ABSTRACT
HYPOTHESIS: The nanoporous polydimethylsiloxane (PDMS) surfaces of a rectangular microfluidic channel, selectively uptakes water molecules, concentrating the solute molecules in an aqueous phase, that could drive phase transitions. Factors such as surface wettability, channel geometry, the surface-to-volume ratio, and surface topography of the confinements could play a key role in tuning the phase transitions spatio-temporally. EXPERIMENTS: Using a lyotropic chromonic liquid crystal as model biological material, confined within nanoporous microfluidic environments, we study molecular assembly driven by nanoporous substrates. By combining timelapse polarized imaging, quantitative image processing, and a simple mathematical model, we analyze the phase transitions and construct a master diagram capturing the role of surface wettability, channel geometry and embedded topography on programmable lyotropic phase transitions. FINDINGS: Intrinsic PDMS nanoporosity and confinement cross-section, together with the imposed wettability regulate the rate of the N-M phase transition; whereas the microfluidic geometry and embedded topography enable phase transition at targeted locations. We harness the emergent long-range order during N-M transition to actuate elasto-advective transport of embedded micro-cargo, demonstrating particle manipulation concepts governed by tunable phase transitions. Our results present a programmable physical route to material assembly in microfluidic environment, and offer a new paradigm for assembling genetic components, biological cargo, and minimal synthetic cells.
ABSTRACT
L-asparaginase (L-ASP) is one of the key enzymes used in therapeutic applications, particularly to treat Acute Lymphocytic Leukemia (ALL). L-asparagine is a non-essential amino acid, which means that it can be synthesized by the body and is not required to be obtained through the diet. The synthesis of L-asparagine occurs primarily in the liver, but it also takes place in other tissues throughout the body. In contrast, leukemic cells cannot synthesize L-asparagine due the absence of L-asparagine synthetase and should obtain it from circulating sources for protein synthesis and cell division processes to ensure their vital functions. L-ASP catalyzes the deamination process of L-asparagine amino-acid into aspartic acid and ammonia, depriving leukemic cells of asparagine. This leads to decreased protein synthesis and cell division in tumor cells. However, using L-ASP has side effects, such as hypersensitivity or allergic reaction, antigenicity, short half-life, temporary blood clearance, and toxicity. L-ASP immobilization can minimize the side effects of L-ASP by stopping the immune system from attacking non-human enzymes and improving the enzyme's performance. The first strategy includes modification of enzyme structure, such as covalent binding (conjugation), adsorption to the support material and cross-linking of the enzyme. The chemical modification of residues, often nonspecific, changes the enzyme's hydrophobicity and surface charge, lowering the enzyme's activity. Also, the first strategy exposes the enzyme's surface to the environment. This eliminates its performance and does not allow targeted delivery of the enzyme. The second strategy is based on the entrapment of the enzyme inside the protecting structure or encapsulation. This strategy offers the same benefits as the first. Still, it also enables reducing toxicity, prolonging in vivo half-life, enhancing stability and activity, enables a targeted delivery and controlled release of the enzyme. Compared to the first strategy, encapsulation does not modify the chemical structure of the enzyme since L-ASP is only effective against leukemia in its native tetrameric form. This review aims to present state of the art in L-ASP formulations developed for reducing the side effects of L-ASP, focusing on describing improvements in their safety. The primary focus in the field remains to be improving the overall performance of the L-ASP formulations. Almost all encapsulation systems allow reducing immune response due to screening the enzyme from antibodies and prolonging its half-life. However, the enzyme's activity and stability depend on the encapsulation system type. Therefore, the selection of the right encapsulation system is crucial in therapy due to its effect on the performance parameters of the L-ASP. Biodegradable and biocompatible materials, such as chitosan, alginate and liposomes, mainly attract the researcher's interest in enzyme encapsulation. The research trends are also moving towards developing formulations with targeted delivery and increased selectivity.
Subject(s)
Antineoplastic Agents , Aspartate-Ammonia Ligase , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Humans , Asparaginase/pharmacology , Asparaginase/chemistry , Asparaginase/therapeutic use , Antineoplastic Agents/adverse effects , Antineoplastic Agents/chemistry , Asparagine/therapeutic use , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathologyABSTRACT
The existing literature on the rise velocities of air bubbles in aqueous surfactant solutions adsorbing at the water-air interface focuses mainly on large bubbles (D > 1.2 mm). In addition, due to the way the bubbles in rising bubble experiments are formed, their size is dependent on interfacial tension (the lower the interfacial tension the smaller the bubble). In this paper, smaller air bubbles (D < 505 ± 3 µm) are used to investigate the effect of the bubble size on the detection of two flotation frothers of different adsorption kinetics via bubble rise velocity measurements. We use an alternative method for bubble generation, allowing us to compare the rise velocity of bubbles of the same size in solutions of frothers of varying bulk concentration. The approach taken (ensuring consistent bubble size) ascertains that the buoyancy force component is kept constant when comparing the different solutions. As a consequence, any variations in the bubble rise velocity can be related to changes in the hydrodynamic drag force acting on a rising bubble. The interfacial behavior of frothers, i.e. the adsorption kinetics, interfacial activity and the maximum amount of molecules adsorbed at the interface, are determined from interfacial tension measurements and adsorption isotherms. The differences in the degree of tangential immobilisation caused by two different frothers are discussed in the context of differences in the structure of the dynamic adsorption layer, which is formed during the bubble rise.
ABSTRACT
The interfacial behavior of surfactants present in a natural extract from Quillaja saponaria Molina bark at the air-solution interface is studied by measurements of interfacial tension, interfacial elasticity, and interfacial reflectance FTIR spectroscopy. The active molecule, saponin, is observed directly at the air-solution interface (via reflectance FTIR spectroscopy) above and below the pKa of the molecule, and spectra confirm the altered charge of the interfacial layer at the two solution conditions. For all concentrations of saponin studied, and at pH values below and above pKa (i.e. pH 3 and 7), a reduction in interfacial tension as a function of time is observed, with some differences in early time-scale adsorption and with lower values of quasi-equilibrium interfacial tension for pH 3. The interfacial layer is seen to be elastic, as determined from measurements of hydrostatic expansion, with some variation at the two pH values, and as a function of concentration. In addition to interfacial layer characterisation, the interaction between two air-solution interfaces is probed using bubble collisions with an air-solution interface. This experiment allows for observation of thin film drainage kinetics and determination of the final foam film thickness for the case when one of the interfaces is at equilibrium while the dynamic adsorption layer is being established at the other. This is the first time when the interactions between such interfaces (i.e. only one being at equilibrium) have been studied. This is of particular importance for the formation stage of foams, during which time many of the interfaces are not at equilibrium. When two interfaces interact across a thin liquid film, pH is seen to significantly influence foam film thickness.