Metabolite Extraction from FFPE Samples

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Solution Overview

Problem

Metabolic profiling of formalin-fixed paraffin-embedded (FFPE) samples is challenging due to chemically reactive conditions, which complicates the reliable detection of metabolites and hinders comprehensive metabolic data analysis.

Innovation Solution

Developed methods for detecting and measuring metabolites in FFPE samples, including the use of mild extraction techniques and a cassette design to minimize extraction volume and maximize metabolite yield, allowing for the determination of tumor status by comparing metabolite expression levels between samples.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of stationary object

If FFPE samples are used for metabolic profiling, then sample preservation and storage are improved, but metabolite detection reliability deteriorates due to chemically reactive conditions

Engineering Contradiction:
Improvesample preservationVSAvoidmetabolite detection reliability
Core Design Contradiction:
Duration of action of stationary objectVSReliability

Solution Approach 1:

The patent extracts metabolites from FFPE samples using specific extraction protocols that overcome the chemically reactive conditions. The extraction process isolates metabolites from the fixed tissue matrix, enabling reliable detection despite the formalin fixation that preserves tissue structure.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent employs parameter changes in the extraction process, including optimizing solvent composition, extraction temperature, and incubation time, to maximize metabolite recovery from FFPE samples while accounting for the chemical modifications introduced by formalin fixation.

Inventive Principle:
Principle #35Parameter changes

2Ease of manufacture

If conventional extraction methods are used on FFPE samples, then procedure simplicity is maintained, but metabolite yield and detection accuracy deteriorate

Engineering Contradiction:
Improveextraction procedure simplicityVSAvoidmetabolite detection accuracy
Core Design Contradiction:
Ease of manufactureVSMeasurement precision

Solution Approach 1:

The extraction process is segmented into multiple sequential steps including deparaffinization, hydration, and metabolite extraction, with each step optimized to address specific challenges of FFPE samples while maintaining overall procedural simplicity.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Preliminary deparaffinization and hydration steps are performed before metabolite extraction to prepare the FFPE samples, removing paraffin interference and restoring tissue permeability, which improves subsequent metabolite recovery without significantly complicating the overall workflow.

Inventive Principle:
Principle #10Preliminary action

3Quantity of substance

If large extraction volumes are used, then metabolite recovery is improved, but resource consumption and processing time deteriorate

Engineering Contradiction:
Improvemetabolite recoveryVSAvoidresource consumption
Core Design Contradiction:
Quantity of substanceVSLoss of energy

Solution Approach 1:

The patent enhances extraction efficiency by combining moderate-volume extractions with repeated cycling and concentration steps, effectively increasing the dimensional complexity of the extraction process to achieve high metabolite recovery without proportionally increasing resource consumption.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

Solution Approach 2:

Multiple extraction cycles are performed on the same sample, with each cycle targeting different metabolite fractions, effectively creating multiple 'copies' of the extraction process to maximize metabolite recovery from a single sample while minimizing total resource use.

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

Enables reliable metabolic data extraction and analysis from FFPE samples, facilitating the identification of differentially expressed metabolites for tumor status determination, thereby supporting personalized medicine and cancer diagnosis.

Implementation Method 1

extracting the one or more metabolites from the FFPE biological sample

Methodology Applied
Scientific EffectSolvation: Solvation

Data Source

PatentUS20200088748A1Metabolic profiling of fixed samples
Publication Date: 2020.03.19 DANA FARBER CANCER INSTITUTE INC
  • US20200088748A1 patent drawing
  • US20200088748A1 patent drawing
  • US20200088748A1 patent drawing

AI summary

The invention provides methods and compositions to evaluate biological samples. The methods comprise obtaining a formalin fixed paraffin embedded (FFPE) preparation of the biological sample, and detecting the presence of one or more metabolites in the FFPE preparation.