Design of Low-intensity Pulsed Ultrasound Device, Intensity Sensor and Its Application to Enhance Vaccine Production

  • Author / Creator
    Xing, Jida
  • The application of low-intensity pulsed ultrasound (LIPUS) technology for therapy has become a promising interdisciplinary research field in biomedical engineering. This thesis covers two important topics in the field: LIPUS design and its biological applications. In therapeutic ultrasound applications, accurate ultrasound output intensities are crucial because the physiological effects of therapeutic ultrasound are very sensitive to the intensity and duration of these applications. Although radiation force balance is a benchmark technique for measuring ultrasound intensity and its output power, it is costly, difficult to operate, and compromised by noise vibration. To overcome these limitations, the development of a low-cost, easy to operate, and vibration-resistant alternative device is necessary for rapid ultrasound intensity measurement. Therefore, a novel two-layer thermoacoustic sensor using an artificial neural network technique was proposed and validated to accurately measure low ultrasound intensities between 30 and 120 mW/cm2 at a frequency of 1.5 MHz. The first layer of the sensor design is a cylindrical absorber made of plexiglass, followed by a second highly attenuating layer composed of polyurethane rubber to absorb ultrasound energy efficiently. The sensor determined ultrasound intensities according to a temperature elevation induced by heat converted from incident acoustic energy. After obtaining multiple parameters of the sensor characteristics through calibration, an artificial neural network was built to correct temperature drifts and increase the reliability of the thermoacoustic measurements through iterative training. After calibration, the designed sensor was able to measure ultrasound intensity in 12 seconds with an average error of 1.31 mW/cm2. For biological experiments, low-intensity pulsed ultrasound (LIPUS) was employed to enhance vaccine production as a unique physical-based approach. In this study, hepatitis B vaccine based on baculovirus-insect cell expression systems (BCESs) was used as a model system to demonstrate how LIPUS technology can increase the vaccine production. The experimental results demonstrated that LIPUS stimulation of 10 minutes per day at a frequency of 1.5 MHz, intensity of 60 mW/cm2 significantly increased both cell growth and vaccine production. The tests also showed that continuous sonication is better than stopping LIPUS stimulation after viral infection. Continuous ultrasound stimulation can achieve about a 40% increase in HBV S1/S2 production, while stopping sonication after viral infection increased the cell productivity by 11%. This finding is very meaningful for efficiently shortening vaccine production time or increasing the yield of proteins for vaccine use, which would reduce the manufacture costs of the vaccines.

  • Subjects / Keywords
  • Graduation date
    Fall 2016
  • Type of Item
  • Degree
    Doctor of Philosophy
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
  • Specialization
    • Biomedical Engineering
  • Supervisor / co-supervisor and their department(s)
  • Examining committee members and their departments
    • Li, Hua (Mathematics and Computer Science)
    • Han, Jie (Electrical and Computer Engineering)
    • Chen, Jie (Electrical and Computer Engineering)
    • Wang, Xihua (Electrical and Computer Engineering)
    • Liang, Hao (Electrical and Computer Engineering)