Supercritical CO2 Histology Processing System

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Solution Overview

Problem

Conventional tissue processing methods for histological analysis are time-consuming, require the use of toxic and flammable solvents like xylene, and do not allow for continuous throughput, leading to delays in diagnosis and safety concerns in pathology laboratories.

Innovation Solution

A method using supercritical or near-supercritical fluids to process biological samples, eliminating the need for organic solvents and enabling rapid processing with minimal reagent use, while maintaining the quality of the specimen for histological analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional dehydration and clearing methods using graded alcohol solutions and xylene are used, then the specimen can be properly prepared for histological analysis, but the processing time is extended to 8-12 hours and toxic solvents must be handled

Engineering Contradiction:
Improvespecimen preparation qualityVSAvoidprocessing time
Core Design Contradiction:
Manufacturing precisionVSLoss of time

Solution Approach 1:

The patent changes the physical state and chemical properties of the processing medium by using supercritical carbon dioxide instead of conventional liquid solvents. By adjusting pressure and temperature parameters to achieve supercritical state, the processing time is dramatically reduced from 8-12 hours to under 2 hours while maintaining specimen quality. The supercritical fluid provides enhanced penetration and extraction capabilities compared to conventional liquid phases.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent utilizes phase transitions of carbon dioxide between supercritical and gaseous states to achieve rapid processing. The CO2 is brought to supercritical conditions for processing, then rapidly depressurized to gaseous state for easy removal from the specimen. This phase transition mechanism eliminates the need for prolonged drying times associated with conventional solvent evaporation while maintaining effective tissue penetration and preparation quality.

Inventive Principle:
Principle #36Phase transitions

2Manufacturing precision

If xylene is used as a clearing agent, then the tissue can be effectively cleared and prepared for impregnation, but safety hazards increase due to high volatility, flammability, and carcinogenicity

Engineering Contradiction:
Improvetissue clearing effectivenessVSAvoidsafety hazards
Core Design Contradiction:
Manufacturing precisionVSObject-affected harmful factors

Solution Approach 1:

The patent replaces the harmful xylene solvent with carbon dioxide, which under supercritical conditions provides equivalent or superior clearing effectiveness. The CO2 can be easily removed by simple depressurization without residual toxicity, eliminating fire hazards and carcinogenic risks. This substitution converts a harmful processing step into a safe one while maintaining or improving tissue preparation quality.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

Carbon dioxide provides an inert processing atmosphere that eliminates the flammability and toxicity concerns associated with xylene. The supercritical CO2 environment is non-flammable, non-toxic, and can be safely handled without special ventilation requirements, thereby eliminating the safety hazards while maintaining effective tissue clearing and preparation capabilities.

Inventive Principle:
Principle #39Inert atmosphere (Inert environment)

3Ease of manufacture

If automated mechanical instruments are used for overnight processing, then the separate steps of fixation, dehydration, clearing, and impregnation can be completed systematically, but continuous throughput is not achieved and diagnostic delays occur

Engineering Contradiction:
Improvesystematic processingVSAvoidcontinuous throughput
Core Design Contradiction:
Ease of manufactureVSProductivity

Solution Approach 1:

The supercritical fluid processing method enables continuous throughput by eliminating the need for overnight batch processing. Multiple specimens can be processed sequentially or simultaneously in the same supercritical CO2 environment without requiring extended drying or clearing times. The rapid phase transition of CO2 from supercritical to gaseous state allows for quick specimen ejection and immediate readiness for the next processing step, achieving continuous operational capability.

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

By changing to supercritical processing conditions, the patent compresses the entire processing sequence into under 2 hours per specimen. The enhanced diffusion and penetration rates under supercritical conditions allow all steps (dehydration, clearing, impregnation) to occur rapidly and continuously, eliminating the time-consuming sequential batch processing of conventional automated instruments while maintaining systematic quality control.

Inventive Principle:
Principle #35Parameter changes

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 method significantly reduces processing time from 8-12 hours to less than 2 hours, produces superior specimen quality, and allows for continuous processing without the use of toxic solvents, enhancing safety and efficiency in pathology laboratories.

Implementation Method 1

contacting the sample with a composition comprising a supercritical or a near supercritical fluid

Methodology Applied
Scientific EffectSupercritical fluid penetration: Supercritical Fluid

Implementation Method 2

impregnating the sample with an embedding medium under a pressure of more than 1 bar

Methodology Applied
Scientific EffectPressure application: Pressurisation

Data Source

PatentUS7618828B2Method for histoprocessing
Publication Date: 2009.11.17 ACADEMISCH ZIEKENHUIS GRONINGEN
  • US7618828B2 patent drawing
  • US7618828B2 patent drawing
  • US7618828B2 patent drawing

AI summary

The invention relates to the processing of a biological sample for histological analysis. In particular, it relates to a rapid automated processing system that can be operated with continuous throughput and that eliminates the use of toxic solvents such as xylene. Provided is a method for processing a biological sample for histological analysis, comprising contacting the sample with a composition comprising a supercritical or near supercritical fluid followed by impregnating the sample under a pressure of more than 1 bar with an embedding medium, preferably paraffin. Also provided is a processor (1) for preparing at least one sample (10) for histological analysis, comprising at least one process reactor (9) for the at least one sample (10), characterized in that the processor (1) comprises supplying means (4) for supplying to the reactor (9) at least one substance of which at least one is in supercritical phase or near supercritical phase and at least one supplying means (7) for adding the embedding medium to the reactor (9) through conduit (8).