Organic Bioelectronics For Neurotransmitter Release At The Speed Of Life

The signaling dynamics in neuronal networks includes processes ranging from lifelong neuromodulation to direct synaptic neurotransmission. In chemical synapses, the time delay it takes to pass a signal from one neuron to the next lasts for less than a millisecond. At the post-synaptic neuron, further signaling is either up- or down-regulated, dependent on the specific neurotransmitter and receptor. While this up- and down-regulation of signals usually runs perfectly well and enables complex performance, even a minor dysfunction of this signaling system can cause major complications, in the shape of neurological disorders. The field of organic bioelectronics has the ability to interface neurons with high spatiotemporal recording and stimulation techniques. Local chemical stimulation, i.e. local release of neurotransmitters, enables the possibility of artificially altering the chemical environment in dysfunctional signaling pathways to regain or restore neural function. To successfully interface the biological nervous system with electronics, a range of demands must be met. Organic bioelectronic techniques and materials are capable of reaching the demands on the biological as well as the electronic side of the interface. These demands span from high performance biocompatible materials, to miniaturized and specific device architectures, and high dose control on demand within milliseconds. The content of this thesis is a continuation of the development of organic bioelectronic devices for neurotransmitter delivery. Organic materials are utilized to electrically control the dose of charged neurotransmitters by translating electric charge into controlled artificial release. The first part of the thesis, Papers 1 and 2, includes further development of the resistor-type release device called the organic electronic ion pump. This part includes material evaluation, microfluidic incorporation, and device design considerations. The aim for the second part of this thesis, Papers 3 and 4, is to enhance temporal performance, i.e. reduce the delay between electrical signal and neurotransmitter delivery to corresponding delay in biological neural signaling, while retaining tight dosage control. Diffusion of neurotransmitters between nerve cells is a slow process, but since it is restricted to short distances, the total time delay is short. In our organic bioelectronic devices, several orders of magnitude in speed can be gained by switching from lateral to vertical delivery geometries. This is realized by two different types of vertical diodes combined with a lateral preload and waste configuration. The vertical diode assembly was further expanded with a control electrode that enables individual addressing in each of several combined release sites. These integrated circuits allow for release of neurotransmitters with high on/off release ratios, approaching delivery times on par with biological neurotransmission.

Wearable Bioelectronics presents the latest on physical and (bio)chemical sensing for wearable electronics. It covers the miniaturization of bioelectrodes and high-throughput biosensing platforms while also presenting a systemic approach for the development of electrochemical biosensors and bioelectronics for biomedical applications. The book addresses the fundamentals, materials, processes and devices for wearable bioelectronics, showcasing key applications, including device fabrication, manufacturing, and healthcare applications. Topics covered include self-powering wearable bioelectronics, electrochemical transducers, textile-based biosensors, epidermal electronics and other exciting applications. Includes comprehensive and systematic coverage of the most exciting and promising bioelectronics, processes for their fabrication, and their applications in healthcare Reviews innovative applications, such as self-powering wearable bioelectronics, electrochemical transducers, textile-based biosensors and electronic skin Examines and discusses the future of wearable bioelectronics Addresses the wearable electronics market as a development of the healthcare industry

For molecules that are not directly electroactive, it is necessary to modify a microelectrode by grafting polymeric or enzymatic membranes capable of translating a local concentration into an electrical current, which is a concept referred to as biosensing. In Microelectrode Biosensors, experts in the field cover the topic of electrochemical biosensor technology as applied to the neurosciences. The volume opens with a section addressing the specific issue of manufacturing biosensors that can be implanted in the central nervous system for neurotransmitter detection, and it then continues with sections on recent studies where biosensors have made a difference in bringing a new level of understanding of signaling mechanisms in neuroscience as well as recent developments in biosensor technology that have not yet been applied to implantable microelectrodes but may have great potential. Written for the Neuromethods series, this work contains the kind of detailed descriptions and implementation advice necessary to achieve successful results. Focused and cutting-edge, Microelectrode Biosensors serves to inspire the wider neuroscience and physiology community to adopt these powerful methods in their own applications in order to move the field forward with the widespread advances that will most likely flow from the adoption of biosensing as part of the standard laboratory toolkit.

This book covers recent advances in the use of electrostimulation therapies in movement disorders, epilepsy, inflammatory bowel disease, memory and cognition, disorders of consciousness, foot drop, dysphagia, brain injury, headache, heart failure, hearing loss, and rheumatoid arthritis. It describes techniques such as vagus nerve stimulation, deep brain stimulation, and electrical stimulation of the pharyngeal nerve. Electroceuticals: Advances in Electrostimulation Therapies is aimed at clinicians and basic researchers in the fields of neurology, neurosurgery, cardiology and rheumatology.

Here the renowned editor Evgeny Katz has chosen contributions that cover a wide range of examples and issues in implantable bioelectronics, resulting in an excellent overview of the topic. The various implants covered include biosensoric and prosthetic devices, as well as neural and brain implants, while ethical issues, suitable materials, biocompatibility, and energy-harvesting devices are also discussed. A must-have for both newcomers and established researchers in this interdisciplinary field that connects scientists from chemistry, material science, biology, medicine, and electrical engineering.

Despite the vital importance of the emerging area of biotechnology and its role in defense planning and policymaking, no definitive book has been written on the topic for the defense policymaker, the military student, and the private-sector bioscientist interested in the "emerging opportunities market" of national security. This edited volume is intended to help close this gap and provide the necessary backdrop for thinking strategically about biology in defense planning and policymaking. This volume is about applications of the biological sciences, here called "biologically inspired innovations," to the military. Rather than treating biology as a series of threats to be dealt with, such innovations generally approach the biological sciences as a set of opportunities for the military to gain strategic advantage over adversaries. These opportunities range from looking at everything from genes to brains, from enhancing human performance to creating renewable energy, from sensing the environment around us to harnessing its power.

Intended for use by advanced undergraduate, graduate and medical students, this book presents a study of the unique biochemical and physiological properties of neurons, emphasising the molecular mechanisms that generate and regulate their activity.

Brain aminergic pathways are organized in parallel and interacting systems, which support a range of functions, from homoeostatic regulations to cognitive, and motivational processes. Despite overlapping functional influences, dopamine, serotonin, noradrenaline and histamine systems provide different contributions to these processes. The histaminergic system, long ignored as a major regulator of the sleep-wake cycle, has now been fully acknowledged also as a major coordinator of attention, learning and memory, decision making. Although histaminergic neurons project widely to the whole brain, they are functionally heterogeneous, a feature which may provide the substrate for differential regulation, in a region-specific manner, of other neurotransmitter systems. Neurochemical preclinical studies have clearly shown that histamine interacts and modulates the release of neurotransmitters that are recognized as major modulators of cognitive processing and motivated behaviours. As a consequence, the histamine system has been proposed as a therapeutic target to treat sleep-wake disorders and cognitive dysfunctions that accompany neurodegenerative and neuroinflammatory pathologies. Last decades have witnessed an unexpected explosion of interest in brain histamine system, as new receptors have been discovered and selective ligands synthesised. Nevertheless, the complete picture of the histamine systems fine-tuning and its orchestration with other pathways remains rather elusive. This Research Topic is intended to offer an inter-disciplinary forum that will improve our current understanding of the role of brain histamine and provide the fundamentals necessary to drive innovation in clinical practice and to improve the management and treatment of neurological disorders.