ULTRASONIC TRANSDERMAL GLUCOSE MONITORING AND INSULIN DELIVERY USING CYMBAL TRANSDUCER ARRAYS

Open Access
Author:
Park, Eun-Joo
Graduate Program:
Bioengineering
Degree:
Doctor of Philosophy
Document Type:
Dissertation
Date of Defense:
July 21, 2009
Committee Members:
  • Nadine Smith, Dissertation Advisor
  • Nadine Barrie Smith, Committee Chair
  • Andrew G Webb, Committee Member
  • Ryan S Clement, Committee Member
  • Richard Joseph Meyer Jr., Committee Member
Keywords:
  • ultrasound
  • cymbal transducer
  • diabetes
  • drug delivery
  • transdermal
  • feedback
Abstract:
As a practically portable ultrasound system for transdermal drug delivery, cymbal transducer arrays have shown promise in several in vivo experiments using small animals. The goal of this study was to evaluate the potential of the cymbal transducer array as a pre-clinical application for transdermal insulin delivery and glucose sensing. In order to achieve this goal, several aspects have been investigated, such as the feasibility of ultrasonic transdermal insulin delivery and glucose sensing in large animals, and a closed-loop feedback controller for regulating glucose levels. To evaluate further the practicability of the cymbal transducer array as a pre-clinical application, in vivo experiments with transdermal insulin delivery were performed in large pigs (~ 200 lbs). The results of the ultrasound exposure group indicate that the glucose level decreased to -74 ± 5 mg/dl at 60 minutes and continued to decrease to -91 ± 9 mg/dl at 90 minutes. In addition to the insulin delivery, the cymbal transducer array has been used in determining the glucose concentration of interstitial fluid. From the perspective of application in humans, the in vivo studies using large pigs were designed to determine the feasibility of the cymbal transducer array in ultrasonic transdermal glucose sensing. After 5 minutes of ultrasound exposure at Isptp = 100 mW/cm2, the glucose levels determined by the ultrasound system and glucose meter were 127 ± 16 mg/dl and 131 ± 5 mg/dl, respectively. Based on the results of transdermal insulin delivery and glucose sensing in large pigs, the ultrasound systems for both applications were combined using a closed-loop feedback controller. Four in vivo experiments were designed with large pigs to demonstrate the feasibility of the combined ultrasound system in noninvasive glucose control. Based on the glucose level measured by ultrasound and biosensors at 20-minute intervals, the ultrasound system of insulin delivery was shown to regulate the glucose level. During the 120-minute experiments, glucose levels were controlled in the range of 104-137 mg/dl as determined by the ultrasound system. Through the in vivo experiments of transdermal insulin delivery and glucose, the ultrasound system using the cymbal transducer array has shown the positive potential of a practically portable device for a clinical application of diabetes care.