Po-Ying Li

Plasma removal of Parylene C

Parylene C, an emerging material in microelectromechanical systems, is of particular interest in biomedical and lab-on-a-chip applications where stable, chemically inert surfaces are desired. Practical implementation of Parylene C as a structural material requires the development of micropatterning techniques for its selective removal. Dry etching methods are currently the most suitable for batch processing of Parylene structures. A performance comparison of three different modes of Parylene C plasma etching was conducted using oxygen as the primary reactive species. Plasma, reactive ion and deep reactive ion etching techniques were explored. In addition, a new switched chemistry process with alternating cycles of fluoropolymer deposition and oxygen plasma etching was examined to produce structures with vertical sidewalls. Vertical etch rates, lateral etch rates, anisotropy and sidewall angles were characterized for each of the methods. This detailed characterization was enabled by the application of replica casting to obtain cross sections of etched structures in a non-destructive manner. Application of the developed etch recipes to the fabrication of complex Parylene C microstructures is also discussed.

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.

MINI DRUG PUMP FOR OPHTHALMIC USE

Purpose: To evaluate the feasibility of developing a novel mini drug pump for ophthalmic use. Methods: Using principles of microelectromechanical systems engineering, a mini drug pump was fabricated. The pumping mechanism is based on electrolysis and the pump includes a drug refill port as well as a check valve to control drug delivery. Drug pumps were tested first on the bench-top and then after implantation in rabbits. For the latter, we implanted 4 elliptical (9.9 × 7.7 × 1.8 mm) non-electrically active pumps into 4 rabbits. The procedure is similar to implantation of a glaucoma aqueous drainage device. To determine the ability to refill and also the patency of the cannula, at intervals of 4–6 weeks after implantation, we accessed the drug reservoir with a transconjunctival needle and delivered approximately as low as 1 µL of trypan blue solution (0.06%) into the anterior chamber. Animals were followed by slit lamp examination, photography, and fluorescein angiography. Results: Bench-top testing showed 2.0 µL/min delivery when using 0.4 mW of power for electrolysis. One-way valves showed reliable opening pressures of 470 mmHg. All implanted devices refilled at 4–6 weeks intervals for 4–6 months. No infection was seen. No devices extruded. No filtering bleb formed over the implant. Conclusions: A prototype ocular mini drug pump was built, implanted, and refilled. Such a platform needs more testing to determine the long term biocompatibility of an electrically-controlled implanted pump. Testing with various pharmacological agents is needed to determine its ultimate potential for ophthalmic use.

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.

A Parylene MEMS Electrothermal Valve

The first microelectromechanical-system normally closed electrothermal valve constructed using Parylene C is described, which enables both low power (in milliwatts) and rapid operation (in milliseconds). This low-power valve is well suited for applications in wirelessly controlled implantable drug-delivery systems. The simple design was analyzed using both theory and modeling and then characterized in benchtop experiments. Operation in air (constant current) and water (current ramping) was demonstrated. Valve-opening powers of 22 mW in air and 33 mW in water were obtained. Following integration of the valve with catheters, our valve was applied in a wirelessly operated microbolus infusion pump, and the in vivo functionality for the appropriateness of use of this pump for future brain mapping applications in small animals was demonstrated.

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.

A Passive Refillable Intraocular MEMS Drug Delivery Device

This paper presents the first passive implantable microelectromechanical systems (MEMS) device for targeted intraocular delivery of therapeutic compounds. In particular, this device addresses the treatment of chronic, difficult to reach diseases that affect the retina including retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy, and glaucoma. The device is composed of three structural polymethyldisiloxane (PDMS) layers that are irreversibly bonded without the use of any adhesives. These layers form an integrated drug delivery device consisting of a refillable reservoir, tube, check valve, and suture tabs. This device requires a single implantation surgery and is capable of repeated delivery of multiple drugs. Characterization of the refillable reservoir and check valve performance is presented. Preliminary surgical implantation results of a mechanical test structure are also presented

Integrated flow sensing for focal biochemical stimulation

A microfluidic platform for focal stimulation of cells and tissue allows precise biochemical control of the extracellular microenvironment. This interface consists of a polymer microchannel having a single pore through which chemicals are selectively diffused or ejected. Towards the realization of realtime feedback control of focal biochemical stimulation, integrated thermal flow sensors were used to monitor fluid release. Delivery of fluorescent dye to rat retina is also presented.

An electrochemical intraocular drug delivery device

This paper presents the first implantable intraocular MEMS drug delivery device capable of being refilled. To avoid repetitive surgeries, a refillable reservoir constructed of silicone rubber is implanted and capable of withstanding multiple needle punctures necessary for drug refill. The device uses electrolysis-actuated pumping to provide long- term drug treatment at therapeutic levels, and a flexible parylene transscleral cannula for precise targeting of difficult-to-reach areas in the eye. This electrochemically driven micropump provides flow rates suitable for ocular drug delivery (pL/min to muL/min). An encapsulation packaging technique was developed for demonstrating device operation in acute surgical studies. Preliminary surgical results in ex vivo porcine eyes are presented.

Implantable MEMS drug delivery pumps for small animal research

Advanced devices capable of selective delivery of compounds to targeted tissues are lacking, especially in small animal research. Biomedical microelectromechanical systems (bioMEMS) are uniquely suited to this application through the combination of scalability and precise control of fluid handling. Polymer-based drug delivery components and pumps for acute and chronic delivery in small animals are discussed.