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Phototherapy is a powerful, noninvasive approach for cancer treatment, with several agents currently in clinical use. Despite the progress and promise, most current phototherapy agents have serious side effects as they can lead to damage to healthy tissue, even when the photosensitizers are fused to targeting molecules due to nonspecific light activation of the unbound photosensitizer. To overcome these limitations, we developed a phototherapy agent that combines a functional ligand and a near infrared phthalocyanine dye. Our target is type 2 cannabinoid receptor (CB2R), considered an attractive therapeutic target for phototherapy given it is overexpressed by many types of cancers that are located at a surface or can be reached by an endoscope. We show that our CB2R-targeted phototherapy agent, IR700DX-mbc94, is specific for CB2R and effective only when bound to the target receptor. Overall, this opens up the opportunity for development of an alternative treatment option for CB2R-positive cancers.
Copyright © 2014 Elsevier Ltd. All rights reserved.
A porous silicon (PSi) grating-coupled Bloch surface and sub-surface wave (BSW/BSSW) biosensor is demonstrated to size selectively detect the presence of both large and small molecules. The BSW is used to sense large immobilized analytes at the surface of the structure while the BSSW that is confined inside but near the top of the structure is used to sensitively detect small molecules. Functionality of the BSW and BSSW modes is theoretically described by dispersion relations, field confinements, and simulated refractive index shifts within the structure. The theoretical results are experimentally verified by detecting two different small chemical molecules and one large 40 base DNA oligonucleotide. The PSi-BSW/BSSW structure is benchmarked against current porous silicon technology and is shown to have a 6-fold higher sensitivity in detecting large molecules and a 33% improvement in detecting small molecules. This is the first report of a grating-coupled BSW biosensor and the first report of a BSSW propagating mode.
© 2013 Published by Elsevier B.V.
Release of neurotransmitters and hormones by calcium-regulated exocytosis is a fundamental cellular process that is disrupted in a variety of psychiatric, neurological, and endocrine disorders. As such, there is significant interest in targeting neurosecretion for drug and therapeutic development, efforts that will be aided by novel analytical tools and devices that provide mechanistic insight coupled with increased experimental throughput. Here, we report a simple, inexpensive, reusable, microfluidic device designed to analyze catecholamine secretion from small populations of adrenal chromaffin cells in real time, an important neuroendocrine component of the sympathetic nervous system and versatile neurosecretory model. The device is fabricated by replica molding of polydimethylsiloxane (PDMS) using patterned photoresist on silicon wafer as the master. Microfluidic inlet channels lead to an array of U-shaped "cell traps", each capable of immobilizing single or small groups of chromaffin cells. The bottom of the device is a glass slide with patterned thin film platinum electrodes used for electrochemical detection of catecholamines in real time. We demonstrate reliable loading of the device with small populations of chromaffin cells, and perfusion/repetitive stimulation with physiologically relevant secretagogues (carbachol, PACAP, KCl) using the microfluidic network. Evoked catecholamine secretion was reproducible over multiple rounds of stimulation, and graded as expected to different concentrations of secretagogue or removal of extracellular calcium. Overall, we show this microfluidic device can be used to implement complex stimulation paradigms and analyze the amount and kinetics of catecholamine secretion from small populations of neuroendocrine cells in real time.
Due to the presence of PCR inhibitors, PCR cannot be used directly on most clinical samples, including human urine, without pre-treatment. A magnetic bead-based strategy is one potential method to collect biomarkers from urine samples and separate the biomarkers from PCR inhibitors. In this report, a 1 mL urine sample was mixed within the bulb of a transfer pipette containing lyophilized nucleic acid-silica adsorption buffer and silica-coated magnetic beads. After mixing, the sample was transferred from the pipette bulb to a small diameter tube, and captured biomarkers were concentrated using magnetic entrainment of beads through pre-arrayed wash solutions separated by small air gaps. Feasibility was tested using synthetic segments of the 140 bp tuberculosis IS6110 DNA sequence spiked into pooled human urine samples. DNA recovery was evaluated by qPCR. Despite the presence of spiked DNA, no DNA was detectable in unextracted urine samples, presumably due to the presence of PCR inhibitors. However, following extraction with the magnetic bead-based method, we found that ∼50% of spiked TB DNA was recovered from human urine containing roughly 5×10(3) to 5×10(8) copies of IS6110 DNA. In addition, the DNA was concentrated approximately ten-fold into water. The final concentration of DNA in the eluate was 5×10(6), 14×10(6), and 8×10(6) copies/µL for 1, 3, and 5 mL urine samples, respectively. Lyophilized and freshly prepared reagents within the transfer pipette produced similar results, suggesting that long-term storage without refrigeration is possible. DNA recovery increased with the length of the spiked DNA segments from 10±0.9% for a 75 bp DNA sequence to 42±4% for a 100 bp segment and 58±9% for a 140 bp segment. The estimated LOD was 77 copies of DNA/µL of urine. The strategy presented here provides a simple means to achieve high nucleic acid recovery from easily obtained urine samples, which does not contain inhibitors of PCR.
The Cosmetic Ingredient Review (CIR) Expert Panel assessed the safety of silica silylate, silica dimethyl silylate, trimethylsiloxysilicate, and trifluoropropyldimethyl/trimethylsiloxysilicate as used in cosmetics. These silylates and surface-modified siloxysilicates function in cosmetics as antifoaming agents, anticaking agents, bulking agents, binders, skin-conditioning agents--emollient, skin-conditioning agents-occlusive, slip modifiers, suspension agents--nonsurfactant, and viscosity increasing agents--nonaqueous. The Expert Panel reviewed the available animal and clinical data as well as information from a previous CIR safety assessment of amorphous silica. The CIR Expert Panel concluded that silica silylate, silica dimethyl silylate, trimethylsiloxysilicate, and trifluoropropyldimethyl/trimethylsiloxysilicate are safe as used when formulated and delivered in the final product not to be irritating or sensitizing to the respiratory tract.
Vanadium dioxide (VO(2)) is a promising reconfigurable optical material and has long been a focus of condensed matter research owing to its distinctive semiconductor-to-metal phase transition (SMT), a feature that has stimulated recent development of thermally reconfigurable photonic, plasmonic, and metamaterial structures. Here, we integrate VO(2) onto silicon photonic devices and demonstrate all-optical switching and reconfiguration of ultra-compact broadband Si-VO(2) absorption modulators (L < 1 μm) and ring-resonators (R ~ λ(0)). Optically inducing the SMT in a small, ~0.275 μm(2), active area of polycrystalline VO(2) enables Si-VO(2) structures to achieve record values of absorption modulation, ~4 dB μm(-1), and intracavity phase modulation, ~π/5 rad μm(-1). This in turn yields large, tunable changes to resonant wavelength,
~ 3 nm, approximately 60 times larger than Si-only control devices, and enables reconfigurable filtering and optical modulation in excess of 7 dB from modest Q-factor (~10(3)), high-bandwidth ring resonators (>100 GHz). All-optical integrated Si-VO(2) devices thus constitute platforms for reconfigurable photonics, bringing new opportunities to realize dynamic on-chip networks and ultrafast optical shutters and modulators.
Understanding cellular interactions with culture substrate features is important to advance cell biology and regenerative medicine. When surface topographical features are considerably larger in vertical dimension and are spaced at least one cell dimension apart, the features act as 3D physical barriers that can guide cell adhesion, thereby altering cell behavior. In the present study, we investigated competitive interactions of cells with neighboring cells and matrix using a novel nanoneedle gradient array. A gradient array of nanoholes was patterned at the surface of fused silica by single-pulse femtosecond laser machining. A negative replica of the pattern was extracted by nanoimprinting with a thin film of polymer. Silica was deposited on top of the polymer replica to form silica nanoneedles. NIH 3T3 fibroblasts were cultured on silica nanoneedles and their behavior was studied and compared with those cultured on a flat silica surface. The presence of silica nanoneedles was found to enhance the adhesion of fibroblasts while maintaining cell viability. The anisotropy in the arrangement of silica nanoneedles was found to affect the morphology and spreading of fibroblasts. Additionally, variations in nanoneedle spacing regulated cell-matrix and cell-cell interactions, effectively preventing cell aggregation in areas of tightly-packed nanoneedles. This proof-of-concept study provides a reproducible means for controlling competitive cell adhesion events and offers a novel system whose properties can be manipulated to intimately control cell behavior.
Copyright © 2012 Elsevier B.V. All rights reserved.
Tuning the Fermi energy of silicon through doping leads to alignment of silicon bands with the redox active sites of photosystem I. Integrating photosystem I films with p-doped silicon results in the highest reported photocurrent enhancement for a biohybrid electrode based on photosystem I.
Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
An integrated silicon photonics coupler for fiber to waveguide conversion was designed employing a transformation optics approach. Quasi-conformal mapping was used to obtain achievable material properties, which were realized by a distorted hexagonal lattice of air holes in silicon. The coupler, measuring only 10 μm in length and fabricated with a single-step lithography process, exhibits a peak simulated transmission efficiency of nearly 100% for in-plane mode conversion and a factor of 5 improvement over butt coupling for fiber to waveguide mode conversion in experimental testing.
Time-dependent laser reflectometry measurements are presented as a means to rigorously characterize analyte diffusion dynamics of small molecules from mesoporous silicon (PSi) films for drug delivery and membrane physics applications. Calculations based on inclusion of a spatially and temporally dependent solute concentration profile in a one-dimensional Fickian diffusion flow model are performed to determine the diffusion coefficients for the selected prototypical polar species, sucrose (340 Da), exiting from PSi films. The diffusion properties of the molecules depend on both PSi pore size and film thickness. For films with average pore diameters between 10-30 nm and film thicknesses between 300-900 nm, the sucrose diffusion coefficient can be tuned between approximately 100 and 550 μm2/s. Extensions of the real-time measurement and modeling approach for determining the diffusivity of small molecules that strongly interact with and corrode the internal surfaces of PSi films are also discussed.