PMMA Encapsulated Near-Infrared Fluorescent Dye for Stable Tissue Marking
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Solution Overview
Problem
Current methods for visualizing non-palpable or difficult-to-locate tissue and lymph nodes during surgery, such as using carbon-based ink or radioactive agents, face issues with stability, migration, and safety, as fluorescent inks tend to degrade and migrate from the intended area.
Innovation Solution
A near-infrared fluorescent dye encapsulated in polymeric microspheres, specifically polymethylmethacrylate (PMMA), polystyrene, polyacrylonitrile, or polyvinyl chloride microspheres, is directly injected into the tissue, providing stable and long-lasting visualization without migration, using a light source to excite the dye for imaging.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Illumination intensity
If fluorescent inks or dyes are used to mark tissue, then visualization of tissue is improved, but the dye degrades and migrates from the area of interest over time
Solution Approach 1:
The patent changes the physical parameters of the marker by using microspheres with specific size ranges (1-100 micrometers) and specific gravity (0.8-1.2 g/cm³) to prevent migration while maintaining visualization capability. The microsphere encapsulation protects the fluorescent dye from degradation.
Solution Approach 2:
The patent uses composite microspheres consisting of a fluorescent dye core encapsulated within a biocompatible polymer shell. This composite structure combines the visualization properties of the fluorescent dye with the stability and non-migratory characteristics of the polymer microsphere.
2Ease of operation
If nano-sized fluorescent dye particles are injected intravascularly to reach tissue of interest, then the particles can enter tissue due to permeability changes, but the particles degrade with time and migrate out of the area of interest
Solution Approach 1:
The patent optimizes the microsphere size parameter (1-100 micrometers) and specific gravity (0.8-1.2 g/cm³) to achieve ideal tissue retention without migration. These parameter changes ensure the particles are large enough to remain stationary but small enough for practical injection and distribution.
Solution Approach 2:
The fluorescent dye is pre-encapsulated within the microsphere structure before injection. This preliminary encapsulation action protects the dye from degradation and prevents premature migration, allowing the marker to reach the target tissue while maintaining stability.
3Ease of operation
If small fluorescent particles are used to mark tissue, then the particles can be injected intravascularly, but coating with surfactant or protein is required to limit degradation and direct particles
Solution Approach 1:
The patent creates a self-contained composite microsphere where the fluorescent dye is encapsulated within a biocompatible polymer matrix. This integrated structure eliminates the need for separate surfactant or protein coatings, simplifying the formulation while maintaining injectability and stability.
Solution Approach 2:
The patent modifies the particle size parameter to the microsphere range (1-100 micrometers) which provides optimal balance between injectability through intravascular routes and resistance to degradation without requiring additional coating layers.
4Reliability
If carbon-based ink is used to mark tissue, then the tissue location is marked, but the ink is difficult to see during surgery
Solution Approach 1:
The patent transitions from carbon-based black ink to fluorescent dyes that emit light in the visible or near-infrared spectrum. This color/emission change dramatically improves visibility during surgery while the microsphere encapsulation ensures the marker remains stable and does not migrate.
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 solution allows for extended visualization of marked tissue for up to 24 months without degradation or migration, enhancing surgical precision and safety by providing a stable and effective means to identify tissues of interest during procedures.
Implementation Method 1
a near-infrared fluorescent dye encapsulated by polymeric microspheres... applying a light source to an area near the tissue, wherein the light source is applied at a wavelength sufficient to excite the near-infrared fluorescent dye
Data Source
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AI summary
The potential use of a PMMA encapsulated near-infrared fluorescent dye includes endoscopic tattooing of intestinal neoplasms, location visualization of non-palpable breast lesions, and, but not limited to, location/visualization of soft tissue lesions in difficult anatomic regions. Commercially available fluorescent imaging systems, both open and laparoscopic, would be used in conjunction to fluoresce these marked tissues, augmenting the surgeon's ability to intraoperatively locate the correct lesion to resect.