Wireless, battery-free optoelectronic systems as subdermal implants for local tissue oximetry

Monitoring regional tissue oxygenation in animal models and potentially in human subjects can yield insights into the underlying mechanisms of local O2-mediated physiological processes and provide diagnostic and therapeutic guidance for relevant disease states. Existing technologies for tissue oxygenation assessments involve some combination of disadvantages in requirements for physical tethers, anesthetics, and special apparatus, often with confounding effects on the natural behaviors of test subjects. This work introduces an entirely wireless and fully implantable platform incorporating (i) microscale optoelectronics for continuous sensing of local hemoglobin dynamics and (ii) advanced designs in continuous, wireless power delivery and data output for tether-free operation. These features support in vivo, highly localized tissue oximetry at sites of interest, including deep brain regions of mice, on untethered, awake animal models. The results create many opportunities for studying various O2-mediated processes in naturally behaving subjects, with implications in biomedical research and clinical practice.Center for Bio-Integrated Electronics at Northwestern University; Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF) [ECCS-1542205]; Materials Research Science and Engineering Center [DMR-1720139]; State of Illinois; Northwestern University; Developmental Therapeutics Core at Northwestern University; Robert H. Lurie Comprehensive Cancer Center [NCI CA060553]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Battery-free, fully implantable optofluidic cuff system for wireless optogenetic and pharmacological neuromodulation of peripheral nerves

Studies of the peripheral nervous system rely on controlled manipulation of neuronal function with pharmacologic and/or optogenetic techniques. Traditional hardware for these purposes can cause notable damage to fragile nerve tissues, create irritation at the biotic/abiotic interface, and alter the natural behaviors of animals. Here, we present a wireless, battery-free device that integrates a microscale inorganic light-emitting diode and an ultralow-power microfluidic system with an electrochemical pumping mechanism in a soft platform that can be mounted onto target peripheral nerves for programmed delivery of light and/or pharmacological agents in freely moving animals. Biocompliant designs lead to minimal effects on overall nerve health and function, even with chronic use in vivo. The small size and light weight construction allow for deployment as fully implantable devices in mice. These features create opportunities for studies of the peripheral nervous system outside of the scope of those possible with existing technologies.NIH Director's Transformative Research [TR01 NS081707]; NIH SPARC Award via the NIBIB of the NIH [U18EB021793, R01 NS42595]; NIMH of the NIH [R41MH116525]; NRSA [F32 DK115122]; McDonnell Center for Cellular and Molecular Neurobiology Postdoctoral Fellowship [T32 DA007261]; Medical Scientist Training Program (MSTP) [T32 GM07200]; University of Missouri-Columbia start-up fund; NINDS NRSA [F31 NS103472]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Perspective: Implantable optical systems for neuroscience research in behaving animal models—Current approaches and future directions

Compared to many other organ systems, the fundamental means by which the central and peripheral nervous systems connect and communicate remain poorly understood. The overall aging of populations in the developed world increases the significance of degenerative and mental health disorders, thereby motivating research into the development of effective therapies, founded on basic insights into the working principles of the brain. Progress in these endeavors can be accelerated by the development of optical tools and techniques capable of tracking and evoking changes in cell-level activity and in system-level neuronal interactions, both in the brain and in the peripherals, especially in unrestricted, freely behaving subjects. This perspective highlights the recent emergence of active optoelectronic platforms that leverage genetically targeted stimulators, inhibitors, and sensors and their vital role in brain research and therapy development. The technological advances that underpin the latest, most powerful device embodiments include miniaturized, highly efficient semiconductor light emitters and detectors that can operate chronically in a fully implantable, battery-free, wireless manner. Recent progress in this field enables a range of powerful modes of operation, with key advantages over traditional systems

Fully Implantable Optoelectronic Systems For Battery-Free, Multimodal Operation In Neuroscience Research

Recently developed ultrasmall, fully implantable devices for optogenetic neuromodulation eliminate the physical tethers associated with conventional set-ups and avoid the bulky head-stages and batteries found in alternative wireless technologies. The resulting systems allow behavioural studies without motion constraints and enable experiments in a range of environments and contexts, such as social interactions. However, these devices are purely passive in their electronic design, thereby precluding any form of active control or programmability; independent operation of multiple devices, or of multiple active components in a single device, is, in particular, impossible. Here we report optoelectronic systems that, through developments in integrated circuit and antenna design, provide low-power operation, and position- and angle-independent wireless power harvesting, with full user-programmability over individual devices and collections of them. Furthermore, these integrated platforms have sizes and weights that are not significantly larger than those of previous, passive systems. Our results qualitatively expand options in output stabilization, intensity control and multimodal operation, with broad potential applications in neuroscience research and, in particular, the precise dissection of neural circuit function during unconstrained behavioural studies

Wireless Optoelectronic Photometers For Monitoring Neuronal Dynamics In The Deep Brain

Capabilities for recording neural activity in behaving mammals have greatly expanded our understanding of brain function. Some of the most sophisticated approaches use light delivered by an implanted fiber-optic cable to optically excite genetically encoded calcium indicators and to record the resulting changes in fluorescence. Physical constraints induced by the cables and the bulk, size, and weight of the associated fixtures complicate studies on natural behaviors, including social interactions and movements in environments that include obstacles, housings, and other complex features. Here, we introduce a wireless, injectable fluorescence photometer that integrates a miniaturized light source and a photodetector on a flexible, needle-shaped polymer support, suitable for injection into the deep brain at sites of interest. The ultrathin geometry and compliant mechanics of these probes allow minimally invasive implantation and stable chronic operation. In vivo studies in freely moving animals demonstrate that this technology allows high-fidelity recording of calcium fluorescence in the deep brain, with measurement characteristics that match or exceed those associated with fiber photometry systems. The resulting capabilities in optical recordings of neuronal dynamics in untethered, freely moving animals have potential for widespread applications in neuroscience research

Context-aware electromagnetic design for continuously wearable biosymbiotic devices

Imperceptible wireless wearable devices are critical to advance digital medicine with the goal to capture clinical-grade biosignals continuously. Design of these systems is complex because of unique interdependent electromagnetic, mechanic and system level considerations that directly influence performance. Typically, approaches consider body location, related mechanical loads, and desired sensing capabilities, however, design for real world application context is not formulated. Wireless power casting eliminates user interaction and the need to recharge batteries, however, implementation is challenging because the use case influences performance. To facilitate a data-driven approach to design, we demonstrate a method for personalized, context-aware antenna, rectifier and wireless electronics design that considers human behavioral patterns and physiology to optimize electromagnetic and mechanical features for best performance across an average day of the target user group. Implementation of these methods result in devices that enable continuous recording of high-fidelity biosignals over weeks without the need for human interaction.24 month embargo; first published 14 March 2023This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

The Surgical Implantation of Novel Epicardial Pacemakers in Rodents

OBJECTIVES: Rodent hearts have been used as models of cardiac disease for many years in the investigation of cardiovascular physiology. Chronic pacing has been used to induce heart failure or arrhythmia in the past. However, the size and durability of the devices, as well as the viability of the animals following the implantation, have been some of the many challenges. In this study, we present a new technique for the successful implantation of wireless cardiac pacemakers in rat hearts. METHODS: We present two novel wireless and battery-free pacemakers that are currently under development. One model is completely biodegradable, while the other is not. Anesthesia is induced in the isofluorane chamber and the rats are intubated using standard technique and connected to the ventilator. A left thoracotomy is performed, the lung is mobilized posteriorly, and the pericardium is opened. The pacemaker electrode is sutured to the epicardium using 6-0 monofilament non-absorbable sutures. The receiver portion of the pacemaker is placed in a subcutaneous pocket. After the chest is closed, the rats are extubated and monitored until sternal recumbency is regained. Afterwards, the rats are placed in a cage with radiofrequency (RF) wireless control stimulator and the data was recorded using a standard small animal electrocardiogram (EKG) recording device. RESULTS: A total of five functioning pacemakers have been implanted. The rats had unremarkable post-operative course and showed long-term survival. The devices were activated and we were able to observe the change of EKG from normal sinus rhythm at 300 to 340 bpm to 400 to 500 ventricular rhythms with wide QRS. Once the remote signal was turned off, we observed a return of cardiac rhythm to normal sinus rhythm. Conclusion: The surgical technique we have developed is an effective and reproducible approach for the implantation of wireless epicardial pacemakers in rats. This will lead to the expanded use of wireless pacemakers in rats that will help recreate human disease patterns in animals

Fully implanted battery-free high power platform for chronic spinal and muscular functional electrical stimulation

Abstract Electrical stimulation of the neuromuscular system holds promise for both scientific and therapeutic biomedical applications. Supplying and maintaining the power necessary to drive stimulation chronically is a fundamental challenge in these applications, especially when high voltages or currents are required. Wireless systems, in which energy is supplied through near field power transfer, could eliminate complications caused by battery packs or external connections, but currently do not provide the harvested power and voltages required for applications such as muscle stimulation. Here, we introduce a passive resonator optimized power transfer design that overcomes these limitations, enabling voltage compliances of ± 20 V and power over 300 mW at device volumes of 0.2 cm2, thereby improving power transfer 500% over previous systems. We show that this improved performance enables multichannel, biphasic, current-controlled operation at clinically relevant voltage and current ranges with digital control and telemetry in freely behaving animals. Preliminary chronic results indicate that implanted devices remain operational over 6 weeks in both intact and spinal cord injured rats and are capable of producing fine control of spinal and muscle stimulation