Physical characteristics of digesta and their influence on flow and mixing in the mammalian intestine: a review

The physical properties of digesta may influence mixing, efficiency of digestion, and absorption within the lumen of the intestine. We review how the physical properties of digesta change during transit through the various segments of the intestine, and how their influence on flow and mixing may be modulated by peristaltic activity. We examine how, in more fluid digesta, the solid and liquid phases interact to influence flow and mixing. Similarly, how in viscid digesta, shear strength, plasticity and elasticity of contained particulate material may influence the permeation of the fluid phase and secretions into and out of the digesta bolus. The manner in which the solid and liquid phases of digesta interact in a partly gaseous environment, such as the lower bowel, to influence bolus cohesion is also examined. Those mechanisms that promote the formation of a less viscous layer at the mucosal interface to promote plug flow are reviewed, and their effect on the efficiency of mixing and digestion discussed. It is recommended that in any future work investigating the character of mixing in the intestine, a wider range of appropriate digesta properties be measured and that, in investigations of intestinal movement, perfusates with similar characteristics to digesta be used.     

Comparison of ESI-MS interfaces for the analysis of UV-crosslinked peptide-nucleic acid complexes

In this report, the effectiveness of high performance liquid chromatography (HPLC) in conjunction with electrospray ionization mass spectrometry (ESI-MS) is examined as a tool for identifying the sites of crosslinking in a protein that has been photoreacted with a non-photolabeled oligonucleotide. ESI-MS and MALDI-MS analyses preceded by off-line microflow and nanoflow HPLC, on-line microflow HPLC/ESI, and on-line nanoflow HPLC/ESI interfaces were performed in order to determine their relative effectiveness in separating mixtures of nucleopeptides and identifying sites of crosslinking on the individual components. The characteristics of these four techniques as well as possibilities for improving the analysis of nucleopeptides by ESI-MS are compared and discussed.     

Convex Grooves in Staggered Herringbone Mixer Improve Mixing Efficiency of Laminar Flow in Microchannel

The liquid streams in a microchannel are hardly mixed to form laminar flow, and the mixing issue is well described by a low Reynolds number scheme. The staggered herringbone mixer (SHM) using repeated patterns of grooves in the microchannel have been proved to be an efficient passive micro-mixer. However, only a negative pattern of the staggered herringbone mixer has been used so far after it was first suggested, to the best of our knowledge. In this study, the mixing efficiencies from negative and positive staggered herringbone mixer patterns as well as from opposite flow directions were tested to investigate the effect of the micro-structure geometry on the surrounding laminar flow. The positive herringbone pattern showed better mixing efficiency than the conventionally used negative pattern. Also, generally used forward flow gives better mixing efficiency than reverse flow. The mixing was completed after two cycles of staggered herringbone mixer with both forward and reverse flow in a positive pattern. The traditional negative pattern showed complete mixing after four and five cycles in forward and reverse flow direction, respectively. The mixing effect in all geometries was numerically simulated, and the results confirmed more efficient mixing in the positive pattern than the negative. The results can further enable the design of a more efficient microfluidic mixer, as well as in depth understanding of the phenomena of positive and negative patterns existing in nature with regards to the surrounding fluids.     

Rare events out of equilibrium: mobility through the liquid–liquid interface

Transition state theory provides a well established means to compute the rate at which rare events occur; however, this is strictly an equilibrium approach. Here we consider a nonequilibrium problem of this nature in the form of transport through a liquid–liquid interface. When two immiscible liquids are coexisting in equilibrium, there will be a certain amount of mixing between the two phases, resulting in a finite linear mobility across the liquid–liquid interface. We derive an exact relationship between the mobility and the local diffusion in the direction perpendicular to the interface. We compute the mobility using both nonequilibrium molecular dynamics and a variety of linear response type approaches, with accurate agreement being obtained for the best of these. Our analysis makes it clear how the local diffusion is influenced by the inhomogeneities of the interface, even when at a distance from it. This nonlocal character to the mobility has not been appreciated before and results in a strong variation in the local diffusion, which is formally coupled to the variation in the potential of mean force. The nonlocal aspect of the diffusion requires the velocity autocorrelation function to be integrated out to far longer times than is the case for homogeneous liquids, and requires special care with regard to the choice of numerical approach.     

Design and applications of a self-aligning liquid junction-electrospray interface for capillary electrophoresis-mass spectrometry

A simple self-aligning liquid junction-electrospray interface for coupling a capillary electrophoresis (CE) system to an atmospheric pressure ionization (API) mass spectrometer (CE-MS) was developed. In contrast to previous liquid junction interfaces, the self-aligning liquid junction interface simplifies the precise alignment of the CE capillary and the sprayer needle and uses a positive make-up flow. Several capillary CE-MS applications were run using both the self-aligning liquid junction interface and the widely used sheath flow interface for comparison purposes. The electrospray stability of the self-aligning liquid junction interface is consistently better even when non-volatile electrolyte solutions are used. At first, some band broadening was obtained with the self-aligning liquid junction interface. Experiments with different CE buffer systems suggested that this band broadening was caused by the materials used in constructing the interface. By using a more inert material for the sprayer needle, the self-aligning liquid junction exhibits excellent electrophoretic resolution, comparable sensitivity, and higher signal-to-noise ratios when run under the same conditions as the sheath flow interface.     

The binary phase behavior of 1,3-dimyristoyl-2-stearoyl-sn-glycerol and 1,2-dimyristoyl-3-stearoyl-sn-glycerol

The binary phase behavior of pure 1,3-dimyristoyl-2-stearoyl-sn-glycerol (MSM) and 1,2-dimyristoyl-3-stearoyl-sn-glycerol (MMS) was investigated in terms of polymorphism, melting and crystallization behavior, SFC, hardness and microstructure. Samples were crystallized at cooling rates of 3.0 and 0.1 degrees C/min. The asymmetric TAG demonstrated lower melting and crystallization points at both cooling rates. All samples crystallized in the beta' polymorph when cooled at 0.1 degrees C/min and in the alpha polymorph when cooled at 3.0 degrees C/min. The experimentally determined kinetic phase diagram of MSM-MMS was monotectic for both cooling rates. This data was well described by a thermodynamic model using the Bragg-Williams approximation for non-ideality of mixing and suggested that in both the solid and liquid states, like pair interactions (MSM-MSM and MMS-MMS) were favored over MSM-MMS interaction. A strong tendency to phase separation in the solid phase was also observed. For both cooling rates, the fit of the SFC (%)-time curves to a modified form of the Avrami model indicated that crystallization occurred in two distinct kinetic steps. Depressions seen in SFC did not correspond to depressions in hardness or melting temperatures.     

Influence of microflow on hepatic sinusoid blood flow and red blood cell deformation

Hepatic sinusoids present complex anatomical structures such as the endothelial sieve pores and the Disse space, which govern the microscopic blood flow in the sinusoids and are associated with structural variations in liver fibrosis and cirrhosis. However, the contributions of the permeability of endothelial and collagen layers and the roughness of hepatocyte microvilli to the features of this microflow remain largely unknown. Here, an immersed boundary method coupled with a lattice Boltzmann method was adopted in an in vitro hepatic sinusoidal model, and flow field and erythrocyte deformation analyses were conducted by introducing three new source terms including permeability of the endothelial layer, resistance of hepatocyte microvilli and collagen layers, and deformation of red blood cells (RBCs). Numerical calculations indicated that alterations in endothelial permeability could significantly affect the flow velocity and flow rate distributions in hepatic sinusoids. Interestingly, a biphasic regulating pattern of shear stress occurred simultaneously on the surface of hepatocytes and the lower side of endothelium, i.e., the shear stress increased with increased thickness of hepatocyte microvilli and collagen layer when the endothelial permeability was high but decreased with the increase of the thickness at low endothelial permeability. Additionally, this specified microflow manipulates typical RBC deformation inside the sinusoid, yielding one-third of the variation of deformable index with varied endothelial permeability. These simulations not only are consistent with experimental measurements using in vitro liver sinusoidal chip but also elaborate the contributions of endothelial and collagen layer permeability and wall roughness. Thus, our results provide a basis for further characterizing this microflow and understanding its effects on cellular migration and deformation in the hepatic sinusoids.     

Biliary cholesterol crystallization characterized by single-crystal cryogenic electron diffraction

Cholesterol crystals are the building blocks of cholesterol gallstones. The exact structure of early-forming crystals is still controversial. We combined cryogenic-temperature transmission electron microscopy with cryogenic-temperature electron diffraction to sequentially study crystal development and structure in nucleating model and native gallbladder biles. The growth and long-term stability of classic cholesterol monohydrate (ChM) crystals in native and model biles was determined. In solutions of model bile with low phospholipid-to-cholesterol ratio, electron diffraction provided direct proof of a novel transient polymorph that had an elongated habit and unit cell parameters differing from those of classic triclinic ChM. This crystal is exactly the monoclinic ChM phase described by Solomonov and coworkers (Biophysical J., In press) in cholesterol monolayers compressed on the air-water interface. We observed no evidence of anhydrous cholesterol crystallization in any of the biles studied. In conclusion, classic ChM is the predominant and stable form in native and model biles. However, under certain (low phospholipid) conditions, transient intermediate polymorphs may form. These findings, documenting single-crystal analysis in bulk solution, provide an experimental approach to investigating factors influencing biliary cholesterol crystal nucleation and growth as well as other processes of nucleation and crystallization in liquid systems.     

A molecular dynamics study on the thermal rectification effect at the solid–liquid interfaces between the face-centred cubic (FCC) of gold (Au) with the surfaces of (100), (110) and (111) crystal planes facing the liquid methane (CH4)

A molecular dynamics study on the solid–liquid (S-L) interfaces for solid wall of gold having the face-centred cubic of (100), (110) and (111) crystal planes contacting liquid methane was examined using non-equilibrium molecular dynamics simulations. An investigation on the thermal rectification effect was performed by measuring the thermal boundary conductance (TBC) at the S-L interface. Thermal rectification can be defined as the differences in the TBC at the interface between the two opposite heat flow directions; one is from the liquid to solid and vice versa. The thermal rectifications are up to 13% for (110) crystal plane, followed by 6% and 0.3% for (111) and (100) crystal planes, respectively. It was found that the TBC at the S-L interface was influenced by the magnitude of the adsorption of liquid molecules at the vicinity of the interface. The results show that due to the different temperature distribution, different magnitude of the adsorption of liquid molecules is generated for the two opposite heat flow directions. On the surface of the solid walls for (110) crystal plane, where lattice-scale corrugation exists, it was found that there exists difference in distance between the surface layers of the solid and liquid across the interface between the cases of the two opposite heat flow directions, which affects the TBC at the interface. The present results suggest that the factors that influence the thermal rectification at the S-L interface are the magnitude of the adsorption of liquid molecules and the surface structure of the solid walls that differ significantly among the three types of crystal planes.     

Human sperm swimming in flow

To study the movement of human sperm, we have developed a microflow cell by miniaturizing our design for a preparative fractionation flow column. The microflow cell enabled us to view the movement of sperm over periods as long as 2 min. Sequential steps of filming, editing, and analysis revealed that the curved swimming patterns of sperm swimming in stagnant fluid become nearly straight tracks when the flow velocity is increased. However, the net swimming speed remained unchanged. Motile sperm accumulated near solid wall surfaces surrounding the fluid and oriented against the direction of the current; the velocity gradient was steepest in these regions. A laminar-flow preparative column separated motile sperm from dead sperm by carrying the nonmotile sperm and debris with the stream while leaving the motile sperm near the surrounding walls.     

Human sperm swimming in flow

Abstract. To study the movement of human sperm, we have developed a microflow cell by miniaturizing our design for a preparative fractionation flow column. The microflow cell enabled us to view the movement of sperm over periods as long as 2 min. Sequential steps of filming, editing, and analysis revealed that the curved swimming patterns of sperm swimming in stagnant fluid become nearly straight tracks when the flow velocity is increased. However, the net swimming speed remained unchanged. Motile sperm accumulated near solid wall surfaces surrounding the fluid and oriented against the direction of the current; the velocity gradient was steepest in these regions. A laminar-flow preparative column separated motile sperm from dead sperm by carrying the nonmotile sperm and debris with the stream while leaving the motile sperm near the surrounding walls.     

Mathematical modeling of non-ideal mixing continuous flow reactors for anaerobic digestion of cattle manure

Most conventional digesters used for animal wastewater treatment include continuously stirred-tank reactors. While imperfect mixing patterns are more common than ideal ones in real reactors, anaerobic digestion models often assume complete mixing conditions. Therefore, their applicability appears to be limited. In this study, a mathematical model for anaerobic digestion of cattle manure was developed to describe the dynamic behavior of non-ideal mixing continuous flow reactors. The microbial kinetic model includes an enzymatic hydrolysis step and four microbial growth steps, together with the effects of substrate inhibition, pH and thermodynamic considerations. The biokinetic expressions were linked to a simple two-region liquid mixing model, which considered the reactor volume in two separate sections, the flow-through and the retention regions. Deviations from an ideal completely mixed regime were represented by changing the relative volume of the flow-through region (a) and the ratio of the internal exchange flow rate to the feed flow rate (b). The effects of the hydraulic retention time, the composition of feed, the initial conditions of the reactor and the degree of mixing on process performance can be evaluated by the dynamic model. The simulation results under different conditions showed that deviations from the ideal mixing regime decreased the methane yield and resulted in a reduced performance of the anaerobic reactors. The evaluation of the impact of the characteristic mixing parameters (a) and (b) on the anaerobic digestion of cattle manure showed that both liquid mixing parameters had significant effects on reactor performance.     

Monoolein lipid phases as incorporation and enrichment materials for membrane protein crystallization

The crystallization of membrane proteins in amphiphile-rich materials such as lipidic cubic phases is an established methodology in many structural biology laboratories. The standard procedure employed with this methodology requires the generation of a highly viscous lipidic material by mixing lipid, for instance monoolein, with a solution of the detergent solubilized membrane protein. This preparation is often carried out with specialized mixing tools that allow handling of the highly viscous materials while minimizing dead volume to save precious membrane protein sample. The processes that occur during the initial mixing of the lipid with the membrane protein are not well understood. Here we show that the formation of the lipidic phases and the incorporation of the membrane protein into such materials can be separated experimentally. Specifically, we have investigated the effect of different initial monoolein-based lipid phase states on the crystallization behavior of the colored photosynthetic reaction center from Rhodobacter sphaeroides. We find that the detergent solubilized photosynthetic reaction center spontaneously inserts into and concentrates in the lipid matrix without any mixing, and that the initial lipid material phase state is irrelevant for productive crystallization. A substantial in-situ enrichment of the membrane protein to concentration levels that are otherwise unobtainable occurs in a thin layer on the surface of the lipidic material. These results have important practical applications and hence we suggest a simplified protocol for membrane protein crystallization within amphiphile rich materials, eliminating any specialized mixing tools to prepare crystallization experiments within lipidic cubic phases. Furthermore, by virtue of sampling a membrane protein concentration gradient within a single crystallization experiment, this crystallization technique is more robust and increases the efficiency of identifying productive crystallization parameters. Finally, we provide a model that explains the incorporation of the membrane protein from solution into the lipid phase via a portal lamellar phase.     

Macromixing hydrodynamic study in draft-tube airlift reactors using electrical resistance tomography

The present study summarizes results of mixing characteristics in a draft tube airlift bioreactor using ERT. This technique offers the possibility for noninvasive and nonintrusive visualization of flow fields in the bioreactor and has rarely been utilized previously to analyze operating parameters and mixing characteristics in this type of bioreactors. Several operating parameters and geometric characteristics were examined. In general, results showed that the increase in superficial gas velocity corresponds to an increase in energy applied and thus, to a decrease in mixing time. This generally corresponded to an increase in liquid circulation velocity and shear rate values. Bottom clearances and draft tube diameters affected flow resistance and frictional losses. The influence of sparger configurations on mixing time and liquid circulation velocity was significant due to their effect on gas distribution. However, the effect of sparger configuration on shear rate was not significant, with 20% reduction in shear rates using the cross-shaped sparger. Fluid viscosity showed a marked influence on both mixing times and circulation velocity especially in the coalescing media of sugar and xanthan gum (XG) solutions. Results from this work will help to develop a clear pattern for operation and mixing that can help to improve several industrial processes, especially the ones related to emerging fields of technology such as the biotechnology industry.     

Solubility, metastable zone width, and racemic characterization of propranolol hydrochloride

Characterization of the racemic species, which can be a racemic compound, a racemic conglomerate, or a pseudoracemate (solid solution), is a prerequisite for the design of crystallization resolution processes. It is useful to determine the solid/liquid equilibrium solubility of the enantiomer mixtures for crystallization operation. For the beta-blocker drug propranolol hydrochloride, Gibbs free energy of formation of racemic compound and entropy of mixing of the (R)- and (S)- enantiomers in the liquid state for racemic conglomerate were calculated. The structural differences between (R, S)-propranolol hydrochloride and its (S)-enantiomer were further investigated by powder X-ray diffraction patterns, infrared spectra, and solid-state NMR spectra. The solubility and metastable zone width of (R, S)- propranolol hydrochloride in a mixed solvent of methanol and acetone were determined by cooling crystallization over the temperature range 3.5-42.5 degrees C. The ternary solubility diagram of (R)-, (S)-propranolol hydrochloride was constructed using the same mixed solvent. The diagram will be useful as a guide for choosing crystallization operation conditions to produce pure enantiomers.     

Small-scale liquid mixing in a bioreactor column with xanthan-gum simulated filamentous media

Using the heat pulse technique, the local mean flow liquid velocity and the mixing conditions for twophase flow in the riser of an airlift bioreactor have been measured and analysed. Xanthan-gum solutions were used as the physical model to some filamentous broths reported in the literature. A two-fold decrease of liquid velocity and diffusional mixing regime are predicted for the course of a fermentation process proceeding in a non-Newtonian biomass growth circulation system.     

The influence of vessel height and top-section size on the hydrodynamic characteristics of airlift fermentors

Fermentations of the yeast Saccharomyces cerevisiae were carried out in a 90 to 250-L working volume concentric tube airlift fermentor. Measurements of liquid circulation velocity, gas hold-up, and liquid mixing were made under varying conditions of gas flowrate, vessel height, and top-section size. Both liquid circulation velocity and mixing time increased with vessel height. Liquid velocity varied approximately in proportion to the square root of column height, supporting a theoretically based relationship. The effect of vessel height on gas hold-up was negligible. The height of the top-section had a significant effect on liquid mixing. Mixing time decreased with increasing size of the top-section up to a critical height. As the top-section was expanded beyond this height, little improvement in mixing was seen. This indicated the presence of a two-zone flow pattern in the top-section. Liquid velocity and gas hold-up were essentially independent of top-section height. (c) 1994 John Wiley & Sons, Inc.     

Frontal impingement of nanojets: formation,disintegration and mixing of nano liquid sheets

We investigate nano liquid sheets formed by frontal impingement of two cylindrical nanojets using the molecular dynamics method. The results show that only with a high enough velocity can a stable liquid sheet be formed because of the strong surface tension effect in nanoscale. In relatively low jet velocity range, the relationship between the intact sheet radius and the jet velocity takes on the power function form with the power being ? 0.502. This relationship is explained by considering the thermal fluctuation effect, thus confirming the dominating role of the thermal fluctuation effect in the disintegration process. The influence of the jet velocity on the time-domain evolution of mixing of the system and the spatial mixing distribution of the liquid sheet are also investigated. Our results suggest that nanojets do not coalesce at the impingement point, the mixing occurs mainly through diffusion. And there is recoil that happens at the stagnation plane.     

Flow Pattern and Mixing in the Multi‐Turbine Agitated Bioreactor Filled with Poly(γ‐Glutamic Acid) Solution

We investigated the flow pattern and mixing behavior of a poly(γ‐glutamic acid) (γ‐PGA) solution in a bioreactor equipped with two Rushton turbines by simulation and experiment. Computational fluid dynamics (CFD) is used to solve the three‐dimensional hydrodynamics in the bioreactor and to obtain the flow patterns and tracer concentration at every point. The flow circulation patterns by inter‐impeller clearance and viscosity and their effects on overall mixing time were studied. Based on the results we can conclude that the impeller clearance should not be larger than 0.2 D for the efficient mixing under non‐aerated condition when the liquid viscosity is above 20 cp, which corresponds to concentrations of 20 g/L or above for γ‐PGA.     

营养及水力条件影响光合细菌生物膜生长特性实验

对平板式生物膜反应器内,流量及底物浓度范围分别为37.8~1080ml/h、0.05~10g/L的不同生长条件下光合产氢细菌生物膜生长特性进行了实验研究,讨论了不同水力及营养条件对沼泽红假单胞菌生物膜表面覆盖率、膜厚、干重和密度的影响。实验结果表明,不同水力及营养条件对生物膜生长速率及结构具有重要影响。在相同的时间间隔内,在高流速条件下光合细菌菌落生长较快,但过高的液体流速会导致部分生物膜脱落;高流速条件易使生物膜形成薄而致密的结构。光合细菌生物膜在循环液底物浓度较高时生长较快,密度也最高;而贫营养条件可以促成结构疏松生物膜在固液界面的形成,这种生物膜结构有利于微生物在低底物浓度条件下底物在生物膜内的传输。