Roya Sheybani

A Parylene Bellows Electrochemical Actuator

We present the first electrochemical actuator with Parylene bellows for large-deflection operation. The bellows diaphragm was fabricated using a polyethylene-glycol-based sacrificial molding technique followed by coating in Parylene C. Bellows were mechanically characterized and integrated with a pair of interdigitated electrodes to form an electrochemical actuator that is suitable for low-power pumping of fluids. Pump performance (gas generation rate and pump efficiency) was optimized through a careful examination of geometrical factors. Overall, a maximum pump efficiency of 90% was achieved in the case of electroplated electrodes, and a deflection of over 1.5 mm was demonstrated. Real-time wireless operation was achieved. The complete fabrication process and the materials used in this actuator are biocompatible, which makes it suitable for biological and medical applications.

High-Efficiency MEMS Electrochemical Actuators and Electrochemical Impedance Spectroscopy Characterization

We present high-efficiency Nafion-coated electrochemical actuators having biocompatible construction suitable for biomedical applications such as drug delivery. High flow rates of up to 141.95 ± 0.46 μL/min were achieved (at 13 mA). Nafion coating increased efficiency across all current values tested and prevented current-induced damage to electrodes. The effects of coating thickness, electroplating, actuator orientation, and changes in temperature on actuator performance were studied. Electrochemical impedance spectroscopy is introduced as a tool for characterizing electrodes, quality of electrochemical cleaning, determining surface area activity, and also for understanding the impact of electrolyte coatings, electroplating, and substrate changes on actuator performance. Parylene and polyetheretherketone (PEEK) were investigated as flexible substrate substitutes for soda lime glass. The higher surface roughness of the PEEK substrate compared to glass led to actuators with improved flow rates.

Implantable MEMS drug delivery device for cancer radiation reduction

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.

High efficiency wireless electrochemical actuators: Design, fabrication and characterization by electrochemical impedance spectroscopy

A wirelessly-actuated high efficiency Nafion®-coated MEMS electrochemical actuator is presented. For the first time, high flow rates were achieved (up to 141µL/min, 13mA) under wireless operation and high efficiency pumping (up to 97%) was obtained with Nafion®-coated electrodes; coating further prevented previously reported current-induced damage to electrodes [1]. Electrochemical impedance spectroscopy (EIS) was used for electrode characterization, electrochemical cleaning, as well as investigation of delamination, electrode polymer coating and surface activation. Parylene and PEEK were investigated as flexible substrate substitutes for soda lime glass. As a result of the combined effect of the rough PEEK surface (increased electrode surface area) and the Nafion® coating, higher efficiency was achieved compared to glass.

MEMS: Enabled Drug Delivery Systems.

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.

Rapid non-lithography based fabrication process and characterization of Parylene C bellows for applications in MEMS electrochemical actuators

We present a rapid (1 day), modular, high-yield (∼90%) fabrication process for Parylene C bellows and their mechanical characterization. Load-deflection testing was performed on bellows of varying convolution numbers (1.0, 2.0, and 3.0) and compared to both finite element modeling (FEM) simulations and an analytical model based on membrane deflection theory. Bellows produced a consistent load response. Actuators (consisting of electrodes, electrolyte, and bellows) were assembled and then integrated into a polydimethylsiloxane (PDMS, or silicone rubber) drug reservoir. Preliminary results indicate accurate (< 5% error) drug delivery during repeated dosing at constant flow rate (3.75 µL/min, 2.0 convolution bellows, 1 mA constant current).

A parylene bellows electrochemical actuator for intraocular drug delivery

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.

Rapid and repeated bolus drug delivery enabled by high efficiency electrochemical bellows actuators

For the first time, rapid and repeatable delivery of precise drug boluses (up to 40 15-second boluses of 19.12 ± 0.73 µL cocaine within 50 minutes) is achieved with a high efficiency MEMS electrolysis actuator. Gas bubble recombination parameters and drug viscosity were investigated. Nafion®-coated electrodes provided superior pumping performance (linearity and repeatability) compared to uncoated electrodes.

Design, fabrication, and characterization of an electrochemically-based dose tracking system for closed-loop drug delivery

A real-time integrated electrochemically-based dose tracking system for closed-loop drug delivery is presented. Thin film Pt sensors were integrated in an electrolytic MEMS drug delivery pump to allow dose tracking via electrochemical impedance measurement. Measurement electrode placement and composition were investigated. A bolus resolution of 230 nL was demonstrated. The sensor was calibrated for use with water (low conductivity) and 1 × PBS (high conductivity), the selected model aqueous drugs. The impedance response is dependent on delivered volume and not affected by actuation parameters. A graphical user interface was created for real-time impedance based dose tracking and leakage/blockage detection in the system. Drift in the impedance response of an idle system after perturbation (actuation) were investigated and mitigated through the use of Pt wire electrodes as opposed to thin film electrodes.

Micro- and nano-fabricated implantable drug-delivery systems: current state and future perspectives

Biography Ellis Meng received her BS degree in engineering and applied science and her MS and PhD degrees in electrical engineering from the California Institute of Technology, Pasadena, in 1997, 1998 and 2003, respectively. She is a professor of Biomedical Engineering and Electrical Engineering at the University of Southern California, Los Angeles where she has been since 2004. She directs the Biomedical Microsystems Laboratory which specializes in biomicroelectromechanical systems, implantable biomedical microdevices, neural interfaces, and microfluidics. She is a recipient of the NSF CAREER, the Wallace H Coulter Foundation Early Career Translational Research, and the ASEE Curtis W McGraw Research Awards. In 2009, she was recognized as one of the TR35 Technology Review Young Innovators under 35. Roya Sheybani received her BS (2008) and MS (2009) degrees in biomedical engineering from the University of Southern California, Los Angeles, where she is currently a PhD candidate in biomedical engineering. She is a member of Tau Beta Pi and was coauthor of an Outstanding Paper Award from the 15th International Conference on Solid-State Sensors, Actuators and Microsystems. She also received the best poster award at the 16th Annual Fred S Grodins Graduate Research Symposium (Grodins, 2012) and the 2nd place Wallace H Coulter Translational Research Partnership innovation award (2013). She is developing closed-loop implantable wireless microelectromechanical systems (MEMS) drug-delivery devices for management of chronic diseases. Drug therapy plays a critical role in the treatment and management of many chronic conditions. Its efficacy is, in part, linked to the administration route and regimen. Many systemically administered drugs are associated with severe side effects [1] that dramatically impact quality of life. Also, while many novel pharmaceutical compounds, including biologics, gene therapies, small molecules and other nanoparticle-based therapeutics, have high specificity and potency, they possess limited bioactivity, relatively short halflife and stability, and have difficulty bypassing physiological barriers to reach targeted tissues [2]. These factors contribute to their limited compatibility with oral or parenteral routes of administration. These administration methods pose challenges for long-term treatment, are associated with a narrow therapeutic window, and require complex dosing schedules with combination therapy or labile active ingredients [3]. Implantable drug-delivery devices can target drug delivery to specific tissues, thereby minimizing side effects associated with systemic delivery. They also improve titration, provide automation and improve compliance. Completely implanted devices can reduce discomfort and eliminate infection risks from transcutaneous parts [4]. Folkman and Long pioneered implantable drugdelivery systems by introducing polymeric membranes (silicone rubber) for controlling release rates in the 1960s [5]. Since then, microand nano-fabrication technologies have enabled implantable miniaturized drugdelivery systems that can provide the desired drug release profile [4]. Drug administration Microand nano-fabricated implantable drug-delivery systems: current state and future perspectives