Sonoporation represents a promising approach to increase targeted drug delivery efficiency by facilitating transport of therapeutic agents to the target tissue with the use of ultrasound. However, most of the current research in sonoporation is performed with external ultrasonic transducers, which hinders the applicability of the therapeutic procedure for treatment of conditions situated deeper into the patient's body, such as liver or intestinal tumours. This Thesis presents the development process of a miniature-sized 1-3 connectivity piezocomposite 1D phased array for intracorporeal sonoporation. The device was to be incorporated into a capsule or catheter and hence the primary design constraint was the reduced size of the piezoelectric element, which was limited to 2.5 mm in width and 12 mm in length. To meet the needs of the intended application, resonance frequencies of 1.5 MHz and 3.0 MHz were considered. A simulation framework was developed for optimization of the miniature array in relation to the peak negative pressure attained at the focus to mitigate the low power output associated with the limited device dimensions. This was implemented through a multiparametric sweep of the 1-3 piezocomposite geometry-related parameters. Devices made with PZT-5H and PMN-29%PT were evaluated. The optimization algorithm was used to determine specifications for phased array designs based on the two materials and the two resonance frequencies. The 1.5 MHz devices comprised 24 elements and the 3.0 MHz ones had 32 elements. The piezocomposites were manufactured using the dice and fill technique and electroded using a novel method of electrode deposition employing spin coating of Ag ink. Subsequently, the prototype devices were driven with a commercial array controller and characterized with a calibrated needle hydrophone in a scanning tank. Two simulation profiles based on finite element analysis and time extrapolation were developed to model the acoustic beams from the arrays, which were compared and calibrated with experimental data for focal distances between 5 mm and 10 mm and beam steering angles from 0° to 40°. The results showed that modelling could be employed reliably for therapeutic planning. Both the 1.5 MHz and the 3.0 MHz, PZT-5H arrays were tested in vitro and shown to induce and control sonoporation of a human epithelial colorectal adenocarcinoma cell layer. Finally, a 24 element, 1.5 MHz, PZT-5H array was implemented in a 40 mm long by 11 mm diameter tethered, biocompatible capsule intended for in vivo operation. The device was characterized in the scanning tank for steering angles in the range 0° to 56° and focal distances between 4.0 mm and 5.7 mm, and the measured beam profiles were correlated with the simulation framework. The capsule will be tested in future ex-vivo and in-vivo experiments on insulin absorption through porcine small bowel by means of sonoporation.
|Date of Award||10 May 2021|
- University Of Strathclyde
|Sponsors||EPSRC (Engineering and Physical Sciences Research Council)|
|Supervisor||Anthony Gachagan (Supervisor) & Jerzy Dziewierz (Supervisor)|