Hydrodynamic Characterization of Phase Separation in Devices with Microfabricated Capillaries

Capillary microseparators have been gaining interest in downstream unit operations, especially for pharmaceutical, space, and nuclear applications, offering efficient separation of two-phase flows. In this work, a detailed analysis of the dynamics of gas–liquid separation at the single meniscus level helped to formulate a model to map the operability region of microseparation devices. A water–nitrogen segmented flow was separated in a microfabricated silicon-glass device, with a main channel (width, W = 600 μm; height, H = 120 μm) leading into an array of 276 capillaries (100 μm long; width = 5 μm facing the main channel and 25 μm facing the liquid outlet), on both sides of the channel. At optimal pressure differences, the wetting phase (water) flowed through the capillaries into the liquid outlet, whereas the nonwetting phase (nitrogen) flowed past the capillaries into the gas outlet. A high-speed imaging methodology aided by computational analysis was used to quantify the length of the liquid slugs and their positions in the separation zone. It was observed that during stable separation, the position of the leading edge of the liquid slugs (advancing meniscus), which became stationary in the separation zone, was dependent only on the outlet pressure difference. The trailing edge of the liquid slugs (receding meniscus) approached the advancing meniscus at a constant speed, thus leading to a linear decrease of the liquid slug length. Close to the liquid-to-gas breakthrough point, that is, when water exited through the gas outlet, the advancing meniscus was no longer stationary, and the slug lengths decreased exponentially. The rates of decrease of the liquid slug length during separation were accurately estimated by the model, and the calculated liquid-to-gas breakthrough pressures agreed with experimental measurements

Experimental and computational investigation of heat transfer in a microwave-assisted flow system

Microwave technology is gaining popularity as a tool for chemical process intensification and an alternative to conventional heating. However, in flow systems non-uniform temperature profiles are commonly encountered and hence methods to characterise and improve them are required. In this work, we studied the effects of various operational parameters-microwave power, inlet flow rate, tube orientation and pressure-on the electric field and temperature profiles of water flowing in a PTFE tube (2.4 mm internal diameter), placed in a commercial single-mode microwave applicator. A finite element model was developed to estimate the longitudinal temperature profiles and the absorbed microwave power, while in situ temperature monitoring was performed by a fibre optic probe placed at multiple locations inside the tube. The water temperature inside the tube increased by increasing the microwave power input and temperature profiles stabilised beyond 20 W, while the percentage absorbed microwave power showed the inverse trend. When changing the tube orientation or decreasing the inlet flow rate, microwave absorption decreased significantly. When the pressure was increased to 2.3 bara, water temperature increased by ~ 20 o C. Results from this study provide valuable insights on achievable temperature profiles and energy efficiency of microwave-assisted flow synthesis systems.

Recent advances in acoustic diagnostics for electrochemical power systems

Acknowledgments The authors would like to gratefully acknowledge the EPSRC for supporting the electrochemical research in the Electrochemical Innovation Lab (EP/R020973/1; EP/R023581/1; EP/N032888/1; EP/R023581/1; EP/P009050/1; EP/M014371/1; EP/M009394; EP/L015749/1; EP/K038656/1) and Innovate UK for funding the VALUABLE project (Grant No. 104182). The authors would also like to acknowledge the Royal Academy of Engineering for funding Robinson and Shearing through ICRF1718\1\34 and CiET1718 respectively and the Faraday Institution (EP/S00353/1, Grant Nos. FIRG003, FIRG014). The authors also acknowledge the STFC for supporting Shearing and Brett (ST/K00171X/1) and ACEA for supporting ongoing research at the EIL. Support from the National Measurement System of the UK Department for Business, Energy and Industrial Strategy is also gratefully acknowledged.Peer reviewedPublisher PD

Mitochondrial Pathway Mediates the Antileukemic Effects of Hemidesmus Indicus, a Promising Botanical Drug

Although cancers are characterized by the deregulation of multiple signalling pathways, most current anticancer therapies involve the modulation of a single target. Because of the enormous biological diversity of cancer, strategic combination of agents targeted against the most critical of those alterations is needed. Due to their complex nature, plant products interact with numerous targets and influence several biochemical and molecular cascades. The interest in further development of botanical drugs has been increasing steadily and the FDA recently approved the first new botanical prescription drug. The present study is designed to explore the potential antileukemic properties of Hemidesmus indicus with a view to contributing to further development of botanical drugs. Hemidesmus was submitted to an extensive in vitro preclinical evaluation.A variety of cellular assays and flow cytometry, as well as a phytochemical screening, were performed on different leukemic cell lines. We have demonstrated that Hemidesmus modulated many components of intracellular signaling pathways involved in cell viability and proliferation and altered the protein expression, eventually leading to tumor cell death, mediated by a loss of mitochondrial transmembrane potential and increased Bax/Bcl-2 ratio. ADP, adenine nucleotide translocator and mitochondrial permeability transition pore inhibitors did not reverse Hemidesmus-induced mitochondrial depolarization. Hemidesmus induced a significant [Ca(2+)](i) raise through the mobilization of intracellular Ca(2+) stores. Moreover, Hemidesmus significantly enhanced the antitumor activity of three commonly used chemotherapeutic drugs (methotrexate, 6-thioguanine, cytarabine). A clinically relevant observation is that its cytotoxic activity was also recorded in primary cells from acute myeloid leukemic patients.These results indicate the molecular basis of the antileukemic effects of Hemidesmus and identify the mitochondrial pathways and [Ca(2+)](i) as crucial actors in its anticancer activity. On these bases, we conclude that Hemidesmus can represent a valuable tool in the anticancer pharmacology, and should be considered for further investigations

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Nonlinear Dynamics of Gas-Liquid Separation in a Capillary Microseparator

Micro-engineered devices (MED) are seeing a significant growth in performing separation processes. Such devices have been implemented in a range of applications from chemical catalytic reactors to product purification systems like microdistillation. One of the biggest advantages of these devices is the dominance of capillarity and interfacial tension forces. A field where MEDs have been used is in gas-liquid separations. These are encountered, for example, after a chemical reactor, where a gaseous component being produced needs immediate removal from the reactor, because it can affect subsequent reactions. The gaseous phase can be effectively removed using an MED with an array of microcapillaries. Phase-separation can then be brought about in a controlled manner along these capillary structures. For a device made from a hydrophilic material (e.g. Si or glass), the wetted phase (e.g. water) flows through the capillaries, while the non-wetted dispersed phase (e.g. gas) is prevented from entering the capillaries, due to capillary pressure. Separation of liquid-liquid flows can also be achieved via this approach. However, the underlying mechanism of phase separation is far from being fully understood. The pressure at which the gas phase enters the capillaries (gas-to-liquid breakthrough) can be estimated from the Young-Laplace equation, governed by the surface tension (γ) of the wetted phase, capillary width (d) and height (h), and the interface equilibrium contact angle (θeq). Similarly, the liquid-to-gas breakthrough pressure (i.e. the point at which complete liquid separation ceases and liquid exits through the gas outlet) can be estimated from the pressure drop across the capillaries via the Hagen-Poiseuille (HP) equation. Several groups reported deviations from these estimates and therefore, included various parameters to account for the deviations. These parameters usually account for (i) flow of wetted phase through ‘n’ capillaries in parallel, (ii) modification of geometric correction factor of Mortensen et al., 2005 and (iii) liquid slug length (LS) and number of capillaries (n) during separation. LS has either been measured upstream of the capillary zone or estimated from a scaling law proposed by Garstecki et al., 2006. However, this approach does not address the balance between the superficial inlet velocity and net outflow of liquid through each capillary (qc). Another shortcoming of these models has been the estimation of the apparent contact angle (θapp), which plays a critical role in predicting liquid-to-gas breakthrough. θapp is either assumed to be equal to θeq or measured with various techniques, e.g. through capillary rise or a static droplet on a flat substrate, which is significantly different from actual dynamic contact angles during separation. In other cases, the Cox-Voinov model has been used to calculate θapp from θeq and capillary number. Hence, the empirical models available in the literature do not predict realistic breakthrough pressures with sufficient accuracy. Therefore, a more detailed in situ investigation of the critical liquid slug properties during separation is necessary. Here we report advancements in the fundamental understanding of two-phase separation in a gas-liquid separation (GLS) device through a theoretical model developed based on critical events occurring at the gas-liquid interfaces during separation

Clinical characteristics of a South Indian cohort of juvenile myoclonic epilepsy probands

Despite the distinctive clinical and electroencephalographic features known for five decades, even today, juvenile myoclonic epilepsy (JME) is frequently unrecognised and misdiagnosed in both developed and developing countries. Utilising 183 JME probands belonging to the South Indian state of Kerala, assembled through a tertiary referral centre for molecular genetic studies, we explored the phenotypic peculiarities, clinical genetics, and problems and pitfalls in the diagnosis of JME. At referral, only six (3.3%) patients carried the diagnostic label of JME, default in diagnosis resulted from failure to elicit the history of myoclonic jerks by the referring physicians. During the mean delay of 8.6± 7.0 years in diagnosing JME, seizure control in the majority was poor due to inappropriate antiepileptic drug (AED) therapy. A history of epileptic seizures was obtained in 6.2% of the first-degree and 2.2% of the second-degree relatives of the probands; 37.7 and 11.1% of them, respectively, were diagnosed as JME. Although most of the clinical features of our cohort were in accordance with the literature, two notable differences we observed were the relatively increased occurrence of absence seizures and low frequency of photoparoxysmal responses. Although the variability in the clinical characteristics of JME may be apparent due to differences in the ascertainment of the data, they may well be an expression of a true clinical heterogeneity, and are in accordance with the complex and variable mode of inheritance and conflicting linkage studies reported for this syndrome from different ethnic groups

Quantitative spatiotemporal mapping of thermal runaway propagation rates in lithium-ion cells using cross-correlated Gabor filtering

Abuse testing of lithium-ion batteries is widely performed in order to develop new safety standards and strategies. However, testing methodologies are not standardised across the research community, especially with failure mechanisms being inherently difficult to reproduce. High-speed X-ray radiography is proven to be a valuable tool to capture events occurring during cell failure, but the observations made remain largely qualitative. We have therefore developed a robust image processing toolbox that can quantify, for the first time, the rate of propagation of battery failure mechanisms revealed by high-speed X-ray radiography. Using Gabor filter, the toolbox selectively tracks the electrode structure at the onset of failure. This facilitated the estimation of the displacement of electrodes undergoing abuse via nail penetration, and also the tracking of objects, such as the nail, as it propagates through a cell. Further, by cross-correlating the Gabor signals, we have produced practical, illustrative spatiotemporal maps of the failure events. From these, we can quantify the propagation rates of electrode displacement prior to the onset of thermal runaway. The highest recorded acceleration (≈ 514 mm s-2) was when a nail penetrated a cell radially (perpendicular to the electrodes) as opposed to axially (parallel to the electrodes). The initiation of thermal runaway was also resolved in combination with electrode displacement, which occurred at a lower acceleration (≈ 108 mm s-2). Our assistive toolbox can also be used to study other types of failure mechanisms, extracting otherwise unattainable kinetic data. Ultimately, this tool can be used to not only validate existing theoretical mechanical models, but also standardise battery failure testing procedures

Temperature-induced liquid crystal microdroplet formation in a partially miscible liquid mixture

Liquid-in-liquid droplets are typically generated by the partitioning of immiscible fluids, e.g. by mechanical shearing with macroscopic homogenisers or microfluidic flow focussing. In contrast, partially miscible liquids with a critical solution temperature display a temperature-dependent mixing behaviour. In this work, we demonstrate how, for a blend of methanol (MeOH) and the thermotropic liquid crystal (LC) 4-Cyano-4 '-pentylbiphenyl (5CB), cooling from a miscible to an immiscible state allows the controlled formation of microdroplets. A near-room-temperature-induced phase separation leads to nucleation, growth and coalescence of mesogen-rich droplets. The size and number of the droplets is tunable on the microscopic scale by variation of temperature quench depth and cooling rate. Further cooling induces a phase transition to nematic droplets with radial configuration, well-defined sizes and stability over the course of an hour. This temperature-induced approach offers a scalable and reversible alternative to droplet formation with relevance in diagnostics, optoelectronics, materials templating and extraction processes