Design and characterization of implantable drug delivery devices with remote pressure measurement

The topic of the thesis is the design and characterization of implantable devices with embedded sensors for remote measurement of osmotic pressure variation. Currently, the effect of osmotic pressure on drug delivery has only been experimentally investigated in vitro; the purpose of the thesis is the development of sensorized devices for continuous monitoring of osmotic pressure both in vitro and in vivo. The first prototypes consist of drug reservoirs with embedded strain sensors fabricated through metal and polymer additive manufacturing processes. The design is supported by FEM numerical model and structural simulations of the system. Experimental characterization of the reservoir in terms of strain-pressure relationship is achieved using a specifically designed test bench. The main design efforts provided involve the capsule sealing and connection to the hydraulic line. The results obtained on titanium and polyamide devices demonstrate the applicability to passive drug delivery systems. To achieve direct pressure measurement, a second device prototype is developed using a digital integrated pressure sensor with I2C interface. Data acquisition and sensor testing are performed through Arduino and C++ coding. The pressure sensor is wired to a miniaturized microcontroller located on a Printed Circuit board (PCB), specifically programmed for continuous pressure data acquisition and remote transmission via Bluetooth Low Energy (BLE) communication protocol. The device is custom made with implantable grade polymeric resin. The body features two chambers on the top part: the drug reservoir and the electronics chamber, that hosts the digital pressure sensor and the PCB. A discoidal battery is located on the bottom part and provides power supply and a semipermeable membrane is embedded on top of the reservoir to allows for osmotic exchange. Extended in vitro experiments demonstrate accuracy of pressure measurements and stability of the remote communication system. The prototype of the remotely controlled implantable device for direct pressure measurement proves the applicability to future in vivo experimentation in order to investigate the effect of osmotic phenomena on drug delivery.