Theoretical investigations on the laser isotope separation of 175Yb for medical applications.

The possibility of laser isotope separation of 175Yb from irradiated natural Yb has been investigated. The optimum process parameters such as powers and bandwidths of the lasers, Doppler broadening and the number density of the atoms have been derived through density matrix calculations. It has been shown that it is possible to produce 175Yb (>42% enriched) at a production rate of 62 µg/hour (or 1.5 mg/day). This corresponds to the production rate of 1350 patient doses (of 7.4 GBq each) per day. The radionuclidic purity of the isotopic mixture is expected to be 99.9999%. The method is highly suitable for the countries having only low-flux nuclear reactors.

A re-activation model for 169Yb intensity modulated brachytherapy sources accounting for spatiotemporal isotopic composition.

BACKGROUND: Intensity modulated brachytherapy based on partially shielded intracavitary and interstitial applicators is possible with a cost-effective 169Yb production method. 169Yb is a traditionally expensive isotope suitable for this purpose, with an average γ-ray energy of 93 keV. Re-activating a single 169Yb source multiple times in a nuclear reactor between clinical uses was shown to theoretically reduce cost by approximately 75% relative to conventional single-activation sources. With re-activation, substantial spatiotemporal variation in isotopic source composition is expected between activations via 168Yb burnup and 169Yb decay, resulting in time dependent neutron transmission, precursor usage, and reactor time needed per re-activation. PURPOSE: To introduce a generalized model of radioactive source production that accounts for spatiotemporal variation in isotopic source composition to improve the efficiency estimate of the 169Yb production process, with and without re-activation. METHODS AND MATERIALS: A time-dependent thermal neutron transport, isotope transmutation, and decay model was developed. Thermal neutron flux within partitioned sub-volumes of a cylindrical active source was calculated by raytracing through the spatiotemporal dependent isotopic composition throughout the source, accounting for thermal neutron attenuation along each ray. The model was benchmarked, generalized, and applied to a variety of active source dimensions with radii ranging from 0.4 to 1.0 mm, lengths from 2.5 to 10.5 mm, and volumes from 0.31 to 7.85 mm3, at thermal neutron fluxes from 1 × 1014 to 1 × 1015 n cm-2 s-1. The 168Yb-Yb2O3 density was 8.5 g cm-3 with 82% 168Yb-enrichment. As an example, a reference re-activatable 169Yb active source (RRS) constructed of 82%-enriched 168Yb-Yb2O3 precursor was modeled, with 0.6 mm diameter, 10.5 mm length, 3 mm3 volume, 8.5 g cm-3 density, and a thermal neutron activation flux of 4 × 1014 neutrons cm-2 s-1. RESULTS: The average clinical 169Yb activity for a 0.99 versus 0.31 mm3 source dropped from 20.1 to 7.5 Ci for a 4 × 1014 n cm-2 s-1 activation flux and from 20.9 to 8.7 Ci for a 1 × 1015 n cm-2 s-1 activation flux. For thermal neutron fluxes ≥2 × 1014 n cm-2 s-1, total precursor and reactor time per clinic-year were maximized at a source volume of 0.99 mm3 and reached a near minimum at 3 mm3. When the spatiotemporal isotopic composition effect was accounted for, average thermal neutron transmission increased over RRS lifetime from 23.6% to 55.9%. A 28% reduction (42.5 days to 30.6 days) in the reactor time needed per clinic-year for the RRS is predicted relative to a model that does not account for spatiotemporal isotopic composition effects. CONCLUSIONS: Accounting for spatiotemporal isotopic composition effects within the RRS results in a 28% reduction in the reactor time per clinic-year relative to the case in which such changes are not accounted for. Smaller volume sources had a disadvantage in that average clinical 169Yb activity decreased substantially below 20 Ci for source volumes under 1 mm3. Increasing source volume above 3 mm3 adds little value in precursor and reactor time savings and has a geometric disadvantage.

Enhancement of skin tumor laser hyperthermia with Ytterbium nanoparticles: numerical simulation.

Laser hyperthermia therapy (HT) has emerged as a well-established method for treating cancer, yet it poses unique challenges in comprehending heat transfer dynamics within both healthy and cancerous tissues due to their intricate nature. This study investigates laser HT therapy as a promising avenue for addressing skin cancer. Employing two distinct near-infrared (NIR) laser beams at 980 nm, we analyze temperature variations within tumors, employing Pennes' bioheat transfer equation as our fundamental investigative framework. Furthermore, our study delves into the influence of Ytterbium nanoparticles (YbNPs) on predicting temperature distributions in healthy and cancerous skin tissues. Our findings reveal that the application of YbNPs using a Gaussian beam shape results in a notable maximum temperature increase of 5 °C within the tumor compared to nanoparticle-free heating. Similarly, utilizing a flat top beam alongside YbNPs induces a temperature rise of 3 °C. While this research provides valuable insights into utilizing YbNPs with a Gaussian laser beam configuration for skin cancer treatment, a more thorough understanding could be attained through additional details on experimental parameters such as setup, exposure duration, and specific implications for skin cancer therapy.

Ytterbium 10-carboxyperylene-3,4,9-tricarboxylates for targeted NIR luminescent bioimaging.

Two new ytterbium coordination compounds Yb(HPTC)(H2O)2 (Yb1) and Yb(HPTC)(Phen) (Yb2) were obtained using 10-carboxyperylene-3,4,9-tricarboxylate ion (HPTC3-) as a sensitizer. Both coordination compounds exhibited intense NIR-II luminescence upon excitation in the visible range and formed stable suspensions with nanoparticles of 50-70 nm in size in an aqueous solution of sodium alginate. Both complexes demonstrated non-toxicity up to at least 25 mg L-1 in two cell cultures: cancer cells MCF7 and embryonic cells HEK293T - making them suitable for bioimaging. For both complexes, the accumulation in cells was directly measured and it was shown that the accumulation of Yb2 was the same for both cell types (0.51-0.52 πg per cell), while Yb1 demonstrated selective accumulation in cancer cells (0.04 πg per cell for HEK293T and 7.00 πg per cell for MCF7). Thus, Yb1 can also be proposed as a selective vis-excited NIR emitting bioprobe.

Brachytherapy at the nanoscale with protein functionalized and intrinsically radiolabeled [169Yb]Yb2O3 nanoseeds.

PURPOSE: Classical brachytherapy of solid malignant tumors is an invasive procedure which often results in an uneven dose distribution, while requiring surgical removal of sealed radioactive seed sources after a certain period of time. To circumvent these issues, we report the synthesis of intrinsically radiolabeled and gum Arabic glycoprotein functionalized [169Yb]Yb2O3 nanoseeds as a novel nanoscale brachytherapy agent, which could directly be administered via intratumoral injection for tumor therapy. METHODS: 169Yb (T½ = 32 days) was produced by neutron irradiation of enriched (15.2% in 168Yb) Yb2O3 target in a nuclear reactor, radiochemically converted to [169Yb]YbCl3 and used for nanoparticle (NP) synthesis. Intrinsically radiolabeled NP were synthesized by controlled hydrolysis of Yb3+ ions in gum Arabic glycoprotein medium. In vivo SPECT/CT imaging, autoradiography, and biodistribution studies were performed after intratumoral injection of radiolabeled NP in B16F10 tumor bearing C57BL/6 mice. Systematic tumor regression studies and histopathological analyses were performed to demonstrate therapeutic efficacy in the same mice model. RESULTS: The nanoformulation was a clear solution having high colloidal and radiochemical stability. Uniform distribution and retention of the radiolabeled nanoformulation in the tumor mass were observed via SPECT/CT imaging and autoradiography studies. In a tumor regression study, tumor growth was significantly arrested with different doses of radiolabeled NP compared to the control and the best treatment effect was observed with ~ 27.8 MBq dose. In histopathological analysis, loss of mitotic cells was apparent in tumor tissue of treated groups, whereas no significant damage in kidney, lungs, and liver tissue morphology was observed. CONCLUSIONS: These results hold promise for nanoscale brachytherapy to become a clinically practical treatment modality for unresectable solid cancers.

Enhancing biomarker detection sensitivity through tag-laser induced breakdown spectroscopy with NELIBS.

Nanoparticle-enhanced laser-induced breakdown spectroscopy and Tag-LIBS are two approaches that have been shown to significantly enhance LIBS sensitivity and specificity. In an effort to combine both of these approaches, we have initiated a study on the effect of the presence of Silver nanoparticle concentrations on Europium (Eu) and Ytterbium (Yb) LIBS signals. These elements are part of metal-loaded polymers conjugated to antibodies. We observe a signal enhancement of the emission lines of about 10 and 12 times for the Europium and Ytterbium lines. This study shows that Europium and Ytterbium are enhanced differently; Europium shows enhancement for both neutral and ionized species while the Ytterbium shows enhancement only for ionized species. Additionally, we found that NPs at 0.1 mg/mL and 0.05 mg/mL achieved maximum enhancement for Eu and Yb, respectively. Based on our findings, the temperature and electron density of Eu and Yb are not significantly different for NPs concentrations, but the total signal intensity is significantly higher for optimum NP concentrations for both Eu and Yb.

Radiopacity and physical properties evaluation of infiltrants with Barium and Ytterbium addition.

Radiopaque properties in the infiltrant should be interesting for clinicians to feel more confident to indicate this treatment. Thus, the aim of this study was to evaluate the effect of the incorporation of barium and ytterbium particles on the physical properties of resin infiltrants. Groups were divided according to the addition of ytterbium oxide (Y) alone (30 or 40%) or Y with barium (YB) (15/15% or 20/20% respectively) in the Icon commercial infiltrant and in the experimental infiltrant base. Digital radiography (n=5), Microradiography (n=5), Microtomography (n=3), degree of conversion (n=5), water sorption (n=16), solubility (n=16), contact angle (n=16), flexural strength (n=16), elastic modulus (n=16) and Energy dispersive X-ray Spectroscopy (n=10) were performed. Analyses were performed using the R program, with a significance level of 5%, and microradiography and Microtomography analyses were evaluated qualitatively. In groups with 30 or 40% of ytterbium, radiopacity was higher or equal to enamel. Microradiography and Microtomography appear to have more radiopacity in groups with 40% (Y). Among the groups with no particle addition, those of the experimental infiltrant presented a higher degree of conversion than those of Icon®. In most groups, there was solubility below the ISO-recommended levels. The addition of particles resulted in higher viscosity. Groups with Icon had higher flexural strength and elastic modulus than groups with experimental infiltrant. The addition of 40% (Y) improved polymerization, had low solubility, and had greater radiopacity than enamel, however negatively affected the viscosity increasing then. Experimental groups with the base showed a higher water sorption than Icon groups.

An efficient new method of ytterbium(III) triflate catalysis approach to the synthesis of substituted pyrroles: DFT, ADMET, and molecular docking investigations.

In this study, the one-pot synthetic methodology for the preparation of substituted pyrroles with diethyl acetylene-dicarboxylate is reported for the various pyrrole derivatives via the Trifimow synthesis process from oximes. This method also offers the literature as a cyclization pathway using a ytterbium triflate catalyst. Another importance of this study is the use of pyrrole derivatives in pharmaceuticals, biological processes, and agrochemicals. From this point of view, the development of a new catalyst in synthetic organic chemistry and the difference in the method is also important. The syntheses of the target substituted pyrroles are accomplished in high yields. Also, all synthesized structures were confirmed by 1H NMR, 13C NMR, and IR spectra. The DFT computations were leveraged for structural and spectroscopic validation of the compounds. Then, FMO and NBO analyses were subsequently employed to elucidate the reactivity characteristics and intramolecular interactions within these compounds. Also, ADMET indices were ascertained to assess potential pharmacokinetic properties, drug-like qualities, and possible adverse effects of these compounds. Last, optimized molecules were analyzed by molecular docking methods against crystal structures of Bovine Serum Albumin and Leukemia Inhibitory Factor, and their binding affinities, interaction details, and inhibition constants were determined.

Yb-Gd Codoped Hydroxyapatite as a Potential Contrast Agent for Tumor-Targeted Biomedical Applications.

Recently, various nanomaterials based on hydroxyapatite (HAp) have been developed for bioimaging applications. In particular, HAp doped with rare-earth elements has attracted significant attention, owing to its enhanced bioactivity and imaging properties. In this study, the wet precipitation method was used to synthesize HAp codoped with Yb and Gd. The synthesized Ybx-Gdx-HAp nanoparticles (NPs) were characterized via various techniques to analyze the crystal phase, functional groups, thermal characteristics, and particularly, the larger surface area. The IR783 fluorescence dye and a folic acid (FA) receptor were conjugated with the synthesized Ybx-Gdx-HAp NPs to develop an effective imaging contrast agent. The developed FA/IR783/Yb-Gd-HAp nanomaterial exhibited improved contrast, sensitivity, and tumor-specific properties, as demonstrated by using the customized LUX 4.0 fluorescence imaging system. An in vitro cytotoxicity study was performed to verify the biocompatibility of the synthesized NPs using MTT assay and fluorescence staining. Photodynamic therapy (PDT) was also applied to determine the photosensitizer properties of the synthesized Ybx-Gdx-HAp NPs. Further, reactive oxygen species generation was confirmed by Prussian blue decay and a 2',7'-dichlorofluorescin diacetate study. Moreover, MDA-MB-231 breast cancer cells were used to evaluate the efficiency of Ybx-Gdx-HAp NP-supported PDT.

Ultralow-quantum-defect single-frequency fiber laser.

A single-frequency distributed-Bragg-reflector fiber laser at 980 nm with a quantum defect of less than 0.6% was developed with a 1.5-cm 12 wt% ytterbium-doped phosphate fiber pumped by a 974.5-nm laser diode. Linearly polarized single-longitude-mode laser with a polarization extinction ratio (PER) of nearly 30 dB and spectral linewidth of less than 1.8 kHz was obtained. A maximum output power of 275 mW was measured at a launched pump power of 620 mW. The performance of the single-frequency fiber laser pumped at 909 nm and 976 nm was also characterized. This research demonstrated an approach to high-power single-frequency fiber laser oscillators with mitigated thermal effects.

Erbium-ytterbium containing upconversion mesoporous bioactive glass microspheres for tissue engineering: luminescence monitoring of biomineralization and drug release.

The development of functional biomaterials with real-time monitoring of mineralization processes, drug release and biodistribution has potential applications but remains an unsolved challenge. Herein, erbium- and ytterbium- containing mesoporous bioactive glass microspheres (MBGs:Er/Yb) with blue and red emission at an excitation wavelength of 980 nm were synthesized by a sol-gel combined with organic template method. As the concentration of Yb3+ ions gradually increases, the emission intensity of the MBGs:Er/Yb exhibits a clear concentration quenching effect. Combined with in vitro bioactivity tests, the optimal molar ratio of Er3+/Yb3+ was determined to be 4:3. Therefore, MBGs:4Er/3Yb was selected for in vitro biomineralization and drug release monitoring. The results of biomineralization monitoring show that the upconversion luminescence intensity is closely related to the degree of biomineralization. The upconversion luminescence intensity of MBGs:4Er/3Yb is quenched with the increase of the degree of biomineralization. The degree of luminescence quenching during biomineralization can be semiquantized. Drug release monitoring experiments showed that the anticancer drug doxorubicin hydrochloride (DOX) was successfully loaded into MBGs:4Er/3Yb and selectively quenched the green emission. When DOX was released, the green emission recovered stably, and It/I0 increased gradually. Moreover, there was a linear relationship between It/I0 and cumulative drug release, indicating that DOX-MBGs:4Er/3Yb is highly sensitive to DOX release, and monitoring the It/I0 values of DOX-MBGs:4Er/3Yb can achieve real-time tracking of the DOX release process to a certain extent. In conclusion, MBGs:4Er/3Yb has potential application as an upconversion luminescence biomonitoring material in the field of bone tissue engineering. STATEMENT OF SIGNIFICANCE: Mesoporous bioactive glasses have great potential for applications in bone tissue repair due to their excellent biological properties, but the effective information of the repair process cannot be grasped in a timely manner. Therefore, real-time monitoring of mineralization and drug release processes will be beneficial to obtain the degree of healing and optimize the amount and distribution of drugs to improve targeted therapeutic effects. For biomaterials, in vitro biological properties determine their biological properties in vivo, where the environment is more complex and diverse, and thus in vitro biomonitoring is particularly crucial. The organic combination of physical properties and biological properties will also provide a feasible idea for the development of biomaterials.

A Linearly Polarized Wavelength-Tunable Q-Switched Fiber Laser with a Narrow Spectral Bandwidth of 112 MHz.

A tunable and narrow-bandwidth Q-switched ytterbium-doped fiber (YDF) laser is investigated in this paper. The non-pumped YDF acts as a saturable absorber and, together with a Sagnac loop mirror, provides a dynamic spectral-filtering grating to achieve a narrow-linewidth Q-switched output. By adjusting an etalon-based tunable fiber filter, a tunable wavelength from 1027 nm to 1033 nm is obtained. When the pump power is 1.75 W, the Q-switched laser pulses with a pulse energy of 10.45 nJ, and a repetition frequency of 11.98 kHz and spectral linewidth of 112 MHz are obtained. This work paves the way for the generation narrow-linewidth Q-switched lasers with tunable wavelengths in conventional ytterbium, erbium, and thulium fiber bands to address critical applications such as coherent detection, biomedicine, and nonlinear frequency conversion.

On-chip erbium-ytterbium-co-doped lithium niobate microdisk laser with an ultralow threshold.

Erbium-ion-doped lithium niobate (LN) microcavity lasers working in the communication band have attracted extensive attention recently. However, their conversion efficiencies and laser thresholds still have significant room to improve. Here, we prepared microdisk cavities based on erbium-ytterbium-co-doped LN thin film by using ultraviolet lithography, argon ion etching, and a chemical-mechanical polishing process. Benefiting from the erbium-ytterbium co-doping-induced gain coefficient improvement, laser emission with an ultralow threshold (∼1 µW) and high conversion efficiency (1.8 × 10-3%) was observed in the fabricated microdisks under a 980-nm-band optical pump. This study provides an effective reference for improving the performance of LN thin-film lasers.

Many-body correlations in one-dimensional optical lattices with alkaline-earth(-like) atoms.

We explore the rich nature of correlations in the ground state of ultracold atoms trapped in state-dependent optical lattices. In particular, we consider interacting fermionic ytterbium or strontium atoms, realizing a two-orbital Hubbard model with two spin components. We analyze the model in one-dimensional setting with the experimentally relevant hierarchy of tunneling and interaction amplitudes by means of exact diagonalization and matrix product states approaches, and study the correlation functions in density, spin, and orbital sectors as functions of variable densities of atoms in the ground and metastable excited states. We show that in certain ranges of densities these atomic systems demonstrate strong density-wave, ferro- and antiferromagnetic, as well as antiferroorbital correlations.

A Novel Near-Infrared Ytterbium Complex [Yb(DPPDA)2](DIPEA) with Φ = 0.46% and τobs = 105 µs.

The luminescent performances of near-infrared (NIR) lanthanide (Ln) complexes were restricted greatly by vibration quenching of X-H (X = C, N, O) oscillators, which are usually contained in ligands and solvents. Encapsulating Ln3+ into a cavity of coordination atoms is a feasible method of alleviating this quenching effect. In this work, a novel ytterbium complex [Yb(DPPDA)2](DIPEA) coordinated with 4,7-diphenyl-1,10-phenanthroline-2,9-dicarboxylic acid (DPPDA) was synthesized and characterized by FT-IR, ESI-MS and elemental analysis. Under the excitation of 335 nm light, [Yb(DPPDA)2](DIPEA) showed two emission peaks at 975 and 1011 nm, respectively, which were assigned to the characteristic 2F5/2 → 2F7/2 transition of Yb3+. Meanwhile, this ytterbium complex exhibited a plausible absolute quantum yield of 0.46% and a luminescent lifetime of 105 µs in CD3OD solution. In particular, its intrinsic quantum yield was calculated to be 12.5%, and this considerably high value was attributed to the near-zero solvent molecules bound to Yb3+ and the absence of X-H oscillators in the first coordination sphere. Based on experimental results, we further proposed that the sensitized luminescence of [Yb(DPPDA)2](DIPEA) occurred via an internal redox mechanism instead of an energy transfer process.

Domino synthesis of 5-aminoimidazoles from Strecker multicomponent adducts via ytterbium-promoted isocyanide insertion/5-exo-dig cyclization.

A new Lewis acid promoted domino isocyanide insertion/5-exo-dig cyclization of readily available Strecker 3-component adducts to 4-substituted 5-aminoimidazole derivatives is herein reported. Despite their potential as relevant heterocyclic scaffolds in medicinal chemistry programs, this class of compounds is still underrepresented, with current synthetic strategies poorly efficient in terms of timing and yields. To this end, we show how the exploitation of unconventional reactivities of isocyanides, promoted by ytterbium-triflate, could represent a key resource to enable a fast and easy access to such an unexplored area of the chemical space.

Construction of a Near-Infrared Luminescent 48-Metal Rectangular Zn(II)-Yb(III) Nanocluster with Carbonate Templates for the Dual-Emissive Detection of Rutin as a Medicinal Ingredient.

An interesting 48-metal Zn(II)-Yb(III) nanocluster (1) with a size of about 1.3 × 2.8 × 3.1 nm was constructed by carbonate templates from a Schiff base ligand. It exhibits ligand-centered emission and near-infrared (NIR) luminescence of Yb(III), which are used in the dual-emissive detection of rutin (Rut) with high sensitivity even in the presence of other interferences. The response behavior can be expressed by the second-order equation I980 nm/I510 nm = A*[Rut]2 + B*[Rut] + C, and the limits of detection to Rut for the emissions of 1 are 2.23 µM and 0.20 nM.

In-Line Mach Zehnder Interferometer Based on Ytterbium Doped Fiber with Up-Taper Structure in Fiber Ring Laser and Its Application in Sensing.

We report an ytterbium (Yb) doped fiber Mach Zehnder interferometer (MZI) based on the up-taper fiber structure in a fiber ring laser (FRL) cavity. Different from the traditional FRL sensing system, in which additional filters are required, the designed structure simultaneously acts as a filter, sensor and gain medium. Furthermore, thanks to the high thermal-optical coefficient of Yb doped fiber, the temperature sensitivity of 0.261 nm/°C can be achieved in the range of 10-50 °C. In addition, benefiting from the unique characteristics of the laser system itself, the designed structure has a narrower linewidth (-0.2 nm) and a higher signal-to-noise ratio (SNR) (-40 dB) than the sensor system based on a broadband light source (BBS). Meanwhile, the refractive index (RI) response and stability of the system are measured. The RI sensitivity is up to 151 nm/RIU, and the wavelength fluctuation range within two hours is less than 0.2 nm. Therefore, the designed structure is expected to play a significant role in human life safety monitoring, aircraft engine temperature monitoring, etc.

Comparative study of upconversion and photoacoustic measurements of Er3+/Yb3+doped La2O3phosphor under 980 nm.

The Er3+/Yb3+doped La2O3phosphor samples were synthesized by the combustion method and then photoluminescence and photoacoustic spectroscopic studies were done. Prepared samples were annealed at 800 °C, 1000 °C and 1300 °C and all samples were found in pure hexagonal phase as confirmed by XRD analysis. From FE-SEM images it is found that particle size increases with increase in annealing temperature. The frequency upconversion emission spectra of samples were recorded by exciting the sample with 980 nm diode laser and maximum emission intensity is obtained for the sample annealed at 1000 °C for 2 h. A photoacoustic cell was designed and wavelength dependent photoacoustic spectra were measured. The effect of sample storage time on radiative and non-radiative emission properties of sample was checked by measuring upconversion emission and photoacoustic spectra, simultaneously. It is observed that the emission intensity and photoacoustic signal both decreases with time. The maximum photoacoustic signal is obtained around 974 nm wavelength and it indicates its potential for photo-thermal therapy using infrared excitation.

Fingerprint multiplex CARS at high speed based on supercontinuum generation in bulk media and deep learning spectral denoising.

We introduce a broadband coherent anti-Stokes Raman scattering (CARS) microscope based on a 2-MHz repetition rate ytterbium laser generating 1035-nm high-energy (≈µJ level) femtosecond pulses. These features of the driving laser allow producing broadband red-shifted Stokes pulses, covering the whole fingerprint region (400-1800 cm-1), employing supercontinuum generation in a bulk crystal. Our system reaches state-of-the-art acquisition speed (<1 ms/pixel) and unprecedented sensitivity of ≈14.1 mmol/L when detecting dimethyl sulfoxide in water. To further improve the performance of the system and to enhance the signal-to-noise ratio of the CARS spectra, we designed a convolutional neural network for spectral denoising, coupled with a post-processing pipeline to distinguish different chemical species of biological tissues.