Diffusion-Dominated Pinch-Off of Ultralow Surface Tension Fluids

We study the breakup of a liquid thread inside another liquid at different surface tensions. In general, the pinch-off of a liquid thread is governed by the dynamics of fluid flow. However, when the interfacial tension is ultralow (2 to 3 orders lower than normal liquids), we find that the pinch-off dynamics can be governed by bulk diffusion. By studying the velocity and the profile of the pinch-off, we explain why the diffusion-dominated pinch-off takes over the conventional breakup at ultralow surface tensions.Comment: 7 pages, 5 figures. Published versio

Additive Manufacturing in Customized Medical Device

The long-established application of rapid prototyping in additive manufacturing (AM) has inspired a revolution in the medical industry into a new era, in which the clinical-driven development of the customized medical device is enabled. This transformation could only be sustainable if clinical concerns could be well addressed. In this work, we propose a workflow that addresses critical clinical concerns such as translation from medical needs to product innovation, anatomical conformation and execution, and validation. This method has demonstrated outstanding advantages over the traditional manufacturing approach in terms of form, function, precision, and clinical flexibility. We further propose a protocol for the validation of biocompatibility, material, and mechanical properties. Finally, we lay out a roadmap for AM-driven customized medical device innovation based on our experiences in Hong Kong, addressing problems of certification, qualification, characterization of three dimensional (3D) printed implants according to medical demands

Effects of SARS-CoV-2 infection on incidence and treatment strategies of hepatocellular carcinoma in people with chronic liver disease

BACKGROUND: Chronic liver disease (CLD) was associated with adverse clinical outcomes among people with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. AIM To determine the effects of SARS-CoV-2 infection on the incidence and treatment strategy of hepatocellular carcinoma (HCC) among patients with CLD. METHODS: A retrospective, territory-wide cohort of CLD patients was identified from an electronic health database in Hong Kong. Patients with confirmed SARS-CoV-2 infection [coronavirus disease 2019 (COVID-19)+CLD] between January 1, 2020 and October 25, 2022 were identified and matched 1:1 by propensity-score with those without (COVID-19-CLD). Each patient was followed up until death, outcome event, or November 15, 2022. Primary outcome was incidence of HCC. Secondary outcomes included all-cause mortality, adverse hepatic outcomes, and different treatment strategies to HCC (curative, non-curative treatment, and palliative care). Analyses were further stratified by acute (within 20 d) and post-acute (21 d or beyond) phases of SARS-CoV-2 infection. Incidence rate ratios (IRRs) were estimated by Poisson regression models. RESULTS: Of 193589 CLD patients (> 95% non-cirrhotic) in the cohort, 55163 patients with COVID-19+CLD and 55163 patients with COVID-19-CLD were included after 1:1 propensity-score matching. Upon 249-d median follow-up, COVID-19+CLD was not associated with increased risk of incident HCC (IRR: 1.19, 95%CI: 0.99-1.42, P = 0.06), but higher risks of receiving palliative care for HCC (IRR: 1.60, 95%CI: 1.46-1.75, P < 0.001), compared to COVID-19- CLD. In both acute and post-acute phases of infection, COVID-19+CLD were associated with increased risks of all-cause mortality (acute: IRR: 7.06, 95%CI: 5.78-8.63, P < 0.001; post-acute: IRR: 1.24, 95%CI: 1.14-1.36, P < 0.001) and adverse hepatic outcomes (acute: IRR: 1.98, 95%CI: 1.79-2.18, P < 0.001; post-acute: IRR: 1.24, 95%CI: 1.13-1.35, P < 0.001), compared to COVID-19-CLD. CONCLUSION: Although CLD patients with SARS-CoV-2 infection were not associated with increased risk of HCC, they were more likely to receive palliative treatment than those without. The detrimental effects of SARS-CoV-2 infection persisted in post-acute phase

Droplet Formation by Rupture of Vibration-Induced Interfacial Fingers

By imposing vibration to a core-annular flow of an aqueous two-phase system (ATPS) with ultralow interfacial tension, we observe a liquid finger protruding from the interface of an expanding jet. We find that the protruded finger breaks up only when its length-to-width ratio exceeds a threshold value. The breakup follows a constant wavelength-to-width ratio that is consistent with that of breakup under Rayleigh-Plateau instability. The mechanism is applicable to aqueous two-phase systems with a large range of viscosity ratios. The protruded finger can break up into small droplets that are monodisperse in size, controllable in generation frequency under a wide range of flow rates. This work suggests a way to generate small water–water droplets with high monodispersity and production rate from a single nozzle

Engineering an Enhanced EGFR Engager: Humanization of Cetuximab for Improved Developability

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase whose proliferative effects can contribute to the development of many types of solid tumors when overexpressed. For this reason, EGFR inhibitors such as cetuximab can play an important role in treating cancers such as colorectal cancer and head and neck cancer. Cetuximab is a chimeric monoclonal antibody containing mouse variable regions that bind to EGFR and prevent it from signaling. Although cetuximab has been used clinically since 2004 to successfully control solid tumors, advances in protein engineering have created the opportunity to address some of its shortcomings. In particular, the presence of mouse sequences could contribute to immunogenicity in the form of anti-cetuximab antibodies, and an occupied glycosylation site in FR3 can contribute to hypersensitivity reactions and product heterogeneity. Using simple framework graft or sequence-/structure-guided approaches, cetuximab was humanized onto 11 new frameworks. In addition to increasing humanness and removing the VH glycosylation site, dynamic light scattering revealed increases in stability, and bio-layer interferometry confirmed minimal changes in binding affinity, with patterns emerging across the humanization method. This work demonstrates the potential to improve the biophysical and clinical properties of first-generation protein therapeutics and highlights the advantages of computationally guided engineering

Emergence of Droplets at the Nonequilibrium All-Aqueous Interface in a Vertical Hele-Shaw Cell

The interfacial phenomena at liquid–liquid interfaces remain the subject of constant fascination in science and technology. Here, we show that fingers forming at the interface of nonequilibrium all-aqueous systems can spontaneously break into an array of droplets. The dynamic formation of droplets at the water–water (w/w) interface is observed when a less dense aqueous phase, for instance, the dextran solution, is placed on a denser aqueous phase, the polyethylene glycol solution, in a vertical Hele-Shaw cell. Because of the gradual diffusion of water from the upper phase into the lower phase, a dense layer appears at the nonequilibrium w/w interface. As a result, a periodic array of fingers emerge and sink. Remarkably, these fingers break up and an array of droplets are emitted from the interface. We characterize the wavelength of fingering by measuring the average distance between the dominant fingers. By varying the initial concentrations of the two nonequilibrium aqueous phases, we identify experimentally a phase diagram with a wide parameter space in which finger breaking occurs. Finally, plenty of droplets, spontaneously formed when one phase is continuously deposited onto another aqueous phase, further confirm the robustness of our experimental results. Our work suggests a simple yet efficient approach with a potential upscalability to generate all-aqueous droplets

Emergence of Droplets at the Nonequilibrium All-Aqueous Interface in a Vertical Hele-Shaw Cell

The interfacial phenomena at liquid–liquid interfaces remain the subject of constant fascination in science and technology. Here, we show that fingers forming at the interface of nonequilibrium all-aqueous systems can spontaneously break into an array of droplets. The dynamic formation of droplets at the water–water (w/w) interface is observed when a less dense aqueous phase, for instance, the dextran solution, is placed on a denser aqueous phase, the polyethylene glycol solution, in a vertical Hele-Shaw cell. Because of the gradual diffusion of water from the upper phase into the lower phase, a dense layer appears at the nonequilibrium w/w interface. As a result, a periodic array of fingers emerge and sink. Remarkably, these fingers break up and an array of droplets are emitted from the interface. We characterize the wavelength of fingering by measuring the average distance between the dominant fingers. By varying the initial concentrations of the two nonequilibrium aqueous phases, we identify experimentally a phase diagram with a wide parameter space in which finger breaking occurs. Finally, plenty of droplets, spontaneously formed when one phase is continuously deposited onto another aqueous phase, further confirm the robustness of our experimental results. Our work suggests a simple yet efficient approach with a potential upscalability to generate all-aqueous droplets

Emergence of Droplets at the Nonequilibrium All-Aqueous Interface in a Vertical Hele-Shaw Cell

The interfacial phenomena at liquid–liquid interfaces remain the subject of constant fascination in science and technology. Here, we show that fingers forming at the interface of nonequilibrium all-aqueous systems can spontaneously break into an array of droplets. The dynamic formation of droplets at the water–water (w/w) interface is observed when a less dense aqueous phase, for instance, the dextran solution, is placed on a denser aqueous phase, the polyethylene glycol solution, in a vertical Hele-Shaw cell. Because of the gradual diffusion of water from the upper phase into the lower phase, a dense layer appears at the nonequilibrium w/w interface. As a result, a periodic array of fingers emerge and sink. Remarkably, these fingers break up and an array of droplets are emitted from the interface. We characterize the wavelength of fingering by measuring the average distance between the dominant fingers. By varying the initial concentrations of the two nonequilibrium aqueous phases, we identify experimentally a phase diagram with a wide parameter space in which finger breaking occurs. Finally, plenty of droplets, spontaneously formed when one phase is continuously deposited onto another aqueous phase, further confirm the robustness of our experimental results. Our work suggests a simple yet efficient approach with a potential upscalability to generate all-aqueous droplets