MICROELECTRODE ARRAY FOR CAPACITIVE TRANSDUCTION OF RETINAL RESPONSES

Neural degenerative diseases and traumatic injuries to the eye affect millions of people worldwide, motivating the development of neural prosthetic interfaces to restore sensory or motor function in affected individuals. Advances in neural sensing and stimulation interface technology will allow a more comprehensive understanding of neural function while leading to the development of hybrid biological-electronic sensor devices for robust, functioning neural prosthetic systems. Current techniques of neural activity sensing employ multi-electrode arrays (MEAs) that typically incorporate metal electrodes and measure currents via an electrochemical junction, leading to corrosion and charge transfer across the electrode-tissue interface. High-density neural interface technology will require active circuitry within the implant; the device must withstand corrosion and induce minimal damage at the electrode/tissue interface. The work shown here demonstrates a prototype neural interface device based on capacitive coupling through hafnium oxide encapsulation of a novel 3D device architecture, advancing neural sensing technology toward long-term implantable neural interfaces. The functionalization of biosensors interfaced with neural tissue is important to ensure that the active components of the sensor are fully protected from the surrounding biological environment. Self-assembled monolayers (SAMs) have been extensively studied as coatings for implantable devices due to their ability to tailor surface properties and relative ease of film formation. We report a series of studies aimed at investigating the stability of phosphonate self-assembled monolayers, octdecylphosphonic acid (ODPA) or perfluorophosphonic acid (PFPA) on various oxide surfaces (SiO2, TiO2, Al2O3 and HfO2) to serve as the biotic-abiotic interface of the prototype neural device developed here. The monolayers were deposited by a series of techniques including self-assembly from solution, tethering by aggregation and growth and Langmuir-Blodgett (LB). SAMs prepared by LB were primarily used in our stability investigations because they were found to be the most uniform and reproducible. All films deposited on oxide-coated substrates were characterized by means of water contact angle measurements, spectroscopic ellipsometry, X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). XPS data conclusively showed covalent phosphonate formation on all substrates except SiO2, which had background spectra that interfered with the data analysis. AFM images of SAMs formed on SiO2 and TiO2 showed significant surface reorganization upon exposure to water within 30 minutes. SAMs formed on Al2O3 and HfO2 were much more stable upon exposure to water. PFPA SAMs on HfO2 were found to be the most stable SAMs studied here in either water or phosphate buffer at room temperature. This is the first report of a SAM-oxide system showing stability for an extended period of time, greater than 20 days. These data suggest that phosphonate SAMs should be considered for implantable neural devices that require longer-term stability under aqueous conditions. To examine the encoding and processing of information by networks of neurons, microelectrode arrays (MEAs) have been developed and applied, but evolving scientific questions and biomedical applications require higher density sampling and wider spatial coverage. The integration of 3D electrodes can provide closer contact with neurons to facilitate detection and resolution of single cell action potentials. The fabrication methods implemented here allows reliable fabrication of a novel MEA consisting of probes with dimensions of a few microns, unlike most other approaches to 3D electrode arrays, which produce structures on the scale of tens of microns or more. The device incorporates over 3,800 micro pillar electrodes, grouped into 60 independent sensors for compatibility with existing electronics, spread over an area of 750 μm2; each sensor site consists of an 8x8 array of micropillars, interconnected by a lead to an output pad of the device. Individual 3D pillars are 3 μm in diameter with a height of 8 μm. Our experience has suggested that such microstructured probes can achieve more intimate contact with the surface of neural tissue, and enhance the quality of neuronal recordings. Electrochemical impedance spectroscopy (EIS) at 1 kHz measured average magnitude and phase shift of 710 W and 17°, respectively, for a single sensor site. These values confirm the robustness of our fabrication process for developing highly conductive 3D microelectrodes. The results shown here demonstrate high-density, three-dimensional microfabrication technology that was applied to the development of an advanced capacitive sensor array for neural tissue. Applications in sensing technology now require electro-neural interface devices to withstand corrosion and induce minimal damage at the electrode/tissue interface. We have developed a platform suitable for hermetic sealing and have shown encapsulation through atomic layer deposition of hafnium oxide over the active components of the device to overcome the direct current limitations of existing MEA technology. EIS was used to study the oxide deposition on the 3D micro pillar sensor array to ensure a pinhole-free dielectric coating. The characteristic impedance magnitudes increase up to 3 orders of magnitude upon oxide deposition and the phase indicates fully capacitive sensor sites. The fabrication process and electrochemical impedance study shown here, demonstrates the usefulness of such techniques for building high-density 3D arrays that can be fully encapsulated with a protective dielectric coating. This work advances the technology towards capacitive sensing of retinal neurons with a robust, non-invasive sensing device. Sensing retinal neurons with the 3D micropillar array developed here was performed for direct current and capacitive configurations of the device. Electroretinograms (ERGs) were recorded and the overall performance of the device was analyzed. The devices showed good consistency across all 60 Pt electrode clusters during characterization and when interfaced with retinal tissue. ERGs were recorded by more than 80% of the direct current electrode sites and the performance was evenly distributed around the mean response. This performance surpasses previous reports of 3D electrode arrays interfaced with retinal tissue, where typically 1-6 electrode signals are recorded successfully. Encapsulation of the device platform was achieved and successful recordings of ERG signals were shown. This work is the first report of sensing the overall electrical behavior of retinal tissue with a coupled capacitive MEA

Chemical Approaches for Nanofabrication Based on Colloidal Lithography with Organosilanes, Nanoparticles and Nickel Films: The Role of Water in Directing Surface Self-Assembly

The capabilities for accomplishing fundamental surface studies with molecular systems are demonstrated in this dissertation using measurement and imaging modes of scanning probe microscopy. Model systems were chosen for investigations of surface self-assembly mechanisms, with an emphasis on understanding the role of interfacial water in surface reactivity. A key strategy for molecular level studies was to prepare nanostructures using protocols with colloidal lithography and scanning probe-based lithography (SPL). Nanofabricated samples were characterized ex situ with contact and tapping-mode atomic force microscopy (AFM) after key reaction steps, providing direct views of changes in surface morphology at the nanoscale. Magnetic sample modulation (MSM) combined with contact mode AFM provided a route to detect the vibration of magnetic nanomaterials in response to an externally applied electromagnetic field. Nanoscale measurements of the size-scaling effects for physical properties such as conductance and nanomagnetism are contemporary topics in the field of nanoscience. Protocols of SPL were used for studies with organic thin films; nanoshaving and nanografting experiments provided a means to prepare ultra-small nanostructures. Nickel-coated nanostructures were constructed on amine-terminated nanorings of aminopropyltriethoxysilane (APTES) using colloidal lithography and chemical steps of electroless deposition (ELD), nickel was deposited by an autocatalytic redox reaction using palladium as a catalyst. Protocols were developed to investigate the role of water in the association and placement of silane molecules on surfaces as a strategy for indirectly tracking the location of water on surfaces. Visible light photocatalysis was used to prepare nanostructured films by immersing surface masks of monodisperse spheres in solutions of an aryl halide and then irradiating the solution with blue light. Films of aryl halide are linked to the surface by C-Au bonds to form robust films that resist the effects of oxidation. Nanostructured films of octaethylporphyrin (OEP) were prepared with immersion particle lithography by reaction with silicon tetrachloride. Porphyrins bound to the surface through covalent Si-O-surface linkages coordinated to the centers of the macrocycles in a kebob arrangement. The Si-O-Si “skewer” strategy was also successful for encapsulating Au nanoparticles with porphyrins to make core-shell nanoparticles. Fundamental studies targeted questions related to controlling surface assembly and interfacial chemistry details

The use of nano/micro-layers, self-healing and slow release coatings to prevent corrosion and biofouling

The mitigation of corrosion and biofouling is a challenge. Through application of chemicals and special techniques can slow these undesired processes, an effective resolution requires a multidisciplinary approach involving scientists, engineers, and metallurgists. In order to understand the importance of the use of nano- and microlayers as well as self-healing coatings, the basic concepts of corrosion, corrosion mechanisms, corrosion inhibition and the microbiologically influenced corrosion will be summarised. The preparation, characterization and application of Langmuir-Blodgett and self assembled nanolayers in corrosive and microbial environment will be discussed. Preparation and characterization of microcapsules/ microspheres and their application in coatings will be demonstrated by a number of examples

Nanoporous Anodic Alumina Photonic Crystals for Optical Chemo- and Biosensing: Fundamentals, Advances, and Perspectives

Optical sensors are a class of devices that enable the identification and/or quantification of analyte molecules across multiple fields and disciplines such as environmental protection, medical diagnosis, security, food technology, biotechnology, and animal welfare. Nanoporous photonic crystal (PC) structures provide excellent platforms to develop such systems for a plethora of applications since these engineered materials enable precise and versatile control of light–matter interactions at the nanoscale. Nanoporous PCs provide both high sensitivity to monitor in real-time molecular binding events and a nanoporous matrix for selective immobilization of molecules of interest over increased surface areas. Nanoporous anodic alumina (NAA), a nanomaterial long envisaged as a PC, is an outstanding platform material to develop optical sensing systems in combination with multiple photonic technologies. Nanoporous anodic alumina photonic crystals (NAA-PCs) provide a versatile nanoporous structure that can be engineered in a multidimensional fashion to create unique PC sensing platforms such as Fabry–Pérot interferometers, distributed Bragg reflectors, gradient-index filters, optical microcavities, and others. The effective medium of NAA-PCs undergoes changes upon interactions with analyte molecules. These changes modify the NAA-PCs’ spectral fingerprints, which can be readily quantified to develop different sensing systems. This review introduces the fundamental development of NAA-PCs, compiling the most significant advances in the use of these optical materials for chemo- and biosensing applications, with a final prospective outlook about this exciting and dynamic field

Memristives Schaltverhalten in selbst-assemblierten Nanopartikel-Systemen

In this work, the self-assembly of functional nanoparticle composites towards integration into future three-dimensional electronic circuitry was investigated. Using complementary surface-functionalization of metal and semiconductor nanoparticles, self-assembly of heterogeneous nanoparticle agglomerates in dispersion and the formation of nanoparticle arrays on oxide surfaces was shown. Electrical characterization of these systems yielded pronounced non-volatile bipolar memristive switching and threshold switching behavior, respectively.In dieser Arbeit wurde die Selbstassemblierung funktionaler Nanopartikelsysteme in Richtung der Integration in zukünftig dreidimensionale elektronische Schaltkreise untersucht. Durch komplementäre Oberflächenfunktionalisierung von Metall- und Halbleiternanopartikeln wurde die Selbstassemblierung von heterogenen Nanopartikel-Agglomeraten in Lösung und die regelmäßige Anordnung von Nanopartikeln auf Oxidoberflächen gezeigt. Die elektrische Charakterisierung dieser Systeme zeigte jeweils ausgeprägtes nicht-volatiles, bipolares memristives Schaltverhalten und Schwellspannungs-Schaltverhalten

Establishment of surface functionalization methods for spore-based biosensors and implementation into sensor technologies for aseptic food processing

Aseptic processing has become a popular technology to increase the shelf-life of packaged products and to provide non-contaminated goods to the consumers. In 2017, the global aseptic market was evaluated to be about 39.5 billion USD. Many liquid food products, like juice or milk, are delivered to customers every day by employing aseptic filling machines. They can operate around 12,000 ready-packaged products per hour (e.g., Pure-Pak® Aseptic Filling Line E-PS120A). However, they need to be routinely validated to guarantee contamination-free goods. The state-of-the-art methods to validate such machines are by means of microbiological analyses, where bacterial spores are used as test organisms because of their high resistance against several sterilants (e.g., gaseous hydrogen peroxide). The main disadvantage of the aforementioned tests is time: it takes at least 36-48 hours to get the results, i.e., the products cannot be delivered to customers without the validation certificate. Just in this example, in 36 hours, 432,000 products would be on hold for dispatchment; if more machines are evaluated, this number would linearly grow and at the end, the costs (only for waiting for the results) would be considerably high. For this reason, it is very valuable to develop new sensor technologies to overcome this issue. Therefore, the main focus of this thesis is on the further development of a spore-based biosensor; this sensor can determine the viability of spores after being sterilized with hydrogen peroxide. However, the immobilization strategy as well as its implementation on sensing elements and a more detailed investigation regarding its operating principle are missing. In this thesis, an immobilization strategy is developed to withstand harsh conditions (high temperatures, oxidizing environment) for spore-based biosensors applied in aseptic processing. A systematic investigation of the surface functionalization’s effect (e.g., hydroxylation) on sensors (e.g., electrolyte-insulator semiconductor (EIS) chips) is presented. Later on, organosilanes are analyzed for the immobilization of bacterial spores on different sensor surfaces. The electrical properties of the immobilization layer are studied as well as its resistance to a sterilization process with gaseous hydrogen peroxide. In addition, a sensor array consisting of a calorimetric gas sensor and a spore-based biosensor to measure hydrogen peroxide concentrations and the spores’ viability at the same time is proposed to evaluate the efficacy of sterilization processes

Nanoelectronic Materials

This thesis explores fabrication methods and characterization of novel materials used in field effect transistors, including metallic nanowires, carbon nanotubes, and graphene. Networks of conductive nanotubes are promising candidates for thin film electrode alternatives due to their desirable transparency, flexibility, and potential for large-scale processing. Silver nanowire and carbon nanotube networks are evaluated for their use as thin film electrode alternatives. Growth of silver nanowires in porous alumina membranes, dispersion onto a variety of substrates, and patterning is described. Metallic carbon nanotubes are suspended in aqueous solutions, airbrushed onto substrates, and patterned. The conductivity and transparency of both networks is evaluated against industry standards. Graphene is a two dimensional gapless semimetal that demonstrates outstanding room temperature mobilities, optical transparency, mechanical strength, and sustains large current densities, all desirable properties for semiconductors used in field effect transistors. Graphene's low on/off ratio and low throughput fabrication techniques have yet to be overcome before it becomes commercially viable. Silicon oxide substrates are common dielectrics in field effect transistors and instrumental in locating mechanically exfoliated graphene. The morphology of two different silicon oxides have been studied statistically with atomic force microscopy and scaling analysis. Tailoring the physical properties of these substrates may provide a control of graphene's electrical properties. A silicon oxide substrate may also be chemically altered to control the properties of graphene. I have modified silicon oxide with self-assembled monolayers with various terminal groups to control the field near the graphene. I characterize the monolayers with atomic force microscopy, x-ray photospectroscopy, and contact angles. I characterize graphene on these substrates using Raman microscopy and transport measurements. Finally, I examine low frequency noise in graphene field effect transistors on conventional silicon oxide substrates. As devices become smaller, the signal to noise ratio of these devices becomes important. Low frequency noise occurs on long time scales and must be controlled for device stability. I measure novel behavior of low frequency noise in multiple graphene devices. The noise may be described electron-hole puddles in the graphene that are caused by trapped charges near the surface of silicon oxide