Medical Applications of Imaging Measurement Techniques Using Nano-Quantum Sensors

At a Glance

Metadata	Details
Publication Date	2023-12-05
Journal	The Brain & Neural Networks
Authors	Hiroshi Yukawa
Institutions	National Institutes for Quantum Science and Technology
Analysis	Full AI Review Included

Technical Documentation & Analysis: Nano-Quantum Sensors for Medical Imaging

This document analyzes the research on Nano-Quantum Sensors (FNDs and QDs) for medical imaging, focusing on the requirements for high-quality diamond materials and integrated device fabrication, and aligning these needs with 6CCVD’s advanced MPCVD diamond capabilities.

Executive Summary

Core Value Proposition: Fluorescent Nanodiamonds (FNDs) containing Nitrogen-Vacancy (NVC) centers are validated as highly stable, low-toxicity nano-quantum sensors for high-resolution bio-imaging and sensing.
Sensing Mechanism: The primary sensing modality is Optically Detected Magnetic Resonance (ODMR), leveraging the temperature-dependent shift of the NVC electronic spin triplet (Zero Field Splitting D = 2.87 GHz).
Key Achievements: Demonstrated single-cell resolution temperature monitoring in stem cells (mASCs) and achieved high-precision thermal mapping (±0.22 °C precision) in living multi-cellular organisms (C. elegans).
Application Focus: The technology is critical for advancing regenerative medicine (stem cell quality control), neuro-medicine, and cancer diagnostics by providing precise, long-term monitoring of intracellular physical parameters (temperature, pH).
Methodological Advancement: Research emphasizes the necessity of integrating high-quality diamond sensors onto microfabricated platforms (on-chip ODMR, antennas, waveguides) to enable high-throughput and in vivo quantum cellular measurements.
6CCVD Relevance: Replication and advancement of this research require ultra-high purity Single Crystal Diamond (SCD) precursors for optimal NVC creation and advanced metalization/polishing services for integrated quantum chip development.

Technical Specifications

The following hard data points were extracted from the analysis of NVC-FND and QD quantum sensing platforms:

Parameter	Value	Unit	Context
Sensor Material (Primary)	FND (NVC)	-	Fluorescent Nanodiamond
NVC Zero Field Splitting (D)	2.87	GHz	Electronic Spin Triplet Resonance Frequency
ODMR Excitation Wavelength	532	nm	Green Laser Excitation
ODMR Fluorescence Wavelength	637	nm	NVC Fluorescence Emission
Microwave Frequency Range	2.80 - 2.92	GHz	Range used for ODMR spectral sweep
FND Particle Size (Figure 1b)	~100	nm	Typical FND dimension
QD Particle Size (Figure 1a)	~30	nm	Typical QD dimension
Temperature Measurement Precision	±0.22	°C	Stable monitoring precision achieved in C. elegans
QD Zeta Potential (Fluclair™)	-11.0	mV	Aqueous ZnS coating for cell compatibility
QD Particle Diameter (Fluclair™)	5.1	nm	Average size of ultra-low toxicity QDs

Key Methodologies

The research relies on advanced material synthesis and complex integrated device fabrication to enable high-resolution quantum sensing:

Quantum Sensor Synthesis: Production of high-quality Fluorescent Nanodiamonds (FNDs) containing stable Nitrogen-Vacancy (NVC) centers, often requiring high-purity diamond precursors.
Cellular Integration: FNDs are introduced into target cells (e.g., mASCs) via endocytosis/macropinocytosis, allowing for ultra-low invasive, single-cell level internal sensing.
ODMR System Construction: Development of specialized optical setups combining laser excitation (532 nm), fluorescence detection (637 nm), and precise microwave (MW) irradiation near the NVC resonance frequency (2.87 GHz).
Parameter Mapping: Measurement of physical parameters (e.g., temperature) by monitoring the frequency shift of the ODMR spectral peak, which is sensitive to changes in the diamond lattice structure.
On-Chip Platform Microfabrication: Use of semiconductor processing techniques (e.g., photolithography, metal deposition) to create integrated quantum sensing chips featuring microfluidic channels, waveguides, and metallic antennas (Au/Cr/Ti) for efficient MW delivery and signal collection.
In Vivo Probing: Application of the integrated platform for real-time, localized temperature monitoring within living organisms (e.g., C. elegans), requiring robust particle tracking algorithms and artifact correction.

6CCVD Solutions & Capabilities

The development of next-generation quantum sensors and integrated ODMR platforms requires diamond materials with exceptional purity, precise geometry, and advanced surface engineering. 6CCVD is uniquely positioned to supply the foundational materials and fabrication services necessary to replicate and scale this research.

Applicable Materials

To maximize NVC coherence time and ODMR contrast—critical for achieving the reported high temperature precision (±0.22 °C)—researchers require the highest quality diamond precursors.

Optical Grade Single Crystal Diamond (SCD): Essential precursor material for creating high-density, high-coherence NVC centers. 6CCVD provides SCD with extremely low nitrogen and defect concentrations, ensuring optimal quantum performance.
Polycrystalline Diamond (PCD) Substrates: For scaling up high-throughput, multi-point sensing arrays (e.g., inch-size ODMR chips), 6CCVD offers large-area PCD wafers up to 125mm diameter.
Custom Thickness Control: We supply SCD and PCD plates with precise thickness control from 0.1µm to 500µm, enabling the fabrication of thin membranes or integrated optical elements required for on-chip ODMR systems.

Customization Potential

The research explicitly details the need for integrated microfabricated structures, including metallic antennas (Figure 4) and precise optical interfaces.

Research Requirement	6CCVD Solution & Capability	Technical Advantage
Integrated Microwave Antennas	In-House Custom Metalization	We offer internal deposition capabilities for critical metals (Au, Pt, Pd, Ti, W, Cu) directly onto diamond substrates, ensuring robust, high-performance microwave antennas and waveguides for efficient 2.87 GHz signal delivery.
High-Quality Optical Interface	Ultra-Precision Polishing	SCD substrates can be polished to an atomic-level surface roughness (Ra < 1nm), minimizing light scattering and maximizing the efficiency of the 532 nm excitation and 637 nm fluorescence collection.
On-Chip Platform Geometry	Custom Dimensions and Laser Cutting	6CCVD provides custom-sized plates and wafers (up to 125mm PCD) and offers precision laser cutting services to achieve the unique geometries required for integrating microfluidics and ODMR components.
Boron Doping for Electrochemistry	Boron-Doped Diamond (BDD)	While the paper focuses on NVC, future quantum sensing platforms may require electrochemical sensing. We supply BDD films for robust, chemically inert electrodes.

Engineering Support

The successful transition from in vitro proof-of-concept to robust in vivo quantum sensing platforms requires deep expertise in material science and quantum defect engineering.

6CCVD’s in-house PhD team specializes in MPCVD growth and post-processing techniques necessary to optimize diamond materials for quantum applications. We can assist researchers with material selection, NVC creation protocols, and surface functionalization strategies for similar Nano-Quantum Sensing and Bio-Imaging projects.

For custom specifications or material consultation, visit 6ccvd.com or contact our engineering team directly.

View Original Abstract

バイオイメージング技術は，これまで基礎生物学研究から臨床応用まで広く用いられてきた．とりわけ，2023年度のノーベル化学賞の対象となった量子ドット（Quantum Dots: QDs），及び窒素—空孔中心（Nitrogen-Vacancy Center: NVC）を有する蛍光性ナノダイヤモンド（Fluorescent Nanodiamonds: FNDs）などの「ナノ量子センサー」は，高い安定性とナノメートル単位の微小サイズを特徴とし，生体内での輸送や長期観察など基礎生物学から臨床応用まで幅広い応用が期待される．本稿では，ナノ量子センサーによるイメージング技術と医学応用の将来展望について，最新の研究成果を交えて解説する．

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Original Source

DOI: https://doi.org/10.3902/jnns.30.168