Method 1

contacting the region with a fluorescently-labeled lymphatic tissue-specific dye, e.g., FITC or rhodamine labeled dextran, and detecting the labeled dye to visualize lymphatic tissue in the region

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS9724035B2In vivo visualization of lymphatic tissue
Publication Date: 2017.08.08 RGT UNIV OF CALIFORNIA
  • US9724035B2 patent drawing
  • US9724035B2 patent drawing
  • US9724035B2 patent drawing

AI summary

Aspects of the invention include methods for visualizing lymphatic tissue in an ocular region, e.g., the cornea, of a living subject, such as a mouse or human. In certain embodiments, the methods include contacting the region with a fluorescently-labeled lymphatic tissue-specific dye, e.g., FITC or rhodamine labeled dextran, and detecting the labeled dye to visualize lymphatic tissue in the region, where the visualization may vary, from an image obtained at a single time to a video over a period of time. The invention finds use in a variety of different applications, including research and therapeutic applications.