Dustin J. Tyler, Ph.D. - US grants

The objective of this research is to develop a flexible neural microelectrode array platform technology that is impervious to aqueous solutions and thus suitable for long-term (~ 20 year) medical implants. The approach is to develop a silicon carbide thin film technology suitable for polymer substrates using these films as mechanically-durable, biocompatible, hermetic coatings. The films will be deposited with a precursor used in integrated circuits but has not been developed for biomedical microsystems. Device prototypes will be evaluated for mechanical durability, chemical and hermetic integrity, dielectric quality and biocompatibility using a battery of conventional tests. Finite element modeling will be used to develop improved designs based on testing results.
From the materials perspective, this research pushes the extremes of silicon carbide deposition technology by focusing on temperature-sensitive substrates. From the technology perspective, this research addresses a critical issue facing next-generation neural implants; hermetic sealing of mechanically flexible microelectrode arrays equipped with electronics and wireless telemetry.
In addition to neural prosthetics, this project will impact the development of other implantable microsystems that suffer from moisture absorption, such retinal prostheses, urologic and cardiac sensor systems, as well as non-medical applications, such as flexible displays and portable power. This research compliments an effort by the Department of Veteran's Affairs to develop microsystem technologies for disabled veterans, specifically those that suffer from paralysis and limb loss. Such technologies will also benefit the non-veteran population. This research will positively impact the nation's technology workforce by involving students from underrepresented groups and local high schools.

DESCRIPTION (provided by applicant): Cortical electrodes offer an intimate interface to the complex activity of the brain. They are an enabling technology for advanced brain therapies that will significantly enhance the human condition, as well as, fundamental tools for investigating the operation of the brain. One of the limiting factors of current technology is a mechanical mismatch between the electrode and the cortical tissue. While a stiff electrode is advantageous during implantation and positioning, a chronically stiff electrode causes micro-motion, micro-damage, and chronic astrocytic response in the brain tissue. An ideal electrode would have a high modulus during insertion and a low modulus thereafter. Inspired by the soft connective tissues of echinoderms, we have embarked on the exploration of a highly innovative and novel general class of polymer nanocomposites, which are targeted to dynamically change their mechanical properties in response to a stimulus, such as temperature or pH change, electrical or optical field, or concentration of specific ions. We propose to exploit chemical stimuli (ion concentrations or pH) for the mechanical switching of polymers that form the basis of adaptive cortical electrodes. Initial feasibility of the mechanically dynamic properties of the composites have already been demonstrated. In this proposal we will further study their properties and develop them for use in biomedical applications. The first aim is to optimize the composition for optimal performance in the cortex environment. The optimal material will be stiff in an ambient environment and dynamically change in response to the chemical environment of the cortex to match the cortical tissue mechanics when implanted. We will characterize the mechanical properties and dynamics, as well as, the basic techniques processing the material into devices designed for biological applications. The second aim is to understand the chronic astrocytic and tissue response to the polymer. The overall goal of this project is create and understand a stimulus-responsive, mechanically dynamic nanocomposite available for biomedical and neuroprosthetic applications. The first application studied in this proposal will be as a substrate for cortical electrodes.

[unreadable] DESCRIPTION (provided by applicant): Upper extremity FES systems have assisted hundreds of individuals with cervical-level (i.e. C3-C6) SCI to use their hands and increase their independence and quality of life. These systems have relied on muscle-based electrodes, especially for the functions of the hand. Peripheral nerve electrodes have been extensively tested in animals and demonstrated selective stimulation and safety. Peripheral nerve electrodes offer several potential advantages compared to muscle-based electrodes, including complete muscle recruitment, multiple functions from a single implant, mechanical isolation from the muscle, lower stimulation power requirements, and no activitydependent recruitment. The long-term goal of this work is to implement highly selective, extraneural cuff electrodes, specifically the flat interface nerve electrode (FINE) in several neuroprosthesis applications. This purpose of this proposal is to assess the feasibility of using the FINE in upper extremity applications. The key steps in assessing feasibility are to collect quantitative measures of the fascicular anatomy of the upper extremity nerves, to select optimal implant locations, to select optimal electrode designs, and to demonstration intraoperatively the selectivity of stimulation with these electrodes. The proposal consists of three specific aims. 1) Generate quantitative anatomical data of the human upper extremity nerves. There is extensive literature on the qualitative anatomy of the upper extremity nerves, but little quantitative data required to design electrode sizes and create computer simulations for prediction electrode performance. 2) Develop neurobiomechanical models of upper extremities. Once the quantitative anatomy is available, finite element method (FEM) models can predict recruitment with cuff electrode stimulation. This provides a tool to optimize the electrode design prior to patient implementation. 3) Demonstrate nerve cuff performance in intraoperative trials. Once an electrode is designed and tested via computer models, the only true test of its capabilities is by testing in humans. Previous studies have shown that intraoperative measures of stimulation selectivity are good predictors of chronic selectivity. Therefore, acute, intraoperative testing can demonstrate whether or not the peripheral nerve stimulation is appropriate for upper extremity neuroprostheses systems. At the completion of the proposed work, we expect to have all the necessary data to show that an all-nerve cuff system can be permanently implanted in a patient to restore upper extremity function in mid- to high-cervical level SCI patients. We expect this work will make a significant impact in upper extremity FES applications and pave the path to other applications, such as neural interfaces for amputee prosthetics. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): The silo academic structure necessary for specialization and depth in learning specific disciplines is detrimental to learning the applicatio of those skills to real-world applications, typically learned in the Design component of the education. Unfortunately, senior design project instruction is often incorporated into the silo model and students work in single discipline project teams on well-defined projects that are focus on the specific discipline. There is a critical need to break this model and develop multidisciplinary undergraduate design teams to meet healthcare needs. The current Case Western Reserve University design curriculum is based on the federal regulations for medical device design controls (21CFR820.30) and the regulatory controls for medical devices as controlled and enforced by the Food and Drug Administration (FDA). Projects that provide the most satisfaction to the BME students are those that directly interact with the clinical environment. Common feedback from clinical project sponsors, however, is that the students were capable and motivated, but the biggest challenge was getting them to understand the realities of the clinical environment. Hands-on experience is a strong catalyst for active learning but waiting until the senior year to introduce a design experience misses the opportunity to engage the students early in their educational development. In this project we will enhance the Case design curriculum through three specific aims. Aim 1 is to develop and implement a CSE multi-disciplinary senior design course. The center piece of the course will be a comprehensive, multi-disciplinary design experience. Aim 2 is to establish an immersive clinical experience such that the students understand first-hand the needs and environment of healthcare projects. Aim 3 is to introduce a hands-on, first-semester freshman design experience to biomedical engineering students. The objective of the course is to introduce students to the joy of engineering; understanding the constraints, goals, and ethics of biomedical design; and engage and motivate students for their BME education. In this project, we will enhance the current design program to create an active and engaging educational experience that starts in the freshman year and culminates with a multi-disciplinary senior design experience that prepares the students for maximum success in the theory and application of biomedical engineering.

DESCRIPTION (provided by applicant): Neural prosthetic solutions to rehabilitation problems have made a significant impact on people's lives in many areas. Neural Engineering and Assistive Technologies are active research areas and expanding into more clinical applications. Strategic collaborations between multiple disciplines are required to advance these new technologies into clinical practice. Cleveland NEW 2011 brought together scientists, engineers, clinicians, and research participants in order to identify collaborative approaches to overcome challenges in neural engineering. Through engaged discussion sessions about the future of neural engineering, attendees identified, refined and narrowed in on four important focus areas for the future of neural engineering research: (1) Development of a modular, fully integrated system to facilitate reaching in high level paralysis patients using natural command signals and suitable for everyday use; (2) Non-invasive method for determining neuronal communication at single cell resolution across the brain for therapeutic and diagnostic applications; (3) Seamlessly integrated neural interfaces with neuron-level resolution and longevity across the patient lifetime; and (4) Collaboration between clinicians, engineers, companies, regulatory bodies, and clinical trials specialists to develop a new framework for clinical study design of medical devices that leverages the flexibility of the technology. The Cleveland Neural Engineering Workshop (NEW) provides a forum to determine these opportunities and consider the future of this field. The purpose of this open captive conference is to bring together leaders committed to providing neural based solutions for individuals with neurological disorders or injury to identify the opportunities and roadblocks for improving clinical care. These leading clinicians, engineers, scientists and research participants will identify the key requirements and/or limitations to advance neural prostheses, identify key collaborative research areas and highlight a visionary research roadmap. Objective outcomes will include a manuscript and white paper reporting the identified opportunities and bottlenecks, new collaborations between investigators from multiple disciplines and funding proposals.

DESCRIPTION (provided by applicant): This continuation of project EB001889 will extend the functional capabilities of recipients of implanted neuroprostheses for restoring lower extremity function after spinal cord injury (SCI) by applying new nerve cuff electrodes that selectively activate fascicles within the human femoral and sciatic nerves to isolate knee extension for standing, and both hip flexion and ankle plantar/dorsiflexion for efficient stepping. The new enabling technologies we will develop and deploy include the Compliant FINE (C-FINE), and an 8-channel nerve cuff module for the Networked Neuroprosthesis System (NNPS). The C-FINE offers distinct advantages over earlier nerve cuff designs, including a shape that matches the native nerve morphology, a contoured stiffness profile for flexibility along the nerve's length, an simple layered construction suitable for micro- fabrication of higher density contact arrays. This new neural interface will significantly simplify implant surgery and improve the performance of lower extremity neuroprostheses, while the new stimulation module for the NNPS will enable the realization of sophisticated systems employing multiple C-FINEs for advanced lower extremity functions. We will implant C-FINEs on the femoral nerves proximal to branching of the innervation to the sartorius and individual heads of the quadriceps in three new recipients of standing systems based on our existing 16- channel implanted stimulators (IST-16). We expect the superior selectivity of the C-FINE to allow independent activation of functionally distinct groups of axons innervating knee extensors and hip flexors. This should maintain or improve the standing performance achieved with other electrodes by increasing the available stimulated knee extension strength, while simultaneously providing access to the nerves that control the hip flexion required for reciprocal stepping. Active plantar/dorsiflexion with balanced inversion/eversion should also greatly improve the quality and speed of walking by injecting propulsive energy for forward progression, and enhancing foot-floor clearance of the swinging limb. We will implant C-FINEs on the tibial and fibular nerves above the knee in three additional subjects, and exploit their selectivity to produce strong ankle plantar/dorsiflexion with balanced inversion/eversion with the new NNPS system. The complex structure of the proximal sciatic nerve has prevented application of existing low-density nerve- based electrodes to the hamstring muscles, which are important for safe and standing and stepping. We expect that a single nerve cuff electrode with high number of contacts located on the proximal sciatic nerve will be able to isolate and fully activate the individual hamstrings to provide strong hip extensio and knee flexion. We will establish the feasibility of high density interfaces to the sciatic nerv in acute intraoperative tests, which will improve the performance and simplify the surgical implantation of future lower extremity neuroprostheses.

DESCRIPTION (provided by applicant): This continuation of project EB001889 will extend the functional capabilities of recipients of implanted neuroprostheses for restoring lower extremity function after spinal cord injury (SCI) by applying new nerve cuff electrodes that selectively activate fascicles within the human femoral and sciatic nerves to isolate knee extension for standing, and both hip flexion and ankle plantar/dorsiflexion for efficient stepping. The new enabling technologies we will develop and deploy include the Compliant FINE (C-FINE), and an 8-channel nerve cuff module for the Networked Neuroprosthesis System (NNPS). The C-FINE offers distinct advantages over earlier nerve cuff designs, including a shape that matches the native nerve morphology, a contoured stiffness profile for flexibility along the nerve's length, an simple layered construction suitable for micro- fabrication of higher density contact arrays. This new neural interface will significantly simplify implant surgery and improve the performance of lower extremity neuroprostheses, while the new stimulation module for the NNPS will enable the realization of sophisticated systems employing multiple C-FINEs for advanced lower extremity functions. We will implant C-FINEs on the femoral nerves proximal to branching of the innervation to the sartorius and individual heads of the quadriceps in three new recipients of standing systems based on our existing 16- channel implanted stimulators (IST-16). We expect the superior selectivity of the C-FINE to allow independent activation of functionally distinct groups of axons innervating knee extensors and hip flexors. This should maintain or improve the standing performance achieved with other electrodes by increasing the available stimulated knee extension strength, while simultaneously providing access to the nerves that control the hip flexion required for reciprocal stepping. Active plantar/dorsiflexion with balanced inversion/eversion should also greatly improve the quality and speed of walking by injecting propulsive energy for forward progression, and enhancing foot-floor clearance of the swinging limb. We will implant C-FINEs on the tibial and fibular nerves above the knee in three additional subjects, and exploit their selectivity to produce strong ankle plantar/dorsiflexion with balanced inversion/eversion with the new NNPS system. The complex structure of the proximal sciatic nerve has prevented application of existing low-density nerve- based electrodes to the hamstring muscles, which are important for safe and standing and stepping. We expect that a single nerve cuff electrode with high number of contacts located on the proximal sciatic nerve will be able to isolate and fully activate the individual hamstrings to provide strong hip extensio and knee flexion. We will establish the feasibility of high density interfaces to the sciatic nerv in acute intraoperative tests, which will improve the performance and simplify the surgical implantation of future lower extremity neuroprostheses.

The Planning Grants for Engineering Research Centers competition was run as a pilot solicitation within the ERC program. Planning grants are not required as part of the full ERC competition, but intended to build capacity among teams to plan for convergent, center-scale engineering research.

This project will develop the foundational plan of an Engineering Research Center (ERC) to form a unique, transformative, and transdisciplinary team that will create, define, understand, and teach the science, technology, ethics, regulatory framework, entrepreneurship methodologies, and societal impact of the rapidly evolving integration of humans and technology. Communication and technology revolutions, such as radio, television, and the internet, have resulted in profound societal changes. The human, however, has basically remained external to the system with technology serving only as a tool. We propose that a conceptual shift toward symbiotic integration of the human with technology will bring the next societal transformation leading to a more connected, global society with new operational models of work, anthropocentric technology, and human-human interaction. We envision a tech-plus, transdisciplinary team of scholars, entrepreneurs, ethicists, and members from partnering institutions (including companies) that will perform convergent research at a new frontier of human incorporation of technology into a sense of self, i.e. a symbiosis between humans and technology. The core is a shift from the current techno-centric approach, where human and technology are separate, to a human-centric technology development paradigm. We seek to shift the societal dialogue from that of a battle between humans and technology (such as artificial intelligence and robotics) to a more productive dialogue of merging the best of humans and technology for the mutual benefit of both. Symbiotic incorporation of technology requires new interfaces to the human that add multiple sensory connections beyond current audio and visual inputs. This symbiotic relationship will augment human capability with those of technology and networked systems. New, symbiotic technology will radically change the future of work, human learning, human-human interaction, human networks, human health, human capability, and society overall for a safer, more prosperous future. The overall goal is to refine the model sufficiently to be compelling for a sustained research and development effort in an ERC for merging Humans, Machines, and Networks through Functional, Symbiotic, Integration On Neural Systems or an ERC for Human Fusions. Prior significant research shows that the core need of incorporation of technology into a human's sense of self, requires 1) a sense of agency over technology and 2) multi-sensory synchrony with technology.

Strictly, this project is a planning grant to develop the ERC structure and processes that will rationally evolve the relationship between humans and technology. Methods from the Science of Team Science (SciTS) will be employed to establish relationships between committed, energized stakeholders in this new, transdisciplinary effort in human-technology symbiosis and a strategic plan to grow and establish sustainable research capacity. The objectives of the project are to 1) assemble the expertise to define the transdisciplinary, tech-plus framework; 2) develop a process and the collaborative tools for the sustained, focused development and study of the new human-technology paradigm, and; 3) establish a central point of engagement for stakeholders and external communities. This project will foster a new dialogue regarding the evolution of the human-technology relationship. Tangible outcomes from the planning process will include social media networking platforms, a central collaboration and dissemination website, and surveys to gauge stakeholder commitment to and refinement of the symbiotic model of human-technology evolution. Successful realization of a symbiotic human-technology paradigm requires a transdisciplinary approach to address significant scientific, technical, ethical, and social challenges. The transdisciplinary model of the ERC for Human Fusions has a technical core addressing anthropocentric technology, multisensory human interfaces, and connection infrastructure. Expanding around this are disciplines to address ethical questions of symbiotic technology, regulatory frameworks to support the ethical principles, entrepreneurial models to introduce new technology, and sociology to understand how symbiotic technologies impact society. These are highly integrated such that each is integral to the development and understanding of the other. The potential ERC will provide leadership, intellectual resources, the establishment of world-class facilities for responsible and effective scientific discovery, technological innovation, and resources in the new symbiotic sciences for education, research and development and translation.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.