Acoustic Spectrometer Research Articles

Process Analytical Technology for the Production of Parenteral Lipid Emulsions According to Good Manufacturing Practices

The good manufacturing practices (GMP) and process analytical technology (PAT) initiatives of the US Food and Drug Administration, in conjunction with International Council for Harmonisation (ICH) quality guidelines Q8, Q9, and Q10, ensure that manufacturing processes for parenteral formulations meet the requirements of increasingly strict regulations. This involves the selection of suitable process analytics for process integration and aseptic processing. In this article, we discuss the PAT requirements for the GMP-compliant manufacturing of parenteral lipid emulsions, which can be used for clinical nutrition or for the delivery of lipophilic active ingredients. There are risks associated with the manufacturing processes, including the potential for unstable emulsions and the formation of large droplets that can induce embolisms in the patient. Parenteral emulsions are currently monitored offline using a statistical approach. Inline analytics, supplemented by measurements of zeta potential, could minimize the above risks. Laser scanning technology, ultrasound attenuation spectroscopy, and photo-optical sensors combined with image analysis may prove to be useful PAT methods. In the future, these technologies could lead to better process understanding and control, thus improving production efficiency.

Ultrasound Study of Magnetic and Non-Magnetic Nanoparticle Agglomeration in High Viscous Media.

Ultrasound attenuation spectroscopy has found wide application in the study of colloidal dispersions such as emulsions or suspensions. The main advantage of this technique is that it can be applied to relatively high concentration systems without sample preparation. In particular, the use of Epstein-Carhart-Allegra-Hawley’s (ECAH) ultrasound scattering theory, along with experimental data of ultrasound velocity or attenuation, provide the method of estimation for the particle or droplet size from nanometers to millimeters. In this study, suspensions of magnetite and silica nanoparticles in high viscous media (i.e., castor oil) were characterized by ultrasound spectroscopy. Both theoretical and experimental results showed a significant difference in ultrasound attenuation coefficients between the suspensions of magnetite and silica nanoparticles. The fitting of theoretical model to experimental ultrasound spectra was used to determine the real size of objects suspended in a high viscous medium that differed from the size distributions provided by electron microscopy imaging. The ultrasound spectroscopy technique demonstrated a greater tendency of magnetic particles toward agglomeration when compared with silica particles whose sizes were obtained from the combination of experimental and theoretical ultrasonic data and were more consistent with the electron microscopy images.

Different Chlorides Attack on the Hydration of Calcium Aluminate Cement at 5~40°C

Calcium aluminate cement (CAC) has excellent resistance to seawater erosion, but the mechanism remains to be explored. Effects of NaCl and CaCl2 on the hydration of CAC at 5, 20 and 40°C were investigated in this paper by X-ray diffraction(XRD), thermal analyzer(TG-DSC), scanning electron microscopy(SEM), acoustic and electroacoustic spectrometer. Results show that the varieties of chlorides have great impacts on the chloride binding ability, mechanical properties and microstructure of cement pastes at different temperatures. At 5°C and 20°C, the formation of C2AH8 is suppressed by chloride attack. Though the addition of NaCl promotes the formation of CAH10, CaCl2 leads to a denser microstructure and the improvement in compressive strength. At 40°C, C2AH8 disappears by chloride attack, while C3AH6 and Friedel’s salt increase. Comparing with the attack of CaCl2, NaCl contributes to the formation of C3AH6. Therefore, it results in a the retraction in compressive strength, ascribing to a coarser structure. In addition, although NaCl is superior in chemical binding ability, CaCl2 has better physical adsorption ability which dominants the binding process, and thus leading to greater amount of bonded chloride than that with NaCl. This research provides the oretical basis for the application of CAC in marine environment.

Study of Dispersions of Carbon Nanotubes Modified by the Method of Rapid Expansion of Supercritical Suspensions.

The effectiveness of carbon nanotubes (CNT) deagglomeration by rapid expansion of supercritical suspensions (RESS) in nitrogen and carbon dioxide fluids was studied in this work. Two different mechanisms of deagglomeration were proposed for these two fluids at various temperature and pressure conditions. Ultrasound attenuation spectroscopy was applied as an express method of determining median diameter and aspect ratio of CNTs. At least twofold reduction of the diameter was shown for CNT bundles processed by RESS technique. Aspect ratio of processed CNTs, calculated from acoustic attenuation spectra, increased to 340. These results were in a good agreement with atomic force microscopy data.

Bulk Viscosity of a Suspension of Silicon Oxide Nanoparticles

Data on the bulk viscosity of an aqueous suspension of SiO2 nanoparticles (Ludox TM-50) have been obtained for the first time using an acoustic spectrometer. A wide range of nanoparticle mass concentrations (from 1 to 50 wt %) has been investigated. Spectra of the ultrasound attenuation coefficient and coefficients of longitudinal and dynamic viscosities have been measured. Dependences of the dynamic and bulk viscosity coefficients of the suspensions on the nanoparticle concentration have been obtained.

Объемная вязкость суспензии наночастиц оксида кремния

Data on the bulk viscosity of an aqueous suspension of SiO2 nanoparticles (Ludox TM-50) were obtained using an acoustic spectrometer for the first time. A wide range of mass concentrations of nanoparticles (from 1 to 50 wt.%) was considered. The spectra of the attenuation coefficient of ultrasound and the coefficients of longitudinal and dynamic viscosity were measured. The dependences of the dynamic and bulk viscosity coefficients of the suspensions on the nanoparticle concentration were obtained.

Lipid-shelled microbubbles for ultrasound-triggered release of xenon

Xenon is a cellular protectant shown to stabilize or reduce neurologic injury in stroke. The goal of this work was to develop lipid-shelled microbubbles for ultrasound-triggered xenon release. Microbubbles loaded with either xenon alone (Xe-MB) or xenon and octafluoropropane (Xe-OFP-MB) were synthesized by high-shear mixing lipids with either 100% xenon, or 90% (v/v) xenon and 10% (v/v) octafluoropropane. The size distribution and the attenuation coefficient of Xe-MB and Xe-OFP-MB were measured using a Coulter counter and a broadband attenuation spectroscopy system, respectively. Gas chromatography/mass spectrometry (GC/MS) was performed to assess the dose and stability of encapsulated xenon. The feasibility of xenon release using 5-MHz pulsed Doppler ultrasound and 220-kHz pulsed ultrasound was tested by ultrasound attenuation spectroscopy. Co-encapsulation of OFP increased the number density, attenuation coefficient, and temporal stability of microbubbles. The GC/MS measurements revealed that 143 ± 20 μL/mg and 131 ± 33 μL/mg of xenon was loaded in Xe-MB and Xe-OFP-MB, respectively. Xe-MB and Xe-OFP-MB retained 54 ± 11% and 66 ± 1% of the xenon payload within 15 min of activation, respectively. Attenuation measurements confirmed ultrasound-triggered xenon release. These results suggest that lipid-shelled microbubbles with OFP could serve as ultrasound-triggered xenon delivery agents to attenuate cellular breakdown.

Acoustic spectrometer with minimized background dissipation.

Apparatus for measurements of internal friction from Q-1∼10-6 and elastic moduli in the kilohertz frequency range in which external friction losses were minimized using a new-type of three-reed tuning fork as a sample under study is described. High sensitivity of the apparatus made it possible to observe a resonance plasticization of diamagnetic LiF crystals under the action of crossed magnetic fields (≈100 μT) in the EPR conditions.

Acoustic spectroscopy for evaluating dimensions of cylindrical carbon nano-objects in colloidal systems

Ultrasound attenuation spectroscopy was applied to develop an express method for determining two dimensions of cylindrical nano-objects in colloids. For this we offered to perform measurements of attenuation spectra for two independent states of colloids: with the isotropic distribution of nano-objects and with orientation of nano-objects across the ultrasound beam. The oriented state of the nano-objects is achieved in the flowing colloid due to flow acceleration in the constricted channel. As a criterion of maximum orientation of nano-objects along the flow we used the decreasing of longitudinal viscosity close to the asymptotic value. A significant difference was found between attenuation spectra measured in two states for three aqueous colloids of carbon nanotubes and nanofibers with aspect ratio from 27 to 415. The diameter values from 5 to 21nm of the nano-objects, calculated from attenuation spectra of oriented state, corresponded to TEM and AFM data. We suggested the methodology for evaluation of the aspect ratio of the cylindrical nano-objects in colloids based on the attenuation spectra in two states of colloids and the calibration function which should be preliminary defined using acoustic and microscopy tests of reference colloids.

Particle sizing with improved genetic algorithm by ultrasound attenuation spectroscopy

As a global optimization algorithm, genetic algorithm is an advantageous tool due to its global convergence, great robustness, suitable for parallel computing and so on. Selection of optimal parameters, e.g., maximum generations, population size, and genetic operators (crossover fraction and mutation fraction), is extremely crucial for particle size characterization by ultrasound attenuation spectroscopy with genetic algorithm. A series of particle system with different distribution functions were numerically investigated in this work. It revealed that the simulated results were consistent with the given particle size distribution when the maximum generations, population size crossover fraction and mutation fraction were appropriate chosen. Furthermore, the anti-noise performance of genetic algorithm and its three improved forms applied in particle system with bimodal distribution were also studied. Two groups of samples (micron-sized glass beads-glycerol suspension and aqueous polystyrene suspension) were investigated experimentally by ultrasound attenuation spectroscopy, and it showed a good agreement between Improved Genetic Algorithm 3 (IGA3) and Microscope Image Analysis (MIA).

Nucleation in food colloids.

Nucleation in food colloids has been studied in detail using ultrasound spectroscopy. Our data show that classical nucleation theory (CNT) remains a sound basis from which to understand nucleation in food colloids and analogous model systems using n-alkanes. Various interpretations and modifications of CNT are discussed with regard to their relevance to food colloids. Much of the evidence presented is based on the ultrasound velocity spectrometry measurements which has many advantages for the study of nucleating systems compared to light scattering and NMR due to its sensitivity at low solid contents and its ability to measure true solid contents in the nucleation and early crystal growth stages. Ultrasound attenuation spectroscopy also responds to critical fluctuations in the induction region. We show, however, that a periodic pressure fluctuation such as a quasi-continuous (as opposed to a pulse comprising only a few pressure cycles) ultrasound field can alter the nucleation process, even at very low acoustic intensity. Thus care must be taken when using ultrasound techniques that the measurements do not alter the studied processes. Quasi-continuous ultrasound fields may enhance or suppress nucleation and the criteria to determine such effects are derived. The conclusions of this paper are relevant to colloidal systems in foods, pharmaceuticals, agro-chemicals, cosmetics, and personal products.

Ultrasound induced colloidal particles oscillation in liquid at elevated temperatures

Ultrasound attenuation spectroscopy provides a unique means for studying various properties of complex fluids such as aggregative stability, particle size, longitudinal rheology, zeta potential, etc. Additionally, ultrasound emerges as an important tool for microfluidics. These features of ultrasound attenuation spectroscopy are dependent upon a theory that describes colloidal particle motion in an ultrasound field. Here we verify experimentally the validity of this well-known theory at elevated temperatures. We measured the attenuation frequency spectra for a stable dispersion of alumina particles (300nm) at different temperatures from 25°C to 50°C. Temperature variation affects water viscosity, which is a key parameter in said theory. We have demonstrated that the theory accounts for such dependence accurately, because critical hydrodynamic relaxation frequency shifts as the theory predicts, and particle size calculated from the measured attenuation spectra remains constant over the complete temperature range.

Aggregation and stability of anisotropic charged clay colloids in aqueous medium in the presence of salt

Na-montmorillonite nanoclay is a colloid of layered mineral silicate. When dispersed in water, this mineral swells on absorption of water and exfoliates into platelets with electric double layers on their surfaces. Even at low particle concentration, the aqueous dispersion can exhibit a spontaneous ergodicity breaking phase transition from a free flowing liquid to nonequilibrium, kinetically arrested and disordered states such as gels and glasses. In an earlier publication [Applied Clay Science, 2015, 114, 8592], we showed that the stability of clay gels can be enhanced by adding a salt later to the clay dispersion prepared in deionized water, rather than by adding the clay mineral to a previously mixed salt solution. Here, we directly track the collapsing interface of sedimenting clay gels using an optical method and show that adding salt after dispersing the clay mineral does indeed result in more stable gels even in very dilute dispersions. These weak gels are seen to exhibit a transient collapse after a finite delay time, a phenomenon observed previously in depletion gels. The velocity of the collapse oscillates with the age of the sample. However, the average velocity of collapse increases with sample age up to a peak value before decreasing at higher ages. With increasing salt concentration, the delay time for transient collapse decreases, while the peak value of the collapsing velocity increases. Using ultrasound attenuation spectroscopy, rheometry and cryogenic scanning electron microscopy, we confirm that morphological changes of the gel network assembly, facilitated by thermal fluctuations, lead to the observed collapse phenomenon. Since clay minerals are used extensively in polymer nanocomposites, as rheological modifiers, stabilizers and gas absorbents, we believe that the results reported in this work are extremely useful for several practical applications and also for understanding geophysical phenomena such as the formation and stability of quicksand and river deltas.

Evaluation of the exfoliation and stability of Na-montmorillonite in aqueous dispersions

In aqueous dispersion, Na-montmorillonite swells due to absorption of water and exfoliate into smaller entities, known as tactoids, with electric double layers on their surfaces. The exfoliation rate of such tactoids in aqueous Laponite dispersion was seen to be greatly reduced at the jamming transition and was reported by this group in a recent article [Langmuir, 2013, 29, 12663–12669]. The work reported here uses ultrasound attenuation spectroscopy experiments on Na-montmorillonite dispersions and shows that the complete exfoliation of tactoids is not achieved even below the jamming concentration. This behavior indicates that screened Coulomb repulsions between and within tactoids, as well as the osmotic pressure of hydrated Na+ ions, play very important roles in the exfoliation kinetics of tactoids. In this work, the phenomenon of tactoid exfoliation is studied systematically by changing clay mineral concentration, ionic conditions and the ages of the dispersions. A signature of an irreversible process of tactoid reformation under certain ionic conditions is also observed. Finally, electroacoustic measurements and rheometry are used to assess the influence of tactoid exfoliation on the stability and viscoelasticity of the arrested phases formed under different ionic conditions.

Recent advances in the rapid acoustic screening of deoxynivalenol in wheat grains

Deoxynivalenol (DON) is a natural and ubiquitous toxic metabolite produced by filamentous fungi of the genusFusarium. Approximately one quarter of the world's food crops (mainly cereals) are affected by mycotoxins such as DON. A rapid and non-destructive method to evaluate the quality and safety of grains is therefore required to eliminate these toxins from the food chain. The first portable acoustic device that predicts the concentration of DON in cereal grains has been developed using a broadband capacitive ultrasonic transducer. An acoustic method was optimised for the rapid prediction of DON in wheat. To measure the performance of this method, a model system comprising 0-100% scabby wheat grains was prepared and a single laboratory validation was carried out. The best regression model between DON concentrations determined by the reference ELISA method and the acoustic technique was obtained at an acoustic frequency of 32.2 kHz, with a correlation coefficient of 0.9852 and a repeatability coefficient of variation of 2.1-9.3%, which is much better than the results achieved by prototype acoustic spectrometers. These data show that acoustic technology allows the online monitoring of DON in cereal grains, such as wheat, because it is possible to analyse multilayer grain beds. Sound absorption depends on the grain size and moisture content, so it is advisable to use the equipment at the point of harvest, where one strain of cereals usually dominates and the grains have a more homogeneous morphology and uniform moisture content.

Use of Ultrasound Attenuation Spectroscopy to Determine the Size Distribution of Clay Tactoids in Aqueous Suspensions

The dispersion processes of aqueous samples of clay are studied using ultrasound attenuation spectroscopy. The attenuation spectra that are acquired in the frequency range 10-100 MHz are used to determine the particle size distributions (PSDs) for different concentrations and ages of the clay suspensions. Our analysis, using equivalent spherical diameter (ESD) for circular discs under Stokes drag in samples of concentrations greater than 1.5% w/v, shows that a substantial fraction of the aggregates in suspension are actually tactoids that are composed of more than one platelet. This is in contrast to the general belief that clay disperses into individual platelets in the concentration range where their suspensions exhibit glassy behavior. We conclude that the incomplete fragmentation of the clay tactoids arises from the rapid enhancement of the intertactoid Coulombic repulsion.

Experimental and numerical analysis of cavitating flow around a hydrofoil

The paper describes experiments carried out in the cavitation tunnel with the rectangular test section of 150 × 150 × 500 mm and the maximum test section inlet velocity of 25 m/s. These experiments have been aimed to visualize the cavitation phenomena as well as to quantify the erosion potential using pitting tests evaluated during the incubation period for the cast-iron prismatic hydrofoil with the modified NACA profile. A bypass section installed in the tunnel has allowed to measure the nuclei content in the inlet flow to the test section using the acoustic spectrometer. The measured data have been compared with the CFD analysis of the cavitation phenomena on the hydrofoil as well as the numerically determined location and magnitude of the first calculated collapses of the cavitating bubbles with a good agreement.

Rapid acoustic screening of deoxynivalenol (DON) in grain

A novel, fast, non-invasive, cheap and quantitative technique to detect deoxynivalenol (DON) in cereal grains is described. This technique is completely different from currently applied wet chemistry techniques and is based on acoustic waves penetrating through and/or reflected by air-filled porous materials such as unconsolidated solid beads of grain. The rapid acoustic technique has been tested for the quantitative determination of DON in wheat. Two types of equipment were used: an acoustic spectrometer with transmission and an acoustic impulse spectrometer with transmission and reflection. To increase the accuracy of the analysis and optimise the acoustic signal an optimal frequency has been determined for both spectrometers. High correlations between DON contaminated wheat samples and the different amounts of shrivelled kernels in mixtures determined by the acoustic technique have been found. The statistical analysis shows that the acoustic method gives sufficiently precise results in the quantitative determination of DON in grain. The technique with in- and on-line capabilities can therefore be used to screen DON in contaminated wheat at point of harvest. Because it is fit for monitoring and high-throughput analysis, the technique solves some of the problems commonly associated with sampling and analysis.

When jelly gets the blues: Audible sound generation with gels and its origin

We report investigations concerning the mechanism for the audible sound generation of humming or ringing gels. As claimed earlier, the sound stems from the resonance of shear modes within the gel body. We present evidence for this claim by comparing the directly measured sound velocity, determined with a simple acoustic spectrometer, with the calculated one from measurements of the shear modulus and the mass density. Data were collected for different gel porosities. Deviations at comparatively small porosities are assumed as due to a frequency-dependent shear modulus.

When jelly gets the bluesAudible sound generation with gels and its origin

We report investigations concerning the mechanism for the audible sound generation of humming or ringing gels. As claimed earlier, the sound stems from the resonance of shear modes within the gel body. We present evidence for this claim by comparing the directly measured sound velocity, determined with a simple acoustic spectrometer, with the calculated one from measurements of the shear modulus and the mass density. Data were collected for different gel porosities. Deviations at comparatively small porosities are assumed as due to a frequency-dependent shear modulus.