Ellis Meng

Micromachined Thermal Flow Sensors—A Review

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.

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.

High strain biocompatible polydimethylsiloxane-based conductive graphene and multiwalled carbon nanotube nanocomposite strain sensors

High performance strain sensors were achieved featuring simple, low-cost construction involving the screen printing of combinations of multi-walled carbon nanotube and graphene nano-platelet nanocomposites on biocompatible and flexible polymer substrates. Conductivity and thermal coefficients of resistance of different conductive nanocomposite sensor materials were measured. The zero current resistance and gauge factor of printed sensors was characterized. The combination of high strain operation (up to 40%), high gauge factor (GF > 100), and biocompatible construction pave the way for applications such as minimally invasive in vivo strain measurements.

3D Parylene sheath neural probe for chronic recordings

OBJECTIVE Reliable chronic recordings from implanted neural probes remain a significant challenge; current silicon-based and microwire technologies experience a wide range of biotic and abiotic failure modes contributing to loss of signal quality. APPROACH A multi-prong alternative strategy with potential to overcome these hurdles is introduced that combines a novel three dimensional (3D), polymer-based probe structure with coatings. Specifically, the Parylene C sheath-based neural probe is coated with neurotrophic and anti-inflammatory factors loaded onto a Matrigel carrier to encourage the ingrowth of neuronal processes for improved recording quality, reduce the immune response, and promote improved probe integration into brain tissue for reliable, long-term implementation compared to its rigid counterparts. MAIN RESULTS The 3D sheath structure of the probe was formed by thermal molding of a surface micromachined Parylene C microchannel, with electrode sites lining the interior and exterior regions of the lumen. Electrochemical characterization of the probes via cyclic voltammetry and electrochemical impedance spectroscopy was performed and indicated suitable electrode properties for neural recordings (1 kHz electrical impedance of ∼200 kΩ in vitro). A novel introducer tool for the insertion of the compliant polymer probe into neural tissue was developed and validated both in vitro using agarose gel and in vivo in the rat cerebral cortex. In vivo electrical functionality of the Parylene C-based 3D probes and their suitability for recording the neuronal activity over a 28-day period was demonstrated by maintaining the 1 kHz electrical impedance within a functional range (<400 kΩ) and achieving a reasonably high signal-to-noise ratio for detection of resolvable multi-unit neuronal activity on most recording sites in the probe. Immunohistochemical analysis of the implant site indicated strong correlations between the quality of recorded activity and the neuronal/astrocytic density around the probe. SIGNIFICANCE 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.

Wafer-Level Parylene Packaging With Integrated RF Electronics for Wireless Retinal Prostheses

This paper presents an embedded chip integration technology that incorporates silicon housings and flexible Parylene-based microelectromechanical systems (MEMS) devices. Accelerated-lifetime soak testing is performed in saline at elevated temperatures to study the packaging performance of Parylene C thin films. Experimental results show that the silicon chip under test is well protected by Parylene, and the lifetime of Parylene-coated metal at body temperature (37°C) is more than 60 years, indicating that Parylene C is an excellent structural and packaging material for biomedical applications. To demonstrate the proposed packaging technology, a flexible MEMS radio-frequency (RF) coil has been integrated with an RF identification (RFID) circuit die. The coil has an inductance of 16 μH with two layers of metal completely encapsulated in Parylene C, which is microfabricated using a Parylene-metal-Parylene thin-film technology. The chip is a commercially available read-only RFID chip with a typical operating frequency of 125 kHz. The functionality of the embedded chip has been tested using an RFID reader module in both air and saline, demonstrating successful power and data transmission through the MEMS coil.

Surface-Micromachined Parylene Dual Valves for On-Chip Unpowered Microflow Regulation

This paper presents the worlds first surface-micromachined parylene dual-valved microfluidic system for on-chip unpowered microflow regulation. Incorporating a normally closed and a normally open passive check valve in a back-to-back configuration inside a microchannel, the dual-valved system has successfully regulated the pressure/flow rate of air and liquid without power consumption or electronic/magnetic/thermal transduction. By exclusively using parylene C (poly-para-xylylene C) as the structural material, the fabricated valves have higher flexibility to shunt flows in comparison to other conventional thin-film valves. A state-of-the-art multilayer polymer surface-micromachining technology is applied here to fabricate parylene microvalves of various designs. The parylene-based devices are completely biocompatible/implantable and provide an economical paradigm for fluidic control in integrated lab-on-a-chip systems. Design, fabrication, and characterization of the parylene dual valves are discussed in this paper. Testing results have successfully demonstrated that the microflow regulation of the on-chip dual-valved system can achieve a bandpass profile in which the pressure control range is 0-50 mmHg with corresponding flow rates up to 2 mL/min for air flow and 1 muL/min flow rate for water flow. This regulation range is suitable for controlling biological conditions in human health care, with potential applications including drug delivery and regulation of elevated intraocular pressure (IOP) in glaucoma patients

Chronically Implanted Pressure Sensors: Challenges and State of the Field

Several conditions and diseases are linked to the elevation or depression of internal pressures from a healthy, normal range, motivating the need for chronic implantable pressure sensors. A simple implantable pressure transduction system consists of a pressure-sensing element with a method to transmit the data to an external unit. The biological environment presents a host of engineering issues that must be considered for long term monitoring. Therefore, the design of such systems must carefully consider interactions between the implanted system and the body, including biocompatibility, surgical placement, and patient comfort. Here we review research developments on implantable sensors for chronic pressure monitoring within the body, focusing on general design requirements for implantable pressure sensors as well as specifications for different medical applications. We also discuss recent efforts to address biocompatibility, efficient telemetry, and drift management, and explore emerging trends.

MEMS-enabled implantable drug infusion pumps for laboratory animal research, preclinical, and clinical applications.

Innovation in implantable drug delivery devices is needed for novel pharmaceutical compounds such as certain biologics, gene therapy, and other small molecules that are not suitable for administration by oral, topical, or intravenous routes. This invasive dosing scheme seeks to directly bypass physiological barriers presented by the human body, release the appropriate drug amount at the site of treatment, and maintain the drug bioavailability for the required duration of administration to achieve drug efficacy. Advances in microtechnologies have led to novel MEMS-enabled implantable drug infusion pumps with unique performance and feature sets. In vivo demonstration of micropumps for laboratory animal research and preclinical studies include acute rapid radiolabeling, short-term delivery of nanomedicine for cancer treatment, and chronic ocular drug dosing. Investigation of MEMS actuators, valves, and other microstructures for on-demand dosing control may enable next generation implantable pumps with high performance within a miniaturized form factor for clinical 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.