A nanofiber based antiviral (TAF) prodrug delivery system.

HIV and hepatitis B are two of the most prevalent viruses globally, and despite readily available preventive treatments unforgiving treatment regimens still exist, such as daily doses of medicine that are challenging to maintain especially in poorer countries. More advanced and longer-lasting delivery vehicles can potentially overcome this problem by reducing maintenance requirements and significantly increase access to medicine. Here, we designed a technology to control the delivery of an antiviral drug over a long timeframe via a nanofiber based delivery scaffold that is both easy to produce and use.

A macrophage-targeted platform for extending drug dosing with polymer prodrugs for pulmonary infection prophylaxis.

Pulmonary melioidosis is a bacterial disease with high morbidity and a mortality rate that can be as high as 40% in resource-poor regions of South Asia. This disease burden is linked to the pathogen's intrinsic antibiotic resistance and protected intracellular localization in alveolar macrophages. Current treatment regimens require several antibiotics with multi-month oral and intravenous administrations that are difficult to implement in under-resourced settings.

Mannose Conjugated Polymer Targeting Biofilms.

Biofilms are one of the most challenging obstacles in bacterial infections. By providing protection against immune responses and antibiotic therapies, biofilms enable chronic colonization and the development of antibiotic resistance. As previous clinical observations and studies have shown, traditional antibiotic therapy alone cannot effectively treat and eliminate biofilm forming infections due to the protection conferred by the biofilm.

Label-free biosensing with a multi-box sub-wavelength phase-shifted Bragg grating waveguide.

Sub-wavelength grating (SWG) metamaterials have been considered to provide promising solutions in the development of next-generation photonic integrated circuits. In recent years, increasied interest has been paid to silicon photonic planar biosensors based on SWG geometries for performance enhancement. In this work, we demonstrate a highly sensitive label-free phase-shifted Bragg grating (PSBG) sensing configuration, which consists of sub-wavelength block arrays in both propagation and transverse directions.

Erratum: Luan, E.X.; Shoman, H.; Ratner, D.M.; Cheung, K.C.; Chrostowski, L. Silicon Photonic Biosensors Using Label-Free Detection. 2018, , 3519.

The authors wish to make the following corrections in their published paper in Sensors [...

Glycan targeted polymeric antibiotic prodrugs for alveolar macrophage infections.

Alveolar macrophages resident in the lung are prominent phagocytic effector cells of the pulmonary innate immune response, and paradoxically, are attractive harbors for pathogens. Consequently, facultative intracellular bacteria, such as Francisella tularensis, can cause severe systemic disease and sepsis, with high morbidity and mortality associated with pulmonary infection. Current clinical treatment, which involves exhaustive oral or intravenous antibiotic therapy, has limitations such as systemic toxicity and off-target effects.

Silicon Photonic Biosensors Using Label-Free Detection.

Thanks to advanced semiconductor microfabrication technology, chip-scale integration and miniaturization of lab-on-a-chip components, silicon-based optical biosensors have made significant progress for the purpose of point-of-care diagnosis. In this review, we provide an overview of the state-of-the-art in evanescent field biosensing technologies including interferometer, microcavity, photonic crystal, and Bragg grating waveguide-based sensors. Their sensing mechanisms and sensor performances, as well as real biomarkers for label-free detection, are exhibited and compared.

Macrophage-targeted drugamers with enzyme-cleavable linkers deliver high intracellular drug dosing and sustained drug pharmacokinetics against alveolar pulmonary infections.

Intracellular bacterial infections localized to the lung alveolar macrophage (AM) remain one of the most challenging settings for antimicrobial therapy. Current systemic antibiotic treatment fails to deliver sustained doses to intracellular bacterial reservoirs, which necessitates prolonged treatment regimens. Herein, we demonstrate a new intracellular enzyme-cleavable polymeric prodrug with tailored ciprofloxacin release profiles in the lungs and AM.

Polymer-augmented liposomes enhancing antibiotic delivery against intracellular infections.

Pulmonary intracellular infections, such as tuberculosis, anthrax, and tularemia, have remained a significant challenge to conventional antibiotic therapy. Ineffective antibiotic treatment of these infections can lead not only to undesired side effects, but also to the emergence of antibiotic resistance. Aminoglycosides (e.

Synthetic Macromolecular Antibiotic Platform for Inhalable Therapy against Aerosolized Intracellular Alveolar Infections.

Lung-based intracellular bacterial infections remain one of the most challenging infectious disease settings. For example, the current standard for treating Franciscella tularensis pneumonia (tularemia) relies on administration of oral or intravenous antibiotics that poorly achieve and sustain pulmonary drug bioavailability. Inhalable antibiotic formulations are approved and in clinical development for upper respiratory infections, but sustained drug dosing from inhaled antibiotics against alveolar intracellular infections remains a current unmet need.

of Silicon-on-Insulator (SOI) strip waveguide resonator sensor.

Evanescent field sensors have shown promise for biological sensing applications. In particular, Silicon-on-Insulator (SOI)-nano-photonic based resonator sensors have many advantages for lab-on-chip diagnostics, including high sensitivity for molecular detection and compatibility with CMOS foundries for high volume manufacturing. We have investigated the optimum design parameters within the fabrication constraints of Multi-Project Wafer (MPW) foundries that result in the highest sensitivity for a resonator sensor.

Sub-wavelength grating for enhanced ring resonator biosensor.

While silicon photonic resonant cavities have been widely investigated for biosensing applications, enhancing their sensitivity and detection limit continues to be an area of active research. Here, we describe how to engineer the effective refractive index and mode profile of a silicon-on-insulator (SOI) waveguide using sub-wavelength gratings (SWG) and report on its observed performance as a biosensor. We designed a 30 μm diameter SWG ring resonator and fabricated it using Ebeam lithography.

Nanostructured glycopolymer augmented liposomes to elucidate carbohydrate-mediated targeting.

Carbohydrate receptors on alveolar macrophages are attractive targets for receptor-mediated delivery of nanostructured therapeutics. In this study, we employed reversible addition fragmentation chain transfer polymerization to synthesize neoglycopolymers, consisting of mannose- and galactose methacrylate-based monomers copolymerized with cholesterol methacrylate for use in functional liposome studies. Glycopolymer-functional liposomes were employed to elucidate macrophage mannose receptor (CD206) and macrophage galactose-type lectin (CD301) targeting in both primary macrophage and immortal macrophage cell lines.

Anti-Retroviral Lectins Have Modest Effects on Adherence of Trichomonas vaginalis to Epithelial Cells In Vitro and on Recovery of Tritrichomonas foetus in a Mouse Vaginal Model.

Trichomonas vaginalis causes vaginitis and increases the risk of HIV transmission by heterosexual sex, while Tritrichomonas foetus causes premature abortion in cattle. Our goals were to determine the effects, if any, of anti-retroviral lectins, which are designed to prevent heterosexual transmission of HIV, on adherence of Trichomonas to ectocervical cells and on Tritrichomonas infections in a mouse model. We show that Trichomonas Asn-linked glycans (N-glycans), like those of HIV, bind the mannose-binding lectin (MBL) that is part of the innate immune system.

Phage lambda capsids as tunable display nanoparticles.

Nanoparticle technologies provide a powerful tool for the development of reagents for use in both therapeutic and diagnostic, or "theragnostic" biomedical applications. Two broad classes of particles are under development, viral and synthetic systems, each with their respective strengths and limitations. Here we adapt the phage lambda system to construct modular "designer" nanoparticles that blend these two approaches.

Performance of ultra-thin SOI-based resonators for sensing applications.

This work presents simulation and experimental results of ultra-thin optical ring resonators, having larger Evanescent Field (EF) penetration depths, and therefore larger sensitivities, as compared to conventional Silicon-on-Insulator (SOI)-based resonator sensors. Having higher sensitivities to the changes in the refractive indices of the cladding media is desirable for sensing applications, as the interactions of interest take place in this region. Using ultra-thin waveguides (<100 nm thick) shows promise to enhance sensitivity for both bulk and surface sensing, due to increased penetration of the EF into the cladding.

Molecular factors in dendritic cell responses to adsorbed glycoconjugates.

Carbohydrates and glycoconjugates have been shown to exert pro-inflammatory effects on the dendritic cells (DCs), supporting pathogen-induced innate immunity and antigen processing, as well as immunosuppressive effects in the tolerance to self-proteins. Additionally, the innate inflammatory response to implanted biomaterials has been hypothesized to be mediated by inflammatory cells interacting with adsorbed proteins, many of which are glycosylated. However, the molecular factors relevant for surface displayed glycoconjugate modulation of dendritic cell (DC) phenotype are unknown.

Identifying human milk glycans that inhibit norovirus binding using surface plasmon resonance.

Human milk glycans inhibit binding between norovirus and its host glycan receptor; such competitive inhibition by human milk glycans is associated with a reduced risk of infection. The relationship between the presence of specific structural motifs in the human milk glycan and its ability to inhibit binding by specific norovirus strains requires facile, accurate and miniaturized-binding assays. Toward this end, a high-throughput biosensor platform was developed based on surface plasmon resonance imaging (SPRi) of glycan microarrays.

Conformationally constrained functional peptide monolayers for the controlled display of bioactive carbohydrate ligands.

In this study, we employed thiolated peptides of the conformationally constrained, strongly helicogenic α-aminoisobutyric acid (Aib) residue to prepare self-assembled monolayers (SAMs) on gold surfaces. Electrochemistry and infrared reflection absorption spectroscopy support the formation of very well packed Aib-peptide SAMs. The immobilized peptides retain their helical structure, and the resulting SAMs are stabilized by a network of intermolecular H bonds involving the NH groups adjacent to the Au surface.

A silicon photonic biosensor using phase-shifted Bragg gratings in slot waveguide.

We present a novel silicon photonic biosensor using phase-shifted Bragg gratings in a slot waveguide. The optical field is concentrated inside the slot region, leading to efficient light-matter interaction. The Bragg gratings are formed with sidewall corrugations on the outside of the waveguide, and a phase shift is introduced to create a sharp resonant peak within the stop band.

Silicon photonic micro-disk resonators for label-free biosensing.

Silicon photonic biosensors are highly attractive for multiplexed Lab-on-Chip systems. Here, we characterize the sensing performance of 3 µm TE-mode and 10 µm dual TE/TM-mode silicon photonic micro-disk resonators and demonstrate their ability to detect the specific capture of biomolecules. Our experimental results show sensitivities of 26 nm/RIU and 142 nm/RIU, and quality factors of 3.

Zwitterionic polymer-modified silicon microring resonators for label-free biosensing in undiluted human plasma.

A widely acknowledged goal in personalized medicine is to radically reduce the costs of highly parallelized, small fluid volume, point-of-care and home-based diagnostics. Recently, there has been a surge of interest in using complementary metal-oxide-semiconductor (CMOS)-compatible silicon photonic circuits for biosensing, with the promise of producing chip-scale integrated devices containing thousands of orthogonal sensors, at minimal cost on a per-chip basis. A central challenge in biosensor translation is to engineer devices that are both sensitive and specific to a target analyte within unprocessed biological fluids.

In vivo targeting of alveolar macrophages via RAFT-based glycopolymers.

Targeting cell populations via endogenous carbohydrate receptors is an appealing approach for drug delivery. However, to be effective, this strategy requires the production of high affinity carbohydrate ligands capable of engaging with specific cell-surface lectins. To develop materials that exhibit high affinity towards these receptors, we synthesized glycopolymers displaying pendent carbohydrate moieties from carbohydrate-functionalized monomer precursors via reversible addition-fragmentation chain transfer (RAFT) polymerization.

Biofunctional paper via the covalent modification of cellulose.

Paper-based analytical devices are the subject of growing interest for the development of low-cost point-of-care diagnostics, environmental monitoring technologies, and research tools for limited-resource settings. However, there are limited chemistries available for the conjugation of biomolecules to cellulose for use in biomedical applications. Herein, divinyl sulfone (DVS) chemistry was demonstrated to immobilize small molecules, proteins, and DNA covalently onto the hydroxyl groups of cellulose membranes through nucleophilic addition.

Nanoscale clustering of carbohydrate thiols in mixed self-assembled monolayers on gold.

Self-assembled monolayers (SAMs) bearing pendant carbohydrate functionality are frequently employed to tailor glycan-specific bioactivity onto gold substrates. The resulting glycoSAMs are valuable for interrogating glycan-mediated biological interactions via surface analytical techniques, microarrays, and label-free biosensors. GlycoSAM composition can be readily modified during assembly by using mixed solutions containing thiolated species, including carbohydrates, oligo(ethylene glycol) (OEG), and other inert moieties.