Polymeric nanoparticles can prove beneficial in oncology as they sidestep limitations associated ... more Polymeric nanoparticles can prove beneficial in oncology as they sidestep limitations associated with traditional small-molecule pharmaceuticals. With respect to drug delivery, polymeric nanoparticles possess structural features that make them suitable as carriers for therapy and imaging contrast, as their core/shell morphology offers an effective method of transport that provides increased tumor access with reduced side effects, especially for drugs with low water solubility. Herein, we present a polymeric nanoparticle made from pluronic F127 and vitamin E-TPGS encapsulating coumarin-6 for the optical imaging of cancer. We explored the biophysical properties of the construct using an array of optical and physical techniques, evaluated its uptake in breast cancer cell lines, the in vivo toxicokinetics in zebrafish, and its biodistribution profile in mouse xenograft models bearing PC3 tumors overexpressing the prostate-specific membrane antigen (PSMA). The biophysical characterization of the nanoformulation, combined with its selective uptake by cancer cells, its low in vivo toxicity profile, and effective tumor targeting demonstrate the versatility and potential of this nanoparticle formulation for drug delivery applications.
The SARS-CoV-2 virus, implicated in the COVID-19 pandemic, recognizes and binds host cells using ... more The SARS-CoV-2 virus, implicated in the COVID-19 pandemic, recognizes and binds host cells using its spike glycoprotein through an angiotensin converting enzyme 2 (ACE-2) receptor-mediated pathway. Recent research suggests that spatial distributions of the spike protein may influence viral interactions with target cells and immune systems. The goal of this study has been to develop a liposome-based virus-like particle (VLP) by reconstituting the SARS-CoV-2 spike glycoprotein within a synthetic nanoparticle membrane, aiming to eventually establish tunability in spike protein presentation on the nanoparticle surface. Here we report on first steps to this goal, wherein liposomal SARS-CoV-2 VLPs were successfully produced via detergent mediated spike protein reconstitution. The resultant VLPs are shown to successfully co-localize in vitro with the ACE-2 receptor on lung epithelial cell surfaces, followed by internalization into these cells. These VLPs are the first step toward the overall goal of this research which is to form an understanding of the relationship between spike protein surface density and cell-level immune response, eventually toward creating better vaccines and anti-viral therapeutics.
The application of fluorescence cross-correlation spectroscopy (FCCS) to measure molecular bindin... more The application of fluorescence cross-correlation spectroscopy (FCCS) to measure molecular binding is examined. Technical challenges and solutions are discussed. Comparisons are made between one-photon excitation, two-color FCCS and two-photon excitation FCCS are made. Applications of FCCS to ligandreceptor binding and to lipid membrane fusion are presented.
ABSTRACT Rotational spectra of four isotopic species of chlorodifluoromethane, CHF235Cl, CHF237Cl... more ABSTRACT Rotational spectra of four isotopic species of chlorodifluoromethane, CHF235Cl, CHF237Cl, CDF235Cl and CDF237Cl, have been extensively measured, and have been analysed for rotational constants, centrifugal distortion constants and chlorine nuclear quadrupole coupling constants. The distortion constants have been combined with vibrational wavenumbers from the literature and with ab initio force constants calculated in the present work to refine the harmonic force field. Ground state effective (r0), substitution (rs) and ground state average (rz) structures have been evaluated for the molecule.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Cultural Studies of Science Education, Mar 3, 2018
In this paper we reflect on the article "I am smart enough to study postsecondary science: a crit... more In this paper we reflect on the article "I am smart enough to study postsecondary science: a critical discourse analysis of latecomers' identity construction in an online forum", by Phoebe Jackson and Gale Seiler (Cult Stud Sci Educ.
European Journal of Organic Chemistry, Aug 3, 2010
A series of 1,7-bis(arylethynyl)-N,N′-bis[2,6-diisopropylphenyl]perylene-3,4:9,10-bis(dicarboximi... more A series of 1,7-bis(arylethynyl)-N,N′-bis[2,6-diisopropylphenyl]perylene-3,4:9,10-bis(dicarboximide)s has been obtained from Sonogashira coupling of the 1,7-dibromoperylene-3,4:9,10-bis(dicarboximide) with p-substituted phenylacetylenes in which the p-substituents include π-donors (dialkylamino, diarylamino, p-(diarylamino)phenyl, alkoxy) and π-acceptors (diarylboryl, p-(diarylboryl)phenyl). The bis(arylethynyl)-substituted chromophores all show two reversible molecular reductions and are all slightly more readily reduced than unsubstituted perylene-3,4:9,10-bis(dicarboximide)s with the electrochemical potentials being rather insensitive to the π-donor or acceptor nature of the aryl group. The amine derivatives also show reversible molecular oxidations. The UV-vis spectra of the chromophores with alkoxy and boryl substituents show red-shifted absorptions relative to unsubstituted perylene diimides with discernible vibronic structure. In contrast, the lowest energy absorptions of the amino derivatives are broad and structureless, suggesting donor-to-acceptor charge-transfer character. Transient absorption spectra for the amine derivatives were interpreted in terms of ultrafast charge separation, followed by charge recombination on a time scale of ca. 80-2000 ps. Two compounds were also synthesized in which an additional stronger, but more weakly coupled, donor group is linked by a nonconjugated bridge to the p-amine donor, to investigate the effect on the charge recombination lifetimes; however, the lifetimes of the charge-separated states, ca. 150 and 1000 ps, were within the range observed for the simple amine systems. Finally, the two-photon absorption properties of three bis(arylethynyl)substituted derivatives were investigated, along with those of 1,7-di(pyrrolidin-1-yl)-N,N′-bis[2,6-diisopropylphenyl]perylene-3,4:9,10-bis(dicarboximide). As with other perylene-3,4:9,10-bis(dicarboximide)s and related species, strong two-photon absorption (>1000 GM) was observed for three of these species close to the one-photon absorption edge; however, an additional feature (100-500 GM) was also observed at longer wavelength. An example with (p-aminophenyl)ethylnyl substituents showed a qualitatively different twophoton spectrum with a cross-section >500 GM being observed over a broad wavelength range.
Introduction It has been known for decades that metals with a thin oxide coating can exhibit inte... more Introduction It has been known for decades that metals with a thin oxide coating can exhibit interference colours by a Fabry-Perot interference phenomenon.1 The colour produced by constructive interference of light reflecting from the air/oxide and oxide/metal interfaces is directly related to the oxide film thickness, and this property has been used as a convenient way to determine oxide film thickness by the unaided eye. Recently, interference colours of nanostructured metal oxides formed at Al, Ti, and Si have been reported. The observed colour of these nanostructured oxide films is dependent on film thickness, surface modification, and porosity of the nanostructures. These parameters have been investigated for potential applications in sensing and displays.2,3 In this study, the interference colours of Ta oxide nanotubular films have been used to create a sensor that allows for the visual detection of heavy metals in water (ppm to ppb levels). Methods and Results We have previously reported that thin films of highly ordered Ta2O5 nanotubes (NTs) can be formed by the anodization of Ta foil.4 The Ta2O5 NTs were prepared by anodization of Ta in a solution containing HF, H2SO4 and H2O in a two-electrode cell configuration. Ta2O5 NT diameter was controlled by the applied voltage, and NT length was varied by controlling the anodization time and HF concentration,5 as shown in Figure 1 (a-d). The colour of the NT film changes with NT length, progressing through brown, deep purple, deep blue, yellow, orange, purple, and blue as NT length increases from 20-500 nm. Beyond a length of ~500 nm, teal and pink colours dominate the visible appearance of the oxide films. The peaks and valleys present in the diffuse reflectance spectrum vary with oxide film thickness, and with the refractive index of the nanotubular film. This was seen to change upon NT infiltration with different analytes (as shown in Figure 1e), allowing for visual sensing applications. Due to the conductive Ta metal NT support, heavy metals, such as Cu, Cd, and Pb, can be electrodeposited inside the NT film, resulting in refractive index change, and thus, a visible colour change. This results in a rapid visual sensor that does not require costly or bulky instrumentation, making it ideal for detecting heavy metals in water in remote locations. Acknowledgements We gratefully acknowledge financial support from the Natural Sciences and Engineering Research Council of Canada (NSERC), and scholarship support from NSERC and Alberta Innovates Technology Futures for CH. We also thank Drs. Dimitre Karpuzov and Shihong Xu (Alberta Centre for Surface Engineering and Science, Edmonton, Alberta) for assistance with the FE-SEM imaging. References (1) Charlesby, A.; Polling, J. J. Proc. R. Soc. A Math. Phys. Eng. Sci. 1955, 227, 434–447. (2) Zhao, B. X.; Meng, G.; Xu, Q.; Han, F. Adv. Mater. 2010, 22, 2637–2641. (3) Lezec, H. J.; McMahon, J. J.; Nalamasu, O.; Ajayan, P. M. Nano Lett. 2007, 7, 329–333. (4) El-Sayed, H.; Singh, S.; Greiner, M. T.; Kruse, P. Nano Lett. 2006, 6, 2995–2999. (5) Horwood, C.; El-Sayed, H.; Birss, V. Electrochim. Acta 2014, 132, 91–97. Figure 1
The spectroscopy and photochemistry of protoporphyrin IX in ethanol and in Triton X-100 micelle s... more The spectroscopy and photochemistry of protoporphyrin IX in ethanol and in Triton X-100 micelle solution have been examined using near-infrared two-photon excitation (TPE). TPE will allow photodynamic therapy with highly localized light dosage. We have determined that the photochemistry subsequent to TPE is very similar to that found for one-photon excitation. Moreover, the photoproducts observed possess very intense TPE fluorescence spectra, which allows their detection at low relative concentrations.
Research on understanding the full extent that an authentic science research experience engages s... more Research on understanding the full extent that an authentic science research experience engages students in how scientists think and act is sparse. 'Learning-science-by-doing-science' (LSDS) is an emerging self-guided process-learning model in postsecondary science education. It offers authentic science research opportunities that drive students to think and act like scientists. This study investigates the LSDS approach as a potential model for science learning at postsecondary level and aims to answer a main research inquirywhat are the students' and teaching staff's perceptions of students' learning gains and the quality of their learning experiences in an authentic research environment within the LSDS model? To answer this question, data were collected from the students, alumni, instructors, teaching assistants and the program director via questionnaires, focus groups and interviews. Students' and staff's lived experiences and their perceptions on their authentic research experiences within the LSDS model were used to articulate the key attributes and stages of the LSDS model. The outcomes of this study can be used to help other science programs implement similar authentic research process learning approaches in their own contexts.
Nanoparticles in the bloodstream are subjected to complex fluid forces as they move through the c... more Nanoparticles in the bloodstream are subjected to complex fluid forces as they move through the curves and branches of healthy or tumor vasculature. While nanoparticles are known to preferentially accumulate in angiogenic vessels, little is known about the flow conditions in these vessels and how these conditions may influence localization. Here, we report a methodology which combines confocal imaging of nanoparticle-injected transgenic zebrafish embryos, 3D modeling of the vasculature, particle mapping, and computational fluid dynamics, to quantitatively assess the effects of fluid forces on nanoparticle distribution in vivo. Six-fold lower accumulation was found in zebrafish arteries compared to the lower velocity veins. Nanoparticle localization varied inversely with shear stress. Highest accumulation was present in regions of disturbed flow found at branch points and curvatures in the vasculature. To further investigate cell-particle association under flow, human endothelial cel...
Engineered nanocomposites (NCs) have recently emerged as materials of great scientific and techno... more Engineered nanocomposites (NCs) have recently emerged as materials of great scientific and technological interest. In these materials, different components are combined to yield a nanoentity with desired properties not afforded by the constituent materials. Designing novel NCs and synthetic routes that enable controlling the size and functionalities remains an active area of research. Here, we present a two-step method of synthesizing Ag–Fe3O4 NCs with tunable sizes. Unlike previously reported structures, the prepared NCs do not have a familiar core–shell architecture. Instead, small Fe3O4 nanoparticles (NPs) are embedded in a larger silver matrix. The superparamagnetic Fe3O4 NPs endow the NC with magnetic properties, enabling easy separation from solution. The degree of the NC response to an external magnetic field can be controlled by varying the concentration of Fe3O4 NPs during the synthesis. The Ag matrix serves to protect the embedded Fe3O4 NPs from degradation and can be used for further functionalization of the NCs with different sulfhydryl containing linkers. To demonstrate utility, we show how decorating the outer layer of the Ag NC with diphenyl-4,4'-dithiol transforms the NCs into a water purifying system capable of sequestering highly toxic Hg2+ ions from solution magnetically.
Two-photon excitation fluorescence cross-correlation spectroscopy (TPE-XCS) is a very suitable me... more Two-photon excitation fluorescence cross-correlation spectroscopy (TPE-XCS) is a very suitable method for studying interactions of two distinctly labeled fluorescent molecules. As such, it lends itself nicely to the study of ligand-receptor interactions. By labeling the ligand with one color of fluorescent dye and the receptor with another, it is possible to directly monitor ligand binding rather than inferring binding by monitoring downstream effects. One challenge of the TPE-XCS approach is that of separating the signal due to the receptor from that of the ligand. Using standard organic fluorescent labels there is almost inevitably spectral cross talk between the detection channels, which must be accounted for in TPE-XCS data analysis. However, using quantum dots as labels for both ligand and receptor this limitation can be alleviated, because of the dot's narrower emission spectra. Using solely quantum dots as fluorescent labels is a novel approach to TPE-XCS, which may be generalizable to many pairs of interacting biomolecules after the proof of principle and the assessment of limitations presented here. Moreover, it is essential that relevant pharmacological parameters such as the equilibrium dissociation constant, K d , can be easily extracted from the XCS data with minimal processing. Herein, we present a modified expression for fractional occupancy based on the auto-and cross-correlation decays obtained from a well-defined ligand-receptor system. Nanocrystalline semiconductor quantum dots functionalized with biotin (l em ¼ 605 nm) and streptavidin (l em ¼ 525 nm) were used for which an average K d value of 0.30 6 0.04 3 10 ÿ9 M was obtained (cf. native system ;10 ÿ15). Additionally, the off-rate coefficient (k off) for dissociation of the two quantum dots was determined as 5 3 10 ÿ5 s ÿ1. This off-rate is slightly larger than for native biotin-streptavidin (5 3 10 ÿ6 s ÿ1); the bulky nature of the quantum dots and restricted motion/orientation of functionalized dots in solution can account for differences in the streptavidin-biotin mediated dot-dot binding compared with those for native streptavidin-biotin.
Nanoparticles are studied with respect to serum albumin binding using a direct and quantitative a... more Nanoparticles are studied with respect to serum albumin binding using a direct and quantitative approach. We find that protein binding saturation occurs at sub-monolayer surface coverage and attribute binding to surface chemistry heterogeneity.
Journal of Undergraduate Research in Alberta, 2016
INTRODUCTION Interactions with the endothelium play a key role in the behaviour of intravenously ... more INTRODUCTION Interactions with the endothelium play a key role in the behaviour of intravenously administered nanoparticle drug carriers [1] . Hence, quantifying cellular association (membrane adhesion and cell internalization) of liposomes with endothelial cells is an effective screening method of biocompatibility and success of new drug carriers. Current methods are inaccurate as concentration does not necessarily equate to local cellular association. The focus of this experiment is to quantify the cellular association between liposomes and two types of human endothelial cells and compare the associations with cells’ cytotoxic response. Cellular association of liposomes as well as cell viability were quantified on cellular level at different concentrations of liposomes. METHODS Two different types of cells, Human Umbilical Vein Endothelial cell, which is a common cell type used in vitro studies, and Human MicroVascular Cell, which is more accurate representation of in vivo, were u...
Photodynamic therapy (PDT), the combined action of a photosensitizer and light to produce a cytot... more Photodynamic therapy (PDT), the combined action of a photosensitizer and light to produce a cytotoxic effect, is an approved therapy for a number of diseases. At present, clinical PDT treatments involve one-photon excitation of the photosensitizer. A major limitation is that damage may be caused to healthy tissues that have absorbed the drug and lie in the beam path. Two-photon excitation may minimize this collateral damage, as the probability of absorption increases with the square of the light intensity, enabling spatial confinement of the photosensitizer activation. A potential application is the treatment of the wet-form of age-related macular degeneration, the foremost cause of central vision loss in the elderly. Herein, the commercial photosensitizers Visudyne Ò and Photofrin Ò are used to demonstrate quantitative in vitro two-photon PDT. A uniform layer of endothelial cells (YPEN-1) was irradiated with a Ti:sapphire laser (300 fs, 865 nm, 90 MHz) using a confocal scanning microscope. Quantification of the two-photon PDT effect was achieved using the permeability stain Hoechst 33258 and a SYTOX Ò Orange viability stain. Visudyne was found to be around seven times more effective as a two-photon photosensitizer than Photofrin under the conditions used, consistent with its higher two-photon absorption cross-section. We also demonstrate for the first time the quadratic intensity dependence of cellular two-photon PDT. This simple in vitro method for quantifying the efficacy of photosensitizers for two-photon excited PDT will be valuable to test specifically designed twophoton photosensitizers before proceeding to in vivo studies in preclinical animal models.
Under physiological conditions, multicomponent biological membranes undergo structural changes wh... more Under physiological conditions, multicomponent biological membranes undergo structural changes which help define how the membrane functions. An understanding of biomembrane structure-function relations can be based on knowledge of the physical and chemical properties of pure phospholipid bilayers. Here, we have investigated phase transitions in dipalmitoylphosphatidylcholine (DPPC) and dioleoylphosphatidylcholine (DOPC) bilayers. We demonstrated the existence of several phase transitions in DPPC and DOPC mica-supported bilayers by both atomic force microscopy imaging and force measurements. Supported DPPC bilayers show a broad L b-L a transition. In addition to the main transition we observed structural changes both above and below main transition temperature, which include increase in bilayer coverage and changes in bilayer height. Force measurements provide valuable information on bilayer thickness and phase transitions and are in good agreement with atomic force microscopy imaging data. A De Gennes model was used to characterize the repulsive steric forces as the origin of supported bilayer elastic properties. Both electrostatic and steric forces contribute to the repulsive part of the force plot.
Polymeric nanoparticles can prove beneficial in oncology as they sidestep limitations associated ... more Polymeric nanoparticles can prove beneficial in oncology as they sidestep limitations associated with traditional small-molecule pharmaceuticals. With respect to drug delivery, polymeric nanoparticles possess structural features that make them suitable as carriers for therapy and imaging contrast, as their core/shell morphology offers an effective method of transport that provides increased tumor access with reduced side effects, especially for drugs with low water solubility. Herein, we present a polymeric nanoparticle made from pluronic F127 and vitamin E-TPGS encapsulating coumarin-6 for the optical imaging of cancer. We explored the biophysical properties of the construct using an array of optical and physical techniques, evaluated its uptake in breast cancer cell lines, the in vivo toxicokinetics in zebrafish, and its biodistribution profile in mouse xenograft models bearing PC3 tumors overexpressing the prostate-specific membrane antigen (PSMA). The biophysical characterization of the nanoformulation, combined with its selective uptake by cancer cells, its low in vivo toxicity profile, and effective tumor targeting demonstrate the versatility and potential of this nanoparticle formulation for drug delivery applications.
The SARS-CoV-2 virus, implicated in the COVID-19 pandemic, recognizes and binds host cells using ... more The SARS-CoV-2 virus, implicated in the COVID-19 pandemic, recognizes and binds host cells using its spike glycoprotein through an angiotensin converting enzyme 2 (ACE-2) receptor-mediated pathway. Recent research suggests that spatial distributions of the spike protein may influence viral interactions with target cells and immune systems. The goal of this study has been to develop a liposome-based virus-like particle (VLP) by reconstituting the SARS-CoV-2 spike glycoprotein within a synthetic nanoparticle membrane, aiming to eventually establish tunability in spike protein presentation on the nanoparticle surface. Here we report on first steps to this goal, wherein liposomal SARS-CoV-2 VLPs were successfully produced via detergent mediated spike protein reconstitution. The resultant VLPs are shown to successfully co-localize in vitro with the ACE-2 receptor on lung epithelial cell surfaces, followed by internalization into these cells. These VLPs are the first step toward the overall goal of this research which is to form an understanding of the relationship between spike protein surface density and cell-level immune response, eventually toward creating better vaccines and anti-viral therapeutics.
The application of fluorescence cross-correlation spectroscopy (FCCS) to measure molecular bindin... more The application of fluorescence cross-correlation spectroscopy (FCCS) to measure molecular binding is examined. Technical challenges and solutions are discussed. Comparisons are made between one-photon excitation, two-color FCCS and two-photon excitation FCCS are made. Applications of FCCS to ligandreceptor binding and to lipid membrane fusion are presented.
ABSTRACT Rotational spectra of four isotopic species of chlorodifluoromethane, CHF235Cl, CHF237Cl... more ABSTRACT Rotational spectra of four isotopic species of chlorodifluoromethane, CHF235Cl, CHF237Cl, CDF235Cl and CDF237Cl, have been extensively measured, and have been analysed for rotational constants, centrifugal distortion constants and chlorine nuclear quadrupole coupling constants. The distortion constants have been combined with vibrational wavenumbers from the literature and with ab initio force constants calculated in the present work to refine the harmonic force field. Ground state effective (r0), substitution (rs) and ground state average (rz) structures have been evaluated for the molecule.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Cultural Studies of Science Education, Mar 3, 2018
In this paper we reflect on the article "I am smart enough to study postsecondary science: a crit... more In this paper we reflect on the article "I am smart enough to study postsecondary science: a critical discourse analysis of latecomers' identity construction in an online forum", by Phoebe Jackson and Gale Seiler (Cult Stud Sci Educ.
European Journal of Organic Chemistry, Aug 3, 2010
A series of 1,7-bis(arylethynyl)-N,N′-bis[2,6-diisopropylphenyl]perylene-3,4:9,10-bis(dicarboximi... more A series of 1,7-bis(arylethynyl)-N,N′-bis[2,6-diisopropylphenyl]perylene-3,4:9,10-bis(dicarboximide)s has been obtained from Sonogashira coupling of the 1,7-dibromoperylene-3,4:9,10-bis(dicarboximide) with p-substituted phenylacetylenes in which the p-substituents include π-donors (dialkylamino, diarylamino, p-(diarylamino)phenyl, alkoxy) and π-acceptors (diarylboryl, p-(diarylboryl)phenyl). The bis(arylethynyl)-substituted chromophores all show two reversible molecular reductions and are all slightly more readily reduced than unsubstituted perylene-3,4:9,10-bis(dicarboximide)s with the electrochemical potentials being rather insensitive to the π-donor or acceptor nature of the aryl group. The amine derivatives also show reversible molecular oxidations. The UV-vis spectra of the chromophores with alkoxy and boryl substituents show red-shifted absorptions relative to unsubstituted perylene diimides with discernible vibronic structure. In contrast, the lowest energy absorptions of the amino derivatives are broad and structureless, suggesting donor-to-acceptor charge-transfer character. Transient absorption spectra for the amine derivatives were interpreted in terms of ultrafast charge separation, followed by charge recombination on a time scale of ca. 80-2000 ps. Two compounds were also synthesized in which an additional stronger, but more weakly coupled, donor group is linked by a nonconjugated bridge to the p-amine donor, to investigate the effect on the charge recombination lifetimes; however, the lifetimes of the charge-separated states, ca. 150 and 1000 ps, were within the range observed for the simple amine systems. Finally, the two-photon absorption properties of three bis(arylethynyl)substituted derivatives were investigated, along with those of 1,7-di(pyrrolidin-1-yl)-N,N′-bis[2,6-diisopropylphenyl]perylene-3,4:9,10-bis(dicarboximide). As with other perylene-3,4:9,10-bis(dicarboximide)s and related species, strong two-photon absorption (>1000 GM) was observed for three of these species close to the one-photon absorption edge; however, an additional feature (100-500 GM) was also observed at longer wavelength. An example with (p-aminophenyl)ethylnyl substituents showed a qualitatively different twophoton spectrum with a cross-section >500 GM being observed over a broad wavelength range.
Introduction It has been known for decades that metals with a thin oxide coating can exhibit inte... more Introduction It has been known for decades that metals with a thin oxide coating can exhibit interference colours by a Fabry-Perot interference phenomenon.1 The colour produced by constructive interference of light reflecting from the air/oxide and oxide/metal interfaces is directly related to the oxide film thickness, and this property has been used as a convenient way to determine oxide film thickness by the unaided eye. Recently, interference colours of nanostructured metal oxides formed at Al, Ti, and Si have been reported. The observed colour of these nanostructured oxide films is dependent on film thickness, surface modification, and porosity of the nanostructures. These parameters have been investigated for potential applications in sensing and displays.2,3 In this study, the interference colours of Ta oxide nanotubular films have been used to create a sensor that allows for the visual detection of heavy metals in water (ppm to ppb levels). Methods and Results We have previously reported that thin films of highly ordered Ta2O5 nanotubes (NTs) can be formed by the anodization of Ta foil.4 The Ta2O5 NTs were prepared by anodization of Ta in a solution containing HF, H2SO4 and H2O in a two-electrode cell configuration. Ta2O5 NT diameter was controlled by the applied voltage, and NT length was varied by controlling the anodization time and HF concentration,5 as shown in Figure 1 (a-d). The colour of the NT film changes with NT length, progressing through brown, deep purple, deep blue, yellow, orange, purple, and blue as NT length increases from 20-500 nm. Beyond a length of ~500 nm, teal and pink colours dominate the visible appearance of the oxide films. The peaks and valleys present in the diffuse reflectance spectrum vary with oxide film thickness, and with the refractive index of the nanotubular film. This was seen to change upon NT infiltration with different analytes (as shown in Figure 1e), allowing for visual sensing applications. Due to the conductive Ta metal NT support, heavy metals, such as Cu, Cd, and Pb, can be electrodeposited inside the NT film, resulting in refractive index change, and thus, a visible colour change. This results in a rapid visual sensor that does not require costly or bulky instrumentation, making it ideal for detecting heavy metals in water in remote locations. Acknowledgements We gratefully acknowledge financial support from the Natural Sciences and Engineering Research Council of Canada (NSERC), and scholarship support from NSERC and Alberta Innovates Technology Futures for CH. We also thank Drs. Dimitre Karpuzov and Shihong Xu (Alberta Centre for Surface Engineering and Science, Edmonton, Alberta) for assistance with the FE-SEM imaging. References (1) Charlesby, A.; Polling, J. J. Proc. R. Soc. A Math. Phys. Eng. Sci. 1955, 227, 434–447. (2) Zhao, B. X.; Meng, G.; Xu, Q.; Han, F. Adv. Mater. 2010, 22, 2637–2641. (3) Lezec, H. J.; McMahon, J. J.; Nalamasu, O.; Ajayan, P. M. Nano Lett. 2007, 7, 329–333. (4) El-Sayed, H.; Singh, S.; Greiner, M. T.; Kruse, P. Nano Lett. 2006, 6, 2995–2999. (5) Horwood, C.; El-Sayed, H.; Birss, V. Electrochim. Acta 2014, 132, 91–97. Figure 1
The spectroscopy and photochemistry of protoporphyrin IX in ethanol and in Triton X-100 micelle s... more The spectroscopy and photochemistry of protoporphyrin IX in ethanol and in Triton X-100 micelle solution have been examined using near-infrared two-photon excitation (TPE). TPE will allow photodynamic therapy with highly localized light dosage. We have determined that the photochemistry subsequent to TPE is very similar to that found for one-photon excitation. Moreover, the photoproducts observed possess very intense TPE fluorescence spectra, which allows their detection at low relative concentrations.
Research on understanding the full extent that an authentic science research experience engages s... more Research on understanding the full extent that an authentic science research experience engages students in how scientists think and act is sparse. 'Learning-science-by-doing-science' (LSDS) is an emerging self-guided process-learning model in postsecondary science education. It offers authentic science research opportunities that drive students to think and act like scientists. This study investigates the LSDS approach as a potential model for science learning at postsecondary level and aims to answer a main research inquirywhat are the students' and teaching staff's perceptions of students' learning gains and the quality of their learning experiences in an authentic research environment within the LSDS model? To answer this question, data were collected from the students, alumni, instructors, teaching assistants and the program director via questionnaires, focus groups and interviews. Students' and staff's lived experiences and their perceptions on their authentic research experiences within the LSDS model were used to articulate the key attributes and stages of the LSDS model. The outcomes of this study can be used to help other science programs implement similar authentic research process learning approaches in their own contexts.
Nanoparticles in the bloodstream are subjected to complex fluid forces as they move through the c... more Nanoparticles in the bloodstream are subjected to complex fluid forces as they move through the curves and branches of healthy or tumor vasculature. While nanoparticles are known to preferentially accumulate in angiogenic vessels, little is known about the flow conditions in these vessels and how these conditions may influence localization. Here, we report a methodology which combines confocal imaging of nanoparticle-injected transgenic zebrafish embryos, 3D modeling of the vasculature, particle mapping, and computational fluid dynamics, to quantitatively assess the effects of fluid forces on nanoparticle distribution in vivo. Six-fold lower accumulation was found in zebrafish arteries compared to the lower velocity veins. Nanoparticle localization varied inversely with shear stress. Highest accumulation was present in regions of disturbed flow found at branch points and curvatures in the vasculature. To further investigate cell-particle association under flow, human endothelial cel...
Engineered nanocomposites (NCs) have recently emerged as materials of great scientific and techno... more Engineered nanocomposites (NCs) have recently emerged as materials of great scientific and technological interest. In these materials, different components are combined to yield a nanoentity with desired properties not afforded by the constituent materials. Designing novel NCs and synthetic routes that enable controlling the size and functionalities remains an active area of research. Here, we present a two-step method of synthesizing Ag–Fe3O4 NCs with tunable sizes. Unlike previously reported structures, the prepared NCs do not have a familiar core–shell architecture. Instead, small Fe3O4 nanoparticles (NPs) are embedded in a larger silver matrix. The superparamagnetic Fe3O4 NPs endow the NC with magnetic properties, enabling easy separation from solution. The degree of the NC response to an external magnetic field can be controlled by varying the concentration of Fe3O4 NPs during the synthesis. The Ag matrix serves to protect the embedded Fe3O4 NPs from degradation and can be used for further functionalization of the NCs with different sulfhydryl containing linkers. To demonstrate utility, we show how decorating the outer layer of the Ag NC with diphenyl-4,4'-dithiol transforms the NCs into a water purifying system capable of sequestering highly toxic Hg2+ ions from solution magnetically.
Two-photon excitation fluorescence cross-correlation spectroscopy (TPE-XCS) is a very suitable me... more Two-photon excitation fluorescence cross-correlation spectroscopy (TPE-XCS) is a very suitable method for studying interactions of two distinctly labeled fluorescent molecules. As such, it lends itself nicely to the study of ligand-receptor interactions. By labeling the ligand with one color of fluorescent dye and the receptor with another, it is possible to directly monitor ligand binding rather than inferring binding by monitoring downstream effects. One challenge of the TPE-XCS approach is that of separating the signal due to the receptor from that of the ligand. Using standard organic fluorescent labels there is almost inevitably spectral cross talk between the detection channels, which must be accounted for in TPE-XCS data analysis. However, using quantum dots as labels for both ligand and receptor this limitation can be alleviated, because of the dot's narrower emission spectra. Using solely quantum dots as fluorescent labels is a novel approach to TPE-XCS, which may be generalizable to many pairs of interacting biomolecules after the proof of principle and the assessment of limitations presented here. Moreover, it is essential that relevant pharmacological parameters such as the equilibrium dissociation constant, K d , can be easily extracted from the XCS data with minimal processing. Herein, we present a modified expression for fractional occupancy based on the auto-and cross-correlation decays obtained from a well-defined ligand-receptor system. Nanocrystalline semiconductor quantum dots functionalized with biotin (l em ¼ 605 nm) and streptavidin (l em ¼ 525 nm) were used for which an average K d value of 0.30 6 0.04 3 10 ÿ9 M was obtained (cf. native system ;10 ÿ15). Additionally, the off-rate coefficient (k off) for dissociation of the two quantum dots was determined as 5 3 10 ÿ5 s ÿ1. This off-rate is slightly larger than for native biotin-streptavidin (5 3 10 ÿ6 s ÿ1); the bulky nature of the quantum dots and restricted motion/orientation of functionalized dots in solution can account for differences in the streptavidin-biotin mediated dot-dot binding compared with those for native streptavidin-biotin.
Nanoparticles are studied with respect to serum albumin binding using a direct and quantitative a... more Nanoparticles are studied with respect to serum albumin binding using a direct and quantitative approach. We find that protein binding saturation occurs at sub-monolayer surface coverage and attribute binding to surface chemistry heterogeneity.
Journal of Undergraduate Research in Alberta, 2016
INTRODUCTION Interactions with the endothelium play a key role in the behaviour of intravenously ... more INTRODUCTION Interactions with the endothelium play a key role in the behaviour of intravenously administered nanoparticle drug carriers [1] . Hence, quantifying cellular association (membrane adhesion and cell internalization) of liposomes with endothelial cells is an effective screening method of biocompatibility and success of new drug carriers. Current methods are inaccurate as concentration does not necessarily equate to local cellular association. The focus of this experiment is to quantify the cellular association between liposomes and two types of human endothelial cells and compare the associations with cells’ cytotoxic response. Cellular association of liposomes as well as cell viability were quantified on cellular level at different concentrations of liposomes. METHODS Two different types of cells, Human Umbilical Vein Endothelial cell, which is a common cell type used in vitro studies, and Human MicroVascular Cell, which is more accurate representation of in vivo, were u...
Photodynamic therapy (PDT), the combined action of a photosensitizer and light to produce a cytot... more Photodynamic therapy (PDT), the combined action of a photosensitizer and light to produce a cytotoxic effect, is an approved therapy for a number of diseases. At present, clinical PDT treatments involve one-photon excitation of the photosensitizer. A major limitation is that damage may be caused to healthy tissues that have absorbed the drug and lie in the beam path. Two-photon excitation may minimize this collateral damage, as the probability of absorption increases with the square of the light intensity, enabling spatial confinement of the photosensitizer activation. A potential application is the treatment of the wet-form of age-related macular degeneration, the foremost cause of central vision loss in the elderly. Herein, the commercial photosensitizers Visudyne Ò and Photofrin Ò are used to demonstrate quantitative in vitro two-photon PDT. A uniform layer of endothelial cells (YPEN-1) was irradiated with a Ti:sapphire laser (300 fs, 865 nm, 90 MHz) using a confocal scanning microscope. Quantification of the two-photon PDT effect was achieved using the permeability stain Hoechst 33258 and a SYTOX Ò Orange viability stain. Visudyne was found to be around seven times more effective as a two-photon photosensitizer than Photofrin under the conditions used, consistent with its higher two-photon absorption cross-section. We also demonstrate for the first time the quadratic intensity dependence of cellular two-photon PDT. This simple in vitro method for quantifying the efficacy of photosensitizers for two-photon excited PDT will be valuable to test specifically designed twophoton photosensitizers before proceeding to in vivo studies in preclinical animal models.
Under physiological conditions, multicomponent biological membranes undergo structural changes wh... more Under physiological conditions, multicomponent biological membranes undergo structural changes which help define how the membrane functions. An understanding of biomembrane structure-function relations can be based on knowledge of the physical and chemical properties of pure phospholipid bilayers. Here, we have investigated phase transitions in dipalmitoylphosphatidylcholine (DPPC) and dioleoylphosphatidylcholine (DOPC) bilayers. We demonstrated the existence of several phase transitions in DPPC and DOPC mica-supported bilayers by both atomic force microscopy imaging and force measurements. Supported DPPC bilayers show a broad L b-L a transition. In addition to the main transition we observed structural changes both above and below main transition temperature, which include increase in bilayer coverage and changes in bilayer height. Force measurements provide valuable information on bilayer thickness and phase transitions and are in good agreement with atomic force microscopy imaging data. A De Gennes model was used to characterize the repulsive steric forces as the origin of supported bilayer elastic properties. Both electrostatic and steric forces contribute to the repulsive part of the force plot.
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Papers by David Cramb