NMR Solute Detection via Solvent Signal Transfer

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Solution Overview

Problem

Nuclear magnetic resonance (NMR) techniques face challenges in generating a positive signal from a solute in a solvent with effective background signal suppression, particularly due to low concentration of solutes and interference from solvent signals.

Innovation Solution

A method involving a preparation sequence with radiofrequency pulses and magnetic field gradient pulses to encode and selectively transfer excitation from the solute to the solvent, using refocusing pulses to isolate the solute signal while dephasing solvent and other solute signals, thereby enhancing signal detection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If direct imaging of specific molecular compounds is used to detect solute concentration, then molecular specificity is improved, but signal strength deteriorates due to limited solute concentration

Engineering Contradiction:
Improvemolecular specificityVSAvoidsignal strength
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent uses solvent protons as an intermediary to transfer the low concentration signal from solute molecules to the abundant solvent pool. Through chemical exchange, the NMR signal from rare solute protons is transferred to common solvent protons, amplifying the detectable signal while maintaining molecular specificity through frequency-selective excitation.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the detection parameter from directly measuring solute proton signal to measuring solvent proton signal that has been modified by chemical exchange with solute. This parameter transformation allows detection of low-concentration solutes through the enhanced signal of abundant solvent molecules.

Inventive Principle:
Principle #35Parameter changes

2Quantity of substance

If chemical exchange saturation transfer is used to increase signal strength, then signal amplification is improved, but background signal suppression deteriorates making it difficult to distinguish solute contribution

Engineering Contradiction:
Improvesignal strengthVSAvoidbackground signal suppression
Core Design Contradiction:
Quantity of substanceVSMeasurement precision

Solution Approach 1:

The patent applies preliminary frequency-selective excitation at the solute resonance frequency before the chemical exchange process. This preliminary action selectively tags solute protons with a specific phase or saturation state, which is then transferred to solvent protons through chemical exchange, allowing subsequent differentiation from non-exchanged solvent signal.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent employs periodic radiofrequency pulse sequences that selectively excite solute protons at their specific resonance frequency. This periodic selective excitation creates a rhythmic modulation of solute magnetization that transfers to solvent through chemical exchange, enabling frequency-domain separation of solute and solvent contributions.

Inventive Principle:
Principle #19Periodic action

3Measurement precision

If resonance frequency selective excitation is applied to detect specific molecules, then molecular identification is improved, but signal detection difficulty increases due to low solute concentration

Engineering Contradiction:
Improvemolecular identificationVSAvoidsignal detection difficulty
Core Design Contradiction:
Measurement precisionVSDifficulty of detecting and measuring

Solution Approach 1:

The patent uses solvent protons as a signal amplifier intermediary. The frequency-selective excitation targets solute protons for molecular identification, and the chemical exchange transfers this selectively excited state to abundant solvent protons, converting the detection difficulty of low-concentration solutes into an easy-to-detect solvent signal enhancement.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 method allows for direct detection of solutes with improved signal strength and reduced interference, enabling better resolution and identification of solutes in NMR imaging.

Implementation Method 1

nuclear magnetic resonance provides a noninvasive method to study organic matter

Methodology Applied
Scientific EffectNuclear magnetic resonance: Resonance

Implementation Method 2

The transverse spin components will then precess around the direction of the applied longitudinal field with a characteristic frequency, an effect called Larmor precession

Methodology Applied
Scientific EffectLarmor precession: Precession

Implementation Method 3

applying a first magnetic field gradient pulse suitable for changing a phase of the nuclear spin

Methodology Applied
Scientific EffectMagnetic field gradient: Magnetic Field

Implementation Method 4

one of its protons is chemically exchanged to a water molecule when in solution. Due to this chemical exchange of the proton, the nuclear spin saturation can be transferred to surrounding water molecules

Methodology Applied
Scientific EffectChemical exchange:

Implementation Method 5

applying a refocusing radiofrequency pulse at a resonance frequency of the solvent for refocusing said nuclear spin transferred to the solvent by chemical exchange

Methodology Applied
Scientific EffectSpin refocusing: Echo

Data Source

PatentEP3502728B1Method and system to detect a solute in a solvent using nuclear magnetic resonance
Publication Date: 2021.05.12 JULIUS MAXIMILIANS UNIV WURZBURG
  • EP3502728B1 patent drawingFigure 1
  • EP3502728B1 patent drawingFigure 2
  • EP3502728B1 patent drawingFigure 3

AI summary

A method of detecting a solute in a solvent using nuclear magnetic resonance, said method comprising the steps of: encoding an excitation in a nuclear spin of the solute comprising at least one preparation sequence, wherein said preparation sequence comprises the steps of: applying a first radiofrequency pulse to the nuclear spin at a resonance frequency of the solute; and applying a first magnetic field gradient pulse suitable for changing a phase of the nuclear spin; and measuring the excitation in the nuclear spin, said measuring including the steps of: applying a refocusing radiofrequency pulse at a resonance frequency of the solvent for refocusing said nuclear spin transferred to the solvent by chemical exchange; applying a second magnetic field gradient pulse to thereby select the excitation in the nuclear spin; and performing a measurement of the excitation in the nuclear spin excited by the first radiofrequency pulse at the resonance frequency of the solute and refocused with the refocusing radiofrequency pulse at the resonance frequency of the solvent.