Differentially Selective Chemosensor with Fluorescence Off-On Responses on Cu2+ and Zn2+ Ions in Aqueous Media and Applications in Pyrophosphate Sensing, Live Cell Imaging, and Cytotoxicity

A new benzoyl hydrazone based chemosensor R is synthesized by Schiff base condensation of 2,6-diformyl-4-methylphenol and phenyl carbohydrazide and acts as a highly selective fluorescence sensor for Cu2+ and Zn2+ ions in aqueous media. The reaction of R with CuCl2 or ZnCl2 forms the corresponding dimeric dicopper(II) Cu-2(R)(CH3O)-(NO3)](2)(CH3O)(2) (R-Cu2+) and dizinc(1) Zn-2(R)(2)](NO3)(2) (R-Zn2+) complexes, which are characterized, as R, by conventional techniques including single-crystal X-ray analysis. Electronic absorption and fluorescence titration studies of R with different metal cations in a CH3CN/0.02 M HEPES buffer medium (pH = 7.3) show a highly selective binding affinity only toward Cu(2+)and Zn2+ ions even in the presence of other commonly coexisting ions such as Ne+, K+, Mg2+, Ca2+, Mn2+, Fe2+, Fe3+, Co2+, Ni2+, Cd2+, and Hg2+. Quantification of the fluorescence titration analysis shows that the chemosensor R can indicate the presence of Cu2+ and Zn2+ even at very low concentrations of 17.3 and 16.5 ppb, respectively. R-Zn2+ acts as a selective metal-based fluorescent sensor for inorganic pyrophosphate ion (PPi) even in the presence of other common anions such as F-, Cl-, Br-, I-, CH3COO-, CO32-, HCO3-, N-3(-), SO42-, PPi, AMP, ADP, and ATP in an aqueous medium. The propensity of R as a bioimaging fluorescent probe to detect Cu2+ and Zn2+ ions in human cervical HeLa cancer cell lines and their cytotoxicity against human cervical (HeLa), breast cancer (MCF7), and noncancer breast epithelial (MCF10a) cells have also been investigated. R-Cu2+ shows better cytotoxicity and sensitivity toward cancer cells over noncancer cells than R and R-Zn2+ under identical conditions, with the appearance of apoptotic bodies.

A Probe for the Selective and Parts-per-Billion-Level Detection of Copper(II) and Mercury(II) using a Micellar Medium and Its Utility in Cell Imaging

A novel colorimetric probe 1 based on the picolyl moiety has been designed and synthesized. Probe 1 is composed of a pyrene and a bispicolyl amine (BPA) unit, in which the BPA moiety acts as a binding unit and the binding phenomenon is sensed from the changes in the signaling subunit. The probe detects Cu2+ specifically in water and both Cu2+ and Hg2+ efficiently in neutral Brij-58 micellar media. The probe shows a color change visible to the naked eye upon addition of metal ions. Notably, in a micellar medium, probe 1 can detect both the Cu2+ and Hg2+ ions even at parts-per-billion levels. Furthermore, the probe shows ratiometric detection of both the metal ions making the sensing quantitative. The two metal ions could be discriminated both visibly under a UV lamp and with the use of fluorescence spectroscopy. The probe could be also used in biological cell lines for the detection of both Hg2+ and Cu2+ ions.

Oxovanadium(IV) complexes of curcumin for cellular imaging and mitochondria targeted photocytotoxicity

Oxovanadium(IV) complexes VO(R-tpy)(cur)](ClO4) (1, 2) of curcumin (Hcur) and terpyridine ligands (R-tpy) where R is phenyl (phtpy in 1) or p-triphenylphosphonium methylphenyl bromide (C6H4CH2PPh3Br) (TPP-phtpy in 2) were prepared and characterized and their DNA photocleavage activity, photocytotoxicity and cellular localization in cancer cells (HeLa and MCF-7) were studied. Acetylacetonate (acac) complexes VO(R-tpy)(acac)](ClO4) of phtpy (3) and TPP-phtpy (4) were prepared and used as the control species. These complexes showed efficient cleavage of pUC19 DNA in visible light of 454 nm and near-IR light of 705 rim. Complexes 1 and 2 showed significant photocytotoxicity in visible light of 400-700 nm. FACS analysis showed sub-G1/G0 phase cell-cycle arrest in cancer cells when treated with 1 and 2 in visible light in comparison with the dark controls. Fluorescence microscopic studies revealed specific localization of the p-triphenylphosphonium complex 2 in the mitochondria of MCF-7 cancer cells whereas no such specificity was observed for complex 1.

Oxovanadium(IV) catecholates of terpyridine bases for cellular imaging and photocytotoxicity in red light

Oxovanadium(IV) catecholates of terpyridyl bases, viz. VO(cat)(L)] (L - phtpy, 1; stpy, 2) and VO(dopa-NBD)(L)] (L = phtpy, 3; stpy, 4), where cat is benzene-1,2-diolate, dopa-NBD is 4-(2-(4-nitrobenzoc]1,2,5]oxadiazol-7-ylamino)ethyl)benzene-1,2-di olate, phtpy is (4'-phenyl)-2,2':6',2 `'-terpyridine and stpy is (2,2':6',2 `'-terpyridin-4'-oxy)ethyl-beta-D-glucopyranoside, were prepared and characterized, and their DNA binding, DNA photo-cleavage activity, photocytotoxicity in red light (600-720 nm), cellular uptake and intracellular localization behaviour were studied. The complexes showed an intense ligand-to-metal charge transfer (LMCT) band at similar to 500 nm. The sugar appended complexes 2 and 4 showed significant uptake into the cancer cells. The dopa-NBD complexes 3 and 4 showing green emission were used for cellular imaging. The complexes showed diffused cellular localization mainly in the cytosol and to a lesser extent into the nucleus as evidenced from the confocal microscopy study. Complexes 1-4 showed significant photocytotoxicity in the PDT spectral window giving low IC50 values, while remaining relatively non-toxic in dark.

Real-time magnetic resonance imaging and electromagnetic articulography database for speech production research (TC)

USC-TIMIT is an extensive database of multimodal speech production data, developed to complement existing resources available to the speech research community and with the intention of being continuously refined and augmented. The database currently includes real-time magnetic resonance imaging data from five male and five female speakers of American English. Electromagnetic articulography data have also been presently collected from four of these speakers. The two modalities were recorded in two independent sessions while the subjects produced the same 460 sentence corpus used previously in the MOCHA-TIMIT database. In both cases the audio signal was recorded and synchronized with the articulatory data. The database and companion software are freely available to the research community. (C) 2014 Acoustical Society of America.

Iron(III) Catecholates for Cellular Imaging and Photocytotoxicity in Red Light

Iron(III) complexes Fe(L)(L') (NO3)]-in which L is phenyl-N, N-bis(pyridin-2-yl) methyl]methanamine (1), (anthracen-9-yl)N, N-bis(pyridin-2-yl) methyl] methanamine (2), (pyreny-1-yl)-N, N-bis(pyridin- 2-yl) methyl] methanamine (3-5), and L' is catecholate (1-3), 4-tert-butyl catecholate (4), and 4-(2-aminoethyl)benzene- 1,2-diolate (5)-were synthesized and their photocytotoxic proper-ties examined. The five electron-paramagnetic complexes displayed a FeIII/ Fe-II redox couple near similar to 0.4 V versus a saturated calomel electrode (SCE) in DMF/0.1m tetrabutylammonium perchlorate (TBAP). They showed unpre-cedented photocytotoxicity in red light (600-720 nm) to give IC50-15 mm in various cell lines by means of apoptosis to generate reactive oxygen species. They were ingested in the nucleus of HeLa and HaCaT cells in 4 h, thereby interacting favorably with calf thymus (ct)-DNA and photocleaving pUC19 DNA in red light of 785 nm to form hydroxyl radicals.

High resolution light-sheet based high-throughput imaging cytometry system enables visualization of intra-cellular organelles

Visualization of intracellular organelles is achieved using a newly developed high throughput imaging cytometry system. This system interrogates the microfluidic channel using a sheet of light rather than the existing point-based scanning techniques. The advantages of the developed system are many, including, single-shot scanning of specimens flowing through the microfluidic channel at flow rate ranging from micro-to nano- lit./min. Moreover, this opens-up in-vivo imaging of sub-cellular structures and simultaneous cell counting in an imaging cytometry system. We recorded a maximum count of 2400 cells/min at a flow-rate of 700 nl/min, and simultaneous visualization of fluorescently-labeled mitochondrial network in HeLa cells during flow. The developed imaging cytometry system may find immediate application in biotechnology, fluorescence microscopy and nano-medicine. (C) 2014 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 Unported License.

Nanomaterial based Magnetic Resonance Imaging of Cancer

Magnetic Resonance Imaging (MRI) is a widely used non-invasive medical tool for detection and diagnosis of cancer. In recent years, MRI has witnessed significant contributions from nanotechnology to incorporate advanced features such as multimodality of nanoparticles, therapeutic delivery, specific targeting and the optical detectability for molecular imaging. Accurate composition, right scheme of surface chemistry and properly designed structure is essential for achieving desired properties of nanomaterials such as non-fouling surface, high imaging contrast, chemical stability, target specificity and/or multimodality. This review provides an overview of the recent progress in theranostic nanomaterials in imaging and the development of nanomaterial based magnetic resonance imaging of cancer. In particular, targeted theranostics is a promising approach along with its targeting strategy in cancer treatment using MRI and multimodal imaging. We also discuss recent advances in integrin mediated targeted MRI of cancer.

High Value of Proton Relaxivity Achieved by Graphene Oxide-Cobalt Ferrite Nanoparticle Composite: A Potential Contrast Agent in Magnetic Resonance Imaging

This work investigates the potential of graphene oxide-cobalt ferrite nanoparticle (GO-CoFe2O4) composite as image contrast enhancing material in Magnetic Resonance Imaging (MRI). In the preset work, GO-CoFe2O4 composites were produced by a two-step synthesis process. In the first step, graphene oxide (GO) was synthesized, and in the second step CoFe2O4 nanoparticles were synthesized in a reaction mixture containing GO to yield graphene GO-CoFe2O4 composite. Proton relaxivity value obtained from the composite was 361 mM(-1)s(-1). This value of proton relaxivity is higher than a majority of reported relaxivity values obtained using several ferrite based contrast agents.

Application of Qualitative Imaging Methods to Electrical Performance-Aware Package Board Design

Package-board co-design plays a crucial role in determining the performance of high-speed systems. Although there exist several commercial solutions for electromagnetic analysis and verification, lack of Computer Aided Design (CAD) tools for SI aware design and synthesis lead to longer design cycles and non-optimal package-board interconnect geometries. In this work, the functional similarities between package-board design and radio-frequency (RF) imaging are explored. Consequently, qualitative methods common to the imaging community, like Tikhonov Regularization (TR) and Landweber method are applied to solve multi-objective, multi-variable package design problems. In addition, a new hierarchical iterative piecewise linear algorithm is developed as a wrapper over LBP for an efficient solution in the design space.

Indigenous Development of an Imaging Flow Cytometer for Clinical and Biological Applications

Flow cytometry is a benchmark technique used for basic research and clinical diagnosis of various diseases. Despite being a high-throughput technique, it fails in capturing the morphology of cells being analyzed. Imaging flow cytometry is a combination of flow-cytometry and digital microscopy, which offers advantages of both the techniques. In this paper, we report on the development of an indigenous Imaging Flow Cytometer, realized with the combination of Optics, Microfluidics, and High-speed imaging. A custom-made bright-field transmission microscope is used to capture images of cells flowing across the microfluidic device. High-throughput morphological analysis on suspension of yeast cells is presented.

Effects of refractive index mismatch in optical CT imaging of polymer gel dosimeters

Purpose: Proposing an image reconstruction technique, algebraic reconstruction technique-refraction correction (ART-rc). The proposed method takes care of refractive index mismatches present in gel dosimeter scanner at the boundary, and also corrects for the interior ray refraction. Polymer gel dosimeters with high dose regions have higher refractive index and optical density compared to the background medium, these changes in refractive index at high dose results in interior ray bending. Methods: The inclusion of the effects of refraction is an important step in reconstruction of optical density in gel dosimeters. The proposed ray tracing algorithm models the interior multiple refraction at the inhomogeneities. Jacob's ray tracing algorithm has been modified to calculate the pathlengths of the ray that traverses through the higher dose regions. The algorithm computes the length of the ray in each pixel along its path and is used as the weight matrix. Algebraic reconstruction technique and pixel based reconstruction algorithms are used for solving the reconstruction problem. The proposed method is tested with numerical phantoms for various noise levels. The experimental dosimetric results are also presented. Results: The results show that the proposed scheme ART-rc is able to reconstruct optical density inside the dosimeter better than the results obtained using filtered backprojection and conventional algebraic reconstruction approaches. The quantitative improvement using ART-rc is evaluated using gamma-index. The refraction errors due to regions of different refractive indices are discussed. The effects of modeling of interior refraction in the dose region are presented. Conclusions: The errors propagated due to multiple refraction effects have been modeled and the improvements in reconstruction using proposed model is presented. The refractive index of the dosimeter has a mismatch with the surrounding medium (for dry air or water scanning). The algorithm reconstructs the dose profiles by estimating refractive indices of multiple inhomogeneities having different refractive indices and optical densities embedded in the dosimeter. This is achieved by tracking the path of the ray that traverses through the dosimeter. Extensive simulation studies have been carried out and results are found to be matching that of experimental results. (C) 2015 American Association of Physicists in Medicine.

Efficient generation of diffraction-limited multi-sheet pattern for biological imaging

We demonstrate a new technique to generate multiple light-sheets for fluorescence microscopy. This is possible by illuminating the cylindrical lens using multiple copies of Gaussian beams. A diffraction grating placed just before the cylindrical lens splits the incident Gaussian beam into multiple beams traveling at different angles. Subsequently, this gives rise to diffraction-limited light-sheets after the Gaussian beams pass through the combined cylindrical lens-objective sub-system. Direct measurement of field at and around the focus of objective lens shows multi-sheet pattern with an average thickness of 7.5 mu m and inter-sheet separation of 380 mu m. Employing an independent orthogonal detection sub-system, we successfully imaged fluorescently-coated yeast cells (approximate to 4 mu m) encaged in agarose gel-matrix. Such a diffraction-limited sheet-pattern equipped with dedicated detection system may find immediate applications in the field of optical microscopy and fluorescence imaging. (C) 2015 Optical Society of America

A Gold Sensors Array for Imaging The Real Tissue Phantom in Electrical Impedance Tomography

Surface electrodes in Electrical Impedance Tomography (EIT) phantoms usually reduce the SNR of the boundary potential data due to their design and development errors. A novel gold sensors array with high geometric precision is developed for EIT phantoms to improve the resistivity image quality. Gold thin films are deposited on a flexible FR4 sheet using electro-deposition process to make a sixteen electrode array with electrodes of identical geometry. A real tissue gold electrode phantom is developed with chicken tissue paste and the fat cylinders as the inhomogeneity. Boundary data are collected using a USB based high speed data acquisition system in a LabVIEW platform for different inhomogeneity positions. Resistivity images are reconstructed using EIDORS and compared with identical stainless steel electrode systems. Image contrast parameters are calculated from the resistivity matrix and the reconstructed images are evaluated for both the phantoms. Image contrast and image resolution of resistivity images are improved with gold electrode array.