Thesis (M.Sc.Eng.) / The use of implantable neural probes has become common, both for stimulation and recording, and their applications range from chronic pain treatment to implementation of brain machine interfaces (BMI). Studies have shown that signal quality of implanted electrodes decays over time mainly due to the immune response. Characterization of the tissue-electrode interface is critical for better understanding of the physiological dynamics and potential performance improvement of the electrode itself and its task. This work describes the fabrication of an implantable electrode with optical measurement capabilities for providing means to characterize the tissue-electrode interface using optical spectroscopy. The electrode has a set of waveguides embedded in its shanks, which are used to inject white light into tissue and then collect the light reflected from the tissue surrounding the shanks. The collected light was analyzed with a spectrometer and the spectra processed to detect changes in optical properties, information that allows to track physiological changes. It is believed that the immune response can be correlated to changes in scattering as more cells are recruited to the injury site. The increased cell density in local injury/implantation sites increases the amount of scattering due to the increased number of cell nuclei and membranes that light encounters in its path. Investigation of scattering and absorption coefficients in such interface and their change over time can provide useful data for modeling and determining physiological parameters like blood oxygenation while the actual shape of the acquired spectra might highlight particular phenomena that can be indicative of scaring process or hemorrhaging. Validation of this system was done using optical phantoms based on polystyrene spheres and solutions with various concentrations of fat emulsion, which yielded scattering coefficients similar to those of brain tissue. Results suggest that the developed optrodes are able to detect differences between samples with different scattering coefficients. Improvements of fabrication process are discussed based on experimental results and future work includes attempting to perform fluorescence measurements of voltage reporters for optogenetic applications. The ultimate goal of this project was to create a novel device that is capable of satisfying the unmet need of tissue characterization at the implanted electrode interface as well as a tool for the optogenetics field suitable for greater depths than those a microscope can achieve.

Neural probes are a promising tool in understanding the brain, alleviating symptoms of various diseases like Parkinson’s Disease and allowing for applications like controlling prosthetics directly using the mind. However, current probes suffer from deleterious glial tissue buildup, poor insulation and low electrode yield. In this work, to improve upon current probes, ultra-compliant probes are fabricated and integrated with biodissolvable needles. Mechanically compliant probes allow for reduction in the body’s immune response chronically whereas biodissolvable needles provide sufficient stiffness during insertion. To achieve this, contributions are made in the categories of probe design concepts, device level processes, and processes in support of final probe assembly. Major contributions include incorporation of interleaved atomic layer deposited ceramics to create hybrid materials that provide better insulation properties, reducing the distance between the electrode and the site-of-interest by developing a gray scale lithography based technique to fabricate protruding electrodes and creating probes that improve electrode yield by integrating liquid crystal polymers into the parylene-C probe structure, which allows the parylene-C probe to actuate. To allow for integration of the biodissolvable needle with the probe, a peel-based process is developed that controls the adhesion between parylene-C to Si using different HMDS conditions and a transfer based process is developed that enables hightemperature annealing. In addition, a generalized design of neural probes using meandering interconnect structures is developed, allowing for rapid mechanical design of probes. This is key for neural probes because of the application specific nature of neural probe design.

Orientadores: Roberto Ricardo Panepucci, Roberto José María Covolan / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Física Gleb Wataghin / Made available in DSpace on 2018-08-30T01:13:32Z (GMT). No. of bitstreams: 1 BenavidesGuevara_JesusArbey_M.pdf: 3401823 bytes, checksum: 461e1559d0928ed82b7c63870d75a3e5 (MD5) Previous issue date: 2015 / Resumo: O desenvolvimento de novas tecnologias aplicadas à pesquisa da atividade elétrica do cérebro é um dos tópicos de vanguarda na atualidade em neurociências. Nas últimas décadas, dispositivos denominados sondas neurais têm sido desenvolvidos, baseados nas técnicas atuais de produção e fabricação de biomedical (ou biological) microelectromechanical systems (Bio-MEMS). Estes dispositivos permitem registrar ou estimular eletricamente diferentes regiões do cérebro in vivo, ou conjuntos de células de cultura, in vitro. A consolidação desta nova tecnologia fornece uma ferramenta de alta precisão para pesquisa em neurociência, além de permitir seu uso clínico em condições patológicas tais como lesão medular, acidente vascular cerebral e distúrbios neurológicos, entre outras. O desenvolvimento de sondas neurais tem-se dado através de estudos que exploram diferentes possibilidades de desenho, fabricação e utilização de novos materiais, orientado pelas possíveis vantagens biológicas, de custo e de fabricação que possam ter. De particular interesse nesta área, é o entendimento dos mecanismos subjacentes ao comportamento eletroquímico durante estimulação e registro de atividade neuronal por microeletrodos do dispositivo, assim como a investigação de materiais que forneçam uma alta densidade de carga durante este processo. Neste projeto, foram fabricadas e caracterizadas sondas neurais baseadas no polímero SU-8, tanto quanto se saiba, as primeiras desenvolvidas no Brasil. Apresenta-se as metodologias empregadas nos processos de fabricação, em que foram testados diferentes protótipos de sondas e sondas funcionais com diferentes geometrias. Metais como Ti/Au, Ti, Cr/Au e TiN foram depositados por meio de sputtering e eletrodeposição. As propriedades eletroquímicas destes materiais condutores foram determinadas por técnicas de voltametria cíclica e espectroscopia de impedância eletroquímica. As sondas de Ti/Au foram as que apresentaram os melhores resultados em nossa pesquisa, tendo em vista a metodologia de fabricação utilizada, que manteve a integridade física dos microeletrodos e do dispositivo em geral, não obstante certas inomogeneidades apresentadas em diferentes etapas da fabricação, que ainda demandam um maior entendimento. Em conclusão, as sondas funcionais de Ti/Au produzidas e caracterizadas neste trabalho se apresentam como um dispositivo potencialmente adequado para registro da atividade neural em modelos animais / Abstract: The development of new technologies applied to the research of the cerebral electrical activity is one of the leading topics in neuroscience today. In recent decades, the so-called neural probe devices have been developed, based on current production and manufacturing techniques of biomedical (or biological) microelectromechanical systems (BioMEMS). These devices allow one to record or electrically stimulate different brain regions in vivo, or systems of cultured cells in vitro. The consolidation of this new technology provides a highly accurate tool for research in neuroscience, and allows their clinical use in pathological conditions such as spinal cord injury, stroke and neurological disorders, among others. The development of neural probes have been given through studies exploring different possibilities of design, manufacture and use of new materials, guided by the possible advantages they might have in terms of biology, manufacturing process and costs. Of particular interest in this area is the understanding of the mechanisms underlying the electrochemical behavior during stimulation and recording of neuronal activity by the microelectrodes of the device, as well as the research of materials providing a high density of charge during this process. In this project, were manufactured and characterized neural probes based on SU-8 polymer, to our knowledge the first developed in Brazil. The methods used in the manufacturing processes are presented for the various tested prototypes of probes and functional probes with different geometries. Metals such as Ti/Au, Ti, Cr/Au and TiN were deposited by sputtering and electrodeposition. The electrochemical properties of these conducting materials were determined by cyclic voltammetry and electrochemical impedance spectroscopy. Probes of Ti/Au showed the best results in our research, taking into consideration the manufacturing methodology, which kept the physical integrity of microelectrodes and the device in general, despite certain inhomogeneities presented in different stages of the manufacturing process, which still demand a greater understanding. In conclusion, the functional Ti/Au probes produced and characterized in this work have shown to be a potentially suitable device for recording neural activity in animal models / Mestrado / Física / Mestre em Física / 2012/151275-2 / CNPQ

Brain Machine Interfaces (BMI) provide a communication pathway between the electrical conducting units of the brain (neurons) and external devices. BMI technology may provide improved neurological and physiological functions to patients suffering from disabilities due to damaged nervous systems. Unfortunately, microelectrodes used in Intracortical Neural Interfaces (INI), a subset of the BMI device family, have yet to demonstrate long-term in vivo performance due to material, mechanical and electrical failures. Many state-of-the-art INI devices are constructed using stacks of multiple materials, such as silicon (Si), titanium (Ti), platinum (Pt), parylene C, and polyimide. Not only must each material tolerate the biological environment without exacerbating the inflammatory response, each of the materials used must physically withstand the environment as well as interact well with each other. One approach to address abiotic mechanisms has been optimizing the materials required to fabricate the INI devices. Silicon Carbide (SiC) is a physically robust, hemo and biocompatible, and chemically inert semiconductor. An ‘all-SiC’, or monolithic SiC, device may be the disruptive technology needed in the BMI field to finally achieve long-term and wide-spread use of this technology in humans. The all-SiC device concept is where SiC serves as all device layers: the base (substrate), the conducting traces (electrodes), and the surface conformal insulating layer. The monolithic SiC neural probe is realized by forming high-quality pn junctions of heavily doped SiC on a layer of the opposite polarity. Heavily doped semiconductors display semi-metallic electrical performance, which allow for efficient electrical conduction in the electrode without the deleterious effects of metal ions interacting with the neural environment. The conformal insulator is realized using amorphous-SiC (a-SiC) which can be patterned to open windows to allow electrical conduction to occur between the electrode tips and the brain. Several generations of monolithic SiC devices have been fabricated, tested and are reported in this dissertation. The devices were fabricated utilizing two polytypes of SiC (4H-SiC and 3C-SiC). The monolithic SiC microelectrodes were fabricated utilizing techniques used in the fabrication of Si based microelectrodes. Monolithic SiC devices fabricated include planar single-ended MEAs (with varying lengths and varying active recording area), 60-channel MEAs for in-vitro studies, and 16-electrode Michigan style neural probes for in-vivo studies. Electrical testing of the pn junction demonstrated that the 4H-SiC device can block a forward bias voltage of up to 2.3V and displays reverse bias leakage below 1 nArms well past -20V. Current leakage between adjacent electrodes was ~7.5 nArms over a voltage range of -50V to +50V. Furthermore, electrochemical results show that the 4H-SiC microelectrodes interact with an electrochemical environment primarily through capacitive mechanisms and has an impedance comparable to gold electrodes. Electrode impedance ranged from 675±130 kΩ (GSA = 496 µm2) to 46.5±4.80 kΩ (GSA = 500K µm2). However, the 4H-SiC devices cannot deliver charge as efficiently as other conventionally used microelectrode materials, such as iridium oxide (IrOx), but a larger water window compensates for this since larger stimulation voltages are supported compared to IrOx. All studies and data collected thus far indicate that the monolithic SiC neural device can aid in the advancement of chronic INI use in clinical settings. The all-SiC devices rely on the integration of only robust and highly compatible SiC material, they may offer a promising solution to probe delamination and biological rejection associated with the use of multiple materials used in many current INI devices. Follow-on work is planned to prove this assertion via in vivo studies.