Dynamic Nuclear Polarization Sample Preparation for NMR Signal Enhancement

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Solution Overview

Problem

Current NMR and MRI techniques face limitations due to low signal-to-noise ratio (SNR), which restricts the detection of trace materials, prolongs measurement times, and limits the resolution and applicability of these methods, especially in medical imaging and surface analysis.

Innovation Solution

A method involving the generation of unstable radicals in a solid sample through electrical ionization or ionizing radiation, followed by cooling and dynamic nuclear polarization (DNP) to enhance nuclear spin polarization, allowing for higher SNR without the need for solvents or specific functional groups, and enabling the use of optically opaque materials.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional NMR measurement methods are used, then the measurement can be performed with standard equipment, but the signal-to-noise ratio is low and measurement time is excessively long

Engineering Contradiction:
Improvesignal-to-noise ratioVSAvoidmeasurement time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent applies preliminary action by generating unstable radicals in the sample before the actual NMR measurement. These pre-generated radicals serve as polarizing agents that transfer polarization to nuclear spins during the measurement, dramatically enhancing the signal-to-noise ratio and reducing measurement time without requiring complex equipment modifications

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent introduces unstable radicals as an intermediary substance that mediates the polarization transfer from electrons to nuclei. These radicals act as a bridge, enabling efficient polarization transfer that directly addresses the low signal-to-noise ratio problem while avoiding the need for lengthy measurements

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If standard NMR techniques are applied, then the method is simple and widely applicable, but trace materials and surface components cannot be detected

Engineering Contradiction:
Improvedetection sensitivityVSAvoidmeasurement protocol complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

By pre-generating unstable radicals in the sample before measurement, the patent achieves high detection sensitivity for trace materials and surface components. This preliminary radical generation step enables the detection of previously undetectable species without significantly complicating the overall measurement protocol

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The sample itself serves the dual function of being both the object of study and the source of polarizing agents. The unstable radicals are generated within the sample matrix, eliminating the need for external polarizing agents or complex sample preparation, thereby maintaining simplicity while achieving high sensitivity

Inventive Principle:
Principle #25Self-service

3Measurement precision

If multiple measurements are averaged to improve signal prominence, then the signal-to-noise ratio improves, but the total measurement time increases excessively

Engineering Contradiction:
Improvesignal prominenceVSAvoidtotal measurement duration
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent fundamentally changes the polarization parameter by introducing unstable radicals that provide non-equilibrium polarization to the nuclear spins. This parameter change allows achieving high signal prominence in a single measurement rather than requiring multiple averaged scans, thereby dramatically reducing total measurement duration

Inventive Principle:
Principle #35Parameter changes

4Measurement precision

If dissolution DNP method is used, then nuclear spin polarization can be enhanced, but the sample must be dissolved in solvent which may alter its native state

Engineering Contradiction:
Improvenuclear spin polarizationVSAvoidsample native state
Core Design Contradiction:
Measurement precisionVSStability of the object's composition

Solution Approach 1:

The patent extracts the solvent requirement from the DNP process by generating unstable radicals directly in the solid or liquid sample matrix. This extraction of the solvent step eliminates the need for dissolution, thereby maintaining the sample's native state while still achieving enhanced nuclear spin polarization through the pre-generated radicals

Inventive Principle:
Principle #2Taking out (Extraction)

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 significantly enhances SNR in NMR and MRI measurements, reducing measurement times and expanding the scope of detectable materials, including those with high surface area and optically opaque samples, while being compatible with clinical applications.

Implementation Method 1

generating unstable radicals in said sample by either (a) electrical ionization of the gas environment in said vessel

Methodology Applied
Scientific EffectElectrical ionization: Ionisation

Implementation Method 2

by subjecting said sample to ionizing radiation with an energy not less than 25 eV

Methodology Applied
Scientific EffectIonizing radiation: Radiation

Implementation Method 3

cooling said sample to a cryogenic temperature

Methodology Applied
Scientific EffectCryogenic cooling: Cryogenics

Implementation Method 4

performing dynamic nuclear polarization (DNP) process on the cooled sample so as to transfer spin polarization from the electron spins to the nuclear spins

Methodology Applied
Scientific EffectDynamic nuclear polarization:

Data Source

PatentEP3316912B1Method for preparation of a sample containing highly polarized nuclear spins
Publication Date: 2022.11.30 TECHNION RES & DEV FOUND LTD
  • EP3316912B1 patent drawingFigure 1A~1C
  • EP3316912B1 patent drawingFigure 2A
  • EP3316912B1 patent drawingFigure 2B

AI summary

A method for the preparation of a highly polarized nuclear spins containing sample of an organic or inorganic material, containing H or OH groups or adsorbed water molecules. Such highly polarized nuclear spins containing samples can be subjected to nuclear magnetic resonance (NMR) measurement and/or can be thawed and immediately administered to an individual undergoing a magnetic resonance imaging (MRI) scan. The method is based on generating unstable radicals on the surface of the sample in the presence of ionized environment followed by cooling the sample to cryogenic temperatures. A device for carrying out a particular step of said method is also discloses.