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Peer-Reviewed Publications

Cell Disruption of S. Cerevisiae by Scalable High-Intensity UltrasoundCELL DISRUPTION OF S. CEREVISIAE BY SCALABLE HIGH-INTENSITY ULTRASOUND

Simon Bystryak, Rasa Santockyte, Alexey S. Peshkovsky, Biochemical Engineering Journal, Volume 99, August 2015, Pages 99-106

Abstract: Ultrasonic disruption of yeast and other microbial cell cultures is commonly used for laboratory-scale protein preparations because it is rapid, efficient and simple to use compared to such methods as high-pressure homogenization (HPH) and bead milling. Lysing by sonication is also more effective than other cell disruption methods for the recovery of periplasmic, membrane-bound, or insoluble recombinant proteins. Until recently, however, due to amplitude limitations of conventional-design pilot and industrial-size sonication equipment, ultrasonic cell disruption was only feasible on the laboratory scale. In this study, we show that Barbell Horn Ultrasonic Technology (BHUT) can be successfully used for the disruption of Sacharomyces cerevisiae (S. cerevisiae) cells on a large scale. In particular, we show that by using pilot-scale BHUT-based equipment, total protein and alkaline phosphatase can be efficiently extracted from S. cerevisiae cells, achieving about an order of magnitude productivity increase factor with respect to laboratory-scale results. Since the size of BHUT-based ultrasonic processors can be increased further, ultrasonic cell disruption now has the ability to develop into a valuable commercial-scale method, potentially superior to HPH and bead milling techniques in this area of application. Download >>


CONTINUOUS-FLOW PRODUCTION OF A PHARMACEUTICAL NANOEMULSION BY HIGH-AMPLITUDE ULTRASOUND: PROCESS SCALE-UPCONTINUOUS-FLOW PRODUCTION OF A PHARMACEUTICAL NANOEMULSION BY HIGH-AMPLITUDE ULTRASOUND: PROCESS SCALE-UP

Alexey S. Peshkovsky, Simon Bystryak, Chemical Engineering and Processing: Process Intensification, Volume 82, August 2014, Pages 132-136

Abstract: High-pressure homogenization (HPH, including microfluidization) and high-amplitude ultrasonic processing are currently the leading two methods used to produce nanoemulsions of superior quality. Despite suffering from multiple important drawbacks, HPH is currently the technology of choice for the industrial manufacture of pharmaceutical nanoemulsions. The ultrasonic nanoemulsification technology is free from most of these drawbacks and frequently used in laboratory studies. The challenge for the ultrasonic method, however, has been bridging the gap between laboratory research and its industrial implementation. Due to limitations of conventional ultrasonic technology, scaling up has not been possible without a significant reduction in ultrasonic amplitudes, which compromises product quality. This limitation has been overcome by Barbell Horn Ultrasonic Technology (BHUT), which permits constructing bench and industrial-scale processors capable of operating at high ultrasonic amplitudes. In the present study, a high-quality MF59®-analog pharmaceutical nanoemulsion has been successfully manufactured using laboratory, bench and industrial-scale high-amplitude ultrasonic processors. The overall laboratory-to-industrial scale-up factor achieved by using BHUT was approximately 55. The ultrasonic amplitude and the resulting product quality were maintained identical at all three scales. To our knowledge, this work is the first reported instance of a successful and systematic industrial scale-up of any high-amplitude ultrasonic process. Download >>


SCALABLE HIGH-POWER ULTRASONIC TECHNOLOGY FOR THE PRODUCTION OF TRANSLUCENT NANOEMULSIONSSCALABLE HIGH-POWER ULTRASONIC TECHNOLOGY FOR THE PRODUCTION OF TRANSLUCENT NANOEMULSIONS

Alexey S. Peshkovsky, Sergei L. Peshkovsky, Simon Bystryak, Chemical Engineering and Processing: Process Intensification, Volume 69, July 2013, Pages 77-82

Abstract: Oil-in-water nanoemulsions are widely used in cosmetics, pharmaceutical, food, agricultural and other industries as delivery systems for active lipophilic compounds and drugs. Translucent nanoemulsions are especially attractive because their extremely small droplet sizes lead to long-term stability, improve absorption by the skin and enable the delivery of exceptionally high concentrations of active substances. High-power ultrasound has previously been successfully used to produce translucent nanoemulsions on laboratory scale. However, due to limitations of conventional ultrasonic liquid processing technology, scaling up has not been possible, restricting industrial implementation of this process. In this study, ultrasonic production of translucent oil-in-water nanoemulsions was optimized on a laboratory scale and then directly scaled up. The ultrasonic amplitude played a significant role in this process, and was determined to be optimal near 90 m peak-to-peak. Barbell Horn Ultrasonic Technology was employed to scale up the process by a factor of 10 without reducing the ultrasonic amplitude or compromising the product quality. The scale-up procedure is described in detail. Further scale-up by a factor of five is theoretically shown to be possible, potentially making high-power ultrasound an important industrial method for producing nanoemulsions. Download >> 


SHOCK-WAVE MODEL OF ACOUSTIC CAVITATION

Sergei Peshkovsky, Alexey Peshkovsky, Ultrasonics Sonochemistry, Volume 15, Issue 4, April 2008, Pages 618-628

Abstract: Shock-wave model of liquid cavitation due to an acoustic wave was developed, showing how the primary energy of an acoustic radiator is absorbed in the cavitation region owing to the formation of spherical shock-waves inside each gas bubble. The model is based on the concept of a hypothetical spatial wave moving through the cavitation region. It permits using the classical system of Rankine–Hugoniot equations to calculate the total energy absorbed in the cavitation region. Additionally, the model makes it possible to explain some newly discovered properties of acoustic cavitation that occur at extremely high oscillatory velocities of the radiators, at which the mode of bubble oscillation changes and the bubble behavior approaches that of an empty Rayleigh cavity. Experimental verification of the proposed model was conducted using an acoustic calorimeter with a set of barbell horns. The maximum amplitude of the oscillatory velocity of the horns’ radiating surfaces was 17 m/s. Static pressure in the calorimeter was varied in the range from 1 to 5 bars. The experimental data and the results of the calculations according to the proposed model were in good agreement. Simple algebraic expressions that follow from the model can be used for engineering calculations of the energy parameters of the ultrasonic radiators used in sonochemical reactors. Download >>


MATCHING A TRANSDUCER TO WATER AT CAVITATION - ACOUSTIC HORN DESIGN PRINCIPLES

Sergei Peshkovsky, Alexey Peshkovsky, Ultrasonics Sonochemistry, Volume 14, Issue 3, March 2007, Pages 314-322

Abstract: High-power ultrasound for several decades has been an integral part of many industrial processes conducted in aqueous solutions. Maximizing the transfer efficiency of the acoustic energy between electromechanical transducers and water at cavitation is crucial when designing industrial ultrasonic reactors with large active volumes. This can be achieved by matching the acoustic impedances of transducers to water at cavitation using appropriately designed ultrasonic horns. In the present work, a set of criteria characterizing the matching capabilities of ultrasonic horns is developed. It is shown that none of the commonly used tapered-shape horns can achieve the necessary conditions. An analytical method for designing five-element acoustic horns with the desirable matching properties is introduced, and five novel types of such horns, most suitable for practical applications, are proposed. An evaluation of the horns’ performance is presented in a set of experiments, demonstrating the validity of the developed theoretical methodology. Power transfer efficiency increase by almost an order of magnitude is shown to be possible with the presented horn designs, as compared to those traditionally utilized.  Download >>

 


High-pressure homogenization (HPH, including microfluidization) and high-amplitude ultrasonic processing are currently the leading two methods used to produce nanoemulsions of superior quality. Despite suffering from multiple important drawbacks, HPH is currently the technology of choice for the industrial manufacture of pharmaceutical nanoemulsions. The ultrasonic nanoemulsification technology is free from most of these drawbacks and frequently used in laboratory studies. The challenge for the ultrasonic method, however, has been bridging the gap between laboratory research and its industrial implementation. Due to limitations of conventional ultrasonic technology, scaling up has not been possible without a significant reduction in ultrasonic amplitudes, which compromises product quality. This limitation has been overcome by Barbell Horn Ultrasonic Technology (BHUT), which permits constructing bench and industrial-scale processors capable of operating at high ultrasonic amplitudes. In the present study, a high-quality MF59®-analog pharmaceutical nanoemulsion has been successfully manufactured using laboratory, bench and industrial-scale high-amplitude ultrasonic processors. The overall laboratory-to-industrial scale-up factor achieved by using BHUT was approximately 55. The ultrasonic amplitude and the resulting product quality were maintained identical at all three scales. To our knowledge, this work is the first reported instance of a successful and systematic industrial scale-up of any high-amplitude ultrasonic process.