NMR Apparatus for Rapid Antigen Detection

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Solution Overview

Problem

Current NMR methods for detecting antigens in small liquid samples are limited by long incubation times and sensitivity, as they rely on enzyme-linked immunosorbent assays (ELISAs) and struggle to differentiate between bulk and surface fluid properties effectively.

Innovation Solution

The development of an NMR apparatus and methods that utilize specialized pulse sequences, such as CPMG, to measure T2 relaxation times and differentiate between bulk and surface fluid properties, allowing for rapid quantitative analysis of antigens by correlating T2 changes with analyte presence.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If ELISA methods are used to detect antigens in small liquid samples, then sensitivity can be achieved, but measurement time becomes excessively long due to required incubation periods

Engineering Contradiction:
Improvedetection sensitivityVSAvoidincubation time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent replaces the biochemical incubation process of ELISA with an NMR-based detection system that uses magnetic field interactions to detect antigens. The NMR apparatus uses a magnet to generate a magnetic field that interacts with hydrogen nuclei in the sample, allowing rapid detection without lengthy incubation periods while maintaining sensitivity through surface-enhanced relaxation effects

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent exploits the phase-like transition in spin states during NMR detection. By using pulse sequences to manipulate nuclear spin states and measure relaxation times, the system achieves rapid antigen detection. The surface proximity effects cause measurable changes in relaxation rates that indicate antigen presence, enabling fast detection without traditional incubation

Inventive Principle:
Principle #36Phase transitions

2Measurement precision

If conventional NMR methods are used, then bulk fluid properties can be measured, but the ability to differentiate surface fluid properties is insufficient

Engineering Contradiction:
Improvefluid property differentiationVSAvoidmeasurement system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent applies local quality by focusing the NMR detection specifically on fluid molecules near the surface of the sample chamber. The design exploits the fact that molecules close to the surface experience different magnetic relaxation rates due to paramagnetic centers at the wall surface. By measuring T2 relaxation times and analyzing surface-specific signals, the system differentiates surface fluid properties from bulk properties without requiring complex additional hardware

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent uses parameter changes in the NMR measurement process, specifically varying pulse sequence parameters and analyzing T2 relaxation time distributions. By measuring relaxation rates at different conditions and analyzing the distribution of relaxation times, the system can distinguish between surface and bulk fluid properties. The surface-proximal molecules exhibit shorter relaxation times due to wall effects, providing a measurable parameter difference

Inventive Principle:
Principle #35Parameter changes

3Quantity of substance

If small liquid samples are analyzed, then sample volume is reduced, but signal detection sensitivity decreases

Engineering Contradiction:
Improvesample volumeVSAvoidsignal detection sensitivity
Core Design Contradiction:
Quantity of substanceVSMeasurement precision

Solution Approach 1:

The patent enhances signal detection in small samples by focusing on the local quality of surface-proximal molecules. Molecules near the chamber surface experience enhanced relaxation effects due to paramagnetic centers at the wall, creating a localized signal enhancement zone. This surface-enhanced NMR effect compensates for the reduced total sample volume by concentrating the detectable signal in a specific region near the surface

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent effectively creates a composite detection environment by combining the liquid sample with the paramagnetic surface material of the sample chamber walls. This composite system generates enhanced relaxation signals from molecules at the liquid-surface interface, providing sufficient signal strength even when the total sample volume is very small. The surface material acts as a signal amplifier for the limited sample volume

Inventive Principle:
Principle #40Composite materials

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

Enables rapid and sensitive detection of antigens in small liquid samples by reducing measurement times and improving sensitivity, allowing for real-time analysis of fluid-surface interactions.

Implementation Method 1

NMR signals as used in methods according to the present disclosure arise from the nuclei of hydrogen atoms in water molecules

Methodology Applied
Scientific EffectNuclear magnetic resonance:

Implementation Method 2

Spin-spin (T2) relaxation occurs when a given ensemble of oscillating hydrogen nuclear axis spins lose coherence

Methodology Applied
Scientific EffectSpin-spin relaxation:

Implementation Method 3

Loss of spin coherence is caused by macroscopic and microscopic fluctuations in the static magnetic field experienced by a freely diffusing nuclear axis spin

Methodology Applied
Scientific EffectMagnetic field: Magnetic Field

Implementation Method 4

A CPMG pulse sequence removes the effects of static magnetic field macroscopic inhomogeneities to specifically measure the contribution from the microscopic environment, by creating a series of spin echoes

Methodology Applied
Scientific EffectSpin echo: Echo

Implementation Method 5

The relaxation time is significantly shorter for a molecule proximate a sample chamber surface or wall area, as compared to a molecule in the bulk volume. This is typically an effect of paramagnetic centers at a wall surface that causes the relaxation time to be shorter

Methodology Applied
Scientific EffectParamagnetism:

Data Source

PatentUS9964501B2Nuclear magnetic resonance apparatus and methods
Publication Date: 2018.05.08 TAICHER GERSH Z
  • US9964501B2 patent drawing
  • US9964501B2 patent drawing
  • US9964501B2 patent drawing

AI summary

A nuclear magnetic resonance (NMR) apparatus includes at least one magnet configured to induce a static magnetic field in a sample of material to be analyzed, wherein the sample is disposed on one side of the at least one magnet. The at least one magnet is configured such that the static magnetic field induced in the sample of material to be analyzed is substantially planar along lines of equal static magnetic field amplitude. A method includes inducing a static magnetic field in a sample of material to be analyzed. The static magnetic field is substantially planar along surfaces of equal amplitude of the static magnetic field. The inducing originates on one side of the sample. A radio frequency magnetic field is induced in the sample substantially orthogonally to the static magnetic field. NMR phenomena excited in the sample are detected.