Paramagnetic Ion Spin Relaxometry for DNA Sequencing

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Solution Overview

Problem

Current ionic current sensing methods for sequencing DNA and other target molecules lack specificity and are error-prone, requiring calibration and often result in high error rates due to interpretation challenges.

Innovation Solution

A method involving a fluid containing target molecules interacting with complementary moieties attached to paramagnetic ions, causing a position change that induces a magnetic effect change, which is detected using electron spin centers like diamond nitrogen vacancies, allowing for precise identification of the target molecules.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If ionic current sensing methods are used for sequencing, then amplification-free and label-free sequencing is achieved, but specificity and measurement precision deteriorate with error rates of 15% or more

Engineering Contradiction:

Improveamplification-free and label-free sequencingVSAvoidspecificity and error rate

Core Design Contradiction:

Ease of manufactureVSMeasurement precision

Solution Approach 1:

The patent introduces a paramagnetic ion as an intermediary between the target molecule and the detection system. The paramagnetic ion serves as a mediator that translates molecular identity into a detectable magnetic signal, thereby improving measurement precision while maintaining the amplification-free and label-free approach

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the ionic current sensing mechanism with a magnetic field detection mechanism using electron spin centers. This substitution of detection physics (from electrical to magnetic) enables higher specificity and lower error rates while preserving the direct sequencing approach

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Difficulty of detecting and measuring

If ionic current sensing is used, then direct molecular detection is achieved, but measurement precision and reliability worsen due to interpretation errors

Engineering Contradiction:

Improvedirect molecular detectionVSAvoidinterpretation error rate

Core Design Contradiction:

Difficulty of detecting and measuringVSReliability

Solution Approach 1:

The patent uses changes in magnetic signal characteristics (analogous to color changes in optical detection) to directly indicate molecular identity. The paramagnetic ion's magnetic signature provides a clear, unambiguous signal that is easier to interpret reliably compared to ionic current patterns

Inventive Principle:

Principle #32Color changes

Solution Approach 2:

The patent substitutes magnetic field detection for ionic current measurement, replacing a system prone to interpretation errors with one that provides more distinct and reliable signals through magnetic resonance or spin relaxation detection

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Measurement precision

If complementary moieties with paramagnetic ions are used, then specificity is improved, but device complexity increases

Engineering Contradiction:

ImprovespecificityVSAvoidstructure complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent employs a universal detection mechanism (electron spin center detecting magnetic fields from any paramagnetic ion) that can identify multiple different target molecules through a single type of sensor. This multi-functionality achieves high specificity without proportionally increasing device complexity

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent achieves specificity by detecting changes in magnetic parameters (such as spin relaxation time or resonance frequency) rather than requiring complex structural variations. Different paramagnetic ions or configurations produce distinct magnetic signatures that can be differentiated through parameter analysis

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

This approach enhances specificity and reduces error rates, enabling label-free and amplification-free sequencing with improved sensitivity and speed, applicable to various applications including DNA sequencing, forensics, and diagnostics.

Implementation Method 1

detecting a magnetic effect change caused by the change in position of the paramagnetic ion

Methodology Applied

Scientific EffectMagnetic effect change: Magnetic Field

Implementation Method 2

the detecting a magnetic effect change comprises detecting a change in spin relaxation of an electron spin center

Methodology Applied

Scientific EffectSpin relaxation: Electron Paramagnetic Resonance

Data Source

PatentUS10281550B2Spin relaxometry based molecular sequencing

Publication Date: 2019.05.07 LOCKHEED MARTIN CORP

AI summary

A method and system for detecting a target molecule. The method includes allowing a fluid containing the target molecule to pass by a complementary moiety attached to a paramagnetic ion so as to cause the complementary moiety and the paramagnetic ion to change a position. A magnetic effect change caused by the change in position of the paramagnetic ion is detected. The target molecule is identified based on the identity of the complementary moiety and the detected magnetic effect change.