NMR Biological Detector Using Magnetic Nanoparticles

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Solution Overview

Problem

Standard high-resolution NMR spectroscopy is ineffective for directly detecting dilute biological objects like tumor cells, bacteria, or viruses in fluid samples due to weak signals being overwhelmed by background water signals, and the rapid transverse relaxation characteristics of these samples make direct detection difficult.

Innovation Solution

An NMR-based biological detector using a microcoil and a magnetic field generator, such as low-field permanent magnets or electromagnets, to detect magnetic nanoparticle-labeled biological objects in a fluid, allowing for routine relaxation time measurements and low-field spectroscopy, particularly for cancer cells, bacterial contaminants, and biological warfare agents in aqueous media.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If standard high-resolution NMR spectroscopy is used to detect biological objects, then detection capability is provided, but the weak signals from dilute biological objects are lost against the much stronger background water signal

Engineering Contradiction:
Improvedetection sensitivityVSAvoidbackground water signal interference
Core Design Contradiction:
Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

The patent introduces magnetic nanoparticles as intermediary agents that bind to biological objects of interest. These nanoparticles serve as mediators between the biological targets and the NMR detection system, enabling indirect detection through their magnetic properties rather than directly detecting the weak NMR signals from the biological objects themselves.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the detection parameter from direct NMR signal detection of biological objects to detection of magnetic nanoparticle properties (such as relaxation time changes) that affect the surrounding water signal. This parameter transformation converts an undetectable signal into a detectable one by measuring the nanoparticle-induced changes in water proton relaxation.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If standard NMR spectroscopy is used for direct detection, then detection is attempted, but the rapid transverse relaxation characteristics of macromolecular, viral, or cellular samples renders their direct detection difficult

Engineering Contradiction:
Improvedetection capabilityVSAvoidtransverse relaxation time
Core Design Contradiction:
Measurement precisionVSDuration of action of stationary object

Solution Approach 1:

Magnetic nanoparticles act as intermediaries that extend the effective detection window. By binding to biological objects, the nanoparticles create a stable magnetic environment that allows detection through their longer-lasting magnetic effects on surrounding water protons, circumventing the rapid transverse relaxation problem of the biological objects themselves.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent substitutes the direct NMR detection mechanism (which fails due to rapid relaxation) with an indirect magnetic detection mechanism. Instead of relying on the NMR signals from biological objects, the system uses magnetic field effects and relaxation time changes induced by magnetic nanoparticles, replacing a failed mechanical detection approach with a successful magnetic field-based approach.

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

3Measurement precision

If magnetic beads with large size are used to enhance signal, then signal amplification is achieved, but the detection volume becomes too large compared to single cell size

Engineering Contradiction:
Improvesignal amplificationVSAvoiddetection volume
Core Design Contradiction:
Measurement precisionVSVolume of moving object

Solution Approach 1:

The patent segments the magnetic detection function into small nanoparticle units that can be individually bound to biological objects. This segmentation allows the magnetic signal amplification function to be distributed across multiple small particles rather than requiring a single large bead, enabling the detection volume to match the scale of individual cells while maintaining signal amplification capability.

Inventive Principle:
Principle #1Segmentation

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

The solution enables the detection of dilute concentrations of magnetic nanoparticle-labeled biological objects with reduced cost, maintenance, and space requirements, while providing portability and high sensitivity, effectively overcoming the limitations of standard NMR spectroscopy.

Implementation Method 1

a microcoil and a magnetic field generator, such as one or more low field permanent magnets or electromagnets, to establish a relatively low magnetic field with energization of the microcoil at a frequency that permits detection by NMR

Methodology Applied
Scientific EffectElectromagnetic Induction: Electromagnetic Induction

Implementation Method 2

to establish a relatively low magnetic field with energization of the microcoil

Methodology Applied
Scientific EffectMagnetic Field: Magnetic Field

Implementation Method 3

SPIONs are enjoying significant uses as biological contrast agents for NMR imaging... The image contrast effects due to SPIONs, which are typically embedded in larger beads, rely on the enhancement of the relaxation rates of water molecules surrounding the beads

Methodology Applied
Scientific EffectSuperparamagnetism: Superparamagnetism

Implementation Method 4

NMR-based biological detector and detection method that involve detection of one or more magnetic nanoparticle-labeled biological objects... with energization of the microcoil at a frequency that permits detection by NMR

Methodology Applied
Scientific EffectNuclear Magnetic Resonance:

Data Source

PatentUS9958516B2Biological detector and method
Publication Date: 2018.05.01 SANDIA CORP
  • US9958516B2 patent drawing
  • US9958516B2 patent drawing
  • US9958516B2 patent drawing

AI summary

A biological detector includes a conduit for receiving a fluid containing one or more magnetic nanoparticle-labeled, biological objects to be detected and one or more permanent magnets or electromagnet for establishing a low magnetic field in which the conduit is disposed. A microcoil is disposed proximate the conduit for energization at a frequency that permits detection by NMR spectroscopy of whether the one or more magnetically-labeled biological objects is/are present in the fluid.