We present the first implantable drug delivery system for controlled dosing, timing, and location in small animals. Current implantable drug delivery devices do not provide control over these factors or are not feasible for implantation in research animals as small as mice. Our system utilizes an integrated electrolysis micropump, is refillable, has an inert drug reservoir for broad drug compatibility, and is capable of adjustment to the delivery regimen while implanted. Electrochemical impedance spectroscopy (EIS) was used for characterization of electrodes on glass substrate and a flexible Parylene substrate. Benchtop testing of the electrolysis actuator resulted in flow rates from 1 to 34 μL/min on glass substrate and up to 6.8 μL/min on Parylene substrate. The fully integrated system generated a flow rate of 4.72 ± 0.35 μL/min under applied constant current of 1.0 mA while maintaining a power consumption of only ~3 mW. Finally, we demonstrated in vivo application of the system for anti-cancer drug delivery in mice.

The first electrochemical actuator with a Parylene bellows for intraocular drug delivery is presented in which the bellows separates the electrolysis actuation chamber from the drug reservoir. The Parylene bellows was fabricated using a novel polyethylene glycol (PEG)-molding process and mechanically characterized. Optimization of the gas generation efficiency of the actuators was performed. We achieved an efficiency approaching 80% and over 1.5 mm deflection with our actuator. Wireless operation was also demonstrated.

Drug delivery systems play a crucial role in the treatment and management of medical conditions. Microelectromechanical systems (MEMS) technologies have allowed the development of advanced miniaturized devices for medical and biological applications. This Review presents the use of MEMS technologies to produce drug delivery devices detailing the delivery mechanisms, device formats employed, and various biomedical applications. The integration of dosing control systems, examples of commercially available microtechnology-enabled drug delivery devices, remaining challenges, and future outlook are also discussed.

Implantable electronic medical devices have achieved remarkable medical advances in the treatment of the most challenging conditions, starting with the introduction of the first implantable pacemaker in 1958. Increasing demand for innovation in existing and novel implantable devices is fuelled by the growing aging population and the increased prevalence of chronic diseases. This perspective article provides an overview of the implantable medical device ecosystem, highlights recent developments, and discusses challenges and opportunities for translation of new innovative implants enabled by microtechnologies and microfabrication.

No abstract

We present a high efficiency wireless MEMS electrochemical bellows actuator capable of rapid and repeatable delivery of boluses for fluid metering and drug delivery applications. Nafion®-coated Pt electrodes were combined with Parylene bellows filled with DI water to form the electrolysis-based actuator. The performance of actuators with several bellows configurations was compared for a range of applied currents (1-10 mA). Up to 75 boluses were delivered with an average pumping flow rate of 114.40 ± 1.63 μL/min. Recombination of gases into water, an important factor in repeatable and reliable actuation, was studied for uncoated and Nafion®-coated actuators. Real-time pressure measurements were conducted and the effects of temperature, physiological back pressure, and drug viscosity on delivery performance were investigated. Lastly, we present wireless powering of the actuator using a class D inductive powering system that allowed for repeatable delivery with less than 2% variation in flow rate values.

We present an implantable micropump with a miniature form factor and completely wireless operation that enables chronic drug administration intended for evaluation and development of cancer therapies in freely moving small research animals such as rodents. The low power electrolysis actuator avoids the need for heavy implantable batteries. The infusion system features a class E inductive powering system that provides on-demand activation of the pump as well as remote adjustment of the delivery regimen without animal handling. Micropump performance was demonstrated using a model anti-cancer application in which daily doses of 30 μL were supplied for several weeks with less than 6% variation in flow rate within a single pump and less than 8% variation across different pumps. Pumping under different back pressure, viscosity, and temperature conditions were investigated; parameters were chosen so as to mimic in vivo conditions. In benchtop tests under simulated in vivo conditions, micropumps provided consistent and reliable performance over a period of 30 days with less than 4% flow rate variation. The demonstrated prototype has potential to provide a practical solution for remote chronic administration of drugs to ambulatory small animals for research as well as drug discovery and development applications.

We present the first implantable MEMS drug delivery device that includes an electrochemical bellows pump, refillable drug reservoir, and dual regulation valve. Multiple drug pump configurations were fabricated, assembled, and tested. Delivery of agents for cancer radiation reduction was demonstrated. In vivo chronic delivery of radiation sensitizing agents in the form of small interfering (siRNA)-gold nanorod complexes (nanoplexes) directly to tumors induced in mice was achieved. Radiation therapy in conjunction with active drug pumping by electrolysis actuation resulted in significant reduction of colon cancer tumor (HT29) size (~50%) over diffusion-based delivery and intravenous injections. To our knowledge, this is the first MEMS drug delivery pump suitable for safe, efficacious, and local delivery of short half-life siRNA in vivo.