Hyperpolarized Sample Transport via Radical Extraction

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Solution Overview

Problem

The limited lifetime of hyperpolarized magnetization in DNP samples prevents the remote production and long-distance transportation of hyperpolarized metabolites due to rapid relaxation caused by paramagnetic polarizing agents, necessitating on-site DNP processing near MRI scanners.

Innovation Solution

A method involving the compartmentalization of molecules and polarizing agents within microcrystals, allowing proton hyperpolarization to be transferred via spin diffusion and cross-polarization, enabling the separation of polarizing agents to minimize relaxation effects, thus allowing hyperpolarized samples to be transported over long distances.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If the sample is kept in solution state within the polarizer to enable DNP polarization transfer, then polarization transfer efficiency is improved, but polarization lifetime is reduced due to rapid relaxation

Engineering Contradiction:
Improvepolarization transfer efficiencyVSAvoidpolarization lifetime
Core Design Contradiction:
ProductivityVSDuration of action of moving object

Solution Approach 1:

The system is divided into two separate compartments: a polarizing agent compartment containing radicals and a sample compartment containing the molecule of interest. This segmentation allows the sample to be polarized efficiently when in contact with the polarizing agent, then separated to preserve the hyperpolarized state for extended periods during transport and storage.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The polarizing agents (radicals) are extracted from the sample compartment after polarization is achieved. This removal eliminates the source of rapid relaxation that would otherwise cause the hyperpolarized state to decay quickly, thereby extending the usable lifetime of the hyperpolarized sample.

Inventive Principle:
Principle #2Taking out (Extraction)

2Duration of action of moving object

If the sample is removed from the polarizer in solid state to preserve polarization, then polarization lifetime is extended, but the sample cannot be effectively polarized without dissolution

Engineering Contradiction:
Improvepolarization lifetimeVSAvoidpolarization achievement
Core Design Contradiction:
Duration of action of moving objectVSEase of manufacture

Solution Approach 1:

The polarization process is completed in advance while the sample is in the polarizer with the polarizing agent present. The sample is hyperpolarized to maximum levels before being removed and separated from the polarizing agent, allowing the beneficial polarized state to be preserved during subsequent transport and storage without requiring continuous presence in the polarizer.

Inventive Principle:
Principle #10Preliminary action

3Reliability

If polarizing agents are present with the sample during transport, then polarization can be maintained, but relaxation effects cause rapid decay of hyperpolarization

Engineering Contradiction:
Improvepolarization maintenanceVSAvoidrelaxation-induced decay
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The polarizing agents are extracted from the sample compartment after the polarization process is complete. This removal eliminates the harmful relaxation effects that would otherwise cause rapid decay of the hyperpolarized state during transport and storage, while the hyperpolarized sample itself is preserved for extended periods.

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 extends the lifetime of hyperpolarization, allowing hyperpolarized samples to be transported and used in remote locations, maintaining significant polarization for extended periods, and enabling the separation of hyperpolarized molecules from relaxation-inducing agents.

Implementation Method 1

Dissolution dynamic nuclear polarization (D-DNP) allows one to increase the NMR polarization

Methodology Applied
Scientific EffectDynamic Nuclear Polarization (DNP):

Implementation Method 2

transferring the electron spin polarization of the polarizing agent in the DNP sample at this low temperature in a magnetic field of at least 2 T to abundant nuclear spins

Methodology Applied
Scientific EffectElectron spin polarization transfer:

Implementation Method 3

allowing for spin diffusion to relay polarization to at least one of: abundant nuclear spins in the molecules of interest

Methodology Applied
Scientific EffectSpin diffusion: Diffusion

Implementation Method 4

performing hetero-nuclear cross-polarization from the abundant nuclear spins of the molecules of interest and/or the abundant nuclear spins in the micro-particulate matrix comprising the molecules of interest or the abundant nuclear spins in the solvent or emulsion or suspension agent comprising the molecules of interest to at least one nuclear spin type different from the abundant nuclear spins in the molecules

Methodology Applied
Scientific EffectHetero-nuclear cross-polarization:

Implementation Method 5

The hyperpolarized microcrystalline sample can be transported to a remote location in a suitable transport device, here an assembly of permanent magnets immersed in liquid helium

Methodology Applied
Scientific EffectCryogenic preservation: Freezing

Data Source

PatentEP3081952B1Transportable long-lived hyperpolarized samples
Publication Date: 2018.12.26 ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE (EPFL)
  • EP3081952B1 patent drawingFigure 1a~2b
  • EP3081952B1 patent drawingFigure 3a~4
  • EP3081952B1 patent drawingFigure 5~6a

AI summary

Proposed is a method for the preparation of a hyperpolarized solution of molecules of interest. The proposed method comprises the following steps: 1) suspending or coating of a micro-particulate matrix, which is crystalline or a non-porous aggregate, and which e.g. is comprising or consisting of the molecules of interest, with a glass-forming solution or suspension e.g. comprising a DNP-suitable polarizing agent at a first temperature at which the micro-particulate matrix is not dissolving; 2) lowering the temperature to a value of at most 15 K leading to a frozen glassy DNP sample; 3) transferring the electron spin polarization of the polarizing agent in the glassy DNP sample at this low temperature in a magnetic field of at least 2 T to abundant nuclear spins of the frozen glass-forming solution or suspension and/or the polarizing agent as well as to abundant nuclear spins of the molecules of interest and hetero-nuclear cross-polarization from the abundant nuclear spins at least in the molecules of interest to at least one different nuclear spin type in the molecules of interest; 4) increasing the temperature and dissolving the molecules of interest which are hyperpolarized with respect of the different nuclear spins, in particular for use in a magnetic resonance imaging or nuclear magnetic resonance experiment.