Channa R. De Silva

Lanthanide(III)-Doped Magnetite Nanoparticles

Nearly monodisperse lanthanide-doped magnetite nanoparticles were obtained by thermally decomposing a mixture of Fe(acac)(3) and Ln(acac)(3) (acac = acetylacetonate; Ln = Sm, Eu, Gd) in the presence of passivating surfactants. Magnetic studies revealed room-temperature ferromagnetic behaviors of these doped nanoparticles, distinctly different from those of the undoped parent magnetite or the doped nanoparticles prepared by a coprecipitation method.

Control of green and red upconversion in NaYF4:Yb3+,Er3+ nanoparticles by excitation modulation

Control of the two strongest upconversion emission lines in NaYF4:Yb3+, Er3+ nanoparticles is demonstrated by varying the excitation repetition rate. This technique may enable new multiplexed sensing modalities based on multicolor luminescent nanoparticles, currently contemplated for biomedical imaging and diagnostics.

Development of melanoma-targeted polymer micelles by conjugation of a melanocortin 1 receptor (MC1R) specific ligand.

The incidence of malignant melanoma is rising faster than that of any other cancer in the United States. Because of its high expression on the surface of melanomas, MC1R has been investigated as a target for selective imaging and therapeutic agents against melanoma. Eight ligands were screened against cell lines engineered to overexpress MC1R, MC4R, or MC5R. Of these, compound 1 (4-phenylbutyryl-His-dPhe-Arg-Trp-NH(2)) exhibited high (0.2 nM) binding affinity for MC1R and low (high nanomolar) affinities for MC4R and MC5R. Functionalization of the ligand at the C-terminus with an alkyne for use in Cu-catalyzed click chemistry was shown not to affect the binding affinity. Finally, formation of the targeted polymer, as well as the targeted micelle formulation, also resulted in constructs with low nanomolar binding affinity.

Fluorescent and Lanthanide Labeling for Ligand Screens, Assays, and Imaging

The use of fluorescent (or luminescent) and metal contrast agents in high-throughput screens, in vitro assays, and molecular imaging procedures has rapidly expanded in recent years. Here we describe the development and utility of high-affinity ligands for cancer theranostics and other in vitro screening -studies. In this context, we also illustrate the syntheses and use of heteromultivalent ligands as targeted imaging agents.

Optimization of time-resolved fluorescence assay for detection of europium-tetraazacyclododecyltetraacetic acid-labeled ligand-receptor interactions

Lanthanide-based luminescent ligand binding assays are superior to traditional radiolabel assays due to improving sensitivity and affordability in high-throughput screening while eliminating the use of radioactivity. Despite significant progress using lanthanide(III)-coordinated chelators such as diethylenetriaminepentaacetic acid (DTPA) derivatives, dissociation-enhanced lanthanide fluoroimmunoassays (DELFIAs) have not yet been successfully used with more stable chelators (e.g., tetraazacyclododecyltetraacetic acid [DOTA] derivatives) due to the incomplete release of lanthanide(III) ions from the complex. Here a modified and optimized DELFIA procedure incorporating an acid treatment protocol is introduced for use with Eu(III)-DOTA-labeled peptides. Complete release of Eu(III) ions from DOTA-labeled ligands was observed using hydrochloric acid (2.0M) prior to the luminescent enhancement step. [Nle(4),d-Phe(7)]-alpha-melanocyte-stimulating hormone (NDP-alpha-MSH) labeled with Eu(III)-DOTA was synthesized, and the binding affinity to cells overexpressing the human melanocortin-4 (hMC4) receptor was evaluated using the modified protocol. Binding data indicate that the Eu(III)-DOTA-linked peptide bound to these cells with an affinity similar to its DTPA analogue. The modified DELFIA procedure was further used to monitor the binding of an Eu(III)-DOTA-labeled heterobivalent peptide to the cells expressing both hMC4 and cholecystokinin-2 (CCK-2) receptors. The modified assay provides superior results and is appropriate for high-throughput screening of ligand libraries.

A hybrid sol-gel reverse-mesa waveguide using lanthanide phosphate nanoparticles for optical amplification

Organic-inorganic hybrid sol-gel materials have been widely used for the fabrication of optoelectronic devices due to advantages such as low cost, low loss, low temperature fabrication, ease of processing, good thermal and mechanical stability, and large refractive index tunability. However, the residual OH-like groups remaining after low temperature treatment have hindered the development of the erbium doped waveguide amplifiers working at ~1550 nm. A variety of means have been adopted to overcome this problem: (1) low vibration energy deuterated or fluorinated polymers have been applied as matrix materials; (2) erbium ions have been incorporated into organic or inorganic complexes for protection and the ligands of the complexes have been further modified to reduce the vibrational energy or increase the pump energy transfer efficiency; and (3) the erbium ions have been shielded in inorganic nanoparticles or other micro-structures. Doping erbium ions along with ytterbium ions to increase the pumping efficiency in lanthanum phosphate nanoparticles appears to be a very promising approach since (i) the emission lifetime is fairly long; (ii) at ~1550 nm the nanoparticles are transparent and have a refractive index very close to that of standard optical fiber; and (iii) the nanoparticles are highly dispersible in most organic media. Here we demonstrate how Er3+/Yb3+ containing lanthanum phosphate nanoparticles dispersed in an organically modified sol-gel can be used in a reverse mesa waveguide to achieve optical signal enhancement. Er3+/Yb3+ containing lanthanum phosphate nanoparticles have been synthesized with a molar ratio of La:Yb:Er = 76:21:3 and dispersed in cyclopentanone with 30wt% hydrolyzed MAPTMS. The composite has been incorporated into a 4mm reverse mesa waveguide prepared using an organic-inorganic hybrid sol-gel material based on MAPTMS and zirconium n-propoxide. An optical signal enhancement of ~2 dB/cm at 1527 nm has been obtained using a 200 mW 980 nm pump laser. Modeling analyses have shown that the overall performance can be further improved. The results indicate that such hybrid sol-gel reverse mesa waveguides using Er3+/Yb3+ containing lanthanum phosphate nanoparticles are very promising for optical amplifiers in integrated optical systems.

Intrinsic Electronic Transitions of the Absorption Spectrum of (OPy)2Ti(TAP)2: Implications Toward Photostructural Modifications

Theoretical calculations based on time-dependent density functional theory are used to characterize the electronic absorption spectrum of a heteroleptic Ti-alkoxide molecule, (OPy)(2)Ti(TAP)(2) [OPy = pyridine carbinoxide, TAP = 2,4,6 tris(dimethylamino)phenoxide] under investigation as a photosensitive precursor for use in optically initiated solution synthesis of the metal oxide. Computational results support the assignment of UV absorption features observed in solid-state precursor films to key intrinsic ground-state transitions that involve ligand-to-metal charge transfer and pi-pi* transitions within the cyclic ligand moieties present. The nature of electron density redistribution associated with these transitions provides early insight into the excitation wavelength dependence of photostructural modification previously observed in this precursor system.

Lanthanide nanoparticle doped low-loss sol-gel amplifier materials

Organic-inorganic hybrid sol-gel materials have attracted increasing attention in recent years as low-cost, rugged materials for integrated optical devices such as optical couplers, splitters, and electro-optic modulators. These materials can be easily processed by spin-coating, wet-etching photolithography, and low-temperature baking. Precise control of waveguide core-cladding refractive indices produces well-confined low-loss propagation and good matching of the absolute refractive index to that of fused silica results in low optical coupling loss to optical fiber. The increased thermal and mechanical stability of these materials, relative to optical polymers, results in numerous packaging options and improved reliability. However organic-inorganic hybrid sol-gel materials have not yet been often used as host of active dopants such as erbium (III) ions for 1550nm optical amplification. This limitation owes primarily to matrix and chelate dominated nonradiative relaxation processes, as high phonon energy OH and OH-like oscillators can bridge off the energy from the excited erbium (III) ions at very high rates. Different strategies have been proposed to protect erbium (III) ions from matrix and chelate quenching, including host and ligand fluorination, and inorganic microstructure shielding. Here we report on our work of encapsulating erbium (III) ions in transparent, refractive index matched, and highly re-dispersible lanthanum phosphate nanoparticles and the work of examining the optical properties of these nanoparticles as active dopants in organic-inorganic hybrid sol-gels adopting 2-methacryloxypropyl trimethoxysilane (MAPTMS) as a precursor. 980nm laser pumped photoluminescence at 1535nm was obtained from solid bulk samples of 300mg La.99Er.01PO4 nanoparticles doped in 1mL hybrid sol-gel. Thick bulk samples of this composition exhibited exceptional clarity and little trace of nanoparticle scattering effects. The lifetime of the nanoparticle doped hybrid sol-gel composite was measured to be 220μs, indicating an intermediate relaxation rate between that of an erbium organic complex and annealed erbium doped glass. La.99Er.01PO4 nanoparticle doped hybrid sol-gel films were also prepared and the refractive index was measured to be 1.4966 at 1550nm, which is very close to that of optical fiber and provides a suitable index difference from an undoped and metal oxide tuned sol-gel at 1.4870 to comprise an efficient single-mode waveguide system.