Medical Applications of Imaging Measurement Techniques Using Nano-Quantum Sensors
At a Glance
Section titled “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 |
Executive Summary
Section titled “Executive Summary”This paper details the development and application of Nano-Quantum Sensors (Nano-QS), specifically Quantum Dots (QDs) and Fluorescent Nanodiamonds (FNDs), for advanced bioimaging and medical diagnostics.
- Core Technology: Utilizes QDs and FNDs (containing Nitrogen-Vacancy, NV, centers) for high-stability, nanoscale sensing, primarily focusing on Optically Detected Magnetic Resonance (ODMR) thermometry.
- FND Achievement: Established a single-cell ODMR thermometry system to measure intracellular temperature in mouse Adipose-derived Stem Cells (mASCs) with high spatial resolution.
- Biological Insight: Demonstrated a critical correlation between mASC function (secretion of regenerative factors like HGF and VEGF) and specific culture temperatures (32 °C vs 37 °C vs 42 °C).
- QD Development: Developed ultra-low toxicity, cadmium-free QDs (FluclairTM, 5.1 nm diameter) optimized for efficient stem cell labeling and long-term in vivo tracking in animal models.
- Clinical Application: Successfully tracked transplanted ASCs in acute liver failure models using in vivo fluorescence imaging, demonstrating the potential for quantitative monitoring of cell therapy efficacy.
- Future Platform: Research is advancing toward integrating Nano-QS with microfluidic/Lab-on-a-Chip platforms, including microfabricated microwave antennas, to enable high-throughput, in vivo-mimicking quantum cell sensing.
Technical Specifications
Section titled “Technical Specifications”| Parameter | Value | Unit | Context |
|---|---|---|---|
| Quantum Dot (QD) Representative Size | 30 | nm | Core semiconductor nanoparticle |
| Fluorescent Nanodiamond (FND) Representative Size | 100 | nm | Containing NV centers |
| NV Center Zero Field Splitting (D) | 2.87 | GHz | Fundamental resonance frequency for ODMR |
| ODMR Microwave Frequency Range | 2.80 ~ 2.92 | GHz | Frequency sweep range for temperature sensing |
| NV Center Excitation Wavelength | 532 | nm | Green laser used for optical pumping |
| NV Center Fluorescence Wavelength | 637 | nm | Red fluorescence emission |
| FluclairTM QD Particle Diameter | 5.1 | nm | Ultra-low toxicity QD for stem cell labeling |
| FluclairTM QD Zeta Potential | -11.0 | mV | Surface charge (ZnS-ZAIS-COOH) |
| FluclairTM QD Excitation Wavelength | 365 | nm | UV light source |
| QD Synthesis Temperature | 70 | °C | Synthesis of ZnS-ZAIS-COOH (ZZC) QDs |
| QD Synthesis Time | 5 | h | Synthesis duration in ethanol |
| Biocompatible Imaging Range (QDs) | 700 ~ 900 | nm | Near-Infrared (NIR) window for deep tissue imaging |
Key Methodologies
Section titled “Key Methodologies”- FND Intracellular Thermometry: FNDs (100 nm) are internalized by target cells (e.g., mASCs) via macropinocytosis. The NV center’s electron spin resonance (ESR) frequency shift, which is highly sensitive to temperature, is measured using the Optically Detected Magnetic Resonance (ODMR) technique.
- ODMR System Configuration: A wide-field fluorescence detection system is coupled with a microwave antenna (operating near 2.87 GHz) and a 532 nm excitation laser to monitor the change in fluorescence intensity (ODMR contrast) as the microwave frequency is swept.
- QD Synthesis and Functionalization: Ultra-low toxicity QDs (FluclairTM, based on ZnS-AgInS2, or ZZC) are synthesized in ethanol at 70 °C for 5 hours. The surface is functionalized using MPA/Tetramethylammonium hydride solution to introduce carboxylic acid (COOH) groups, ensuring biocompatibility and stability (Zeta potential -11.0 mV).
- Stem Cell Tracking In Vivo: QDs are used to label ASCs. These labeled cells are transplanted into animal models (e.g., mice with acute liver failure or rats with lung transplants). Cell localization and retention are monitored quantitatively over time using in vivo fluorescence imaging systems (e.g., IVIS Spectrum).
- Microfluidic Platform Development: Microfabrication techniques are used to create microfluidic channels and integrated microwave antenna structures on a chip. This platform aims to enable efficient magnetic field delivery and fluidic control for high-throughput, on-chip quantum cell sensing.
Commercial Applications
Section titled “Commercial Applications”- Regenerative Medicine & Cell Therapy Quality Control:
- Real-time, non-invasive assessment of stem cell (MSC, iPSC) viability and functional status based on intracellular temperature and pH prior to transplantation.
- Long-term, quantitative monitoring of transplanted cell fate, migration, and therapeutic efficacy in vivo using NIR-optimized QDs.
- Quantum Sensing and Metrology:
- Development of highly stable, biocompatible quantum probes (FNDs) for measuring physical parameters (temperature, pH, pressure) within complex biological systems at the nanoscale.
- Drug Discovery and High-Throughput Screening:
- Creation of microfluidic Lab-on-a-Chip devices integrated with Nano-QS for analyzing single-cell responses to drug candidates under controlled, in vivo-mimicking microenvironments.
- Advanced Diagnostics (Oncology/Inflammation):
- High-resolution detection and mapping of localized physiological anomalies (e.g., elevated temperature or altered pH) associated with early-stage cancer or inflammatory diseases at the single-cell level within tissues.
- Neuroscience and Physiology Research:
- Non-invasive imaging of neural activity and metabolic dynamics in living organisms using Nano-QS to resolve activity-dependent changes in temperature or proton dynamics.
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．