High-throughput measurement of elastic moduli of microfibers by rope coiling.

There are many fields where it is of interest to measure the elastic moduli of tiny fragile fibers, such as filamentous bacteria, actin filaments, DNA, carbon nanotubes, and functional microfibers. The elastic modulus is typically deduced from a sophisticated tensile test under a microscope, but the throughput is low and limited by the time-consuming and skill-intensive sample loading/unloading. Here, we demonstrate a simple microfluidic method enabling the high-throughput measurement of the elastic moduli of microfibers by rope coiling using a localized compression, where sample loading/unloading are not needed between consecutive measurements. The rope coiling phenomenon occurs spontaneously when a microfiber flows from a small channel into a wide channel. The elastic modulus is determined by measuring either the buckling length or the coiling radius. The throughput of this method, currently 3,300 fibers per hour, is a thousand times higher than that of a tensile tester. We demonstrate the feasibility of the method by testing a nonuniform fiber with axially varying elastic modulus. We also demonstrate its capability for in situ inline measurement in a microfluidic production line. We envisage that high-throughput measurements may facilitate potential applications such as screening or sorting by mechanical properties and real-time control during production of microfibers.

Rayleigh-Taylor Instability in Soft Viscoelastic Solids.

We present an experimental characterization of the gravity-driven Rayleigh-Taylor instability in viscoelastic solids. The instability creates periodic patterns on the free surface of the soft solids that are distinct from the previously studied elastic Rayleigh-Taylor instability. The experimental results are supported by the linear stability analysis reported here. We identify the dependence of the steady-state pattern of deformations on the gel's geometry, complex shear modulus, and surface tension. This study provides quantitative measures applicable to the design of tunable surface textures, soft machines, and 3D structures.

Ocean emission of microplastic.

Microplastics are globally ubiquitous in marine environments, and their concentration is expected to continue rising at significant rates as a result of human activity. They present a major ecological problem with well-documented environmental harm. Sea spray from bubble bursting can transport salt and biological material from the ocean into the atmosphere, and there is a need to quantify the amount of microplastic that can be emitted from the ocean by this mechanism. We present a mechanistic study of bursting bubbles transporting microplastics. We demonstrate and quantify that jet drops are efficient at emitting microplastics up to 280µm in diameter and are thus expected to dominate the emitted mass of microplastic. The results are integrated to provide a global microplastic emission model which depends on bubble scavenging and bursting physics; local wind and sea state; and oceanic microplastic concentration. We test multiple possible microplastic concentration maps to find annual emissions ranging from 0.02 to 7.4-with a best guess of 0.1-mega metric tons per year and demonstrate that while we significantly reduce the uncertainty associated with the bursting physics, the limited knowledge and measurements on the mass concentration and size distribution of microplastic at the ocean surface leaves large uncertainties on the amount of microplastic ejected.

Thiazole, isatin and phthalimide derivatives tested in vivo against cancer models: a literature review of the last six years.

BACKGROUND: Cancer is a disease characterized by the abnormal multiplication of cells and is the second leading cause of death in the world. The search for new effective and safe anticancer compounds is ongoing due to factors such as low selectivity, high toxicity, and multidrug resistance. Thus, heterocyclic compounds derived from isatin, thiazole and phthalimide that have achieved promising in vitro anticancer activity have been tested in vivo and in clinical trials. OBJECTIVE: This review focused on the compilation of promising data from thiazole, isatin, and phthalimide derivatives, reported in the literature between 2015 and 2022, with in vivo anticancer activity and clinical trials. METHOD: A bibliographic search was carried out in the PUBMED, MEDLINE, ELSEVIER, and CAPES PERIODIC databases, selecting relevant works for each pharmacophoric group with in vivo antitumor activity in the last 6 years. RESULTS: In our study, 68 articles that fit the scope were selected and critically analyzed. These articles were organized considering the type of antitumor activity and their year of publication. Some compounds reported here demonstrated potent antitumor activity against several tumor types. CONCLUSION: This review allowed us to highlight works that reported promising structures for the treatment of various cancer types and also demonstrated that the privileged structures thiazole, isatin and phthalimide are important in the design of new syntheses and molecular optimization of compounds with antitumor activity.

Flows of a nonequilibrated aqueous two-phase system in a microchannel.

Liquid-liquid phase separation is a rich and dynamic process, which recently has gained new interest, especially in biology and for material synthesis. In this work, we experimentally show that co-flow of a nonequilibrated aqueous two-phase system within a planar flow-focusing microfluidic device results in a three-dimensional flow, as the two nonequilibrated solutions move downstream along the length of the microchannel. After the system reaches steady-state, invasion fronts from the outer stream are formed along the top and bottom walls of the microfluidic device. The invasion fronts advance towards the center of the channel, until they merge. We first show by tuning the concentration of polymer species within the system that the formation of these fronts is due to liquid-liquid phase separation. Moreover, the rate of invasion from the outer stream increases with increasing polymer concentrations in the streams. We hypothesize the invasion front formation and growth is driven by Marangoni flow induced by the polymer concentration gradient along the width of the channel, as the system is undergoing phase separation. In addition, we show how at various downstream positions the system reaches its steady-state configuration once the two fluid streams flow side-by-side in the channel.

Controlling extrudate volume fraction through poroelastic extrusion of entangled looped fibers.

When a suspension of spherical or near-spherical particles passes through a constriction the particle volume fraction either remains the same or decreases. In contrast to these particulate suspensions, here we observe that an entangled fiber suspension increases its volume fraction up to 14-fold after passing through a constriction. We attribute this response to the entanglements among the fibers that allows the network to move faster than the liquid. By changing the fiber geometry, we find that the entanglements originate from interlocking shapes or high fiber flexibility. A quantitative poroelastic model is used to explain the increase in velocity and extrudate volume fraction. These results provide a new strategy to use fiber volume fraction, flexibility, and shape to tune soft material properties, e.g., suspension concentration and porosity, during delivery, as occurs in healthcare, three-dimensional printing, and material repair.

Fibro-Gel: An All-Aqueous Hydrogel Consisting of Microfibers with Tunable Release Profile and its Application in Wound Healing.

Injectable hydrogels are valuable tools in tissue engineering and regenerative medicine due to their unique advantages of injectability with minimal invasiveness and usability for irregularly shaped sites. However, it remains challenging to achieve scalable manufacturing together with matching physicochemical properties and on-demand drug release for a high level of control over biophysical and biomedical cues to direct endogenous cells. Here, the use of an injectable fibro-gel is demonstrated, a water-filled network of entangled hydrogel microfibers, whose physicochemical properties and drug release profiles can be tailored to overcome these shortcomings. This fibro-gel exhibits favorable in vitro biocompatibility and the capability to aid vascularization. The potential use of the fibro-gel for advancing tissue regeneration is explored with a mice excision skin model. Preliminary in vivo tests indicate that the fibro-gel promotes wound healing and new healthy tissue regeneration at a faster rate than a commercial gel. Moreover, it is demonstrated that the release of distinct drugs at different rates can further accelerate wound healing with higher efficiency, by using a two-layer fibro-gel model. The combination of injectability and tailorable properties of this fibro-gel offers a promising approach in biomedical fields such as therapeutic delivery, medical dressings, and 3D tissue scaffolds for tissue engineering.

Outlining the Molecules Tested In Vivo for Chagas Disease, Malaria, and Schistosomiasis Over the Last Six Years - A Literature Review Focused on New Synthetic Drug Identities and Repurposing Strategies.

BACKGROUND: COVID-19 disrupted NTD programs in 60% of countries, impairing public health goals. Thus, boosting NTD's research knowledge is demanding, and in vivo screening of candidates allows for the prospect of promising options based on their overall profile. OBJECTIVE: In this work, we highlighted the relevant research done between 2015-2021 in the fields of synthetic and repurposed drugs that were tested in vivo for Chagas disease, malaria, and schistosomiasis. METHODS: MEDLINE, PUBMED, CAPES PERIODIC, and ELSEVIER databases were used for a comprehensive literature review of the last 6 years of research on each area/disease. RESULTS: Overall, research focused on nitro heterocyclic, aromatic nitro, nucleoside, and metal-based scaffolds for analogue-based drug generation. Repurposing was widely assessed, mainly with heterocyclic drugs, their analogues, and in combinations with current treatments. Several drug targets were aimed for Chagas treatment, specific ones such as iron superoxide dismutase, and more general ones, such as mitochondrial dysfunction. For malaria, hemozoin is still popular, and for schistosomiasis, more general structural damage and/or reproduction impairment were aimed at in vitro analysis of the mechanism of action. CONCLUSION: Latest in vivo results outlined trends for each disease - for Chagas Disease, heterocyclics as thiazoles were successfully explored; for Malaria, quinoline derivatives are still relevant, and for schistosomiasis, repurposed drugs from different classes outstood in comparison to synthetic compounds. This study uprises the continuous development of Chagas disease, malaria, and schistosomiasis drugs, providing researchers with tools and information to address such unmet therapeutic needs.

Synthesis, ADMET Prediction, and Antitumor Profile of Phenoxyhydrazine- 1,3-thiazoles Derivatives.

BACKGROUND: Cancer is one of the most important barriers to increasing life expectancy in all countries in the 21st century. Investigations of new anti-cancer drugs with low side effects are an urgent demand for medicinal chemists. Considering the known antitumor and immunomodulatory activity of thiazoles, this work presents the synthesis and antineoplastic activity of new thiazoles. METHODS: The 22 new compounds (2a-v) were synthesized from different thiosemicarbazones and 2-bromoacetophenone. The compounds were evaluated on: MOLT-4, HL-60, HL-60/MX1, MM1S, SKMEL-28, DU145, MCF-7, and T47d. RESULTS: Compound 2b induced cellular viability on MOLT-4 (37.1%), DU145 (41.5%), and HL- 60/MX1 (58.8%) cells. On MOLT-4 cells, compound 2b exhibited an IC50 of 8.03 µM, and against DU145 cells, an IC50 of 6.04µM. Besides, at IC50 and fold of IC50, 20% to 30% of dead cells were found, most due to necrosis/late apoptosis. Most compounds no showed cytotoxicity against fibroblast cells L929 at the concentrations tested. The compound did not alter the cell cycle of DU145 cells when compared to the negative control. Therefore, compound 2b stands out against DU145 and MOLT-4 cells. CONCLUSION: Our study reinforced the importance of 1,3-thiazoles nuclei in antitumor activity. In addition, derivative 2b stands out against DU145 and MOLT-4 cells and could be a starting point for developing new antineoplastic agents.

Identification of Novel Zika Virus Inhibitors: A Screening using Thiosemicarbazones and Thiazoles Templates.

BACKGROUND: Zika virus (ZIKV) remains an important cause of congenital infection, fetal microcephaly, and Guillain-Barré syndrome in the population. In 2016, WHO declared a cluster of microcephaly cases and other neurological disorders reported as a global public health emergency in Brazil. There is still no specific treatment for Zika virus fever, only palliative care. Therefore, there is a need for new therapies against this disease. According to the literature, thiosemicarbazone, phthalimide and thiazole are privileged structures with several biological activities, including antiviral activity against various viruses. OBJECTIVE: Based on this, this work presents an antiviral screening using previously synthesized compounds derived from thiosemicarbazone, phthalimide, and thiazole as new hits active against ZIKV. METHODS: After synthesis and characterization, all compounds were submitted to Cytotoxicity by MTT and Antiviral activity against ZIKV assays. RESULTS: Compounds 63, 64, 65, and 73 exhibited major reductions in the ZIKV title from this evaluation. Compounds 63 (99.74%), 64 (99.77%), 65 (99.92%), and 73 (99.21%) showed a higher inhibition than the standard 6MMPr (98.74%) at the CC20 dose. These results revealed new chemical entities with anti-ZIKV activity. CONCLUSION: These derivatives are promising candidates for further assays. In addition, the current approach brings a new privileged scaffolding, which may drive future drug discovery for ZIKV.

Shear-induced migration of confined flexible fibers.

We report an experimental study of the shear-induced migration of flexible fibers in suspensions confined between two parallel plates. Non-Brownian fiber suspensions are imaged in a rheo-microscopy setup, where the top and the bottom plates counter-rotate and create a Couette flow. Initially, the fibers are near the bottom plate due to sedimentation. Under shear, the fibers move with the flow and migrate towards the center plane between the two walls. Statistical properties of the fibers, such as the mean values of the positions, orientations, and end-to-end lengths of the fibers, are used to characterize the behaviors of the fibers. A dimensionless parameter Λeff, which compares the hydrodynamic shear stress and the fiber stiffness, is used to analyze the effective flexibility of the fibers. The observations show that the fibers that are more likely to bend exhibit faster migration. As Λeff increases (softer fibers and stronger shear stresses), the fibers tend to align in the flow direction and the motions of the fibers transition from tumbling and rolling to bending. The bending fibers drift away from the walls to the center plane. Further increasing Λeff leads to more coiled fiber shapes, and the bending is more frequent and with larger magnitudes, which leads to more rapid migration towards the center. Different behaviors of the fibers are quantified with Λeff, and the structures and the dynamics of the fibers are correlated with the migration.

Electrostatic wrapping of a microfiber around a curved particle.

The dynamics of the wrapping of a charged flexible microfiber around an oppositely charged curved particle immersed in a viscous fluid is investigated. We observe that the wrapping behavior varies with the radius and Young's modulus of the fiber, the radius of the particle, and the ionic strength of the surrounding solution. We find that wrapping is primarily a function of the favorable interaction energy due to electrostatics and the unfavorable deformation energy needed to conform the fiber to the curvature of the particle. We perform an energy balance to predict the critical particle radius for wrapping, finding reasonably good agreement with experimental observations. In addition, we use mathematical modeling and observations of the deflected shape of the free end of the fiber during wrapping to extract a measurement of the Young's modulus of the fiber. We evaluate the accuracy and potential limitations of this in situ measurement when compared to independent mechanical tests.

Self-Propelled Supracolloidal Fibers from Multifunctional Polymer Surfactants and Droplets.

Advanced synthetic materials are needed to produce nano- and mesoscale structures that function autonomously, catalyze reactions, and convert chemical energy into motion. This paper describes supracolloidal fiber-like structures that are composed of self-adhering, or "sticky," oil-in-water emulsion droplets. Polymer zwitterion surfactants serve as the key interfacial components of these materials, enabling multiple functions simultaneously, including acting as droplet-stabilizing surfactants, interdroplet adhesives, and building blocks of the fibers. This fiber motion, a surprising additional feature of these supracolloidal structures, is observed at the air-water interface and hinged on the chemistry of the polymer surfactant. The origin of this motion is hypothesized to involve transport of polymer from the oil-water interface to the air-water interface, which generates a Marangoni (interfacial) stress. Harnessing this fiber motion with functional polymer surfactants, and selection of the oil phase, produced worm-like objects capable of rotation, oscillation, and/or response to external fields. Overall, these supracolloidal fibers fill a design gap between self-propelled nano/microscale particles and macroscale motors, and have the potential to serve as new components of soft, responsive materials structures.

Regime Map and Triple Point in Selective Withdrawal.

Entrainment in selective withdrawal occurs when both the top and bottom phases are withdrawn through a capillary tube oriented perpendicular to a flat gravitationally separated liquid-liquid interface. The tube introduces two distinct features to the conditions for fluid entrainment. First, the ratio of the two phases being withdrawn is affected by the region of influence of the flow upstream of the tube's orifice. Second, a minimum withdrawal flow rate must be reached for entrainment regardless of the distance between the interface and the tube. We show that these phenomena can be understood based on the Reynolds number that governs the external flow field around the capillary tube and the capillary number that regulates the effect of the viscosity and capillarity.

A quantitative study of the effect of flow on the photopolymerization of fibers.

Pulsed-UV light in the continuous flow of a photo-crosslinkable liquid can result in gelation and is a useful method to produce soft microfibers with uniform sizes. With modeling and experiments, we characterize some aspects of this fiber fabrication process. We model the spatial concentration profiles of radical species and molecular oxygen in the flow direction during light exposure, and predict the critical conditions for the onset of fiber formation and compare these predictions with experimental observations. We also characterize the different regimes of microfiber production (no polymerization, non-uniform fibers, and uniform microfibers), qualitatively characterize the rigidity of the fibers, and demonstrate that we can predictably control the length of the produced microfibers for a range of process parameters.

Representative subsampling of sedimenting blood.

It is often necessary to extract a small amount of a suspension, such as blood, from a larger sample of the same material for the purposes of diagnostics, testing or imaging. A practical challenge is that the cells in blood sediment noticeably on the time scale of a few minutes, making a representative subsampling of the original sample challenging. Guided by experimental data, we develop a Kynch sedimentation model to discuss design considerations that ensure a representative subsampling of blood, from a container of constant cross-sectional area, for the entire range of physiologically relevant hematocrit over a specified time of interest. Additionally, we show that this design may be modified to exploit the sedimentation and perform subsampling to achieve either higher or lower hematocrit relative to that of the original sample. Thus, our method provides a simple tool to either concentrate or dilute small quantities of blood or other sedimenting suspensions.

Controlled generation of spiky microparticles by ionic cross-linking within an aqueous two-phase system.

Microparticles are used in a variety of different fields, such as drug delivery. Recently, non-spherical microparticle generation has become desirable. The high surface-to-volume ratio of non-spherical microparticles allows for enhanced targeting, and attachment to cells and tissue. Current non-spherical microparticle generation techniques require complicated setup, and utilizing natural micrograins, such as pollen grains, as non-spherical delivery vehicles, requires extensive post-processing. Here, we describe a unique and facile chemical synthesis approach, for controlled generation of pollen-like microparticles, based on ionic cross-linking of alginate and calcium chloride (CaCl2), within an all-biocompatible aqueous two-phase system (ATPS) of dextran (DEX) and polyethylene glycol (PEG). Our technique controls the length of spikes that emerge on the surface of these microparticles. We anticipate that these pollen-like spiky microparticles may be used as drug delivery vehicles, and this new chemical synthesis approach may be used for generating other biomaterials.

Design of a microfluidic device for the measurement of the elastic modulus of deformable particles.

A microfluidic technique recently proposed in the literature to measure the interfacial tension between a liquid droplet and an immiscible suspending liquid [Hudson et al., Appl. Phys. Lett., 2005, 87, 081905], [Cabral and Hudson, Lab Chip, 2006, 6, 427] is suitably adapted to the characterization of the elastic modulus of soft particles in a continuous-flow process. A microfluidic device consisting of a cylindrical pipe with a reduction in cross-section is designed, and the deformation and velocity of incompressible elastic particles suspended in a Newtonian liquid are tracked as they move along the centerline through the constriction. Kinematic and shape information is exploited to calculate the particle's elastic modulus by means of the theory of elastic particle deformation in extensional flow. The approach is validated for different orders of magnitude of the elastic capillary number through experiments and numerical simulations.

Laboratory layered latte.

Inducing thermal gradients in fluid systems with initial, well-defined density gradients results in the formation of distinct layered patterns, such as those observed in the ocean due to double-diffusive convection. In contrast, layered composite fluids are sometimes observed in confined systems of rather chaotic initial states, for example, lattes formed by pouring espresso into a glass of warm milk. Here, we report controlled experiments injecting a fluid into a miscible phase and show that, above a critical injection velocity, layering emerges over a time scale of minutes. We identify critical conditions to produce the layering, and relate the results quantitatively to double-diffusive convection. Based on this understanding, we show how to employ this single-step process to produce layered structures in soft materials, where the local elastic properties vary step-wise along the length of the material.

Flow-induced gelation of microfiber suspensions.

The flow behavior of fiber suspensions has been studied extensively, especially in the limit of dilute concentrations and rigid fibers; at the other extreme, however, where the suspensions are concentrated and the fibers are highly flexible, much less is understood about the flow properties. We use a microfluidic method to produce uniform concentrated suspensions of high aspect ratio, flexible microfibers, and we demonstrate the shear thickening and gelling behavior of such microfiber suspensions, which, to the best of our knowledge, has not been reported previously. By rheological means, we show that flowing the suspension triggers the irreversible formation of topological entanglements of the fibers resulting in an entangled water-filled network. This phenomenon suggests that flexible fiber suspensions can be exploited to produce a new family of flow-induced gelled materials, such as porous hydrogels. A significant consequence of these flow properties is that the microfiber suspension is injectable through a needle, from which it can be extruded directly as a hydrogel without any chemical reactions or further treatments. Additionally, we show that this fiber hydrogel is a soft, viscoelastic, yield-stress material.