Liquid-liquid slug flow: Hydrodynamics and pressure drop

In this paper, the hydrodynamics and the pressure drop of liquid-liquid slug flow in round microcapillaries are presented. Two liquid-liquid flow systems are considered, viz. water-toluene and ethylene glycol/water-toluene. The slug lengths of the alternating continuous and dispersed phases were measured as a function of the slug velocity (0.03-0.5 m/s), the organic-to-aqueous flow ratio (0.1-4.0), and the microcapillary internal diameter (248 and 498 mu m). The pressure drop is modeled as the sum of two contributions: the frictional and the interface pressure drop. Two models are presented, viz, the stagnant film model and the moving film model. Both models account for the presence of a thin liquid film between the dispersed phase slug and the capillary wall. It is found that the film velocity is of negligible influence on the pressure drop. Therefore, the stagnant film model is adequate to accurately predict the liquid-liquid slug flow pressure drop. The influence of inertia and the consequent change of the slug cap curvature are accounted for by modifying Bretherton's curvature parameter in the interface pressure drop equation. The stagnant film model is in good agreement with experimental data with a mean relative error of less than 7%.

Slug-dependent upregulation of L1CAM is responsible for the increased invasion potential of pancreatic cancer cells following long-term 5-FU treatment

BACKGROUND: Pancreatic adenocarcinoma is a lethal disease with 5-year survival of less than 5%. 5-fluorouracil (5-FU) is a principal first-line therapy, but treatment only extends survival modestly and is seldom curative. Drug resistance and disease recurrence is typical and there is a pressing need to overcome this. To investigate acquired 5-FU resistance in pancreatic adenocarcinoma, we established chemoresistant monoclonal cell lines from the Panc 03.27 cell line by long-term exposure to increasing doses of 5-FU.

RESULTS: 5-FU-resistant cell lines exhibited increased expression of markers associated with multidrug resistance explaining their reduced sensitivity to 5-FU. In addition, 5-FU-resistant cell lines showed alterations typical for an epithelial-to-mesenchymal transition (EMT), including upregulation of mesenchymal markers and increased invasiveness. Microarray analysis revealed the L1CAM pathway as one of the most upregulated pathways in the chemoresistant clones, and a significant upregulation of L1CAM was seen on the RNA and protein level. In pancreatic cancer, expression of L1CAM is associated with a chemoresistant and migratory phenotype. Using esiRNA targeting L1CAM, or by blocking the extracellular part of L1CAM with antibodies, we show that the increased invasiveness observed in the chemoresistant cells functionally depends on L1CAM. Using esiRNA targeting β-catenin and/or Slug, we demonstrate that in the chemoresistant cell lines, L1CAM expression depends on Slug rather than β-catenin.

CONCLUSION: Our findings establish Slug-induced L1CAM expression as a mediator of a chemoresistant and migratory phenotype in pancreatic adenocarcinoma cells.

Gas-liquid two phase flow through a vertical 90deg elbow bend

Pressure drop data are reported for two phase air-water flow through a vertical to horizontal 90° elbow bend set in 0.026 m i.d. pipe. The pressure drop in the vertical inlet tangent showed some significant differences to that found for straight vertical pipe. This was caused by the elbow bend partially choking the inflow resulting in a build-up of pressure and liquid in the vertical inlet riser and differences in the structure of the flow regimes when compared to the straight vertical pipe. The horizontal outlet tangent by contrast gave data in general agreement with literature even to exhibiting a drag reduction region at low liquid rates and gas velocities between 1 and 2 m s -1. The elbow bend pressure drop was best correlated in terms of le/d determined using the actual pressure loss in the inlet vertical riser. The data showed a general increase with fluid rates that tapered off at high fluid rates and exhibited a negative pressure region at low rates. The latter was attributed to the flow being smoothly accommodated by the bend when it passed from slug flow in the riser to smooth stratified flow in the outlet tangent. A general correlation was presented for the elbow bend pressure drop in terms of total Reynolds numbers. A modified Lockhart-Martinelli model gave prediction of the data.

A Universal Flow Regime Map for Horizontal Two-Phase Flow in Pipes

A new universal flow map has been developed for two-phase co-current flow. The map has been successfully tested against wide variety of data. Flow regime transition predictors suggested by other authors have been shown to be useful. New transitional models are proposed for the stratified to annular regimes, blow through slug and intermittent regimes.

Self-potential signatures associated with an injection experiment at an in situ biological permeable reactive barrier

Strategies available to evaluate the performance of in situ permeable reactive barriers are currently not well developed and often rely on fluid and media sampling directly from the permeable reactive barrier (PRB). Here, we investigate the utility of the self-potential (SP) method as a technique to monitor in situ PRB performance. Our field study was conducted at in situ biological PRB in Portadown, Northern Ireland, UK, which was emplaced to assist in the remediation of groundwater contamination (e.g., hydrocarbons, ammonia) that resulted from the operations and waste disposal practices of a former gasworks. Borehole SP measurements were collected during the injection of contaminant groundwater slugs in an attempt to monitor/detect the response of the microbial activity associated with the breakdown of the added contaminants into the PRB. In addition, an uncontaminated groundwater slug was injected into a different portion of the PRB as a ‘control’ and SP measurements were collected for comparison to the SP response of the contaminant slugs. The results of the SP signals due to the contaminant injections show that the magnitude of the response was relatively small (<10 mV) yet showed a consistent decrease during both contaminant injections. The net decrease in SP recorded during the contaminant injections slowly rebounded to near background values through ~44 hours post-injection. The SP response during the uncontaminated injection showed a slight, albeit negligible (within the margin of error), 1 mV increase in the measured SP signals, in contrast to the contaminant injections. The results of the SP signals recorded from the uncontaminated groundwater injection also persisted through a period of ~47 hours after injection but show a net increase in SP relative to pre-injection values. Based on the difference in SP response between the contaminated and uncontaminated injections, we suggest that the responses are likely to be the result of differences in the chemistry of the injection types (contaminated versus uncontaminated) and in situ groundwater. We argue that the SP signals associated with the contaminated injections are dominated by diffusion (electrochemical) potential, possibly enhanced by a microbial effect. While the results of our investigation show a consistent SP response associated with the contaminant injections that is dominated by diffusional effects, further studies are required in order to better understand the effect of microbial activity on SP signals and the potential utility for the SP method to detect/monitor changes that may be indicative of biological PRB performance.

Phase-Transfer Catalysis in Segmented Flow in a Microchannel: Fluidic Control of Selectivity and Productivity

Precise control over the interfacial area of aqueous and organic slugs in segmented flow in a microchannel reactor provides an attractive means to optimize the yield and productivity of a phase-transfer-catalyzed reaction. Herein, we report the selective alkylation of phenylacetonitrile to the monoalkylated product in a microchannel of 250-mu m internal diameter operated in a continuous and solvent-free manner in the slug-flow regime. The conversion of phenylacetonitrile increased from 40% to 99% as a result of a 97% larger slug surface-to-volume ratio when the volumetric aqueous-to-organic phase flow ratio was raised from 1.0 to 6.1 at the same residence time. The larger surface-to-volume ratio significantly promoted catalyst phase transfer but decreased selectivity because of the simultaneous increase of the rate of the consecutive reaction to the dialkylated product. There exists all Optimum flow ratio with a maximum productivity. Conversion and selectivity in the microchannel reactor were both found to be significantly larger than in a stirred reactor.

Non-aqueous silicone elastomer gels as a vaginal microbicide delivery system for the HIV-1 entry inhibitor maraviroc

Aqueous semi-solid polymeric gels, such as those based on hydroxyethylcellulose (HEC) and polyacrylic acid (e.g. Carbopol®), have a long history of use in vaginal drug delivery. However, despite their ubiquity, they often provide sub-optimal clinical performance, due to poor mucosal retention and limited solubility for poorly water-soluble actives. These issues are particularly pertinent for vaginal HIV microbicides, since many lead candidates are poorly water-soluble and where a major goal is the development of a coitally independent, once daily gel product. In this study, we report the use of a non-aqueous silicone elastomer gel for vaginal delivery of the HIV-1 entry inhibitor maraviroc. In vitro rheological, syringeability and retention studies demonstrated enhanced performance for silicone gels compared with a conventional aqueous HEC gel, while testing of the gels in the slug model confirmed a lack of mucosal irritancy. Pharmacokinetic studies following single dose vaginal administration of a maraviroc silicone gel in rhesus macaques showed higher and sustained MVC levels in vaginal fluid, vaginal tissue and plasma compared with a HEC gel containing the same maraviroc loading. The results demonstrate that non-aqueous silicone gels have potential as a formulation platform for coitally independent vaginal HIV microbicides.

Pressure drop of gas–liquid Taylor flow in round micro-capillaries for low to intermediate Reynolds numbers

In this paper, a model is presented that describes the pressure drop of gas-liquid Taylor flow in round capillaries with a channel diameter typically less than 1 mm. The analysis of Bretherton (J Fluid Mech 10:166-188, 1961) for the pressure drop over a single gas bubble for vanishing liquid film thickness is extended to include a non-negligible liquid film thickness using the analysis of Aussillous and Qu,r, (Phys Fluids 12(10):2367-2371, 2000). This result is combined with the Hagen-Poiseuille equation for liquid flow using a mass balance-based Taylor flow model previously developed by the authors (Warnier et al. in Chem Eng J 135S:S153-S158, 2007). The model presented in this paper includes the effect of the liquid slug length on the pressure drop similar to the model of Kreutzer et al. (AIChE J 51(9):2428-2440, 2005). Additionally, the gas bubble velocity is taken into account, thereby increasing the accuracy of the pressure drop predictions compared to those of the model of Kreutzer et al. Experimental data were obtained for nitrogen-water Taylor flow in a round glass channel with an inner diameter of 250 mu m. The capillary number Ca (gl) varied between 2.3 x 10(-3) and 8.8 x 10(-3) and the Reynolds number Re (gl) varied between 41 and 159. The presented model describes the experimental results with an accuracy of +/- 4% of the measured values.

Liquid-Liquid Flow in a Capillary Microreactor: Hydrodynamic Flow Patterns and Extraction Performance

The capillary micro reactor, with four stable operating flow patterns and a throughput range from grams per hour to kilograms per hour, presents an attractive alternative to chip-based and microstructured reactors for laboratory- and pilot-scale applications. In this article, results for the extraction of 2-butanol from toluene under different flow patterns in a water/toluene flow in long capillary microreactors are presented. The effects of the capillary length (0.4-2.2 m), flow rate (0.1-12 mL/min), and aqueous-to-organic volumetric flow ratio (0.25-9) on the slug, bubbly, parallel, and annular flow hydrodynamics were investigated. Weber-number-dependent flow maps were composed for capillary lengths of 0.4 and 2 m that were used to interpret the flow pattern formation in terms of surface tension and inertia forces. When the capillary length was decreased from 2 to 0.4 m, a transition from annular to parallel flow was observed. The capillary length had little influence on slug and bubbly flows. The flow patterns were evaluated in terms of stability, surface-to-volume ratio, throughput, and extraction efficiency. Slug and bubbly flow operations yielded 100% thermodynamic extraction efficiency, and increasing the aqueous-to-organic volumetric ratio to 9 allowed for 99% 2-butanol extraction. The parallel and annular flow operating windows were limited by the capillary length, thus yielding maximum 2-butanol extractions of 30% and 47% for parallel and annular flows, respectively.

Hydrodynamics and mixer-induced bubble formation in micro bubble columns with single and multiple-channels

A hydrodynamic characterization of an industrially used gas-liquid contacting microchannel. device is discussed, viz. the micro bubble column of IMM. Furthermore, similar characterization of a gas-liquid flow microchip of TU/e, with two tailored mixer designs, is used to solve fundamental issues on hydrodynamics, and therefore, to achieve further design and operating optimization of that chip and the IMM device. Flow pattern maps are presented in a dimensionless fashion for further predictions on new fluidic systems for optimum single-channel multiphase operation. Bubble formation was investigated in the two types of mixers and pinch-off and hydrodynamic decay mechanisms are observed. The impact of these mechanisms on bubble size, bubble size distributions, and on the corresponding flow patterns, i.e., the type of mixer design, can be decisive for the flow pattern map and thus, may be used to alter flow pattern maps. The bubble sizes and their distribution were improved for the tailored designs, i.e., smaller and more regular bubbles were generated. Finally, the impact of multi-channel distribution for gas and liquid flow is demonstrated. Intermediate flow patterns such as slug-annular flow, also found for single-phase operation, and the simultaneous coexistence of flow regimes are presented, with the latter providing evidence of flow maldistribution.

Indirect-drive inertial confinement fusion using highly supersonic, radiatively cooled, plasma slugs

We present a new approach to indirect-drive inertial confinement fusion which makes use of highly supersonic, radiatively cooled, slugs of plasma to energize a hohlraum. 2D resistive magnetohydrodynamic simulations of slug formation in shaped liner Z -pinch implosions are presented along with 2D-radiation-hydrodynamic simulations of the slug impacting a converter foil and 3D-view-factor simulations of a double-ended hohlraum. Results for the Z facility at Sandia National Laboratory indicate that two synchronous slugs of 250 kJ kinetic energy could be produced, resulting in a capsule surface temperature of similar to225 eV .

Numbered-up gas-liquid micro/milli channels reactor with modular flow distributor

Gas-liquid processing in microreactors remains mostly restricted to the laboratory scale due to the complexity and expenditure needed for an adequate numbering-up with a uniform flow distribution. Here, the numbering-up is presented for multi-phase (gas-liquid) flow in microreactor suitable for a production capacity of kg/h. Based on the barrier channels concept, the barrier-based micro/milli reactor (BMMR) is designed and fabricated to deliver flow non-uniformity of less than 10%. The BMMR consists of eight parallel channels all operated in the Taylor flow regime and with a liquid flow rate up to 150. mL/min. The quality of the flow distribution is reported by studying two aspects. The first aspect is the influence of different viscosities, surface tensions and flow rates. The second aspect is the influence of modularity by testing three different reaction channels type: (1) square channels fabricated in a stainless steel plate, (2) square channels fabricated in a glass plate, and (3) circular channels (capillaries) made of stainless steel. Additionally, the BMMR is compared to that of a single channel regard the slug and bubble lengths and bubble generation frequency. The results pave the ground for bringing multi-phase flow in microreactor one step closer for large scale production via numbering-up. © 2012 Elsevier B.V.

Mutant p53 expression in fallopian tube epithelium drives cell migration

Ovarian cancer is the fifth leading cause of cancer death among US women. Evidence supports the hypothesis that high-grade serous ovarian cancers (HGSC) may originate in the distal end of the fallopian tube. Although a heterogeneous disease, 96% of HGSC contain mutations in p53. In addition, the "p53 signature," or overexpression of p53 protein (usually associated with mutation), is a potential precursor lesion of fallopian tube derived HGSC suggesting an essential role for p53 mutation in early serous tumorigenesis. To further clarify p53-mutation dependent effects on cells, murine oviductal epithelial cells (MOE) were stably transfected with a construct encoding for the R273H DNA binding domain mutation in p53, the most common mutation in HGSC. Mutation in p53 was not sufficient to transform MOE cells but did significantly increase cell migration. A similar p53 mutation in murine ovarian surface epithelium (MOSE), another potential progenitor cell for serous cancer, was not sufficient to transform the cells nor change migration suggesting tissue specific effects of p53 mutation. Microarray data confirmed expression changes of pro-migratory genes in p53(R273H) MOE compared to parental cells, which could be reversed by suppressing Slug expression. Combining p53(R273H) with KRAS(G12V) activation caused transformation of MOE into high-grade sarcomatoid carcinoma when xenografted into nude mice. Elucidating the specific role of p53(R273H) in the fallopian tube will improve understanding of changes at the earliest stage of transformation. This information can help develop chemopreventative strategies to prevent the accumulation of additional mutations and reverse progression of the "p53 signature" thereby, improving survival rates.