Magnetic Resonance Contrast Agent Disks for Multiplexed Cell Tracking

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Solution Overview

Problem

Current magnetic resonance imaging (MRI) contrast agents lack the ability to distinguish between different cell types at the single-cell level, and existing T2* agents are limited in their ability to provide detailed cellular tracking due to broadening of water hydrogen proton lines and monochrome contrast, necessitating an improved method for cellular differentiation and tracking.

Innovation Solution

Development of magnetic resonance contrast agents comprising uniform, ferromagnetic or paramagnetic disks with controlled magnetic moments and sizes, which can be coated for bioconjugation and targeting, and used in methods that involve spatial separation and analysis to achieve super-resolution tracking and multiplexed imaging.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Illumination intensity

If conventional T2* contrast agents (SPIO, MPIO) are used for cellular tracking, then strong monochrome contrast is achieved, but the ability to distinguish between different cell types is lost due to continuous spatial decay of external fields broadening water hydrogen proton lines

Engineering Contradiction:
Improvecontrast intensityVSAvoidcell type differentiation capability
Core Design Contradiction:
Illumination intensityVSLoss of information

Solution Approach 1:

The invention segments the magnetic field interaction by using uniformly magnetized disks with controlled magnetic moments that produce discrete, non-overlapping Larmor frequencies. Each cell type is labeled with disks having specific magnetic moments, creating distinct frequency signatures that can be individually detected, thereby segmenting the previously continuous frequency spectrum into discrete, distinguishable channels.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention changes the key parameter from continuous spatial field decay to discrete magnetic moment values. By controlling the magnetic moment of uniformly sized disks to specific quantized values, the system transforms the broad continuous frequency distribution into discrete frequency lines, enabling multiplexed detection of different cell types while maintaining strong contrast.

Inventive Principle:
Principle #35Parameter changes

2Adaptability or versatility

If uniformly magnetized disks with controlled magnetic moments are used, then multiplexed detection of different cell types is enabled, but manufacturing precision requirements increase to maintain uniform size and magnetic moment

Engineering Contradiction:
Improvecell type differentiation capabilityVSAvoiddisk uniformity control
Core Design Contradiction:
Adaptability or versatilityVSManufacturing precision

Solution Approach 1:

The invention applies local quality by ensuring uniform magnetization within each disk while allowing variation in magnetic moment between disks. The uniform size and composition of each disk provide consistent local properties, while the controlled variation in total magnetic moment (through different disk numbers or arrangements) enables differentiation without requiring extreme manufacturing precision at the individual disk level.

Inventive Principle:
Principle #3Local quality

3Measurement precision

If higher concentrations of T2* contrast agents are used to improve detection sensitivity, then signal strength increases, but cell viability is compromised

Engineering Contradiction:
Improvedetection sensitivityVSAvoidcell toxicity
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The invention changes the detection parameter from relying on concentration-dependent signal strength to relying on frequency-specific detection. By tuning the Larmor frequency to match the discrete frequency of target cells labeled with specific magnetic moment disks, the system achieves high detection sensitivity at lower concentrations, reducing toxic effects on cell viability.

Inventive Principle:
Principle #35Parameter changes

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 precise differentiation and tracking of cells, allowing for enhanced cellular biology research and early disease detection by providing a high-resolution, color-coded imaging capability with reduced agent concentration requirements, improving upon existing MRI contrast agents.

Implementation Method 1

Each disk may have magnetic moment from about 10−14 A·m2 to about 10−11 A·m2... The magnetic material of the magnetic resonance contrast agent may comprise a ferromagnetic, paramagnetic, superparamagnetic, magnetic alloy, or a magnetic compound

Methodology Applied
Scientific EffectLarmor frequency: Magnetic Field

Data Source

PatentUS10215825B2Magnetic microstructures for magnetic resonance imaging
Publication Date: 2019.02.26 THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE COMMERCE
  • US10215825B2 patent drawing
  • US10215825B2 patent drawing
  • US10215825B2 patent drawing

AI summary

The present invention relates to a magnetic resonance structure with a cavity or a reserved space that provides contrast and the additional ability to frequency-shift the spectral signature of the NMR-susceptible nuclei such as water protons by a discrete and controllable characteristic frequency shift that is unique to each MRS design. The invention also relates to nearly uniform solid magnetic resonance T2* contrast agents that have a significantly higher magnetic moment compared to similarly-sized existing MRI contrast agents. The invention also relates to a magnetic resonance sensor that alters it shape in response to a condition of an environment such that the condition may be detected.