Tissue Marking Ink with Formalin-Reactive Adhesion

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Solution Overview

Problem

Commercially available inks for marking tissue specimens face issues such as poor adhesion to formalin-treated tissues, migration, smearing, and difficulty in distinguishing colors under different lighting conditions, leading to inaccurate cancer cell identification and potential false positives during pathology analysis.

Innovation Solution

Development of ink compositions with specific formulations including alkali soluble styrene, ethyl hydroxyethyl cellulose, colorants, and a novel fixing solution to ensure adhesion, prevent migration, and maintain color integrity, along with a unique colorant selection for clear visibility under both reflective and transmitted light.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional inks are used to mark tissue specimens, then the marking process is simple and quick, but the ink adheres poorly to formalin-treated tissues and migrates during pathology processing

Engineering Contradiction:
Improveink adhesionVSAvoidink composition
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs composite ink formulations combining multiple polymers (polyvinyl alcohol, carboxymethyl cellulose, gelatin), dyes, and formalin-reactive compounds. This composite approach enables the ink to simultaneously achieve strong adhesion to formalin-fixed tissue, resistance to migration during processing, and visibility under different lighting conditions, resolving the contradiction between reliability and complexity.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The ink composition parameters are specifically optimized to change properties in response to formalin treatment. The formalin-reactive compounds undergo chemical transformation when exposed to formalin, enhancing ink-tissue binding strength. This parameter change strategy allows the ink to adapt to the fixed tissue environment, improving adhesion without requiring complex application procedures.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If conventional inks are used for tissue marking, then the application process is straightforward, but the colors are difficult to distinguish under different lighting conditions (reflective vs. transmitted light)

Engineering Contradiction:
Improvecolor differentiationVSAvoidcolorant selection
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent selects dyes with specific spectral properties that create local quality differences in color appearance under different lighting conditions. Each ink formulation contains colorants optimized to provide distinct visual characteristics in both reflected and transmitted light, enabling pathologists to easily differentiate between multiple marked regions regardless of the lighting mode used during examination.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The ink formulations utilize dyes that exhibit different color transmission and reflection properties. The colorant selection ensures that each ink produces a characteristic color signature that remains distinguishable across varying lighting conditions, solving the problem of color differentiation while maintaining a manageable formulation complexity.

Inventive Principle:
Principle #32Color changes

3Reliability

If the ink is applied to tissue before formalin fixation, then the tissue processing workflow is simplified, but the ink smears and migrates during subsequent processing steps

Engineering Contradiction:
Improveink stabilityVSAvoidprocessing workflow
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent incorporates formalin-reactive compounds into the ink formulation that undergo chemical changes upon exposure to formalin. This preliminary chemical preparation within the ink allows it to rapidly bond to the tissue matrix during or after fixation, preventing smearing and migration during subsequent processing steps while maintaining compatibility with standard workflow sequences.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The ink formulation acts as an intermediary between the tissue and the formalin fixation process. The formalin-reactive compounds in the ink create chemical bridges that strengthen the ink-tissue bond during fixation, preventing later migration. This intermediary role allows the ink to remain stable throughout processing without requiring modifications to the overall workflow.

Inventive Principle:
Principle #24Intermediary (Mediator)

4Loss of time

If thin ink formulations are used to ensure quick drying, then the drying time is reduced, but the ink runs and drips on the tissue surface

Engineering Contradiction:
Improvedrying timeVSAvoidmarking fidelity
Core Design Contradiction:
Loss of timeVSReliability

Solution Approach 1:

The patent optimizes the ink formulation parameters, specifically the balance between water content, polymer concentration, and viscosity modifiers. This parameter optimization enables the ink to dry quickly on the tissue surface while maintaining sufficient viscosity to prevent running and dripping, achieving both fast drying and marking fidelity simultaneously.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The ink formulation is designed to create a stable, non-migrating mark that accurately copies the intended tissue boundary. The polymer and dye combination ensures that once the ink dries, it forms a stable layer that resists smearing and migration, preserving the fidelity of the original marking despite the quick drying process.

Inventive Principle:
Principle #26Copying

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 ink compositions adhere well to various tissue types, prevent smearing and migration, maintain color integrity, and ensure accurate cancer cell identification, reducing the risk of false positives and improving surgical precision.

Implementation Method 1

The ink compositions adhere well to various tissue types

Methodology Applied
Scientific EffectAdhesion: Adhesive

Implementation Method 2

a fixing solution that are used to mark tissue specimens... a novel fixing solution to ensure adhesion, prevent migration

Methodology Applied
Scientific EffectChemical bonding: Chemical Bonding

Data Source

PatentUS10492886B2Ink for marking a tissue specimen
Publication Date: 2019.12.03 VECTOR SURGICAL LLC
  • US10492886B2 patent drawing
  • US10492886B2 patent drawing
  • US10492886B2 patent drawing

AI summary

An ink composition for marking a tissue specimen is provided. The ink composition has a general formula of 30.0 wt. % to 54.0 wt. % of an alkali soluble styrene; 0.3 wt. % to 1.7 wt. % ethyl hydroxyethyl cellulose; 8.0 wt. % to 35.0 wt. % colorant; 0.0 wt. % to 13.0 wt. % pigment; 23.0 wt. % to 47.0 wt. % deionized water; 0.35 wt. % to 1.65% defoamer and 0.1 wt. % to 1.1 wt. % preservative. The inks in accordance with the invention may have a peak transmission in the visible spectrum at a wavelength of from 322 nm to 716 nm or having a lineal UV-Vis spectrum with no visible peak transmission between 250 nm and 950 nm. When applied to a tissue specimen the ink compositions do not bleed onto adjacent tissue margins. When view under a microscope the color of the ink compositions can be distinguished from each other.