Bioengineered Tissue Reference Controls for IHC Validation

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Solution Overview

Problem

Traditional human tissue reference controls for immunohistochemical and molecular tests are unreliable due to variability caused by pre-analytical variables and are not readily available in sufficient quantities for standardized validation across laboratories, leading to inconsistent test results.

Innovation Solution

Bioengineered human tissue reference controls are created by growing cancer cells in specific phases, pre-screening for marker expression, co-culturing with stromal cells, and processing to form standardized blocks that consistently express diagnostic and prognostic markers, thereby eliminating antigenic drift and ensuring high concordance with actual human tissues.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional human tissue reference controls are used for validation of IHC, FISH or CISH test results, then the testing process can be performed, but the test results are inconsistent and unreliable due to pre-analytical variables

Engineering Contradiction:

Improvereliability of test resultsVSAvoidconsistency of marker expression

Core Design Contradiction:

ReliabilityVSMeasurement precision

Solution Approach 1:

The patent changes the fundamental parameters of tissue preparation by using bioengineered tissue models with controlled genetic modifications and standardized processing protocols. This eliminates the variability inherent in traditional human tissue controls, achieving consistent marker expression and reliable test results across different laboratories.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates standardized copies of tissue structures through bioengineering techniques, producing controlled tissue models that replicate the essential features of human tissues while eliminating pre-analytical variables. These engineered tissues serve as reliable reference controls with consistent marker expression profiles.

Inventive Principle:

Principle #26Copying

2Quantity of substance

If traditional human tissue reference controls are used, then validation of test results is attempted, but sufficient quantities are not readily available for standardized validation across laboratories

Engineering Contradiction:

Improveavailability of reference controlsVSAvoidstandardization across laboratories

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

The patent transforms the availability and standardization problem by using bioengineered tissue models that can be produced in controlled quantities with standardized protocols. This enables sufficient supply of reference controls while maintaining consistency across different laboratory settings.

Inventive Principle:

Principle #35Parameter changes

3Adaptability or versatility

If different protocols for fixation and processing of tissue are used at different laboratories, then local tissue processing can be optimized, but pre-analytical variables are introduced causing intrinsic problems

Engineering Contradiction:

Improveflexibility in tissue processingVSAvoidmarker expression consistency

Core Design Contradiction:

Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The patent creates standardized tissue models that can be processed using uniform protocols, eliminating the pre-analytical variables introduced by different laboratory protocols. The engineered tissues provide consistent marker expression while allowing for necessary processing flexibility.

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 bioengineered controls provide high concordance and unequivocal results, significantly outperforming traditional controls with a high degree of reproducibility and reliability, reducing the need for frequent replacement and allowing for efficient validation of IHC, FISH, and CISH test results.

Implementation Method 1

growing cancer cells in specific phases, pre-screening for marker expression, co-culturing with stromal cells

Methodology Applied

Scientific EffectCell culture:

Implementation Method 2

growing cancer cells in specific phases

Methodology Applied

Scientific EffectDifferentiation:

Implementation Method 3

processing to form standardized blocks that consistently express diagnostic and prognostic markers

Methodology Applied

Scientific EffectFixation:

Data Source

PatentUS20240167923A1Bioengineered and standardized Human Tissue Reference Controls for Validation of IHC, FISH or CISH Cancer Test Results

Publication Date: 2024.05.23 SLMP LLC

AI summary

A method of making a tissue reference control block is disclosed wherein cancer cells are selected with a known positivity or negativity for a specific marker and cancer cells are grown to a certain phase. The cancer cells are screened for an expression of the specific marker and the screened cancer cells are mixed with stromal cells and co-cultured in a bio-reactor bag. A spheroid grown from the co-cultured mixture of cells is harvested, fixed, and embedded in a core of a paraffin block.