NMR Water Relaxation for Vaccine Freeze Detection

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current methods for detecting freeze-induced damage in vaccines and pharmaceutical products are either invasive, require trained personnel, or are not reliable, leading to significant wastage and potential administration of ineffective vaccines.

Innovation Solution

A noninvasive method using solvent nuclear magnetic resonance (NMR) to measure the transverse relaxation rate of water (R2) in sealed pharmaceutical product containers, allowing for quick and reliable determination of whether the contents have been frozen.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If visual observation or Shake Test is used to detect freezing, then the method is simple and requires no special equipment, but it requires trained personnel, is time-consuming, and may lead to incorrect decisions

Engineering Contradiction:

Improvesimplicity of detection methodVSAvoidreliability of freezing detection

Core Design Contradiction:

Ease of manufactureVSReliability

Solution Approach 1:

The patent replaces the mechanical Shake Test with a nuclear magnetic resonance (NMR) spectroscopy method. The NMR technique measures changes in the magnetic properties of water molecules caused by freezing, providing objective, quantitative data about the physical state of the vaccine without requiring manual shaking or visual inspection. This substitution eliminates subjectivity and improves reliability while maintaining ease of use through automated measurement.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent utilizes changes in NMR relaxation parameters (specifically T2 relaxation time) that occur when water in the vaccine freezes. By measuring these physical parameter changes, the method provides an objective, quantitative assessment of freezing status that is more reliable than visual observation or manual shaking tests.

Inventive Principle:

Principle #35Parameter changes

2Ease of operation

If vials are opened for testing, then the detection method is straightforward, but the vials are compromised and no longer usable

Engineering Contradiction:

Improveease of testingVSAvoidloss of usable vaccine

Core Design Contradiction:

Ease of operationVSLoss of substance

Solution Approach 1:

The patent uses NMR spectroscopy as an intermediary measurement technique that can detect freezing through the magnetic properties of water molecules without requiring physical access to or opening of the vial. The measurement can be performed through the sealed container wall, acting as an intermediary that allows detection without compromising the integrity of the vaccine vial.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces mechanical opening of vials with a non-contact NMR measurement system. The NMR instrument measures magnetic resonance signals through the sealed vial container, eliminating the need to open or compromise the vial integrity while still providing accurate freezing detection.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Reliability

If temperature monitoring devices are used, then freezing can be detected, but the devices must be opened or compromised to test individual vials

Engineering Contradiction:

Improvedetection capabilityVSAvoidcomplexity of testing procedure

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent replaces complex temperature monitoring devices with a simplified NMR-based detection method. Instead of using multiple temperature sensors, data loggers, or complex monitoring systems that require opening or compromising vials, the NMR method provides direct detection of freezing through magnetic property measurements that can be performed on sealed containers.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

4Reliability

If the Shake Test is performed, then freezing can be detected, but it takes 5-45 minutes and requires trained observers

Engineering Contradiction:

Improvefreezing detection accuracyVSAvoidtime required for detection

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The patent replaces the time-consuming Shake Test with rapid NMR spectroscopy measurement. The NMR technique provides automated, objective measurement of freezing status that can be performed much faster than manual shaking and visual observation, eliminating the 5-45 minute time requirement while maintaining high detection accuracy through quantitative physical measurement.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

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 provides immediate, sensitive, and quantitative results, enabling the identification of freeze-damaged products without opening the containers, thus minimizing waste and ensuring vaccine potency.

Implementation Method 1

solvent nuclear magnetic resonance (NMR) to measure the transverse relaxation rate of water (R2)

Methodology Applied

Scientific EffectNuclear Magnetic Resonance:

Data Source

PatentUS20250130186A1Detection of pharmaceutical product freezing history using water proton nmr

Publication Date: 2025.04.24 UNIV OF MARYLAND

AI summary

A method of using the relaxation rate (R1 and/or R2) of solvent NMR signal to invasively or noninvasively assess whether vaccines and other aqueous-based pharmaceutical products have been frozen during transport and/or storage.