Temperature and pH-dependent behaviors of mAb drugs: A case study for trastuzumab

The distortions in the high-order structure of therapeutic monoclonal antibodies (mAbs) under different environmental conditions acutely affect mAb stability, resulting in altered safety, efficacy, and shelf-life profiles. The overall stability of mAbs depends on many factors, and it requires complementary techniques for an in-depth analysis. The stability of mAbs can be characterized by differential centrifugal sedimentation (DCS), differential scanning calorimetry (DSC), differential scanning fluorimetry (DSF), and size exclusion chromatography (SEC) techniques. In this report, temperature-ramped dynamic light scattering (DLS), and circular dichroism (CD) spectroscopy were employed as complementary tools to show how temperature and pH affect the aggregation of a model mAb, trastuzumab, in solution. The results showed that the aggregation onset temperature of trastuzumab defined by DLS was 75 degrees C, which decreases the amount of beta-sheets and causes a slight increase in helix structures. Moreover, the melting temperature of trastuzumab was determined to be between 80-83 degrees C by temperature-ramped CD spectrophotometry, which is in line with the Tm of trastuzumab's Fab region tested with DSC. Thus, unfolding and aggregation of trastuzumab start simultaneously at 75 degrees C, and unfolding triggers the aggregation. The temperature-ramped CD and DLS methods are robust tools to determine the thermal behavior of biosimilars in various solution conditions. Their complementary usage provides solid scientific background for regulatory applications and a better understanding of mAb instability and its relationship with structural changes

Plasmonic titanium nitride nanohole arrays for refractometric sensing

Group IVB metal nitrides have attracted great interest as alternative plasmonic materials. Among them, titanium nitride (TiN) stands out due to the ease of deposition and relative abundance of Ti compared to those of Zr and Hf metals. Even though they do not have Au or Ag-like plasmonic characteristics, they offer many advantages, from high mechanical stability to refractory behavior and complementary metal oxide semiconductor-compatible fabrication to tunable electrical/optical properties. In this study, we utilized reactive RF magnetron sputtering to deposit plasmonic TiN thin films. The flow rate and ratio of Ar/N2 and oxygen scavenging methods were optimized to improve the plasmonic performance of TiN thin films. The stoichiometry and structure of the TiN thin films were thoroughly investigated to assess the viability of the optimized operation procedures. To assess the plasmonic performance of TiN thin films, periodic nanohole arrays were perforated on TiN thin films by using electron beam lithography and reactive ion etching methods. The resulting TiN periodic nanohole array with varying periods was investigated by using a custom microspectroscopy setup for both reflection and transmission characteristics in various media to underline the efficacy of TiN for refractometric sensing.101111321 ; EP/Y030273/

Optical engineering of titanium nitride thin films for nanoplasmonic biosensing

Over the last years, promising concepts and practical approaches of miniaturized devices with remarkable features in the field of plasmonics have drawn a lot of attention. Generally, noble metals have been used in this field due to their high electrical conductivity, tunable plasmon frequencies, and chemical stability. However, they have a barrier for high volume production and for high-performance applications because of their high costs and loss mechanism in visible and near infrared region. Noble metals, like gold and silver, does not allow tunability in their optical properties. Therefore, research has begun to find and improve alternative plasmonic materials to replace noble metals. The transition metal nitrides (TMNs) have been suggested as an alternative for their low cost, chemical stability, and compatibility with biological mediums when compared in the literature for nanoplasmonic biosensing applications. Especially, their plasmonic response can be tuned with nanostructural and stoichiometrical change. This thesis provides brief introduction for detection methods for nanoplasmonic sensing. A lithography approach, nanosphere lithography, is explained for future work in this research due to its simplicity and cost-effectiveness in patterning surfaces towards biosensing applications. Noble metals and TMNs will be compared, particularly suggested titanium nitride (TiN) thin films belonging to the 4B transition metal group in the periodic table. Thin-film fabrication was done under reactive radio-frequency sputtering. This study offers a route for optimization of TiN film fabrication and demonstrates several ways to reduce oxygen contaminant concentration in sputtering. Produced thin films’ characterizations were done with energy-dispersive spectroscopy, X-ray diffraction, Raman spectroscopy, four-point probe measurement, variable angle spectroscopic ellipsometry to evaluate the compositional, electrical, morphological, and optical properties. Room temperature, purging with argon gas, overnight vacuum, and substrate heating sputtering are compared. All three approaches towards decreasing oxygen presence during deposition and enhancing crystollographic structure showed improvement in the conductivity and crystallinity of the thin films

Monoclonal antibodies for diagnostic and therapeutic systems to combat microbial infections

Diagnosis and effective therapy of microbial infections are often complicated processes. Antibodies can be used for rapid, specific diagnosis and therapy of those infections because of target selectivity and specificity. Monoclonal antibodies show higher target specificity compared to polyclonal antibodies. Single epitopes specificity of monoclonal antibodies makes them the leading therapeutic and diagnostic tool against microbial infections by lowering the potential of off-target reactions and misleading diagnosis. Employing monoclonal antibodies to diagnose and treat microbial infections has been attracting significant attention despite some economic obstacles. This chapter focuses on the potential diagnostic and therapeutic use of monoclonal antibodies to combat different microbial infections, including bacterial infections, viral infections, and some other infections in vivo and in vitro. The recent advances made in monoclonal antibody development against various microbial diseases for diagnostic and therapeutic purposes are discussed. Finally, some key challenges in designing, manufacturing, and developing monoclonal antibodies for diagnostic and therapeutic systems and their limitations and future trends are explained

Wearable nano-based gas sensors for environmental monitoring and encountered challenges in optimization

With a rising emphasis on public safety and quality of life, there is an urgent need to ensure optimal air quality, both indoors and outdoors. Detecting toxic gaseous compounds plays a pivotal role in shaping our sustainable future. This review aims to elucidate the advancements in smart wearable (nano)sensors for monitoring harmful gaseous pollutants, such as ammonia (NH3), nitric oxide (NO), nitrous oxide (N2O), nitrogen dioxide (NO2), carbon monoxide (CO), carbon dioxide (CO2), hydrogen sulfide (H2S), sulfur dioxide (SO2), ozone (O3), hydrocarbons (CxHy), and hydrogen fluoride (HF). Differentiating this review from its predecessors, we shed light on the challenges faced in enhancing sensor performance and offer a deep dive into the evolution of sensing materials, wearable substrates, electrodes, and types of sensors. Noteworthy materials for robust detection systems encompass 2D nanostructures, carbon nanomaterials, conducting polymers, nanohybrids, and metal oxide semiconductors. A dedicated section dissects the significance of circuit integration, miniaturization, real-time sensing, repeatability, reusability, power efficiency, gas-sensitive material deposition, selectivity, sensitivity, stability, and response/recovery time, pinpointing gaps in the current knowledge and offering avenues for further research. To conclude, we provide insights and suggestions for the prospective trajectory of smart wearable nanosensors in addressing the extant challenges

Plasmonic Titanium Nitride Nanohole Arrays for Refractometric Sensing.

Publication status: PublishedGroup IVB metal nitrides have attracted great interest as alternative plasmonic materials. Among them, titanium nitride (TiN) stands out due to the ease of deposition and relative abundance of Ti compared to those of Zr and Hf metals. Even though they do not have Au or Ag-like plasmonic characteristics, they offer many advantages, from high mechanical stability to refractory behavior and complementary metal oxide semiconductor-compatible fabrication to tunable electrical/optical properties. In this study, we utilized reactive RF magnetron sputtering to deposit plasmonic TiN thin films. The flow rate and ratio of Ar/N2 and oxygen scavenging methods were optimized to improve the plasmonic performance of TiN thin films. The stoichiometry and structure of the TiN thin films were thoroughly investigated to assess the viability of the optimized operation procedures. To assess the plasmonic performance of TiN thin films, periodic nanohole arrays were perforated on TiN thin films by using electron beam lithography and reactive ion etching methods. The resulting TiN periodic nanohole array with varying periods was investigated by using a custom microspectroscopy setup for both reflection and transmission characteristics in various media to underline the efficacy of TiN for refractometric sensing