Design, Fabrication, and Validation of a Highly Miniaturized Wirelessly Powered Neural Implant

We have recently witnessed an explosion in the number of neurons that can be recorded and/or stimulated simultaneously during neurophysiological experiments. Experiments have progressed from recording or stimulation with a single electrode to Micro-Electrode Array (MEA) such as the Utah Array. These MEAs can be instrumented with current drivers, neural amplifiers, digitizers and wireless communication links. The broad interest in these MEAs suggests that there is a need for large scale neural recording and stimulation. The ultimate goal is to coordinate the recordings and stimulation of potentially thousands of neurons from many brain areas. Unfortunately, current state-of-the-art MEAs are limited by their scalability and long-term stability because of their physical size and rigid configuration. Furthermore, some applications prioritize a distributed neural interface over one that offers high resolution. Examples of biomedical applications that necessitate an interface with neurons from many sites in the brain include: i) understanding and treating neurological disorders that affect distributed locations throughout the CNS; ii) revolutionizing our understanding of the brain by studying the correlations between neural networks from different regions of the brain and the mechanisms of cognitive functions; and iii) covering larger area in the sensorimotor cortex of amputees to more accurately control robotic prosthetic limbs or better evoke a sense of touch. One solution to make large scale, fully specifiable, electrical stimulation and recording possible, is to disconnect the electrodes from the base, so that they can be arbitrarily placed, using a syringe, freely in the nervous system. To overcome the challenges of system miniaturization, we propose the “microbead”, an ultra-small neural stimulating implant, that is currently implemented in a 130nm CMOS technology with the following characteristics: 200 μm × 200 μm × 80 μm size; optimized wireless powering, all micro-electronics on single chip; and integrated electrodes and coil. The stimulating microbead is validated in a sciatic nerve by generating leg movements. A recording microbead is also investigated with following characteristics: wireless powering using steerable phased coil array, miniaturized front-end, and backscattering telemetry. These microbeads could eventually replace the rigid arrays that are currently the state-of-the-art in electrophysiology set-ups

High-aspect-ratio tridimensional electrode arrays for neural applications

Tese de Doutoramento em Engenharia Biomédica.Neural electrodes are a valuable tool that allows neuroscientists to monitor the neural activity of the brain with great spatial and temporal resolution. Micro and nanotechnology has allowed the development of high-density neural electrode arrays. In the present work, two different materials were used to perform neural arrays, namely silicon and aluminum. The main objective was the ability to reach areas of the brain between 2 mm and 4 mm deep due to its importance in small animal models such as the rat. In such animals, important brain structures such as the hippocampus are situated in this range of depth. Another key objective was the fabrication of probes with high-aspect-ratio in order to minimize tissue displacement and consequent adverse reactions caused by implantation. Four different prototypes each using a specific fabrication approach, were performed and described in detail. Two of these prototypes were performed with aluminum while the other two were performed with silicon. Standard microfabrication processes such as dicing, wet-etching, physical vapor deposition, and non-standard processes such as thermomigration, aluminum anodizing, polymer casting, and sanding were used. The combination of these standard and nonstandard processes allowed a simpler and cheaper fabrication approach when compared with commercially available arrays. The first aluminum prototype was composed by 100 micropillars with a gold electrode at each tip. The aluminum micropillars were encapsulated by aluminum oxide and were 3 mm long with an aspect-ratio of 12:1. The second version was composed by 25 micropillars encapsulated with medical grade epoxy each with a platinum electrode at the tip. Each micropillar was 3 mm long with an aspect-ratio of 19:1. The first silicon prototype was composed by 100 silicon micropillars, each 3 mm long with an aspect-ratio of 5:1. The second version was composed by 36 silicon micropillars encapsulated with medical grade epoxy, each with a platinum electrode at the tip. Each micropillar was 4 mm long with an aspect-ratio of 22:1. A slanted version of the second prototype was also fabricated, allowing progressively increasing penetration depths. Mechanical characterization was performed by implantation in agar gel and porcine cadaver brain while electrical characterization was performed by electrochemical impedance tests as well as cyclic voltammetry. Overall, aluminum showed to be a suitable alternative to silicon in terms of structural material. Also, a dicing based approach proved to be a cost-effective method able to perform high-aspect-ratio neural arrays.Os elétrodos neuronais são uma ferramenta que proporciona aos neurocientistas a capacidade de monitorizar a atividade neuronal do cérebro com uma grande resolução temporal e espacial. As micro e nanotecnologias proporcionaram o desenvolvimento de matrizes de elétrodos neuronais com alta densidade. No presente trabalho dois materiais foram usados para fabricar matrizes de elétrodos neuronais, nomeadamente o silício e o alumínio. O objetivo principal foi a capacidade de chegar a zonas do cérebro entre os 2 mm e 4 mm de profundidade devido a sua importância em modelos animais de pequeno porte como o rato. Nestes animais, estruturas cerebrais importantes como o hipocampo estão situadas nesta gama de profundidades. Outro objetivo chave foi o fabrico de elétrodos com alta razão de aspeto, de forma a minimizar a compressão de tecido neuronal e consequentes reações adversas causadas pela implantação. Quatro protótipos, cada um utilizando um tipo de fabrico específico foram desenvolvidos e descritos em detalhe. Dois desses protótipos foram fabricados com alumínio, enquanto os outros dois foram feitos em silício. Foram usados processos de microfabrico standard como corte com disco, corrosão química, deposição de filmes finos, e também processos não standard como termomigração, anodização do alumínio, molde de polímeros e lixamento. A combinação de processos standard e não standard permitiram uma abordagem de fabrico mais simples e barata quando comparada com a abordagem utilizada em elétrodos comercialmente disponíveis. O primeiro protótipo de alumínio foi composto por 100 micropilares com um elétrodo de ouro na ponta. Os micropilares de alumínio foram encapsulados com óxido de alumínio e tinham 3 mm de comprimento resultando numa razão de aspeto de 12:1. A segunda versão foi composta por 25 micropilares encapsulados com epóxi biocompatível, cada com um elétrodo de platina na ponta. Cada micropillar tinha 3 mm de comprimento com uma razão de aspeto de 5:1. O primeiro protótipo de silício foi composto por 100 micropilares de silício, cada com 3 mm de comprimento e com razão de aspeto de 5:1. A segunda versão foi composta por 36 micropilares de silício encapsulados com epóxi biocompatível e cada com um elétrodo de platina na ponta. Cada micropillar tinha 4 mm de comprimento resultando numa razão de aspeto de 22:1. Uma versão inclinada do segundo protótipo também foi fabricada, permitindo profundidades de penetração progressivas. A caracterização mecânica foi feita através de implantações em gelatina de agar e em cérebro de porco, enquanto a caracterização elétrica foi feita através de testes de impedância eletroquímica assim como testes de voltametria cíclica. No geral, o alumínio demonstrou ser uma alternativa viável ao silício em termos de material estrutural. A abordagem baseada no corte com disco provou ser um método económico capaz de realizar matrizes de elétrodos neuronais de grande razão de aspeto.Portuguese Foundation for Science and Technology (FCT) (SFRH/BD/89509/2012)

Cooperative Manipulation using a Magnetically Navigated Microrobot and a Micromanipulator

The cooperative manipulation of a common object using two or more manipulators is a popular research field in both industry and institutions. Different types of manipulators are used in cooperative manipulation for carrying heavy loads and delicate operations. Their applications range from macro to micro. In this thesis, we are interested in the development of a novel cooperative manipulator for manipulation tasks in a small workspace. The resultant cooperative manipulation system consists of a magnetically navigated microrobot (MNM) and a motorized micromanipulator (MM). The MNM is a small cylinder permanent magnet with 10mm diameter and 10mm height. The MM model is MP-285 which is a commercialized product. Here, the MNM is remotely controlled by an external magnetic field. The property of non-contact manipulation makes it a suitable choice for manipulation in a confined space. The cooperative manipulation system in this thesis used a master/slave mechanism as the central control strategy. The MM is the master side. The MNM is the slave side. During the manipulation process, the master manipulator MM is always position controlled, and it leads the object translation according to the kinematic constraints of the cooperative manipulation task. The MNM is position controlled at the beginning of the manipulation. In the translation stage, the MNM is switched to force control to maintain a successful holding of the object, and at the same time to prevent damaging the object by large holding force. Under the force control mode, the motion command to the MNM is calculated from a position-based impedance controller that enforces a relationship between the position of the MNM and the force. In this research, the accurate motion control of both manipulators are firstly studied before the cooperative manipulation is conducted. For the magnetic navigation system, the magnetic field in its workspace is modeled using an experimental measurement data-driven technique. The developed model is then used to develop a motion controller for navigating of a small cylindrical permanent magnet. The accuracy of motion control is reached at 20 µm in three degrees of freedom. For the motorized micromanipulator, a standard PID controller is designed to control its motion stage. The accuracy of the MM navigation is 0.8 µm. Since the MNM is remotely manipulated by an external magnetic field in a small space, it is challenging to install an on-board force sensor to measure the contact force between the MNM and the object. Therefore, a dual-axial o_-board force determination mechanism is proposed. The force is determined according to the linear relation between the minimum magnetic potential energy point and the real position of the MNM in the workspace. For convenience, the minimum magnetic potential energy point is defined as the Bmax in the literature. In this thesis, the dual-axial Bmax position is determined by measuring the magnetic ux density passing through the workspace using four Hall-effect sensors installed at the bottom of an iron pole-piece. The force model is experimentally validated in a horizontal plane with an accuracy of 2 µN in the x- and y- direction of horizontal planes. The proposed cooperative manipulator is then used to translate a hard-shell small object in two directions of a vertical plane, while one direction is constrained with a desired holding force. During the manipulation process, a digital camera is used to capture the real-time position of the MNM, the MM end-effector, and the manipulated object. To improve the performance of force control on the MNM, the proposed dual-axial force model is used to examine the compliant force control of the MNM while it is navigated to contact with uncertain environments. Here, uncertain refers to unknown environmental stiffness. An adaptive position-based impedance controller is implemented to estimate the stiffness of the environment and the contact force. The controller is examined by navigating the MNM to push a thin aluminum beam whose stiffness is unknown. The studied cooperative manipulation system has potential applications in biomedical microsurgery and microinjection. It should be clarified that the current system setup with 10mm ×10 mm MNM is not proper for this micromanipulation. In order to conduct research on microinjection, the size of the MNM and the end-effector of the MNM should be down-scaled to micrometers. In addition, the navigation accuracy of the MNM should also be improved to adopt the micromanipulation tasks

Proceedings of the 2018 Canadian Society for Mechanical Engineering (CSME) International Congress

Published proceedings of the 2018 Canadian Society for Mechanical Engineering (CSME) International Congress, hosted by York University, 27-30 May 2018

Microfluidics and Nanofluidics Handbook

The Microfluidics and Nanofluidics Handbook: Two-Volume Set comprehensively captures the cross-disciplinary breadth of the fields of micro- and nanofluidics, which encompass the biological sciences, chemistry, physics and engineering applications. To fill the knowledge gap between engineering and the basic sciences, the editors pulled together key individuals, well known in their respective areas, to author chapters that help graduate students, scientists, and practicing engineers understand the overall area of microfluidics and nanofluidics. Topics covered include Finite Volume Method for Numerical Simulation Lattice Boltzmann Method and Its Applications in Microfluidics Microparticle and Nanoparticle Manipulation Methane Solubility Enhancement in Water Confined to Nanoscale Pores Volume Two: Fabrication, Implementation, and Applications focuses on topics related to experimental and numerical methods. It also covers fabrication and applications in a variety of areas, from aerospace to biological systems. Reflecting the inherent nature of microfluidics and nanofluidics, the book includes as much interdisciplinary knowledge as possible. It provides the fundamental science background for newcomers and advanced techniques and concepts for experienced researchers and professionals

Nevada Test Site-Directed Research, Development, and Demonstration

The Nevada Test Site-Directed Research, Development, and Demonstration (SDRD) program completed a very successful year of research and development activities in FY 2005. Fifty new projects were selected for funding this year, and five FY 2004 projects were brought to conclusion. The total funds expended by the SDRD program were $5.4 million, for an average per project cost of just under$100,000. Two external audits of SDRD accounting practices were conducted in FY 2005. Both audits found the program's accounting practices consistent with the requirements of DOE Order 413.2A, and one included the observation that the NTS contractor ''did an exceptional job in planning and executing year-start activities.'' Highlights for the year included: the filing of 18 invention disclosures for intellectual property generated by FY 2005 projects; programmatic adoption of 17 FY 2004 SDRD-developed technologies; participation in the tri-lab Laboratory Directed Research and Development (LDRD) and SDRD program review that was broadly attended by NTS, NNSA, LDRD, and U.S. Department of Homeland Security representatives; peer reviews of all FY 2005 projects; and the successful completion of 55 R&D projects, as presented in this report

Fabrication and Microassembly of a mm-Sized Floating Probe for a Distributed Wireless Neural Interface

A new class of wireless neural interfaces is under development in the form of tens to hundreds of mm-sized untethered implants, distributed across the target brain region(s). Unlike traditional interfaces that are tethered to a centralized control unit and suffer from micromotions that may damage the surrounding neural tissue, the new free-floating wireless implantable neural recording (FF-WINeR) probes will be stand-alone, directly communicating with an external interrogator. Towards development of the FF-WINeR, in this paper we describe the micromachining, microassembly, and hermetic packaging of 1-mm3 passive probes, each of which consists of a thinned micromachined silicon die with a centered Ø(diameter) 130 μm through-hole, an Ø81 μm sharpened tungsten electrode, a 7-turn gold wire-wound coil wrapped around the die, two 0201 surface mount capacitors on the die, and parylene-C/Polydimethylsiloxane (PDMS) coating. The fabricated passive probe is tested under a 3-coil inductive link to evaluate power transfer efficiency (PTE) and power delivered to a load (PDL) for feasibility assessment. The minimum PTE/PDL at 137 MHz were 0.76%/240 μW and 0.6%/191 μW in the air and lamb head medium, respectively, with coil separation of 2.8 cm and 9 kΩ receiver (Rx) loading. Six hermetically sealed probes went through wireless hermeticity testing, using a 2-coil inductive link under accelerated lifetime testing condition of 85 °C, 1 atm, and 100%RH. The mean-time-to-failure (MTTF) of the probes at 37 °C is extrapolated to be 28.7 years, which is over their lifetime