To date, many drug delivery devices have been proposed, however, so far, none of them can provide all of the functions of (1) implantability, (2) precise flow control, (3) drug refillability, and (4) targeted drug delivery. In addition, for diseased tissues located in small organs (such as the eyeball) or for small animal models (such as mice) used in genetic or human disease research, (5) small device footprint and (6) reliability are required for the new generation drug delivery system. Current drug delivery techniques, such as sustained release implants or microreservoirs, offer a portion of the functions that mentioned above, but none of them can fulfill all of the requirements listed. The main reason is that these devices possess simple structures and usually provide only single function. Therefore, to fulfill all of the requirements, a multi-component device is needed.
In this thesis, we presented two system-level implantable bioMEMS drug delivery devices based on micromachining technology suitable for chronic ocular drug administration and acute drug injection in small animals. Each device contains several individual components and each component provides one of the previous mentioned functions. Combining of all these functions, these system-level devices can achieve the treatment of incurable eye diseases such as glaucoma or realize advanced engineering research such as real-time functional neuroimaging.
Two major components are introduced: (1) an electrolysis actuator and (2) a Parylene electrothermal valve. First, the MEMS electrolysis micropump features low power consumption with large actuation force which is suitable for implantation. Electrolysis pumping provides precise flow control (pL/min to μL/min) with either bolus or continuous delivery mode. The pump is microfabricated so the reduced footprint is suitable for ocular implantation. The structure of the pump is simple, so it is reliable compared to mechanical micropumps.
The first MEMS normally-closed, low power, and on-demand electrothermal valve constructed using Parylene C that enables both low power (mW) and rapid (ms) operation suitable of small animal implantation. It is also microfabricated with small device dimension. The valve can be reliably activated using constant current, linear current ramping and variable current ramping.
Each of these components was integrated into two system-level drug delivery devices: (1) an intraocular drug delivery device for the treatment of eye disease and (2) a microbolus infusion pump for real-time functional neuroimaging. First, the intraocular drug delivery device is capable of being refilled and enables targeted intraocular drug delivery. The refillable design permits long-term drug therapy and avoids repetitive surgeries. A flexible Parylene transscleral cannula allows targeted delivery to tissues in both the anterior and posterior segments of the eye. Both the ex vivo and in vivo testing were performed demonstrating the feasibility of this device for ocular drug delivery.
Finally, a disposable microbolus infusion pump integrated with the previous Parylene electrothermal valve for one-time, rapid drug delivery application. The design of the reservoir was optimized for implantation in a 40-gram mouse. A reproducible pump-generated flow rate was measured and no leakage was observed from the reservoir which could withstand up to 10 punctures without leakage. We demonstrated wireless operation of the microbolus infusion pump and validated its functionality in vivo for use in functional neuroimaging applications in small animals.