Part 1: Upper-limb motor impairments arise from a wide range of clinical conditions including amputations, spinal cord injury, or stroke. Addressing lost hand function, therefore, is a major focus of rehabilitation interventions; and research in robotic hands and hand exoskeletons aimed at restoring fine motor control functions gained significant speed recently. Integration of these robots with neural control mechanisms is also an ongoing research direction. We will develop prosthetic and wearable hands controlled via nested control that seamlessly blends neural control based on human brain activity and dynamic control based on sensors on robots. These Hand Augmentation using Nested Decision (HAND) systems will also provide rudimentary tactile feedback to the user. The HAND design framework will contribute to the assistive and augmentative robotics field. The resulting technology will improve the quality of life for individuals with lost limb function. The project will help train engineers skilled in addressing multidisciplinary challenges. Through outreach activities, STEM careers will be promoted at the K-12 level, individuals from underrepresented groups in engineering will be recruited to engage in this research project, which will contribute to the diversity of the STEM workforce. Part 2: The team previously introduced the concept of human-in-the-loop cyber-physical systems (HILCPS). Using the HILCPS hardware-software co-design and automatic synthesis infrastructure, we will develop prosthetic and wearable HAND systems that are robust to uncertainty in human intent inference from physiological signals. One challenge arises from the fact that the human and the cyber system jointly operate on the same physical element. Synthesis of networked real-time applications from algorithm design environments poses a framework challenge. These will be addressed by a tightly coupled optimal nested control strategy that relies on EEG-EMG-context fusion for human intent inference. Custom distributed embedded computational and robotic platforms will be built and iteratively refined. This work will enhance the HILCPS design framework, while simultaneously making novel contributions to body/brain interface technology and assistive/augmentative robot technology. Specifically we will (1) develop a theoretical EEG-EMG-context fusion framework for agile HILCPS application domains; (2) develop theory for and design novel control theoretic solutions to handle uncertainty, blend motion/force planning with high-level human intent and ambient intelligence to robustly execute daily manipulation activities; (3) further develop and refine the HILCPS domain-specific design framework to enable rapid deployment of HILCPS algorithms onto distributed embedded systems, empowering a new class of real-time algorithms that achieve distributed embedded sensing, analysis, and decision making; (4) develop new paradigms to replace, retrain or augment hand function via the prosthetic/wearable HAND by optimizing performance on a subject-by-subject basis.

Errors in cyber-physical systems can lead to disastrous consequences. Classic examples date back to the Therac-25 radiation incidents in 1987 and the Ariane 5 rocket crash in 1996. More recently, Toyota's unintended acceleration bug was caused by software errors, and certain cars were found vulnerable to attacks that can take over key parts of the control software, allowing attackers to even disable the brakes remotely. Pacemakers have also been found vulnerable to attacks that can cause deadly consequences for the patient. To reduce the chances of such errors happening, this project investigates the application of a technique called Foundational Verification to cyber-physical systems. In Foundational Verification, the system being developed is proved correct, in full formal detail, using a proof assistant. The main intellectual merit of the proposal is the attainment of previously unattainable levels of safety for cyber-physical systems because proofs in Foundational Verification are carried out in complete detail. To ensure that the techniques in this project are practical, they are evaluated within the context of a real flying quadcopter. The project's broader significance and importance is the improved correctness, safety and security of cyber-physical systems. In particular, this project lays the foundation for ushering in a new level of formal correctness for cyber-physical systems. Although the initial work focuses on quadcopters, the concepts, ideas, and research contributions have the potential for transformative impact on other kinds of systems, including power-grid software, cars, avionics and medical devices (from pacemakers and insulin pumps to defibrillators and radiation machines).

Laboratory-on-a-chip (LoC) technology is poised to improve global health through development of low-cost, automated point-of-care testing devices. In countries with few healthcare resources, clinics often have drugs to treat an illness, but lack diagnostic tools to identify patients who need them. To enable low-cost diagnostics with minimal laboratory support, this project will investigate domain-specific LoC programming language and compiler design in conjunction with device fabrication technologies (process flows, sensor integration, etc.). The project will culminate by building a working LoC that controls fluid motion through electronic signals supplied by a host PC; a forensic toxicology immunoassay will be programmed in software and executed on the device. This experiment will demonstrate benefits of programmable LoC technology including miniaturization (reduced reagent consumption), automation (reduced costs and uncertainties associated with human interaction), and general-purpose software-programmability (the device can execute a wide variety of biochemical reactions, all specified in software). Information necessary to reproduce the device, along with all software artifacts developed through this research effort, will be publicly disseminated. This will promote widespread usage of software-programmable LoC technology among researchers in the biological sciences, along with public and industrial sectors including healthcare and public health, biotechnology, water supply management, environmental toxicity monitoring, and many others. This project designs and implements a software-programmable cyber-physical laboratory-on-a-chip (LoC) that can execute a wide variety of biological protocols. By integrating sensors during fabrication, the LoC obtains the capability to send feedback in real-time to the PC controller, which can then make intelligent decisions regarding which biological operations to execute next. To bring this innovative and transformative platform to fruition, the project tackles several formidable research challenges: (1) cyber-physical LoC programming models and compiler design; (2) LoC fabrication, including process flows and cyber-physical sensor integration; and (3) LoC applications that rely on cyber-physical sensory feedback and real-time decision-making. By constructing a working prototype LoC, and programming a representative feedback-driven forensic toxicology immunoassay, the project demonstrates that the proposed system can automatically execute biochemical reactions that require a closed feedback loop. Expected broader impacts of the proposed work include reduced cost and increased reliability of clinical diagnostics, engagement with U.S. companies that use LoC technology, training of graduate and undergraduate students, increased engagement and retention efforts targeting women and underrepresented minorities, student-facilitated peer-instruction at UC Riverside, a summer residential program for underrepresented minority high-school students at the University of Tennessee, collaborations with researchers at the Oak Ridge National Laboratory, and creation, presentation, and dissemination of tutorial materials to promote the adoption and use of software-programmable LoCs among the wider scientific community.

Epilepsy is one of the most common neurological disorders, affecting between 0.4% and 1% of the world's population. While seizures can be controlled in approximately two thirds of newly diagnosed patients through the use of one or more antiepileptic drugs (AEDs), the remainder experience seizures even on multiple medications. The primary impacts of the chronic condition of epilepsy on a patient are a lower quality of life, loss of productivity, comorbidities, and increased risk of death. Epilepsy is an intermittent brain disorder, and in localization-related epilepsy, which is the most common form of epilepsy, one or a few discrete brain areas (the seizure focus or seizure foci) are believed to be responsible for seizure initiation. More recent approaches with implantable electrical stimulation seizure control devices hold value as a therapeutic option for the control of seizures. These devices, directly or indirectly, target the seizure focus and seek to control its expression. In this project we will build a multichannel brain implantable device based on emerging cyber physical system (CPS) principles. This brain implantable CPS device will incorporate key design features to make the device dependable, scalable, composable, certifiable, and interoperable. The device will operate over the life of an animal, or a patient, and continuously record brain activity and stimulate the brain when seizure related activity is detected to abort an impending seizure. Episodic brain disorders such as epilepsy have a considerable impact on a patient's productivity and quality of life and may be life-threatening when seizures cannot be controlled with medications. The goal of this project is to create a second generation brain-implantable sensing and stimulating device (BISSD) based on emerging CPS principles and practice. The development of a BISSD as a exemplifies several defining aspects that inform and illustrate core CPS principles. First, to meet the important challenge of regulatory approval a composable, scalable and certifiable framework that supports testing in multiple species is proposed. Second, a BISSD must be wholly integrated with the patient and fully cognizant at every instant of brain state, including dynamic changes in both the normal and abnormal expression of brain physiology and therapeutic intervention. Thus, this project seeks a tight conjunction of the cyber solution that must monitor itself and monitor and stimulate the brain using implanted, adaptable, distributed, and networked electrodes, and the physical system which in this case is the intermittently failing human brain. Third, a BISSD must function for an extensive period of time, up to the life of the patient, because each surgery to place and retrieve a BISSD carries an attendant risk. This requirement necessitates a dependable solution, which this project seeks to reliably achieve through both an understanding of the brain's foreign body response and a unique hierarchical fault-tolerant design. Fourth, an advanced salient approaches to acquire, compress, and analyze sensor signals to achieve real-time monitoring and control of seizures is employed. This project should yield a powerful, scalable CPS framework for robust fault-tolerant implantable medical devices with real-time processing that can grow with advances in sensors, sensing modalities, time-series analysis, real-time computation, control, materials, power and knowledge of underlying biology. The USA has a competitive advantage in the control of seizures in medically refractory epilepsy. In the modern era, epilepsy surgery evolved in the USA in the 1970s and spread from here to other parts of the world. Similarly, the USA enjoys a competitive advantage in BISSDs, and success in this effort will enable the USA to build on and maintain this advantage. In addition to epilepsy, advances made here can be expected to benefit the treatment of other neurological and psychiatric brain disorders.

Children affected by neurological conditions (e.g., Cerebral Palsy, Muscular Atrophy, Spina Bifida and Severe head trauma) often develop significant disabilities including impaired motor control. In many cases, walking becomes a non-functional and exhausting skill that demands the use of the aids or the substitution of function, such as wheelchair. This usually cause these children not to acquire locomotion skills, and consequently to lose their independence. However, it is well understood that bipedal locomotion, an essential human characteristic, ensures the best physiological motor pattern acquisition. For this reason, in children with neurological and neuromuscular diseases, independent walking is a significant rehabilitation goal that must be pursued in a specific temporal window due to the plasticity of central nervous system. In other words, children with neurological conditions have a small window of time to acquire locomotion skills through assisted walking rehearsals. The objective of this research work is to create and experimentally validate a set of technologies that form the framework for the development of adaptive, self-balancing, and modular exoskeleton robotics systems for children with neurological disorders. It is our belief that the exoskeleton (and its associated infrastructure) resulting from this research will offer an effective tool to promote locomotion skill acquisition, and in general health, during a critical period in the early life of children with neurological conditions. This research proposal develops a data-driven human-machine modeling specific to physiological conditions. This creates regression models that predict the user behavior without explicit modeling the complex human musculoskeletal dynamics and motor control mechanism. Additionally this research project formulates a safe adaptive control problem as a model predictive control (MPC) problem. In this method, an optimal input sequence is computed by solving a constrained finite-time optimal control problem where exoskeleton intrusion (input from exoskeleton) is minimized to maximize the user's intent to promote learning. This project further develops a novel approach for stabilizing and preventing fall of the exoskeleton and the child as a whole. This method allows a child wearing an exoskeleton to learn locomotion skills described above with less likelihood of falls. This research project furthermore evaluates the developed technologies in terms of efficiency and efficacy and creates a novel fun game using exoskeleton for children to promote locomotion skills.