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PubMed1998

A simple mechanical mixer for small viscous lipid-containing samples.

The construction and performance characteristics of a simple device for rapid and convenient hydration and mixing of small volumes (10-500 microliters) of viscous hydrated lipid samples for use in X-ray diffraction/scattering and other applications are described. The mixer has been used successfully over the past several years in studies of the equilibrium properties of lipid mesophases and of the kinetics and mechanism of phase transitions. It is a low dead-volume (3.6-11.2 microliters) device that was built to facilitate maximal transfer of homogeneously hydrated lipid from the mixer into 1 mm diameter X-ray capillaries with minimal loss of water during transfer and sample manipulation. The device consists of inexpensive, commercially available parts, the most important of which are two microsyringes joined by a small-bore coupling needle. Also described in this report is a technique for determining the water content of the small volume, hydrated samples prepared with the mixer and an accessory for conveniently heating and/or degassing samples during mixing. Inadvertent sample heating that occurs during mixing is described.

Lipids↗

PubMed1999

Applicability of a scale-up methodology for wet granulation processes in Collette Gral high shear mixer-granulators.

This study investigates the extension of a scale-up methodology based on dimensionless power relationships, to a series of vertical mixer-granulators in which the bowl is removable, i.e. both impeller and chopper blades are mounted on top-driven vertical shafts positioned through the lid. Granulation runs were carried out in several bowl sizes belonging to the series of Collette Gral mixer-granulators, ranging from 8 to 600 l capacities. It was shown that under certain conditions a common scale-up master curve could be drawn from the data gathered for each bowl, thus permitting the use of such a curve for the determination of mixer-granulator power consumption at a defined granulation end-point. The results also helped to clarify the concept of similitude, both geometrical and dynamic, which is implied in the methodology. The importance of wall slippage (as promoted by the insertion of a PTFE lining into the bowls) and batch size are illustrated.

Algorithms↗

PubMed2004

Femtomole mixer for microsecond kinetic studies of protein folding.

We have developed a microfluidic mixer for studying protein folding and other reactions with a mixing time of 8 mus and sample consumption of femtomoles. This device enables us to access conformational changes under conditions far from equilibrium and at previously inaccessible time scales. In this paper, we discuss the design and optimization of the mixer using modeling of convective diffusion phenomena and a characterization of the mixer performance using microparticle image velocimetry, dye quenching, and Forster resonance energy-transfer (FRET) measurements of single-stranded DNA. We also demonstrate the feasibility of measuring fast protein folding kinetics using FRET with acyl-CoA binding protein.

Acyl Coenzyme A↗

PubMed1999

Process control in a high shear mixer-granulator using wet mass consistency: the effect of formulation variables.

This work investigates the relationships between the wet mass consistency/viscosity of samples prepared in a mixer-granulator and physical properties of the dry granules produced from the wet mass; namely, size distribution, bulk density (Hausner ratio), friability, and flow avalanching behavior. The correlation between the consistency of the wet mass and the downstream dry granule properties confirms that consistency is the key parameter to control in wet granulation by mechanical agitation. Variations in the formulation affect the dimensionless power relationship of the mixer-granulator considered; that is, the equivalence between wet mass consistency and mixer net power consumption, which is actually the parameter used to monitor the wet granulation process. The same variations in formulation also affect the relationships between wet mass consistency and dry granule properties.

Algorithms↗

PubMed2001

Static micromixers based on large-scale industrial mixer geometry.

Mixing liquids at the micro-scale is difficult because the low Reynolds numbers in microchannels and in microreactors prohibit the use of conventional mixing techniques based on mechanical actuators and induce turbulence. Static mixers can be used to solve this mixing problem. This paper presents micromixers with geometries very close to conventional large-scale static mixers used in the chemical and food-processing industry. Two kinds of geometries have been studied. The first type is composed of a series of stationary rigid elements that form intersecting channels to split, rearrange and combine component streams. The second type is composed of a series of short helix elements arranged in pairs, each pair comprised of a right-handed and left-handed element arranged alternately in a pipe. Micromixers of both types have been designed by CAD and manufactured with the integral microstereolithography process, a new microfabrication technique that allows the manufacturing of complex three-dimensional objects in polymers. The realized mixers have been tested experimentally. Numerical simulations of these micromixers using the computational fluid dynamics (CFD) program FLUENT are used to evaluate the mixing efficiency. With a low pressure drop and good mixing efficiency these truly three-dimensional micromixers can be used for mixing of reactants or liquids containing cells in many microTAS applications.

Journal Article↗

PubMed1986

Control of air contaminants at mixers and mills used in tire manufacturing.

The National Institute for Occupational Safety and Health (NIOSH) has completed an evaluation of control techniques for airborne vapors and particulates in tire manufacturing. As part of this evaluation, Banbury mixers and mills were studied. This equipment is used to mix elastomers, carbon black, oil and other ingredients into a homogeneous mixture. These mixing and milling operations normally generate aerosols. Control of these air contaminants may be accomplished by using the following: local exhaust ventilation, equipment configuration and material substitution. Results of personal sampling for total aerosols at Banbury mixers showed the geometric means of mixer operators' exposures at five plants ranged from 0.08 to 1.54 mg/m3. Similar sampling at three plants for milling operations showed the geometric means of milling operators' exposures ranged from 0.20 to 1.22 mg/m3.

Air Pollutants, Occupational↗

PubMed1999

Scaleup of a pharmaceutical granulation in planetary mixers.

The scaleup of a pharmaceutical granulation in a series of planetary mixers with increasing bowl capacity between 5 and 200 liters has been studied by applying the classical dimensionless numbers of Power, Reynolds, and Froude to define the power consumption profile of each mixer as a function of the processing conditions in dimensionless form. Experiments were performed using a formulation based on dicalcium phosphate dihydrate containing pregelatinized starch, with water being added at a fixed rate. Samples were taken at different power consumptions and assessed using mixer torque rheometry. Geometrically similar machines gave the same dimensionless relationship, but when similarity was compromised by the use of modified bowls and blades, different relationships occurred. The results show that, for geometrically similar machines, it is possible to calculate the power consumption at a predefined granulation endpoint at any given operating condition at any scale.

Chemistry, Pharmaceutical↗

PubMed2006

Soft mixer assignment in a hierarchical generative model of natural scene statistics.

Gaussian scale mixture models offer a top-down description of signal generation that captures key bottom-up statistical characteristics of filter responses to images. However, the pattern of dependence among the filters for this class of models is prespecified. We propose a novel extension to the gaussian scale mixture model that learns the pattern of dependence from observed inputs and thereby induces a hierarchical representation of these inputs. Specifically, we propose that inputs are generated by gaussian variables (modeling local filter structure), multiplied by a mixer variable that is assigned probabilistically to each input from a set of possible mixers. We demonstrate inference of both components of the generative model, for synthesized data and for different classes of natural images, such as a generic ensemble and faces. For natural images, the mixer variable assignments show invariances resembling those of complex cells in visual cortex; the statistics of the gaussian components of the model are in accord with the outputs of divisive normalization models. We also show how our model helps interrelate a wide range of models of image statistics and cortical processing.

Animals↗

PubMed2001

Porous polymer monoliths: simple and efficient mixers prepared by direct polymerization in the channels of microfluidic chips.

Porous monolithic polymers have been prepared by photoinitiated polymerization of mixtures consisting of 2-hydroxyethyl methacrylate, ethylene dimethacrylate, UV-sensitive free radical initiator and porogenic solvent within channels of specifically designed microfluidic chips and used as micromixers. Substituting azobisisobutyronitrile with 2,2-dimethoxy-2-phenylacetophenone considerably accelerated the kinetics of the polymerization. Mixtures of cyclohexanol and 1 -dodecanol and of hexane and methanol were used, respectively, to control the porous properties and therefore the mixing efficiency of the device. The performance of the monolithic mixers has been tested by pumping aqueous solutions of two fluorescent dyes at various flow rates and monitoring the point at which the boundary of both streams completely disappears. Best results were achieved with a monolithic mixer containing very large irregular pores.

Acetophenones↗

PubMed2007

Alkaline-cell lysis through in-line static mixer reactor for the production of plasmid DNA for gene therapy.

A state-of-the-art in-line static mixer reactor (ISMR) was invented to lyse E. coli cells and neutralize the cell lysate continuously and efficiently for the extraction of plasmid DNA. It comprised two connected static dynamic mixers, each 0.01 m in diameter and 0.9 m in length, one for lysis and one for neutralization. Cells were lysed using concentrated alkaline with 1% SDS and the lysate was neutralized at feed rates of cell suspension:lysis solution:neutralization solution of 125:250:125, 250:500:250, and 500:1,000:500 mL/min. Distances for the mixtures to reach color homogeneity were dependent on feed rates. The higher the feed rates the shorter the mixing distances and times. However, complete cell lysis and neutralization were independent of color homogeneity. Lysate viscosity and neutralized floc size decreased and floc density increased, as distances and feed rates increased. High plasmid yields were obtained from both lysis and neutralization at feed rate ratios of 125:250:125 and 250:500:250 mL/min within mixing distances < or =0.6 m. Poor mixing performance and plasmid yield were obtained at a high feed rate of 500:1,000: 500 mL/min when residence and reaction times were less than 2 s and from mixing distances > or =0.6 m at all feed rates due to a longer exposure to strong alkali and shear flow. This invention showed excellent performance with scaleable potential for the commercial manufacture of plasmid DNA.

DNA, Superhelical↗

PubMed1989

A corner-reflector mixer mount for far infrared wavelengths.

A new type of corner-reflector mixer mount, which has the advantages of ease of fabrication and assembly as well as frequency versatility, has been designed and constructed. The mixer works with arbitrary antenna lengths > or = 4 lambda with the reflector to antenna spacing adjusted to give a strong and symmetric central lobe. The predicted response patterns have been experimentally verified for various antenna lengths and operating frequencies between 800 and 2000 GHz. An important design feature is the incorporation of a microstrip matching network which eliminates IF impedance mismatch and provides mechanical isolation of the whisker antenna.

Astronomy↗

PubMed2004

Chaotic mixer improves microarray hybridization.

Hybridization is an important aspect of microarray experimental design which influences array signal levels and the repeatability of data within an array and across different arrays. Current methods typically require 24h and use target inefficiently. In these studies, we compare hybridization signals obtained in conventional static hybridization, which depends on diffusional target delivery, with signals obtained in a dynamic hybridization chamber, which employs a fluid mixer based on chaotic advection theory to deliver targets across a conventional glass slide array. Microarrays were printed with a pattern of 102 identical probe spots containing a 65-mer oligonucleotide capture probe. Hybridization of a 725-bp fluorescently labeled target was used to measure average target hybridization levels, local signal-to-noise ratios, and array hybridization uniformity. Dynamic hybridization for 1h with 1 or 10ng of target DNA increased hybridization signal intensities approximately threefold over a 24-h static hybridization. Similarly, a 10- or 60-min dynamic hybridization of 10ng of target DNA increased hybridization signal intensities fourfold over a 24h static hybridization. In time course studies, static hybridization reached a maximum within 8 to 12h using either 1 or 10ng of target. In time course studies using the dynamic hybridization chamber, hybridization using 1ng of target increased to a maximum at 4h and that using 10ng of target did not vary over the time points tested. In comparison to static hybridization, dynamic hybridization reduced the signal-to-noise ratios threefold and reduced spot-to-spot variation twofold. Therefore, we conclude that dynamic hybridization based on a chaotic mixer design improves both the speed of hybridization and the maximum level of hybridization while increasing signal-to-noise ratios and reducing spot-to-spot variation.

DNA↗

PubMed2006

Artificially sweetened versus regular mixers increase gastric emptying and alcohol absorption.

BACKGROUND: Mixed alcoholic drinks are increasingly being consumed in "diet" varieties, which could potentially empty more rapidly from the stomach and thereby increase the rate of alcohol absorption when compared with "regular" versions containing sugar. METHODS: We studied 8 healthy males twice in randomized order. On each day, they consumed an orange-flavored vodka beverage (30 g ethanol in 600 mL), made with either "regular" mixer containing sucrose (total 478 kcal), or "diet" mixer (225 kcal). RESULTS: Gastric half-emptying time measured by ultrasound (mean+/-standard deviation) was less for the "diet" than the "regular" drink (21.1+/-9.5 vs 36.3+/-15.3 minutes, P <.01). Both the peak blood ethanol concentration (0.053+/-0.006 vs 0.034+/-0.008 g%, P <.001) and the area under the blood ethanol concentration curve between 0 and 180 minutes (5.2+/-0.7 vs 3.2+/-0.7 units, P <.001) were greater with the "diet" drink. CONCLUSIONS: Substitution of artificial sweeteners for sucrose in mixed alcoholic beverages may have a marked effect on the rate of gastric emptying and the blood alcohol response.

Absorption↗

PubMed1988

Multi-stage mixer-settler planet centrifuge. Preliminary studies on partition of macromolecules with organic-aqueous and aqueous-aqueous two-phase solvent systems.

A rotary-seal-free planetary centrifuge holds a separation column which consists of multiple partition units (ca. 200) connected in series with transfer tubes. In the cavity of each partition unit the transfer tube extends to form a mixer which vibrates to stir the contents under an oscillating force field generated by the planetary motion of the centrifuge. Consequently, solutes locally introduced at the inlet of the column are subjected to an efficient partition process in each partition unit and separated according to their partition coefficients. The mixer tube equipped with a flexible silicone rubber joint was found to produce excellent results for partition with viscous polymer phase systems. The capability of the method was demonstrated on separation of cytochrome c and lysozyme using a PEG-aqueous dibasic potassium phosphate-aqueous two-phase solvent system.

Animals↗

PubMed1999

Melt pelletisation of a hygroscopic drug in a high shear mixer. Part 1. Influence of process variables.

The applicability of a high shear mixer for melt pelletisation of binary mixtures of sodium valproate and glycerol monostearate was investigated. The effects of binder concentration, impeller speed, jacket temperature and massing time on mean pellet size and size distribution were examined in a 2(4)-factorial design. Binder concentration and impeller speed were found to be the most important variables influencing the mean granule size and size distribution. An increase in each of those accelerated the granule growth. Due to the solubility of the drug in the molten binder very low amounts of binder were necessary for the formation of pellets. The modified high shear mixer was found to be suitable for batch sizes of 1-4 kg; granule growth was delayed with increasing load. A common pellet growth pattern, which can be divided into three phases, was derived and confirmed from all trials. The process was monitored by means of a torque measuring system. The torque-time curve can be used to detect the beginning of the destruction phase.

Chemistry, Pharmaceutical↗

PubMed1999

Screening of high shear mixer melt granulation process variables using an asymmetrical factorial design.

The effects of process conditions on the granulometric characteristics of a placebo formulation prepared in a 10 l high shear mixer by single-step melt granulation were studied. The factors under investigation were: binder grade, mixer load, presence of the deflector (all of analysed at two levels), binder concentration, impeller speed, massing time, type of impeller blades (these four at three levels) and jacket temperature (considered at four levels). Two granule characteristics were analysed: the geometric mean diameter and the percentage of particles finer than 315 microm. In order to screen simultaneously the above-mentioned factor levels, an asymmetrical factorial design was adopted, which allowed the reduction in the number of runs from 2592 to 25. Additionally, this technique permitted the selection of the factor levels which have the major 'weight' on the two granule characteristics under study. Two additional trials were performed to attest the screening validity.

Chemistry, Pharmaceutical↗

PubMed2001

Effects of physical properties of powder particles on binder liquid requirement and agglomerate growth mechanisms in a high shear mixer.

A study was performed in order to elucidate the effects of the physical properties of small powder particles on binder liquid requirement and agglomerate growth mechanisms. Three grades of calcium carbonate having different particle size distribution, surface area, and particle shape but approximately the same median particle size (4-5 microm), were melt agglomerated with polyethylene glycol (PEG) 3000 or 20,000 in an 8-l high shear mixer at three impeller speeds. The binder liquid requirement was found to be very dependent on the packing properties of the powder, a denser packing resulting in a lower binder liquid requirement. The densification of the agglomerates in the high shear mixer could be approximately predicted by compressing a powder sample in a compaction simulator. With the PEG having the highest viscosity (PEG 20,000), the agglomerate formation and growth occurred primarily by the immersion mechanism, whereas PEG 3000 gave rise to agglomerate growth by coalescence. Powder particles with a rounded shape and a narrow size distribution resulted in breakage of agglomerates with PEG 3000, whereas no breakage was seen with PEG 20,000. Powder particles having an irregular shape and surface structure could be agglomerated with PEG 20,000, whereas agglomerate growth became uncontrollable with PEG 3000. When PEG 20,000 was added as a powder instead of flakes, the resultant agglomerates became rounder and the size distribution narrower.

Calcium Carbonate↗

PubMed2002

Scaling-up of a lactose wet granulation process in Mi-Pro high shear mixers.

The high shear wet granulation upscaling possibilities of a Pro-C-epT Mi-Pro 250 ml with a batch size of 40 g were investigated by down-scaling an alpha-lactose monohydrate wet granulation process from a Collette Gral 10 (8 l batch size) to a Pro-C-epT Mi-Pro with different bowl volumes of 5 l, and 1900, 900 and 250 ml. The wet granulation process was optimised in the Gral 10, next an octagonal design was build around the central point. Two process parameters, the impeller tip speed and the water content, were varied at three levels, which resulted in a two-factor three-level experimental design. alpha-Lactose monohydrate 200 M was granulated using a polyvinylpyrollidone K 30 (2.5% on dry material) binder solution. The granules were dried at 25 degrees C for 24 h, sieved and characterised. The granules were compressed to tablets. In all mixer volumes the used impeller tip speed range did not influence the granule or tablet properties. In all bowl volumes the influence of water concentration on actual yield, particle size distribution and granule friability was similar. All batch sizes resulted in tablets of similar quality. For the selected formulation the lab scale Mi-Pro high shear mixers with different bowl volumes could be used to determine the optimal process parameters and to scale up to the Collette Gral 10 pilot scale.

Lactose↗