Quantitative 1H-NMR Blood Alcohol Analysis

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Solution Overview

Problem

Current methods for determining blood alcohol concentration, such as gas chromatography and enzymatic methods, require complex calibration, significant resources, and can be inaccurate, especially when samples are stored, and only licensed professionals can collect blood samples, limiting the number of samples that can be processed.

Innovation Solution

The method uses 1H-NMR spectroscopy on whole capillary blood samples, mixed with a deuterated solvent and an internal standard, to accurately and quickly determine ethanol concentration, allowing for simple sampling by non-medical personnel and stable storage without significant ethanol degradation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If gas chromatography or enzymatic methods are used to determine blood alcohol concentration, then measurement accuracy can be achieved, but device complexity and calibration requirements increase significantly

Engineering Contradiction:
Improveblood alcohol concentration measurement accuracyVSAvoidinstrument and calibration complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces complex mechanical/chromatographic separation systems with NMR spectroscopy, which uses magnetic field interactions to directly detect ethanol protons. This substitution eliminates the need for complex gas chromatography columns, carriers, and enzymatic reaction systems, while maintaining measurement accuracy through direct spectral detection of ethanol molecules in whole blood.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent uses deuterated ethanol as an internal standard that serves as a reference copy for calibration. By adding a known amount of deuterated ethanol to the blood sample, the method creates a reference signal that can be directly compared to the ethanol signal from the sample, eliminating the need for complex external calibration procedures while ensuring measurement accuracy.

Inventive Principle:
Principle #26Copying

2Duration of action of stationary object

If conventional methods are used with stored blood samples, then measurement can be performed, but ethanol concentration degrades over time leading to measurement errors

Engineering Contradiction:
Improvesample storage durationVSAvoidethanol concentration accuracy
Core Design Contradiction:
Duration of action of stationary objectVSMeasurement precision

Solution Approach 1:

The patent applies preliminary action by adding deuterated solvent and deuterated ethanol internal standard to the blood sample immediately at the time of collection. This preliminary stabilization prevents ethanol degradation before storage, locking in the ethanol concentration and allowing accurate measurement even after prolonged storage periods without requiring frozen conditions.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent changes the chemical environment parameter by introducing deuterated solvent and deuterated ethanol, which alters the NMR spectral parameters. This parameter change creates distinct, easily distinguishable signals for ethanol measurement and provides internal reference signals that remain stable during storage, enabling accurate measurement regardless of storage duration.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If only licensed doctors can collect blood samples, then measurement reliability is ensured, but productivity and number of samples processed decreases

Engineering Contradiction:
Improveblood sampling reliabilityVSAvoidnumber of samples processed
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent extracts the blood sampling function from the exclusive domain of licensed doctors by developing a method that uses capillary blood samples that can be collected by non-medical personnel. This extraction allows broader participation in sample collection while maintaining reliability through the robustness of the NMR measurement method and the use of internal standards for quality control.

Inventive Principle:
Principle #2Taking out (Extraction)

4Reliability

If double determination with two different methods is required by law, then measurement reliability improves, but time consumption and resource requirements increase

Engineering Contradiction:
Improvelegal measurement reliabilityVSAvoiddetermination time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent achieves universality by making the NMR method with deuterated internal standard sufficiently reliable to potentially serve as a single determination method that could replace the current requirement for double determination. The method's robustness, traceability through internal standards, and resistance to degradation allow it to stand alone as a reliable measurement approach, reducing time and resource requirements while maintaining legal reliability.

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

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 high-accuracy, rapid analysis of large numbers of samples with minimal resources, maintains ethanol concentration stability over time, and allows for traceable results, making it suitable for legal and clinical use.

Implementation Method 1

determination of the concentration of ethanol in the blood, in vitro and in particular to a method for determining the blood alcohol concentration using quantitative 1H-NMR spectroscopy

Methodology Applied
Scientific EffectNuclear magnetic resonance:

Implementation Method 2

by adding a volume-related excess of deuterated solvent to the blood taken (whole blood), the blood sample obtained can be stabilized against a change in the concentration of ethanol

Methodology Applied
Scientific EffectIsotope separation:

Data Source

PatentEP2936128B1Method for determining blood-alcohol concentration using quantitative NMR spectroscopy
Publication Date: 2016.10.26 DIEHL BERND
  • EP2936128B1 patent drawingFigure 1
  • EP2936128B1 patent drawingFigure 2
  • EP2936128B1 patent drawingFigure 3

AI summary

The invention relates to a method in which the alcohol concentration in blood is determined in vitro using quantitative 1H-NMR spectroscopy. Said method comprises the steps of: a) receiving and measuring a predetermined amount of whole blood using a capillary; b) mixing the predetermined amount of whole blood with a deuterated solvent and a predetermined amount of an internal standard, c) producing a 1H-NMR spectrum of the mixture obtained in step b), and d) determining the concentration of ethanol in the blood sample by comparing the signals of the ethanol to the signals of the internal standard in the 1H-NMR spectrum which has been generated. Said method allows a large number of samples to be examined in a short space of time and with a high degree of precision. In addition, it has been shown that capillary blood can also be examined without any loss of precision. This allows simple sample taking that can also be carried out by people other than doctors. Moreover, it has been shown that the measured samples can be stored for many months without any substantial decline in the amount of ethanol in the blood sample.