Rapid DNP Hyperpolarization Using Cross-Polarized High γ Nuclei

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Solution Overview

Problem

Current hyperpolarization techniques for NMR investigations, such as dissolution DNP, are limited by long preparation times and high costs due to the use of expensive radicals like trityl, and replacing them with cheaper radicals like TEMPO results in lower polarization levels and longer preparation times, especially for nuclei with long longitudinal relaxation times like 13C.

Innovation Solution

A method combining Dissolution DNP with Cross Polarization, using high γ nuclei with short relaxation times and a broad EPR line polarizing agent, such as TEMPO, to achieve rapid and high polarization levels of low γ nuclei like 13C, by exploiting the faster polarization build-up rate of high γ nuclei in strong magnetic fields and higher temperatures, thereby simplifying cooling processes and reducing apparatus expenses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If dissolution DNP is applied to nuclei with long T1 times (such as 13C) to achieve hyperpolarization, then high polarization levels can be obtained, but the preparation time becomes excessively long (on the order of one hour)

Engineering Contradiction:
Improvepolarization levelVSAvoidpreparation time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent introduces high γ nuclei (such as protons with short T1) as an intermediary species. These nuclei are first polarized by DNP, then their polarization is transferred to the low γ nuclei (such as 13C) via cross-polarization. This mediator approach allows the final hyperpolarization of long-T1 nuclei to occur much faster than direct DNP, reducing preparation time from hours to minutes while maintaining high polarization levels.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If trityl radicals are used as polarizing agents to achieve high polarization levels in 13C DNP, then polarization levels of 30-35% can be obtained, but the cost becomes excessively high

Engineering Contradiction:
Improvepolarization levelVSAvoidcost
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The patent replaces expensive trityl radicals with cheaper alternatives such as TEMPO radicals. While TEMPO may have different polarization characteristics, the overall cost reduction is achieved. The invention compensates for any potential performance differences by using the high γ nucleus intermediary approach, which enables rapid polarization transfer and maintains high final polarization levels at lower cost.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Measurement precision

If the temperature is lowered to 1.5 K or below to improve DNP efficiency, then better polarization can be achieved, but the apparatus complexity and difficulty of obtaining such temperatures increases

Engineering Contradiction:
Improvepolarization levelVSAvoidtemperature control system
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent changes the operating temperature from cryogenic levels (1.5 K or below) to higher temperatures (1.8-300 K, preferably 1.8-100 K). This parameter change simplifies the temperature control requirements and reduces apparatus complexity. The invention compensates for the reduced thermal polarization at higher temperatures by using the high γ nucleus intermediary and cross-polarization mechanism, which efficiently transfers polarization regardless of the moderate temperature range.

Inventive Principle:
Principle #35Parameter changes

4Ease of manufacture

If TEMPO radicals are used instead of trityl radicals to reduce cost, then the polarization level in 13C DNP decreases considerably

Engineering Contradiction:
ImprovecostVSAvoidpolarization level
Core Design Contradiction:
Ease of manufactureVSMeasurement precision

Solution Approach 1:

The patent uses high γ nuclei (such as protons) polarized by TEMPO radicals as an intermediary. Even though TEMPO may not directly polarize 13C efficiently, it effectively polarizes the high γ nuclei. The polarization is then transferred to 13C via cross-polarization, achieving high final polarization levels despite using the cheaper TEMPO radical instead of trityl.

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 approach allows for quick and high-level hyperpolarization of low γ nuclei, significantly reducing preparation times and maintaining high polarization levels, even at higher temperatures, thus enhancing signal intensity and throughput in NMR experiments.

Implementation Method 1

a method for producing hyperpolarized sample material for use in an NMR (nuclear magnetic resonance) investigation, in particular for use in an in vivo MRI (magnetic resonance imaging) experiment

Methodology Applied
Scientific EffectDynamic Nuclear Polarization (DNP):

Implementation Method 2

wherein an EPR line of the polarizing agent (Pa) has a width wPa wherein wPa>1⁄2ωhg

Methodology Applied
Scientific EffectElectron Paramagnetic Resonance (EPR): Electron Paramagnetic Resonance

Implementation Method 3

transferred the polarization from the protons to 13C

Methodology Applied
Scientific EffectCross Polarization:

Implementation Method 4

wherein the target material is exposed to a static magnetic field B0, with B0≧4.0 T

Methodology Applied
Scientific EffectMagnetic Field: Magnetic Field

Implementation Method 5

wherein the target material is at a cryogenic temperature Tcr, so that the target material is solid

Methodology Applied
Scientific EffectCryogenic Temperature: Cryogenics

Data Source

PatentUS20130274111A1Method and device for rapid DNP
Publication Date: 2013.10.17 BRUKER SWITZERLAND AG
  • US20130274111A1 patent drawing
  • US20130274111A1 patent drawing
  • US20130274111A1 patent drawing

AI summary

A method for producing hyperpolarized sample material for use in magnetic resonance investigations involves preparing a target material containing high γ nuclei with a short T1, a polarizing agent with a broad EPR line, and low γ nuclei with a long T1. The polarizing agent in the target material is irradiated with microwave radiation, wherein the target material is at a cryogenic temperature and exposed to a static magnetic field B0≧4.0 T, thus polarizing the high γ nuclei by DNP, and the polarization is transferred from the high γ nuclei to the low γ nuclei by Cross Polarization. A dissolved sample material is prepared containing the hyperpolarized low γ nuclei from the target material. Nuclei with a long longitudinal relaxation time T1 can thereby be quickly hyperpolarized to a high polarization level.