Mid-Infrared Spectroscopy Tissue Fixation Quality Assessment

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Solution Overview

Problem

Current methods for assessing the quality of tissue thin sections prior to further processing are inadequate, as they often result in damage that cannot be reversed, leading to inconsistencies and inaccuracies in histopathological analysis, particularly due to uncertainties in fixation processes like formalin fixation and alcohol-only-fixation, which affect protein structure and morphology.

Innovation Solution

An automated method using mid-infrared (MIR) spectroscopy to evaluate the quality of cellular samples by identifying a fixation signature in the MIR spectrum and applying classification and/or quantification algorithms to determine the fixation state, allowing for the assessment of tissue quality before further processing.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If tissue samples undergo fixation processing to preserve microarchitecture and prevent destruction of macromolecular structures, then the reliability of tissue representation is improved, but the ability to assess fixation quality before further processing deteriorates

Engineering Contradiction:
Improvetissue representation reliabilityVSAvoidfixation quality assessment difficulty
Core Design Contradiction:
ReliabilityVSDifficulty of detecting and measuring

Solution Approach 1:

The patent applies preliminary action by performing MIR spectroscopy analysis on tissue samples immediately after fixation to assess fixation quality before proceeding to staining and other processing steps. This allows early detection of fixation issues without waiting through the entire processing pipeline, enabling timely corrective actions or reprocessing decisions.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent introduces MIR spectroscopy as an intermediary technique that provides indirect but reliable information about fixation quality. Instead of directly observing fixation effects on tissue morphology (which requires complex histological processing), the method uses molecular vibration spectra as an intermediary indicator to assess fixation state, cross-linking程度, and tissue preservation quality.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Loss of information

If traditional fixation assessment methods are used after staining, then diagnostic information is obtained, but precious stains and antibodies cannot be recovered and damage cannot be reversed

Engineering Contradiction:
Improvestain and antibody lossVSAvoidquality assessment reliability
Core Design Contradiction:
Loss of informationVSReliability

Solution Approach 1:

The patent performs quality assessment before staining by using MIR spectroscopy on fixed tissue samples. This preliminary evaluation identifies samples with inadequate fixation or processing issues before precious stains and antibodies are applied, preventing wasteful processing of unsuitable samples and enabling early intervention or reprocessing.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent creates a spectral copy or fingerprint of the tissue sample using MIR spectroscopy that contains information about fixation quality and tissue integrity. This spectral representation serves as a non-destructive assessment tool that preserves the original sample and its stains, allowing quality evaluation without consuming or damaging valuable staining reagents.

Inventive Principle:
Principle #26Copying

3Adaptability or versatility

If fixation protocols are varied to optimize different tissue types and applications, then adaptability is improved, but consistency and reproducibility of fixation quality deteriorate

Engineering Contradiction:
Improvefixation protocol adaptabilityVSAvoidfixation quality consistency
Core Design Contradiction:
Adaptability or versatilityVSManufacturing precision

Solution Approach 1:

The patent implements feedback by using MIR spectroscopy to objectively measure and quantify fixation quality across different tissue types and protocols. This provides real-time or near-real-time information about fixation effectiveness, allowing laboratories to monitor and adjust their protocols to maintain consistent quality standards while adapting to different tissue characteristics and application requirements.

Inventive Principle:
Principle #23Feedback

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 enables the evaluation of tissue quality by distinguishing between acceptably fixed, under-fixed, and over-fixed samples, reducing errors and inconsistencies in histopathological analysis, thereby improving diagnostic accuracy and resource allocation.

Implementation Method 1

evaluating a quality state of a cellular sample by: (a) identifying a quality signature in a mid-infrared spectroscopy (MIR) spectrum of the cellular sample

Methodology Applied
Scientific EffectMid-infrared spectroscopy: Absorption Spectroscopy

Data Source

PatentEP3368885B1Methods and systems for analyzing the quality of tissue fixation using mid-infrared spectroscopy
Publication Date: 2020.06.03 VENTANA MEDICAL SYSTEMS INC
  • EP3368885B1 patent drawingFigure 1
  • EP3368885B1 patent drawingFigure 2
  • EP3368885B1 patent drawingFigure 3

AI summary

A method of evaluating the quality state (such as a fixation status) of a cellular sample is provided. A MIR spectrum (220) of the sample is obtained, and a classification (211) or quantification (231) algorithm is applied to the MIR spectrum to identify features (221) indicative of the quality state and/or to classify the sample. The quality state may then be used to determine whether the sample is appropriate for an analytical method and/or whether remedial processing (such as further fixation) is appropriate.