Canada

As a result of the growing world-wide antibiotic resistance crisis, many currently existing antibiotics have been shown to be ineffective due to bacteria developing resistive mechanisms. There are a limited variety of potent antibiotics that are successful at suppressing microbial growth, such as polymyxin B, however, are deemed as a last resort due to their high toxicity. Adverse side effects associated with polymyxin B treatment include nephrotoxicity, neurotoxicity, and hypersensitivity. Previous research has focused on the development of an effective drug delivery system that can inhibit bacterial growth while minimizing negative side effects. In particular, nanoparticles have been of interest as they can be conjugated to a drug of interest, allowing for effective drug transport to the target. Despite their potential, an antibiotic delivery system has yet to be established, due to the nanoparticles lacking specificity and lack of biocompatibility and rejection. Here, we present a novel antimicrobial drug delivery method that uses modified red blood cells (RBC) that are encapsulated around polymyxin B. These RBC-based antibiotics are made specific to certain bacteria through the addition of the corresponding antibodies to their cell membranes. We investigate whether this drug delivery system is effective at inhibiting bacterial growth and selective, which is important to minimize the negative side effects seen with conventional polymyxin B treatment. This RBC based platform is potentially advantageous to synthetic nanoparticle-based approaches because of their biocompatibility and bioavailability, resulting in longer retention time in the human body.

CAP Virtual Congress 2021

Novel drug delivery system for antibiotic therapy using modified erythrocyte liposomes

drug-delivery

liposomes

biophysics

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technical paper

The solid polymer light-emitting electrochemical cell (PLEC) possesses a polymer homojunction that is reminiscent of a conventional p-n junction but also exhibits distinct features that are profoundly intriguing. The PLEC junction is formed under bias when the propagating p- and n-doping fronts in the semiconducting polymer make contact. The PLEC junction can be immobilized by cooling after the initial junction formation. Once the junction is fixed by cooling, the “frozen-junction” PLEC exhibits a unipolar electroluminescence (EL) and photovoltaic response. Further, the resulting frozen junction can be relaxed, or partially de-doped into a p-i-n junction by controlled manipulation of ion motion. The as-frozen p-n junction can be relaxed with repeated thermal cycles. More precisely, the de-doping was carried out in a single heating/cooling cycle during which a constant reverse bias (RB) current was applied to monitor the extent of de-doping and the magnitude of RB EL. It is on a frozen polymer p-i-n junction that the most puzzling electroluminescent phenomenon was observed. A model is developed that explains the reverse bias EL as caused by the tunnel injection of electrons and holes from bandgap states into a de-doped “intrinsic” region between the p- and n-doped regions. Moreover, the RB EL exhibits hypersensitivity to temperature when the de-doped cell was cooled. There is currently no explanation to this drastic EL enhancement by cooling. Several possible causes have been ruled out through a series of control experiments.

Temperature Sensitive Electroluminescence Observed in a Reverse Biased, Frozen Polymer P-I-N Junction

Recently, there has been considerable interest to study the nonlinear properties of ensembles of
metallic nanoparticles and quantum dots [1,2]. Nonlinear optical properties can be used for
processing the information content of data images, on which the research can potentially induce a
revolution in electronic as well as photonic nanotechnology and nanomedicine. We have studied
the energy transport due to the Kerr nonlinearity in plasmonic nanohybrids. The Kerr coefficient
has been calculated by using the quantum density matrix method in the dipole-dipole coupling
between quantum dots. Induced dipoles are created when the probe photon falls on the metallic
nanoparticles. These metallic nanoparticles interact with each other via dipole-dipole interaction.
We showed that the power is transferred from the metallic nanoparticles to the quantum dots
through surface plasmon polaritons. During this process, enhancement in the energy transfer in the
quantum dots is found. We have also predicted that the power spectrum peak would split into two
peaks due to the strong coupling between excitons and the dipole-dipole interaction. Considering
one peak as ON position and two peaks as OFF position, the present findings can be applied to
fabricate nanoswitches. The Kerr nonlinear plasmonics in metallic nanohybrids can also be used
for medical applications since there will be no damaging effect on the body.
[1] J Guo, K Black, J Hu, M Singh, Journal of Physics: Condensed Matter 30 (18), 185301 (2018).
[2] M.R. Singh; Phys. Rev. A102, 013708 (2020).

Kerr Nonlinearity and Energy Transport in Quantum Dots and Metallic Nanoparticles

Entropy stabilized oxides, containing a large number of different elements, exhibiting simple crystal structure have shown interesting properties such as colossal dielectric permittivity, superionic conductivity and enhanced exchange coupling.
To study how the ionic character can be tuned by using different mixtures of oxides, the effective charge for the rocksalt structure high entropy oxide (CuCoMgZnNi)O and medium entropy oxides including (CoMgZnNi)O, (CuMgZnNi)O, (CuCoZnNi)O, (CuCoMgNi)O were calculated by using Scott formula for effective charge and the data from infrared reflectance measurements. The data suggest that (CoMgZn Ni)O has the highest ionic character and the lowest ionic character belongs to (CuCoZnNi)O which has the the lowest effective charge.

Effective Charges in Entropy Stabilized Oxides

During the Covid-19 pandemic, face masks have become the new norm with their widespread use in public as part of a multi-barrier approach for infection control, including physical distancing, hand hygiene, and altered social behaviour. Masks provide benefits to both the mask wearer and to those in their proximity when they are worn by all individuals in a common area. The gold standard in personal protective equipment (PPE) remains the N95 respirator, made of synthetic materials with electrostatic properties that filter and retain more than 95% of aerosols <1 µm and larger in size. N95 respirators degrade during washing and disinfection, and as such are single use disposable PPE. Similarly, surgical-style masks made of polypropylene and non-woven materials are unsuited to frequent washing/decontamination with heat or detergents. Owing to their disposable nature, most commercially available PPE such as the above are unsustainable for supplying the public due to supply interruptions, high cost over time, and a lack of aesthetic attributes (colour, pattern) to encourage use.

As a result, textile manufacturers and a new cottage industry of homemade mask makers, including volunteers making donated masks for vulnerable populations, can provide fabric face masks to the public. Recently, the U.S. CDC indicated that commercial manufacturers of face masks will require testing although the conditions of such standards have yet to be outlined. Recently, Dr. Tam has made recommendations for mask materials to elevate the quality of masks being worn by the public, however these recommendations are not easily translatable to actual mask construction and such recommendations are based on very limited testing of fabric masks.

This presentation will discuss the development of a test apparatus for assessing mask efficacy by measuring the aerosols transmitted through the masks. We use a laser-based system, using relatively inexpensive diode lasers to illuminate the exhaled particles, a webcam for data acquisition, and Python-based particle tracking software. We make the approximation that the intensity of the scattered light from the droplets is proportional to the size of the droplet, but we will be able to quantify the droplet size by analyzing the data with Mie scattering theory.

Reference:
https://advances.sciencemag.org/content/6/36/eabd3083?te=1&nl=running&emc=edit_ru_20200822

Laser-based mask characterization for prophylaxis of Covid-19

Phytoglycogen occurs naturally in the form of compact, 42 nm diameter glucose-based nanoparticles in the kernels of sweet corn. Its highly branched, dendritic structure leads to interesting and useful properties that make the particles ideal as unique additives in personal care, nutrition and biomedical formulations. The properties of phytoglycogen nanoparticles can be altered through chemical modifications such as acid hydrolysis, which not only reduces their diameter but also alters their internal structure, producing significant changes to the interactions between particles in solution. As the acid hydrolyzed particles are packed beyond their glass transition volume fraction, the dependence of the zero-shear viscosity on the effective volume fraction abruptly changes from behaviour well-described by the Vogel-Fulcher-Tammann equation to more Arrhenius-like behaviour, with the transition marked by a pronounced kink in the data. This result is consistent with a reduction in stiffness for acid hydrolyzed phytoglycogen nanoparticles with a corresponding reduction in their fragility index.

Size and Stiffness Reduction of Phytoglycogen Nanoparticles Through Acid Hydrolysis

Time-domain terahertz (THz) spectroscopy has been widely exploited in studying semiconductors, superconductors, topological insulators, and metal-organic frameworks. A high-sensitivity THz system can resolve weak spectroscopic features and a broadband system allows experimentalists to rely on additional spectral information to investigate novel phenomena in materials. In a standard configuration relying on difference frequency mixing to generate and detect THz radiation, the spectroscopy signal can be improved by increasing the nonlinear interaction length inside a nonlinear crystal. However, the accessible spectral bandwidth is then limited by phase-matching conditions. Here we demonstrate a time-resolved THz system relying on noncollinear THz generation and detection schemes in thick nonlinear crystals to perform high-sensitivity and broadband spectroscopy. This concept relies on a phase grating etched on the front surface of two 2-mm thick gallium phosphide (GaP) crystals (THz generation and detection crystals) to diffract the incident near-infrared pulses. Our scheme exploits the long interaction length in these crystals to improve the signal strength and dynamic range in the system. In addition, the noncollinear geometry yields optimizable phase-matching conditions to access a broad spectral bandwidth. We compare our results with those obtained with a traditional broadband collinear system using a pair of thin GaP crystals without gratings. The noncollinear geometry shows a significant increase of the maximum signal amplitude, by a factor of 20, while also achieving a large spectral bandwidth reaching up to 7 THz. We also achieve a dynamic range above 80 dB between 1.1 and 4.3 THz. Our concept could be extended to other nonlinear crystals besides GaP to improve THz generation and detection in different spectral regions. In conclusion, this work paves the way towards high-sensitivity THz spectroscopy over a broad bandwidth in low power experiments and could enable high-field THz generation above 3 THz.

Broadband and high sensitivity THz system with grating-assisted noncollinear phase-matching

In an earlier study on the Wiedemann–Franz Law and the thermoelectric figure of merit (FoM), we studied the electronic effects in detail. We briefly investigated the role of the lattice thermal conductivity in enhancing the FoM and derived the characteristic equations in the form of an offset-logarithmic function (a special case of the generalized Lambert W function) [1]. This work follows up with analytical and numerical solutions to the offset-log function and provides better insight into the materials parameter space. We find the extrema of the lattice thermal conductivity and comment on its role in optimizing the figure of merit.

[1] Yadav, A., Deshmukh, P. C., Roberts, K., Jisrawi, N. M., & Valluri, S. R. (2019). “An analytic study of the Wiedemann–Franz law and the thermoelectric figure of merit”, Journal of Physics Communications, 3 (10), 105001.

An Analytical study of the role of lattice conductivity in the enhancement of the thermoelectric figure of merit

Optical parametric amplifiers deliver intense ultrashort pulses with broadly tuneable frequencies, useful for strong field physics, high harmonic generation, and attosecond experiments. Currently, this nonlinear amplification scheme relies on the second order nonlinearity, $\chi^{(2)}$,which is made possible only by crystals without centro-symmetry. More recently, investigations into a non-collinear setup show an increase in the phase matching bandwidth, leading to the creation even shorter pulses [1]. In this presentation, we discuss our research involving non-collinear parametric amplification of ultrashort pulses using wide bandgap materials with centrosymmetry, previously reported as Kerr instability amplification (KIA) [2]. 

We find that by using these crystals that exploit the next order nonlinearity, $\chi^{(3)}$,we can choose our amplifying medium from a more general class of crystals and still can generate gain factors of g = 50 /mm, or amplification factors of > $10^{12}$ [3]. Without the constraint of centrosymmetry, we have a greater selection by varying the bandgap, thermal properties, and linear and nonlinear indices of refraction. We developed pulse propagation models to optimize the critical parameters for amplification, and we find that the amplified pulse duration is much shorter than the pump and can be independent of the seed. We test several high bandgap dielectrics to optimize our scheme. We experimentally demonstrate the octave spanning amplification, showing that KIA is closely linked to degenerate four-wave mixing. We also spectrally and temporally characterize the amplified pulses to show the agreement with theory.

References
[1] H. Fattahi et al, Third-generation femtosecond technology, Optica 1 45-63 (2014)
[2] G. Vampa, TJ Hammond et al, Kerr instability amplification, Science 359 673-675 (2018)
[3] M. Nesrallah et al, Theory of Kerr instability amplification, Optica 5 271-278 (2018)

Multi-octave Parametric Amplification for Ultrashort Laser Pulses

How diffusivity (e.g., of proteins in the plane of biomembranes) is impacted by obstruction has been explored using Lattice Monte Carlo methods for random and periodic obstacle configurations. However real systems are neither periodic nor totally random. We present a study of transient and steady-state molecular diffusion in two-dimensional ”Fuzzy” systems of immobile obstacles, \textit{i.e.,} systems which bridge the gap between the ideal periodic and random limits. In particular, we examine whether there are ”diffusion phase transitions”, i.e., abrupt quantitative and/or qualitative changes at some critical degree of disorder. For instance, while the crossover length $r^*$ (describing the transition from anomalous to normal diffusion) decreases when the concentration of obstacles, $\phi$, increases in a periodic system, it is the opposite for random systems. Interestingly, $r^*(\phi)$ can become a very weak function of $\phi$ in some fuzzy systems. We investigate several ways of creating tunable disorder leading to different behaviour, and we introduce a parameter describing how the disorder in fuzzy systems impacts diffusion. Furthermore we introduce a new relation between the crossover length $r^*$, and the properties of the (anomalous) transient regime, including the excess diffusivity that it generates. Finally we propose new connections between the properties of the transient and steady-state regimes, most notably the possibility of estimating the steady state diffusion coefficient using early time (transient) data.

Diffusion in a membrane in the presence of immobile obstacles: the role of disorder

SnIP is an exciting new quasi-1D van der Waals semiconductor with a unique double-helix structure at the atomic scale that shows promise as a new material for flexible electronics. However, due to the high resistivity of as-grown SnIP its true potential is not clear. In this work, we study SnIP-nanowire thin films using time-resolved THz spectroscopy (TRTS), a powerful ultrafast optical tool that enables picosecond-resolution measurement of the complex photoconductivity spectrum. Modeling the dispersion of the conductivity allows us to extract the carrier scattering rate, however, the choice of model can yield different values. We discuss our results in terms of the two most common models in the field, the Drude-Smith model and the plasmon model, and show how fluence-dependent spectroscopic studies can be used to differentiate the two experimentally. Moreover, with knowledge of the effective mass, the scattering rate enables us to calculate the carrier mobility. We performed an ab-initio study of the electronic structure in SnIP and extracted the effective mass tensor for several bands near the Fermi level. Along with the carrier scattering rate, we find a carrier mobility as high as 280 cm^2 V^-1s^-1, which is remarkably high for such a soft and flexible material and suggests that it is ideally suited for flexible electronics. Moreover, we find a large anisotropy in the electronic structure, which is due to the low symmetry and unique bond arrangement in SnIP. In the effective mass approximation, the preferred transport direction is band dependent, with preferential electron and hole transport parallel and perpendicular to the double-helix axis, respectively. Furthermore, we show that over a wide range of energies the conduction band dispersion shows quasi-2D behavior and discuss possible experimental evidence of this in our TRTS data.

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Novel drug delivery system for antibiotic therapy using modified erythrocyte liposomes

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