Search for: All records

Rapid Room-Temperature Aerosol Dehydration (RTAD) is a novel, scalable drying technology for powderization and thermal stabilization of pharmaceutical drug products. Compared to conventional spray drying processes, typically using droplets of 10–200 lm in diameter generated by high-shear spraying, RTAD uses much smaller droplets with diameter 0.1 to 20 lm produced in modified liquid atomization processes. These fine droplets evaporate rapidly within 10–100 ms under room-temperature conditions, thereby reducing drying-induced stresses for thermally sensitive biologics. In this study, we used Green Fluorescent Protein (GFP) as a model biological molecule to optimize the design of the RTAD system and the process parameters. We experimentally investigated the effects of droplet size, multiphase flow patterns in the drying chamber, and application of polysorbate 20 as a model surfactant on GFP fluorescence after drying and powder reconstitution. The experiments demonstrated that the presence of surfactant in the formulation significantly influenced the GFP fluorescence intensity, especially for smaller droplets. The numerical studies using Computational Fluid Dynamics simulations revealed that the drying of droplets was dependent on the patterns of multiphase flow in the drying chamber, which can impact the intensity of GFP fluorescence in the produced dry powders. Non-axisymmetric flows and closed circulating streamlines near the drying gas inlet resulted in considerably longer particle residence times, which we infer means that GFP molecules were subjected to excess stress that negatively impacted the GFP fluorescence intensity. Through iterative optimization of the chamber design, process parameters and feedstock formulation, we achieved recovery of the GFP fluorescence intensity that exceeded 96% in the obtained dry powders. This work establishes GFP as a sensitive model biologic and its fluorescence intensity as a powerful tool to rapidly assess process efficiency and the ability to preserve bioactivity after dehydration. The study has broad implications for the design and scale-up of drying technologies, which can potentially transform the production of dry powder biopharmaceuticals. 

Abstract Despite centuries of investigation, bubbles continue to unveil intriguing dynamics relevant to a multitude of practical applications, including industrial, biological, geophysical, and medical settings. Here we introduce bubbles that spontaneously start to ‘gallop’ along horizontal surfaces inside a vertically-vibrated fluid chamber, self-propelled by a resonant interaction between their shape oscillation modes. These active bubbles exhibit distinct trajectory regimes, including rectilinear, orbital, and run-and-tumble motions, which can be tuned dynamically via the external forcing. Through periodic body deformations, galloping bubbles swim leveraging inertial forces rather than vortex shedding, enabling them to maneuver even when viscous traction is not viable. The galloping symmetry breaking provides a robust self-propulsion mechanism, arising in bubbles whether separated from the wall by a liquid film or directly attached to it, and is captured by a minimal oscillator model, highlighting its universality. Through proof-of-concept demonstrations, we showcase the technological potential of the galloping locomotion for applications involving bubble generation and removal, transport and sorting, navigating complex fluid networks, and surface cleaning. The rich dynamics of galloping bubbles suggest exciting opportunities in heat transfer, microfluidic transport, probing and cleaning, bubble-based computing, soft robotics, and active matter. 

The nucleolus is a multiphasic biomolecular condensate that facilitates ribosome biogenesis, a complex process involving hundreds of proteins and RNAs. The proper execution of ribosome biogenesis likely depends on the material properties of the nucleolus. However, these material properties remain poorly understood due to the challenges of in vivo measurements. Here, we use micropipette aspiration (MPA) to directly characterize the viscoelasticity and interfacial tensions of nucleoli within transcriptionally activeXenopus laevisoocytes. We examine the major nucleolar subphases, the outer granular component (GC) and the inner dense fibrillar component (DFC), which itself contains a third small phase known as the fibrillar center (FC). We show that the behavior of the GC is more liquid-like, while the behavior of the DFC/FC is consistent with that of a partially viscoelastic solid. To determine the role of ribosomal RNA in nucleolar material properties, we degrade RNA using RNase A, which causes the DFC/FC to become more fluid-like and alters interfacial tension. Together, our findings suggest that RNA underlies the partially solid-like properties of the DFC/FC and provide insights into how material properties of nucleoli in a near-native environment are related to their RNA-dependent function. 

Single-chain nanoparticles (SCNPs) formviaintramolecular folding and cross-linking of polymers. We examine how dimensionless design parameters dictate SCNP morphology, highlighting the influence of shear flow. 

Surface-attached cells can sense and respond to shear flow, but planktonic (free-swimming) cells are typically assumed to be oblivious to any flow that carries them. Here, we find that planktonic bacteria can transcriptionally respond to flow, inducing expression changes that are beneficial in flow. Specifically, we use microfluidic experiments and quantitative modeling to show that in the presence of flow, planktonicPseudomonas aeruginosainduce shear rate–dependent genes that promote growth in low-oxygen environments. Untangling this mechanism revealed that in flow, motileP. aeruginosaspatially redistribute, leading to cell density changes that activate quorum sensing, which in turn enhances the oxygen uptake rate. In diffusion-limited environments, including those commonly encountered by bacteria, flow-induced cell density gradients also independently generate oxygen gradients that alter gene expression. Mutants deficient in this flow-responsive mechanism exhibit decreased fitness in flow, suggesting that this dynamic coupling of biological and mechanical processes can be physiologically significant. 

In fiber spinning of photopolymers, surface tension limits the diameter of the fiber that can be produced due to the Rayleigh–Plateau instability. Submerging a pre-fiber jet in a miscible environment liberates the system from capillary effects, thus allowing the jet to be stretched into thin threads without instability. In this work, we systematically investigated a spinning method using miscible liquids, called jet-assisted wet spinning (JAWS), where stretching is achieved by a nearby submerged liquid jet. The diameter of the pre-fiber jet is a function of its flow rate and position relative to the assisting submerged liquid jet. A particular case where the main jet is modeled as the Landau–Squire jet is used to demonstrate the tracer-like thinning behavior of the pre-fiber jet. Experiments show that buoyancy has a significant impact on the pre-fiber jet diameter because of its influence on the entrainment trajectory. Overall, our results demonstrate the potential for the parallelization of JAWS for high-throughput fiber production.