Novel flexible parylene-based high-density electrode arrays have been developed for functional electrical stimulation in retinal and spinal cord applications. These electrode arrays are microfabricated according to single-metal-layer and, most recently, dual-metal-layer processes. A new heat-molding process has been implemented to conform electrode arrays to approximate the curvature of canine retinas, and chronic implantation studies have been undertaken to study the mechanical effects of parylene-based prostheses on the retina, with excellent results to date. Electrode arrays have also been implanted and tested on the spinal cords of murine models, with the ultimate goal of facilitation of locomotion after spinal cord injury; these arrays provide a higher density and better spatial control of stimulation and recording than is typically possible using traditional fine-wire electrodes. Spinal cord stimulation typically elicited three muscle responses, an early (direct), a middle (monosynaptic), and a late (polysynaptic) response, classified based on latency after stimulation. Stimulation at different rostrocaudal levels of the cord yielded markedly different muscle responses, highlighting the need for such high-density arrays.

Microfabrication has greatly matured and proliferated in use amongst many disciplines. There has been great interest in micromachined flow sensors due to the benefits of miniaturization: low cost, small device footprint, low power consumption, greater sensitivity, integration with on-chip circuitry, etc. This paper reviews the theory of thermal flow sensing and the different configurations and operation modes available. Material properties relevant to micromachined thermal flow sensing and selection criteria are also presented. Finally, recent applications of micromachined thermal flow sensors are presented. Detailed tables of the reviewed devices are included.

The provided electrophysiological and immunohistochemical data provide strong support to the viability of the developed probe technology. Furthermore, the obtained data provide insights into further optimization of the probe design, including tip geometry, use of neurotrophic and anti-inflammatory drugs in the Matrigel coating, and placement of the recording sites.

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 acquisition of high-fidelity, long-term neural recordings in vivo is critically important to advance neuroscience and brain–machine interfaces. For decades, rigid materials such as metal microwires and micromachined silicon shanks were used as invasive electrophysiological interfaces to neurons, providing either single or multiple electrode recording sites. Extensive research has revealed that such rigid interfaces suffer from gradual recording quality degradation, in part stemming from tissue damage and the ensuing immune response arising from mechanical mismatch between the probe and brain. The development of “soft” neural probes constructed from polymer shanks has been enabled by advancements in microfabrication; this alternative has the potential to mitigate mismatch-related side effects and thus improve the quality of recordings. This review examines soft neural probe materials and their associated microfabrication techniques, the resulting soft neural probes, and their implementation including custom implantation and electrical packaging strategies. The use of soft materials necessitates careful consideration of surgical placement, often requiring the use of additional surgical shuttles or biodegradable coatings that impart temporary stiffness. Investigation of surgical implantation mechanics and histological evidence to support the use of soft probes will be presented. The review concludes with a critical discussion of the remaining technical challenges and future outlook.

An implantable manually-actuated drug delivery device, consisting of a refillable drug reservoir, flexible cannula, check valve, and suture tabs, was investigated as a new approach for delivering pharmaceuticals to treat chronic ocular diseases. Devices are fabricated by molding and bonding three structured layers of polydimethylsiloxane. A 30 gauge non-coring needle was used to refill the reservoir; this size maximized the number of repeated refills while minimizing damage to the reservoir. The check valve cracking pressure was 76 +/- 8.5 mmHg (mean +/- SE, n = 4); the valve sustained > 2000 mmHg of reverse pressure without leakage. Constant delivery at 1.57 +/- 0.2 microL/sec and 0.61 +/- 0.2 microL/sec (mean +/- SE, n = 4) under 500 mmHg and 250 mmHg of applied pressure, respectively, was obtained in benchtop experiments. The valve closing time constant was 10.2 s for 500 mmHg and 14.2 s for 250 mmHg. Assembled devices were successfully demonstrated in benchtop, ex vivo, and in vivo experiments.

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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.