Ronalee Lo

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.

In-Plane Bandpass Regulation Check Valve in Heat-Shrink Packaging for Drug Delivery

The first check valve featuring dual regulation of in-plane flow and heat-shrink tubing packaging is presented. This modular design is optimized for integration into low-profile fluidic devices requiring flow control, such as drug delivery devices. Theoretical and finite-element-modeling (FEM) analyses were performed to guide valve design and these results were confirmed experimentally. The valve regulates flow between 150-900 mmHg (20-120 kPa) and withstands ≫ 500 mmHg (66.7 kPa) of reverse pressure. The heat-shrink packaging scheme does not require adhesives and is extremely robust (≫2000 mmHg without leakage).

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

A Modular Heat-Shrink-Packaged Check Valve With High Pressure Shutoff

A novel check valve featuring adhesiveless packaging in heat-shrink tubing and dual regulation of in-plane flow is presented. The modular design enables simple replacement of valve components to modify valve behavior and performance. The specific design is intended for low-profile fluidic applications requiring flow control, such as drug delivery devices. The heat-shrink packaging scheme is extremely robust and can withstand >; 2000 mmHg (266.6 kPa) without leakage. Three different valve geometries were investigated and evaluated with theoretical and finite-element modeling analyses. Repeated flow regulation experiments on a fully packaged, hydrated valve demonstrated flow regulation between 25 and 2000 mmHg (3.33-266.6 kPa) and leak-free closure up to 500 mmHg (66.7 kPa) of reverse pressure with no observed stiction. The valve closing time constants were also determined.

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.

A Reusable In-Plane Polymer Integrated Microfluidic Interconnect

A novel reusable, in-plane polymer interconnect directly integrated into a microfluidic system is demonstrated. This approach features plug-and-play style connections to microfluidic networks in which commercially available non-coring syringe needles are simply inserted through pre-defined polydimethylsiloxane (PDMS) septums to form rapid, on-demand connections to microchannels. These septums are mechanically anchored by one layer of SU-8 that also forms the microchannels. Interconnect design, fabrication, theoretical analysis, and experimental results (pull-out force and leakage) are presented.