Folate Form Quantification via LC-MRM/MS for Clinical Risk Prediction

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Solution Overview

Problem

Current methods for measuring folate levels in biological samples are limited by their inability to distinguish between different forms of folate, leading to inadequate predictive value for folate-related pathologies and insufficient identification of individuals at risk for conditions like neural tube defects and cardiovascular disease.

Innovation Solution

A method involving the measurement of specific folate forms such as 5-methyltetrahydrofolate (5-MTHF), tetrahydrofolate (THF), and 5,10-MTHF using techniques like isotope dilution liquid chromatography-multiple reaction monitoring/mass spectrometry (LC-MRM/MS) to provide accurate and qualitative assessment of folate levels, allowing for improved diagnosis and risk prediction.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If total folate measurement is used, then measurement simplicity is maintained, but measurement precision and predictive value are reduced

Engineering Contradiction:
Improvemeasurement simplicityVSAvoidfolate level measurement accuracy
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent segments total folate measurement into measurement of specific folate forms (5-MTHF, THF, 5,10-MTHF) to distinguish between different folate types. This segmentation allows precise identification of functional folate status while maintaining the ability to assess overall folate nutrition through multiple measurements.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent changes the measurement parameter from a single total folate concentration to multiple specific folate form concentrations. By measuring different folate forms (5-MTHF, THF, 5,10-MTHF) and their ratios, the system achieves both precision in identifying folate deficiency and practical clinical utility.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If multiple folate forms are measured, then disease prediction accuracy is improved, but measurement complexity increases

Engineering Contradiction:
Improvedisease risk prediction accuracyVSAvoidmeasurement system complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The measurement system is segmented into specific assays for different folate forms (5-MTHF, THF, 5,10-MTHF), each with standardized procedures. This segmentation enables accurate disease prediction through multiple parameters while maintaining laboratory workflow efficiency through established analytical methods.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent creates a multi-functional measurement approach where the same laboratory infrastructure and analytical techniques can quantify different folate forms. The system universally applies to various clinical scenarios including neural tube defect risk assessment, cardiovascular disease prediction, and monitoring of folate supplementation response.

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Measurement precision

If folate forms are distinguished, then diagnostic precision is improved, but loss of information about total folate status increases

Engineering Contradiction:
Improvefolate form differentiation accuracyVSAvoidoverall folate status information
Core Design Contradiction:
Measurement precisionVSLoss of information

Solution Approach 1:

The patent merges the measurement of individual folate forms with the assessment of total folate status through integrated analysis. By measuring 5-MTHF, THF, and 5,10-MTHF simultaneously and calculating their ratios, the system preserves overall folate status information while providing precise differentiation of folate forms and their functional implications.

Inventive Principle:
Principle #5Merging (Combining)

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 enhances the accuracy of folate level measurements, reduces misclassification of hyperhomocysteineemia, and enables more precise prediction of disease states and responses to vitamin supplements and medications, thereby improving diagnostic and therapeutic strategies.

Implementation Method 1

isotope dilution liquid chromatography-multiple reaction monitoring/mass spectrometry (LC-MRM/MS)

Methodology Applied
Scientific EffectLiquid chromatography: Chromatography

Implementation Method 2

isotope dilution liquid chromatography-multiple reaction monitoring/mass spectrometry (LC-MRM/MS)

Methodology Applied
Scientific EffectMass spectrometry:

Data Source

PatentUS8541243B2Method for assessment of folate phenotypes, disease risk and response to therapy
Publication Date: 2013.09.24 THE TRUSTEES OF THE UNIV OF PENNSYLVANIA
  • US8541243B2 patent drawing
  • US8541243B2 patent drawing
  • US8541243B2 patent drawing

AI summary

The invention provides a method for measuring the levels of 5-methyltetrahydrofolate (5-MTHF), tetrahydrofolate (THF), and 5,10-MTHF in a biological sample. The method includes employing an isotope dilution liquid chromatography-multiple reaction monitoring/mass spectrometry (LC-MRM/MS) methodology.