Fusion Peptide Biomarker Detection via FP-MRM Mass Spectrometry

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Solution Overview

Problem

Current biomarkers for cancer diagnosis lack specificity and sensitivity, making early detection challenging, and there is a need for novel biomarkers that can accurately identify cancer at an early stage.

Innovation Solution

The development of fusion peptide multiple reaction monitoring (FP-MRM) mass spectrometry (MS) for detecting specific fusion peptides resulting from chromosomal translocations, which are unique to certain cancer subtypes, allowing for sensitive and specific detection of cancer biomarkers like NPM-ALK in anaplastic large cell lymphoma.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional biomarkers are used for cancer diagnosis, then diagnosis can be performed, but specificity and sensitivity are inadequate

Engineering Contradiction:
Improvebiomarker specificity and sensitivityVSAvoiddiagnostic accuracy
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent extracts and focuses on fusion peptides resulting from chromosomal translocations as specific biomarkers. By isolating these unique peptide sequences that are characteristic of specific cancer subtypes, the method achieves high specificity and sensitivity for cancer diagnosis, overcoming the limitations of conventional biomarkers that lack adequate diagnostic accuracy.

Inventive Principle:
Principle #2Taking out (Extraction)

2Measurement precision

If fusion peptide detection methods are developed, then sensitivity and specificity improve, but detection complexity increases

Engineering Contradiction:
Improvefusion peptide detection sensitivityVSAvoiddetection method complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent employs stable isotope-labeled peptide standards as intermediaries in the mass spectrometry detection process. These labeled standards serve as references to identify and quantify fusion peptides through multiple reaction monitoring, enabling sensitive and specific detection while providing a systematic approach to manage the complexity of the detection method.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Loss of time

If early detection is achieved with novel biomarkers, then prognosis improves, but validation requirements increase

Engineering Contradiction:
Improvetime for early detectionVSAvoidbiomarker validation accuracy
Core Design Contradiction:
Loss of timeVSManufacturing precision

Solution Approach 1:

The patent performs preliminary validation by detecting fusion peptides in cell lines with known translocation status and clinical samples before applying the method to diagnostic purposes. This preliminary characterization ensures accuracy and reliability of the biomarker detection, establishing the foundation for reliable early detection in clinical practice.

Inventive Principle:
Principle #10Preliminary action

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

FP-MRM-MS enables the accurate detection and quantification of fusion peptides at low levels, providing high sensitivity and specificity for diagnosing cancer, with 100% specificity and no false positives or negatives in clinical samples, suitable for early detection and monitoring of tumor cells.

Implementation Method 1

fusion peptide multiple reaction monitoring (FP-MRM) mass spectrometry (MS)

Methodology Applied
Scientific EffectMass spectrometry:

Implementation Method 2

multiple reaction monitoring (MRM) via mass spectrometry

Methodology Applied
Scientific EffectMultiple reaction monitoring:

Data Source

PatentUS9284594B2Compositions and methods relating to fusion protein biomarkers
Publication Date: 2016.03.15 THE RGT UNIV OF MICHIGAN
  • US9284594B2 patent drawing
  • US9284594B2 patent drawing
  • US9284594B2 patent drawing

AI summary

The present invention provides fusion proteins as biomarkers specific for chromosomal translocation-based conditions (e.g., cancer), related methods for detecting fusion protein biomarkers associated with chromosomal translocation-based conditions, related methods for quantifying amount of fusion protein expression, and related methods for diagnosing chromosomal translocation-based conditions through detection of such fusion protein biomarkers. Such fusion protein biomarkers and related methods additionally find use in research settings.