Wireless Intraocular Pressure Sensing Using Microfabricated Minimally Invasive Flexible-Coiled LC Sensor Implant

This paper presents an implant-based wireless pressure sensing paradigm for long-range continuous intraocular pressure (IOP) monitoring of glaucoma patients. An implantable parylene-based pressure sensor has been developed, featuring an electrical LC-tank resonant circuit for passive wireless sensing without power consumption on the implanted site. The sensor is microfabricated with the use of parylene C (poly-chlorop- xylylene) to create a flexible coil substrate that can be folded for smaller physical form factor so as to achieve minimally invasive implantation, while stretched back without damage for enhanced inductive sensor–reader coil coupling so as to achieve strong sensing signal. A data-processed external readout method has also been developed to support pressure measurements. By incorporating the LC sensor and the readout method, wireless pressure sensing with 1-mmHg resolution in longer than 2-cm distance is successfully demonstrated. Other than extensive on-bench characterization, device testing through six-month chronic in vivo and acute ex vivo animal studies has verified the feasibility and efficacy of the sensor implant in the surgical aspect, including robust fixation and long-term biocompatibility in the intraocular environment. With meeting specifications of practical wireless pressure sensing and further reader development, this sensing methodology is promising for continuous, convenient, direct, and faithful IOP monitoring

Microfabricated Implantable Parylene-Based Wireless Passive Intraocular Pressure Sensors

This paper presents an implantable parylene-based wireless pressure sensor for biomedical pressure sensing applications specifically designed for continuous intraocular pressure (IOP) monitoring in glaucoma patients. It has an electrical LC tank resonant circuit formed by an integrated capacitor and an inductor coil to facilitate passive wireless sensing using an external interrogating coil connected to a readout unit. Two surface-micromachined sensor designs incorporating variable capacitor and variable capacitor/inductor resonant circuits have been implemented to realize the pressure-sensitive components. The sensor is monolithically microfabricated by exploiting parylene as a biocompatible structural material in a suitable form factor for minimally invasive intraocular implantation. Pressure responses of the microsensor have been characterized to demonstrate its high pressure sensitivity (> 7000 ppm/mmHg) in both sensor designs, which confirms the feasibility of pressure sensing with smaller than 1 mmHg of resolution for practical biomedical applications. A six-month animal study verifies the in vivo bioefficacy and biostability of the implant in the intraocular environment with no surgical or postoperative complications. Preliminary ex vivo experimental results verify the IOP sensing feasibility of such device. This sensor will ultimately be implanted at the pars plana or on the iris of the eye to fulfill continuous, convenient, direct, and faithful IOP monitoring

Cell patterning on photolithographically defined parylene-C:SiO2 substrates

Cell patterning platforms support broad research goals, such as construction of predefined in vitro neuronal networks and the exploration of certain central aspects of cellular physiology. To easily combine cell patterning with Multi-Electrode Arrays (MEAs) and silicon-based ‘lab on a chip’ technologies, a microfabrication-compatible protocol is required. We describe a method that utilizes deposition of the polymer parylene-C on SiO(2 )wafers. Photolithography enables accurate and reliable patterning of parylene-C at micron-level resolution. Subsequent activation by immersion in fetal bovine serum (or another specific activation solution) results in a substrate in which cultured cells adhere to, or are repulsed by, parylene or SiO(2) regions respectively. This technique has allowed patterning of a broad range of cell types (including primary murine hippocampal cells, HEK 293 cell line, human neuron-like teratocarcinoma cell line, primary murine cerebellar granule cells, and primary human glioma-derived stem-like cells). Interestingly, however, the platform is not universal; reflecting the importance of cell-specific adhesion molecules. This cell patterning process is cost effective, reliable, and importantly can be incorporated into standard microfabrication (chip manufacturing) protocols, paving the way for integration of microelectronic technology

Parylene Based Flexible Multifunctional Biomedical Probes And Their Applications

MEMS (Micro Electro Mechanical System) based flexible devices have been studied for decades, and they are rapidly being incorporated into modern society in various forms such as flexible electronics and wearable devices. Especially in neuroscience, flexible interfaces provide tremendous possibilities and opportunities to produce reliable, scalable and biocompatible instruments for better exploring neurotransmission and neurological disorders. Of all the types of biomedical instruments such as electroencephalography (EEG) and electrocorticography (ECoG), MEMS-based needle-shape probes have been actively studied in recent years due to their better spatial resolution, selectivity, and sensitivity in chronical invasive physiology monitoring. In order to address the inherent issue of invasiveness that causes tissue damage, research has been made on biocompatible materials, implanting methods and probe structural design. In this dissertation, different types of microfabricated probes for various applications are reviewed. General methods for some key fabrication steps include photolithography patterning, chemical vapor deposition, metal deposition and dry etching are covered in detail. Likewise, three major achievements, which aim to the tagets of flexibility, functionality and mechanical property are introduced and described in detail from chapter 3 to 5. The essential fabrication processes based on XeF2 isotropic silicon etching and parylene conformal deposition are covered in detail, and a set of characterization is summarized

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

Parylene Based Flexible Multifunctional Biomedical Probes And Their Applications

MEMS (Micro Electro Mechanical System) based flexible devices have been studied for decades, and they are rapidly being incorporated into modern society in various forms such as flexible electronics and wearable devices. Especially in neuroscience, flexible interfaces provide tremendous possibilities and opportunities to produce reliable, scalable and biocompatible instruments for better exploring neurotransmission and neurological disorders. Of all the types of biomedical instruments such as electroencephalography (EEG) and electrocorticography (ECoG), MEMS-based needle-shape probes have been actively studied in recent years due to their better spatial resolution, selectivity, and sensitivity in chronical invasive physiology monitoring. In order to address the inherent issue of invasiveness that causes tissue damage, research has been made on biocompatible materials, implanting methods and probe structural design. In this dissertation, different types of microfabricated probes for various applications are reviewed. General methods for some key fabrication steps include photolithography patterning, chemical vapor deposition, metal deposition and dry etching are covered in detail. Likewise, three major achievements, which aim to the tagets of flexibility, functionality and mechanical property are introduced and described in detail from chapter 3 to 5. The essential fabrication processes based on XeF2 isotropic silicon etching and parylene conformal deposition are covered in detail, and a set of characterization is summarized

Micromachined three-dimensional electrode arrays for in-vitro and in-vivo electrogenic cellular networks

This dissertation presents an investigation of micromachined three-dimensional microelectrode arrays (3-D MEAs) targeted toward in-vitro and in-vivo biomedical applications. Current 3-D MEAs are predominantly silicon-based, fabricated in a planar fashion, and are assembled to achieve a true 3-D form: a technique that cannot be extended to micro-manufacturing. The integrated 3-D MEAs developed in this work are polymer-based and thus offer potential for large-scale, high volume manufacturing. Two different techniques are developed for microfabrication of these MEAs - laser micromachining of a conformally deposited polymer on a non-planar surface to create 3-D molds for metal electrodeposition; and metal transfer micromolding, where functional metal layers are transferred from one polymer to another during the process of micromolding thus eliminating the need for complex and non-repeatable 3-D lithography processes. In-vitro and in-vivo 3-D MEAs are microfabricated using these techniques and are packaged utilizing Printed Circuit Boards (PCB) or other low-cost manufacturing techniques. To demonstrate in-vitro applications, growth of 3-D co-cultures of neurons/astrocytes and tissue-slice electrophysiology with brain tissue of rat pups were implemented. To demonstrate in-vivo application, measurements of nerve conduction were implemented. Microelectrode impedance models, noise models and various process models were evaluated. The results confirmed biocompatibility of the polymers involved, acceptable impedance range and noise of the microelectrodes, and potential to improve upon an archaic clinical diagnostic application utilizing these 3-D MEAs.Ph.D.Committee Chair: Mark G. Allen; Committee Member: Elliot L. Chaikof; Committee Member: Ionnis (John) Papapolymerou; Committee Member: Maysam Ghovanloo; Committee Member: Oliver Bran

Dual-side and three-dimensional microelectrode arrays fabricated from ultra-thin silicon substrates

A method for fabricating planar implantable microelectrode arrays was demonstrated using a process that relied on ultra-thin silicon substrates, which ranged in thickness from 25 to 50 µm. The challenge of handling these fragile materials was met via a temporary substrate support mechanism. In order to compensate for putative electrical shielding of extracellular neuronal fields, separately addressable electrode arrays were defined on each side of the silicon device. Deep reactive ion etching was employed to create sharp implantable shafts with lengths of up to 5 mm. The devices were flip-chip bonded onto printed circuit boards (PCBs) by means of an anisotropic conductive adhesive film. This scalable assembly technique enabled three-dimensional (3D) integration through formation of stacks of multiple silicon and PCB layers. Simulations and measurements of microelectrode noise appear to suggest that low impedance surfaces, which could be formed by electrodeposition of gold or other materials, are required to ensure an optimal signal-to-noise ratio as well a low level of interchannel crosstalk

Generalized Parity-Time Symmetry Condition for Enhanced Sensor Telemetry

Wireless sensors based on micro-machined tunable resonators are important in a variety of applications, ranging from medical diagnosis to industrial and environmental monitoring.The sensitivity of these devices is, however, often limited by their low quality (Q) factor.Here, we introduce the concept of isospectral party time reciprocal scaling (PTX) symmetry and show that it can be used to build a new family of radiofrequency wireless microsensors exhibiting ultrasensitive responses and ultrahigh resolution, which are well beyond the limitations of conventional passive sensors. We show theoretically, and demonstrate experimentally using microelectromechanical based wireless pressure sensors, that PTXsymmetric electronic systems share the same eigenfrequencies as their parity time (PT)-symmetric counterparts, but crucially have different circuit profiles and eigenmodes. This simplifies the electronic circuit design and enables further enhancements to the extrinsic Q factor of the sensors