Size, polyglycerol grafting, and net surface charge of iron oxide nanoparticles determine their interaction and toxicity in Caenorhabditis elegans.

The widespread application of engineered nanoparticles (NPs) in environmental remediation has raised public concerns about their toxicity to aquatic organisms. Although appropriate surface modification can mitigate the ecotoxicity of NPs, the lack of polymer coating to inhibit toxicity completely and the insufficient knowledge about charge effect hinder the development of safe nanomaterials. Herein, we explored the potential of polyglycerol (PG) functionalization in alleviating the environmental risks of NPs. Iron oxide NPs (ION) of 20, 100, and 200 nm sizes (IONS, IONM and IONL, respectively) were grafted with PG to afford ION-PG. We examined the interaction of ION and ION-PG with Caenorhabditis elegans (C. elegans) and found that PG suppressed non-specific interaction of ION with C. elegans to reduce their accumulation and to inhibit their translocation. Particularly, IONS-PG was completely excluded from worms of all developmental stages. By covalently introducing sulfate, carboxyl and amino groups onto IONS-PG, we further demonstrated that positively charged IONS-PG-NH3+ induced high intestinal accumulation, cuticle adhesion and distal translocation, whereas the negatively charged IONS-PG-OSO3- and IONS-PG-COO- were excreted out. Consequently, no apparent deleterious effects on brood size and life span were observed in worms treated by IONS-PG and IONS-PG bearing negatively charged groups. This study presents new surface functionalization approaches for developing ecofriendly nanomaterials.

Diamond quantum sensors in microfluidics technology.

Diamond quantum sensing is an emerging technology for probing multiple physico-chemical parameters in the nano- to micro-scale dimensions within diverse chemical and biological contexts. Integrating these sensors into microfluidic devices enables the precise quantification and analysis of small sample volumes in microscale channels. In this Perspective, we present recent advancements in the integration of diamond quantum sensors with microfluidic devices and explore their prospects with a focus on forthcoming technological developments.

Glass-patternable notch-shaped microwave architecture for on-chip spin detection in biological samples.

We report a notch-shaped coplanar microwave waveguide antenna on a glass plate designed for on-chip detection of optically detected magnetic resonance (ODMR) of fluorescent nanodiamonds (NDs). A lithographically patterned thin wire at the center of the notch area in the coplanar waveguide realizes a millimeter-scale ODMR detection area (1.5 × 2.0 mm2) and gigahertz-broadband characteristics with low reflection (∼8%). The ODMR signal intensity in the detection area is quantitatively predictable by numerical simulation. Using this chip device, we demonstrate a uniform ODMR signal intensity over the detection area for cells, tissue, and worms. The present demonstration of a chip-based microwave architecture will enable scalable chip integration of ODMR-based quantum sensing technology into various bioassay platforms.

π-Topology and ultrafast excited-state dynamics of remarkably photochemically stabilized pentacene derivatives with radical substituents.

Pentacene derivatives with both π-radical- and TIPS-substituents (1m and 1p) were synthesized and their photochemical properties and excited-state dynamics were evaluated. The pentacene-radical-linked systems 1m (1p) showed a remarkable improvement in photochemical stability, which was 187 (139) times higher than that of 6,13-bis(triisopropylsilylethynyl)pentacene. Transient absorption spectroscopy showed that this remarkable photostabilization is due to the ultrafast intersystem crossing induced by effective π-conjugation between the radical substituent and pentacene moiety. The relationship between π-topology and the photochemical stability is also discussed based on the excited-state dynamics.

Diamond quantum thermometry: from foundations to applications.

Diamond quantum thermometry exploits the optical and electrical spin properties of colour defect centres in diamonds and, acts as a quantum sensing method exhibiting ultrahigh precision and robustness. Compared to the existing luminescent nanothermometry techniques, a diamond quantum thermometer can be operated over a wide temperature range and a sensor spatial scale ranging from nanometres to micrometres. Further, diamond quantum thermometry is employed in several applications, including electronics and biology, to explore these fields with nanoscale temperature measurements. This review covers the operational principles of diamond quantum thermometry for spin-based and all-optical methods, material development of diamonds with a focus on thermometry, and examples of applications in electrical and biological systems with demand-based technological requirements.

Wide-field fluorescent nanodiamond spin measurements toward real-time large-area intracellular thermometry.

Measuring optically detected magnetic resonance (ODMR) of diamond nitrogen vacancy centers significantly depends on the photon detectors used. We study camera-based wide-field ODMR measurements to examine the performance in thermometry by comparing the results to those of the confocal-based ODMR detection. We show that the temperature sensitivity of the camera-based measurements can be as high as that of the confocal detection and that possible artifacts of the ODMR shift are produced owing to the complexity of the camera-based measurements. Although measurements from wide-field ODMR of nanodiamonds in living cells can provide temperature precisions consistent with those of confocal detection, the technique requires the integration of rapid ODMR measurement protocols for better precisions. Our results can aid the development of camera-based real-time large-area spin-based thermometry of living cells.

Long-term safety and efficacy of alogliptin, a DPP-4 inhibitor, in patients with type 2 diabetes: a 3-year prospective, controlled, observational study (J-BRAND Registry).

INTRODUCTION: Given an increasing use of dipeptidyl peptidase-4 (DPP-4) inhibitors to treat patients with type 2 diabetes mellitus in the real-world setting, we conducted a prospective observational study (Japan-based Clinical Research Network for Diabetes Registry: J-BRAND Registry) to elucidate the safety and efficacy profile of long-term usage of alogliptin. RESEARCH DESIGN AND METHODS: We registered 5969 patients from April 2012 through September 2014, who started receiving alogliptin (group A) or other classes of oral hypoglycemic agents (OHAs; group B), and were followed for 3 years at 239 sites nationwide. Safety was the primary outcome. Symptomatic hypoglycemia, pancreatitis, skin disorders of non-extrinsic origin, severe infections, and cancer were collected as major adverse events (AEs). Efficacy assessment was the secondary outcome and included changes in hemoglobin A1c (HbA1c), fasting blood glucose, fasting insulin and urinary albumin. RESULTS: Of the registered, 5150 (group A: 3395 and group B: 1755) and 5096 (3358 and 1738) were included for safety and efficacy analysis, respectively. Group A patients mostly (>90%) continued to use alogliptin. In group B, biguanides were the primary agents, while DPP-4 inhibitors were added in up to ~36% of patients. The overall incidence of AEs was similar between the two groups (42.7% vs 42.2%). Kaplan-Meier analysis revealed the incidence of cancer was significantly higher in group A than in group B (7.4% vs 4.8%, p=0.040), while no significant incidence difference was observed in the individual cancer. Multivariate Cox regression analysis revealed that the imbalanced patient distribution (more elderly patients in group A than in group B), but not alogliptin usage per se, contributed to cancer development. The incidence of other major AE categories was with no between-group difference. Between-group difference was not detected, either, in the incidence of microvascular and macrovascular complications. HbA1c and fasting glucose decreased significantly at the 0.5-year visit and nearly plateaued thereafter in both groups. CONCLUSIONS: Alogliptin as a representative of DPP-4 inhibitors was safe and durably efficacious when used alone or with other OHAs for patients with type 2 diabetes in the real world setting.

Real-time nanodiamond thermometry probing in vivo thermogenic responses.

Real-time temperature monitoring inside living organisms provides a direct measure of their biological activities. However, it is challenging to reduce the size of biocompatible thermometers down to submicrometers, despite their potential applications for the thermal imaging of subtissue structures with single-cell resolution. Here, using quantum nanothermometers based on optically accessible electron spins in nanodiamonds, we demonstrate in vivo real-time temperature monitoring inside Caenorhabditis elegans worms. We developed a microscope system that integrates a quick-docking sample chamber, particle tracking, and an error correction filter for temperature monitoring of mobile nanodiamonds inside live adult worms with a precision of ±0.22°C. With this system, we determined temperature increases based on the worms' thermogenic responses during the chemical stimuli of mitochondrial uncouplers. Our technique demonstrates the submicrometer localization of temperature information in living animals and direct identification of their pharmacological thermogenesis, which may allow for quantification of their biological activities based on temperature.

A quantum thermometric sensing and analysis system using fluorescent nanodiamonds for the evaluation of living stem cell functions according to intracellular temperature.

Intracellular thermometry techniques play an important role in elucidating the relationship between the intracellular temperature and stem cell functions. However, there have been few reports on thermometry techniques that can detect the intracellular temperature of cells during several days of incubation. In this study, we developed a novel quantum thermometric sensing and analysis system (QTAS) using fluorescent nanodiamonds (FNDs). FNDs could label adipose tissue-derived stem cells (ASCs) at high efficiency with 24 h of incubation, and no cytotoxicity was observed in ASCs labeled with less than 500 µg mL-1 of FNDs. The peak of FNDs was confirmed at approximately 2.87 GHz with the characteristic fluorescence spectra of NV centers that could be optically detected (optically detected magnetic resonance [ODMR]). The ODMR peak clearly shifted to the high-frequency side as the temperature decreased and gave a mean temperature dependence of -(77.6 ± 11.0) kHz °C-1, thus the intracellular temperature of living ASCs during several days of culturing could be precisely measured using the QTAS. Moreover, the intracellular temperature was found to influence the production of growth factors and the degree of differentiation into adipocytes and osteocytes. These data suggest that the QTAS can be used to investigate the relationship between intracellular temperature and cellular functions.

Monitoring spin coherence of single nitrogen-vacancy centers in nanodiamonds during pH changes in aqueous buffer solutions.

We report on the sensing stability of quantum nanosensors in aqueous buffer solutions for the two detection schemes of quantum decoherence spectroscopy and nanoscale thermometry. The electron spin properties of single nitrogen-vacancy (NV) centers in 25 nm-sized nanodiamonds have been characterized by observing individual nanodiamonds during a continuous pH change from 4 to 11. We have determined the stability of the NV quantum sensors during the pH change as the fluctuations of ±12% and ±0.2 MHz for the spin coherence time (T 2) and the resonance frequency (ω 0) of their mean values, which are comparable to the instrument error of the measurement system. We discuss the importance of characterizing the sensing stability during the pH change and how the present observation affects the measurement scheme of nanodiamond-based NV quantum sensing.

Observation of the linewidth broadening of single spins in diamond nanoparticles in aqueous fluid and its relation to the rotational Brownian motion.

Capturing the fast rotational motion of single nanoparticles has been hindered owing to the difficulty of acquiring directional information under the optical diffraction limit. Here, we report the linewidth broadening of the electron spin resonance of single nitrogen vacancy (NV) centers that matches the rotational diffusion constant of the host nanodiamonds. When nanodiamonds are gradually detached from the substrates that they were fixed to, their optically detected spin resonance peaks are broadened by 1.8 MHz, which corresponds to the rotational diffusion constant of nanoparticles with a diameter of 11.4 nm from the Einstein-Smoluchowski relation.

Strategies to enhance the excitation energy-transfer efficiency in a light-harvesting system using the intra-molecular charge transfer character of carotenoids.

Fucoxanthin is a carotenoid that is mainly found in light-harvesting complexes from brown algae and diatoms. Due to the presence of a carbonyl group attached to polyene chains in polar environments, excitation produces an excited intra-molecular charge transfer. This intra-molecular charge transfer state plays a key role in the highly efficient (∼95%) energy-transfer from fucoxanthin to chlorophyll a in the light-harvesting complexes from brown algae. In purple bacterial light-harvesting systems the efficiency of excitation energy-transfer from carotenoids to bacteriochlorophylls depends on the extent of conjugation of the carotenoids. In this study we were successful, for the first time, in incorporating fucoxanthin into a light-harvesting complex 1 from the purple photosynthetic bacterium, Rhodospirillum rubrum G9+ (a carotenoidless strain). Femtosecond pump-probe spectroscopy was applied to this reconstituted light-harvesting complex in order to determine the efficiency of excitation energy-transfer from fucoxanthin to bacteriochlorophyll a when they are bound to the light-harvesting 1 apo-proteins.

Fiber-Coupled Diamond Micro-Waveguides toward an Efficient Quantum Interface for Spin Defect Centers.

We report the direct integration and efficient coupling of nitrogen vacancy (NV) color centers in diamond nanophotonic structures into a fiber-based photonic architecture at cryogenic temperatures. NV centers are embedded in diamond micro-waveguides (µWGs), which are coupled to fiber tapers. Fiber tapers have low-loss connection to single-mode optical fibers and hence enable efficient integration of NV centers into optical fiber networks. We numerically optimize the parameters of the µWG-fiber-taper devices designed particularly for use in cryogenic experiments, resulting in 35.6% coupling efficiency, and experimentally demonstrate cooling of these devices to the liquid helium temperature of 4.2 K without loss of the fiber transmission. We observe sharp zero-phonon lines in the fluorescence of NV centers through the pigtailed fibers at 100 K. The optimized devices with high photon coupling efficiency and the demonstration of cooling to cryogenic temperatures are an important step to realize fiber-based quantum nanophotonic interfaces using diamond spin defect centers.

Manipulation of single nanodiamonds to ultrathin fiber-taper nanofibers and control of NV-spin states toward fiber-integrated λ-systems.

We report on the coupling of single nitrogen vacancy (NV) centers to ultrathin fiber-taper nanofibers by the manipulation of single diamond nanocrystals on the nanofibers under real-time observation of nanodiamond fluorescence. Spin-dependent fluorescence of the single NV centers is efficiently detected through the nanofiber. We show control of the spin sub-level structure of the electronic ground state using an external magnetic field and clearly observe a frequency fine tuning of [Formula: see text]. This observation demonstrates a possibility of realizing fiber-integrated quantum λ-systems, which can be used for various quantum information devices including push-pull quantum memory and quantum gates.

Detailed numerical analysis of photon emission from a single light emitter coupled with a nanofiber Bragg cavity.

Coupling of a single dipole with a nanofiber Bragg cavity (NFBC) approximating an actually fabricated structure was numerically analyzed using three dimensional finite-difference time-domain simulations for different dipole positions. For the given model structure, the Purcell factor and coupling efficiency reached to 19.1 and 82%, respectively, when the dipole is placed outside the surface of the fiber. Interestingly, these values are very close to the highest values of 20.2 and 84% obtained for the case when the dipole was located inside the fiber at the center. The analysis performed in this study will be useful in improving the performance of single-photon emitter-related quantum devices using NFBCs.

Optical tracking of picosecond coherent phonon pulse focusing inside a sub-micron object.

By means of an ultrafast optical technique, we track focused gigahertz coherent phonon pulses in objects down to sub-micron in size. Infrared light pulses illuminating the surface of a single metal-coated silica fibre generate longitudinal-phonon wave packets. Reflection of visible probe light pulses from the fibre surface allows the vibrational modes of the fibre to be detected, and Brillouin optical scattering of partially transmitted light pulses allows the acoustic wavefronts inside the transparent fibre to be continuously monitored. We thereby probe acoustic focusing in the time domain resulting from generation at the curved fibre surface. An analytical model, supported by three-dimensional simulations, suggests that we have followed the focusing of the acoustic beam down to a ~150-nm diameter waist inside the fibre. This work significantly narrows the lateral resolution for focusing of picosecond acoustic pulses, normally limited by the diffraction limit of focused optical pulses to ~1 µm, and thereby opens up a new range of possibilities including nanoscale acoustic microscopy and nanoscale computed tomography.

Measuring the charge density of a tapered optical fiber using trapped microparticles.

We report the measurements of charge density of tapered optical fibers using charged particles confined in a linear Paul trap at ambient pressure. A tapered optical fiber is placed across the trap axis at a right angle, and polystyrene microparticles are trapped along the trap axis. The distance between the equilibrium position of a positively charged particle and the tapered fiber is used to estimate the amount of charge per unit length of the fiber without knowing the amount of charge of the trapped particle. The charge per unit length of a tapered fiber with a diameter of 1.6 µm was measured to be 2-1+3×10-11 C/m.

Ultrathin fiber-taper coupling with nitrogen vacancy centers in nanodiamonds at cryogenic temperatures.

We demonstrate cooling of ultrathin fiber tapers coupled with nitrogen vacancy (NV) centers in nanodiamonds to cryogenic temperatures. Nanodiamonds containing multiple NV centers are deposited on the subwavelength 480-nm-diameter nanofiber region of fiber tapers. The fiber tapers are successfully cooled to 9 K using our home-built mounting holder and an optimized cooling speed. The fluorescence from the nanodiamond NV centers is efficiently channeled into a single guided mode and shows characteristic sharp zero-phonon lines (ZPLs) of both neutral and negatively charged NV centers. The present nanofiber/nanodiamond hybrid systems at cryogenic temperatures can be used as NV-based quantum information devices and for highly sensitive nanoscale magnetometry in a cryogenic environment.

Highly efficient coupling of nanolight emitters to a ultra-wide tunable nanofibre cavity.

Solid-state microcavities combining ultra-small mode volume, wide-range resonance frequency tuning, as well as lossless coupling to a single mode fibre are integral tools for nanophotonics and quantum networks. We developed an integrated system providing all of these three indispensable properties. It consists of a nanofibre Bragg cavity (NFBC) with the mode volume of under 1 µm(3) and repeatable tuning capability over more than 20 nm at visible wavelengths. In order to demonstrate quantum light-matter interaction, we establish coupling of quantum dots to our tunable NFBC and achieve an emission enhancement by a factor of 2.7.

Numerical simulations of nanodiamond nitrogen-vacancy centers coupled with tapered optical fibers as hybrid quantum nanophotonic devices.

Tapered optical fibers are promising one-dimensional nanophotonic waveguides that can provide efficient coupling between their fundamental mode and quantum nanoemitters placed inside them. Here, we present numerical studies on the coupling of single nitrogen-vacancy (NV) centers (single point dipoles) in nanodiamonds with tapered fibers. Our results lead to two important conclusions: (1) A maximum coupling efficiency of 53.4% can be realized for the two fiber ends when the NV bare dipole is located at the center of the tapered fiber. (2) NV centers even in 100-nm-sized nanodiamonds where bulk-like optical properties were reported show a coupling efficiency of 22% at the taper surface, with the coupling efficiency monotonically decreasing as the nanodiamond size increases. These results will be helpful in guiding the development of hybrid quantum devices for applications in quantum information science.