Nanodiamond NV Center Probe for Real-Time Protein Structure Analysis

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Solution Overview

Problem

Current methods for analyzing protein structure in biological systems are limited by low sensitivity and time resolution, and the use of fluorescent probes is hindered by toxicity and inability to non-invasively observe structural changes in real-time.

Innovation Solution

A nanodiamond particle with enhanced Optically-Detected Magnetic Resonance (ODMR) intensity is developed by modifying its surface with functional groups containing heteroatoms, such as hydroxyl or carboxyl groups, to serve as a fluorescent molecular probe for precise and real-time protein structure analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of time

If fluorescent molecular probes are used for real-time observation of protein structure, then time resolution and real-time measurement capability are improved, but spatial resolution remains low and measurement sensitivity is insufficient

Engineering Contradiction:
Improvetime resolutionVSAvoidspatial resolution
Core Design Contradiction:
Loss of timeVSMeasurement precision

Solution Approach 1:

The patent changes the physical parameters of the fluorescent probe by incorporating NV centers in nanodiamond particles, which have unique optical and magnetic properties. This enables simultaneous achievement of high time resolution through real-time fluorescence monitoring and improved spatial resolution through the atomic-level precision of NV center positioning and ODMR detection.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses composite nanodiamond particles containing NV centers as the fluorescent probe. These composite structures combine the advantages of diamond lattice stability with the quantum properties of NV centers, enabling both high spatial resolution for structural measurement and high time resolution for dynamic monitoring.

Inventive Principle:
Principle #40Composite materials

2Ease of manufacture

If conventional fluorescent substances are used for molecular probe, then fluorescence observation is possible, but toxicity occurs making non-invasive measurement difficult

Engineering Contradiction:
Improvefluorescence observation capabilityVSAvoidtoxicity
Core Design Contradiction:
Ease of manufactureVSObject-affected harmful factors

Solution Approach 1:

The patent employs nanodiamond particles as disposable, biocompatible fluorescent probes that can be safely introduced into biological systems. The nanodiamonds serve as temporary measurement tools that do not accumulate toxicity, enabling non-invasive real-time observation without long-term harmful effects on the observed system.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The nanodiamond particle creates an inert, biocompatible environment for fluorescence observation. The diamond lattice structure provides chemical stability and inertness, preventing toxic interactions with biological systems while maintaining fluorescence observation capability through the NV centers.

Inventive Principle:
Principle #39Inert atmosphere (Inert environment)

3Measurement precision

If NMR method is used for protein structure analysis, then spatial resolution at atomic level is improved, but sensitivity and time resolution are low preventing real-time observation

Engineering Contradiction:
Improvespatial resolutionVSAvoidsensitivity
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent replaces the conventional NMR detection mechanism with an optically-detected magnetic resonance (ODMR) system using NV centers. This substitution uses optical detection methods instead of traditional NMR signal detection, achieving atomic-level spatial resolution through NV center positioning while dramatically improving sensitivity and enabling real-time observation through fast optical detection speeds.

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

The enhanced ODMR intensity allows for precise and real-time analysis of protein structures in biological systems, overcoming the limitations of existing methods by providing high sensitivity and non-invasive measurement capabilities.

Implementation Method 1

An optically-detected magnetic resonance method (ODMR method) has been known as means allowing detection of magnetic resonance of a sample with high sensitivity. With the ODMR method, magnetic resonance is detected with high sensitivity by simultaneously emitting excitation light and applying high-frequency magnetic field to a sample and sensing change in amount of emission of fluorescence.

Methodology Applied
Scientific EffectOptically-Detected Magnetic Resonance (ODMR):

Implementation Method 2

A nanodiamond particle including a defect complex consisting of a nitrogen atom and a vacancy (hereinafter also denoted as an 'NV center') in a diamond crystal has been known to emit fluorescence at the NV center and vary an amount of emission of fluorescence with magnetic resonance.

Methodology Applied
Scientific EffectMagnetic resonance:

Data Source

PatentUS9465035B2Nanodiamond particle and method of manufacturing the same, and fluorescent molecular probe and method of analyzing structure of protein
Publication Date: 2016.10.11 THE JAPAN SCI & TECH AGENCY
  • US9465035B2 patent drawing
  • US9465035B2 patent drawing
  • US9465035B2 patent drawing

AI summary

A nanodiamond particle including an NV center having ODMR intensity enhanced, of which surface is modified with a functional group containing a heteroatom, is provided. This nanodiamond particle as being chemically modified can serve for a fluorescent molecular probe which can be made use of in a biological system. By tracking a rotational motion of the NV center included in this fluorescent molecular probe, structural change of a protein can be analyzed in real time. The functional group containing a heteroatom can be at least any functional group of a hydroxyl group and a hydroxyalkyl group, or a carboxyl group.