Lawrence Yu

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.

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.

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.

Matrigel coatings for Parylene sheath neural probes

The biologically derived hydrogel Matrigel (MG) was used to coat a Parylene-based sheath intracortical electrode to act as a mechanical and biological buffer as well as a matrix for delivering bioactive molecules to modulate the cellular response and improve recording quality. MG was loaded with dexamethasone to reduce the immune response together with nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) to maintain neuronal density and encourage neuronal ingrowth toward electrodes within the sheath. Coating the Parylene sheath electrode with the loaded MG significantly improved the signal-to-noise ratio for neural events recorded from the motor cortex in rat for more than 3 months. Electron microscopy showed even coverage of both the Parylene substrate and the platinum recording electrodes. Electrochemical impedance spectroscopy (EIS) of coated electrodes in 1× phosphate-buffered saline demonstrated low impedance required for recording neural signals. This result was confirmed by in vivo EIS data, showing significantly decreased impedance during the first week of recording. Dexamethasone, NGF, and BDNF loaded into MG were released within 1 day in 1× phosphate-buffered saline. Although previous studies showed that MG loaded with either the immunosuppressant or the neurotrophic factor cocktail provided modest improvement in recording quality in a 1-month in vivo study, the combination of these bioactive molecules did not improve the signal quality over coating probes with only MG in a 3-month in vivo study. The MG coating may further improve recording quality by optimizing the in vivo release profile for the bioactive molecules.

A microbubble pressure transducer with bubble nucleation core

A microchannel-based microbubble (μB) transducer (μBPT) having a μB nucleation core (μBNC) was developed to achieve low power operation in wet environments. In this work, we investigate μB dynamics within the transducer structure and pressure transduction. The transducer leverages electrochemical impedance (EI)-based measurement to monitor the instantaneous response of μB size changes induced by hydrostatic pressure changes. We demonstrated on-demand μB nucleation by electrolysis and real-time pressure tracking (-93 Ω/mmHg over 0-350 mmHg). Repeatable, efficient electrolytic generation of stable microbubbles (<; 1.5 nL with <; 2% size variation) was achieved using a μBNC structure attached centrally to the microchannel. Biocompatible construction (only Parylene and Pt), small footprint, low power consumption (<; 60 μW), and liquid-based operation of μBPTs are ideal for in vivo pressure monitoring applications.

An Electrochemical Microbubble-Based MEMS Pressure Sensor

A novel pressure transducer concept is introduced in which external pressure variations induce changes in the volume of a trapped microbubble (μB) in an electrolyte solution. These volumetric changes are monitored by electrochemical impedance-based measurements and may be used for pressure tracking applications. Microbubbles are nucleated on-demand by electrolysis within a confinement chamber with high precision (measured size RSD ~1%). This pressure transducer concept was developed specifically for operation in liquid environments and features biocompatible construction, small footprint (<;0.1 mm2), and low power consumption (<;1 nW). This combination of features is ideal for in vivo pressure monitoring applications.

An implantable time of flight flow sensor

A micro time of flight (TOF) electrochemical impedance (EI) flow sensor μEIFS suitable for implantation and integration with a catheter was developed. The transducer utilizes two pairs of electrodes to monitor using EI measurement the passage of a gas bubble generated upstream. High precision measurement of bubble TOF (SD <; 6% of mean) was achieved over the velocity range 0.83-83 μm/s. The volumetric flow rate was inversely proportional (linearized, r2 = 0.99) to time of flight. Biocompatible construction (only Parylene C and platinum), low power consumption, and low profile thin film format make the μEIFS ideally suited for chronic in vivo monitoring with immediate application in tracking flow within hydrocephalus shunts.

3D Parylene sheath probes for reliable, long-term neuroprosthetic recordings

Parylene C neural probes with a 3D sheath structure are introduced as a novel interface for long-term intracortical neural recording. 3D sheath structures were assembled from surface micromachined Parylene microchannels by thermoforming the thermoplastic around a solid microwire mold. Multiple Pt electrodes lined the interior and exterior of the sheath. Electrochemical characterization of the electrodes confirmed impedance values (50-250 KΩ at 1 kHz) suitable for neural recordings. A novel insertion approach was developed that temporarily stiffens the neural probes for surgical implantation and optimized in agarose brain tissue model. Sheath probes implanted into rat cortex recorded neural signals for four weeks. To achieve long-term, reliable recordings, the sheath structures will be coated with eluting neurotrophic factors to promote and attract neural ingrowth towards electrode sites.

An Electrochemical Impedance-Based Thermal Flow Sensor for Physiological Fluids

A novel electrochemical-thermal flow sensor was developed for use in physiological liquids. The sensor was constructed out of a platinum resistive heater and platinum sensing electrodes on a Parylene C substrate, rendering it flexible and fully biocompatible. During heating, changes in electrochemical impedance across the sensing electrodes were used to detect changes in temperature, and highly sensitive flow measurements were achieved with overheat temperatures of only 1 °C. The sensors biocompatibility and low overheat temperature make it an ideal candidate for chronic in vivo applications.

Passive, wireless transduction of electrochemical impedance across thin-film microfabricated coils using reflected impedance

A new method of wirelessly transducing electrochemical impedance without integrated circuits or discrete electrical components was developed and characterized. The resonant frequency and impedance magnitude at resonance of a planar inductive coil is affected by the load on a secondary coil terminating in sensing electrodes exposed to solution (reflected impedance), allowing the transduction of the high-frequency electrochemical impedance between the two electrodes. Biocompatible, flexible secondary coils with sensing electrodes made from gold and Parylene C were microfabricated and the reflected impedance in response to phosphate-buffered saline solutions of varying concentrations was characterized. Both the resonant frequency and impedance at resonance were highly sensitive to changes in solution conductivity at the secondary electrodes, and the effects of vertical separation, lateral misalignment, and temperature changes were also characterized. Two applications of reflected impedance in biomedical sensors for hydrocephalus shunts and glucose sensing are discussed.