RESUMEN
Social interactions occur between multiple individuals, but what is the detailed relationship between the neural dynamics across their brains? To address this question across timescales and levels of neural activity, we used wireless electrophysiology to simultaneously record from pairs of bats engaged in a wide range of natural social interactions. We found that neural activity was remarkably correlated between their brains over timescales from seconds to hours. The correlation depended on a shared social environment and was most prominent in high frequency local field potentials (>30 Hz), followed by local spiking activity. Furthermore, the degree of neural correlation covaried with the extent of social interactions, and an increase in correlation preceded their initiation. These results show that inter-brain correlation is an inherent feature of natural social interactions, reveal the domain of neural activity where it is most prominent, and provide a foundation for studying its functional role in social behaviors.
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Encéfalo/fisiología , Quirópteros/fisiología , Neuronas/fisiología , Potenciales de Acción , Animales , Femenino , Masculino , Conducta Social , Tecnología InalámbricaRESUMEN
In vivo pharmacology and optogenetics hold tremendous promise for dissection of neural circuits, cellular signaling, and manipulating neurophysiological systems in awake, behaving animals. Existing neural interface technologies, such as metal cannulas connected to external drug supplies for pharmacological infusions and tethered fiber optics for optogenetics, are not ideal for minimally invasive, untethered studies on freely behaving animals. Here, we introduce wireless optofluidic neural probes that combine ultrathin, soft microfluidic drug delivery with cellular-scale inorganic light-emitting diode (µ-ILED) arrays. These probes are orders of magnitude smaller than cannulas and allow wireless, programmed spatiotemporal control of fluid delivery and photostimulation. We demonstrate these devices in freely moving animals to modify gene expression, deliver peptide ligands, and provide concurrent photostimulation with antagonist drug delivery to manipulate mesoaccumbens reward-related behavior. The minimally invasive operation of these probes forecasts utility in other organ systems and species, with potential for broad application in biomedical science, engineering, and medicine.
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Estimulación Encefálica Profunda/métodos , Optogenética/métodos , Animales , Encéfalo/efectos de los fármacos , Sistemas de Liberación de Medicamentos , Ratones , Sondas Moleculares , Tecnología InalámbricaRESUMEN
Wireless modules that provide telecommunications and power-harvesting capabilities enabled by radio-frequency (RF) electronics are vital components of skin-interfaced stretchable electronics1-7. However, recent studies on stretchable RF components have demonstrated that substantial changes in electrical properties, such as a shift in the antenna resonance frequency, occur even under relatively low elastic strains8-15. Such changes lead directly to greatly reduced wireless signal strength or power-transfer efficiency in stretchable systems, particularly in physically dynamic environments such as the surface of the skin. Here we present strain-invariant stretchable RF electronics capable of completely maintaining the original RF properties under various elastic strains using a 'dielectro-elastic' material as the substrate. Dielectro-elastic materials have physically tunable dielectric properties that effectively avert frequency shifts arising in interfacing RF electronics. Compared with conventional stretchable substrate materials, our material has superior electrical, mechanical and thermal properties that are suitable for high-performance stretchable RF electronics. In this paper, we describe the materials, fabrication and design strategies that serve as the foundation for enabling the strain-invariant behaviour of key RF components based on experimental and computational studies. Finally, we present a set of skin-interfaced wireless healthcare monitors based on strain-invariant stretchable RF electronics with a wireless operational distance of up to 30 m under strain.
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Elasticidad , Electrónica , Diseño de Equipo , Ondas de Radio , Piel , Estrés Mecánico , Dispositivos Electrónicos Vestibles , Tecnología Inalámbrica , Humanos , Electrónica/instrumentación , Tecnología Inalámbrica/instrumentación , Monitoreo Fisiológico/instrumentaciónRESUMEN
Direct and precise monitoring of intracranial physiology holds immense importance in delineating injuries, prognostication and averting disease1. Wired clinical instruments that use percutaneous leads are accurate but are susceptible to infection, patient mobility constraints and potential surgical complications during removal2. Wireless implantable devices provide greater operational freedom but include issues such as limited detection range, poor degradation and difficulty in size reduction in the human body3. Here we present an injectable, bioresorbable and wireless metastructured hydrogel (metagel) sensor for ultrasonic monitoring of intracranial signals. The metagel sensors are cubes 2 × 2 × 2 mm3 in size that encompass both biodegradable and stimulus-responsive hydrogels and periodically aligned air columns with a specific acoustic reflection spectrum. Implanted into intracranial space with a puncture needle, the metagel deforms in response to physiological environmental changes, causing peak frequency shifts of reflected ultrasound waves that can be wirelessly measured by an external ultrasound probe. The metagel sensor can independently detect intracranial pressure, temperature, pH and flow rate, realize a detection depth of 10 cm and almost fully degrade within 18 weeks. Animal experiments on rats and pigs indicate promising multiparametric sensing performances on a par with conventional non-resorbable wired clinical benchmarks.
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Implantes Absorbibles , Encéfalo , Hidrogeles , Monitoreo Fisiológico , Ondas Ultrasónicas , Tecnología Inalámbrica , Animales , Masculino , Ratas , Encéfalo/fisiología , Hidrogeles/química , Concentración de Iones de Hidrógeno , Inyecciones/instrumentación , Presión Intracraneal , Monitoreo Fisiológico/instrumentación , Monitoreo Fisiológico/métodos , Ratas Sprague-Dawley , Porcinos Enanos , Temperatura , Factores de Tiempo , Tecnología Inalámbrica/instrumentaciónRESUMEN
Integrated microwave photonics (MWP) is an intriguing technology for the generation, transmission and manipulation of microwave signals in chip-scale optical systems1,2. In particular, ultrafast processing of analogue signals in the optical domain with high fidelity and low latency could enable a variety of applications such as MWP filters3-5, microwave signal processing6-9 and image recognition10,11. An ideal integrated MWP processing platform should have both an efficient and high-speed electro-optic modulation block to faithfully perform microwave-optic conversion at low power and also a low-loss functional photonic network to implement various signal-processing tasks. Moreover, large-scale, low-cost manufacturability is required to monolithically integrate the two building blocks on the same chip. Here we demonstrate such an integrated MWP processing engine based on a 4 inch wafer-scale thin-film lithium niobate platform. It can perform multipurpose tasks with processing bandwidths of up to 67 GHz at complementary metal-oxide-semiconductor (CMOS)-compatible voltages. We achieve ultrafast analogue computation, namely temporal integration and differentiation, at sampling rates of up to 256 giga samples per second, and deploy these functions to showcase three proof-of-concept applications: solving ordinary differential equations, generating ultra-wideband signals and detecting edges in images. We further leverage the image edge detector to realize a photonic-assisted image segmentation model that can effectively outline the boundaries of melanoma lesion in medical diagnostic images. Our ultrafast lithium niobate MWP engine could provide compact, low-latency and cost-effective solutions for future wireless communications, high-resolution radar and photonic artificial intelligence.
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Microondas , Niobio , Óptica y Fotónica , Óxidos , Fotones , Inteligencia Artificial , Diagnóstico por Imagen/instrumentación , Diagnóstico por Imagen/métodos , Melanoma/diagnóstico por imagen , Melanoma/patología , Óptica y Fotónica/instrumentación , Óptica y Fotónica/métodos , Radar , Tecnología Inalámbrica , HumanosRESUMEN
Social interactions represent a ubiquitous aspect of our everyday life that we acquire by interpreting and responding to visual cues from conspecifics1. However, despite the general acceptance of this view, how visual information is used to guide the decision to cooperate is unknown. Here, we wirelessly recorded the spiking activity of populations of neurons in the visual and prefrontal cortex in conjunction with wireless recordings of oculomotor events while freely moving macaques engaged in social cooperation. As animals learned to cooperate, visual and executive areas refined the representation of social variables, such as the conspecific or reward, by distributing socially relevant information among neurons in each area. Decoding population activity showed that viewing social cues influences the decision to cooperate. Learning social events increased coordinated spiking between visual and prefrontal cortical neurons, which was associated with improved accuracy of neural populations to encode social cues and the decision to cooperate. These results indicate that the visual-frontal cortical network prioritizes relevant sensory information to facilitate learning social interactions while freely moving macaques interact in a naturalistic environment.
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Macaca , Corteza Prefrontal , Aprendizaje Social , Corteza Visual , Animales , Potenciales de Acción , Conducta Cooperativa , Señales (Psicología) , Toma de Decisiones/fisiología , Función Ejecutiva/fisiología , Macaca/fisiología , Neuronas/fisiología , Estimulación Luminosa , Corteza Prefrontal/citología , Corteza Prefrontal/fisiología , Recompensa , Aprendizaje Social/fisiología , Corteza Visual/citología , Corteza Visual/fisiología , Tecnología InalámbricaRESUMEN
Transient molecules in the gastrointestinal tract such as nitric oxide and hydrogen sulfide are key signals and mediators of inflammation. Owing to their highly reactive nature and extremely short lifetime in the body, these molecules are difficult to detect. Here we develop a miniaturized device that integrates genetically engineered probiotic biosensors with a custom-designed photodetector and readout chip to track these molecules in the gastrointestinal tract. Leveraging the molecular specificity of living sensors1, we genetically encoded bacteria to respond to inflammation-associated molecules by producing luminescence. Low-power electronic readout circuits2 integrated into the device convert the light emitted by the encapsulated bacteria to a wireless signal. We demonstrate in vivo biosensor monitoring in the gastrointestinal tract of small and large animal models and the integration of all components into a sub-1.4 cm3 form factor that is compatible with ingestion and capable of supporting wireless communication. With this device, diseases such as inflammatory bowel disease could be diagnosed earlier than is currently possible, and disease progression could be more accurately tracked. The wireless detection of short-lived, disease-associated molecules with our device could also support timely communication between patients and caregivers, as well as remote personalized care.
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Biomarcadores , Técnicas Biosensibles , Sulfuro de Hidrógeno , Inflamación , Óxido Nítrico , Animales , Biomarcadores/análisis , Biomarcadores/metabolismo , Técnicas Biosensibles/instrumentación , Técnicas Biosensibles/métodos , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/metabolismo , Modelos Animales , Tracto Gastrointestinal/metabolismo , Tracto Gastrointestinal/microbiología , Cápsulas/administración & dosificación , Probióticos/metabolismo , Bacterias/metabolismo , Luminiscencia , Progresión de la Enfermedad , Inflamación/diagnóstico , Inflamación/metabolismo , Óxido Nítrico/análisis , Óxido Nítrico/metabolismo , Sulfuro de Hidrógeno/análisis , Sulfuro de Hidrógeno/metabolismo , Tecnología Inalámbrica/instrumentación , Administración Oral , Tecnología de Sensores Remotos/instrumentación , Tecnología de Sensores Remotos/métodos , Factores de Tiempo , Humanos , Tamaño CorporalRESUMEN
Fibre lithium-ion batteries are attractive as flexible power solutions because they can be woven into textiles, offering a convenient way to power future wearable electronics1-4. However, they are difficult to produce in lengths of more than a few centimetres, and longer fibres were thought to have higher internal resistances3,5 that compromised electrochemical performance6,7. Here we show that the internal resistance of such fibres has a hyperbolic cotangent function relationship with fibre length, where it first decreases before levelling off as length increases. Systematic studies confirm that this unexpected result is true for different fibre batteries. We are able to produce metres of high-performing fibre lithium-ion batteries through an optimized scalable industrial process. Our mass-produced fibre batteries have an energy density of 85.69 watt hour per kilogram (typical values8 are less than 1 watt hour per kilogram), based on the total weight of a lithium cobalt oxide/graphite full battery, including packaging. Its capacity retention reaches 90.5% after 500 charge-discharge cycles and 93% at 1C rate (compared with 0.1C rate capacity), which is comparable to commercial batteries such as pouch cells. Over 80 per cent capacity can be maintained after bending the fibre for 100,000 cycles. We show that fibre lithium-ion batteries woven into safe and washable textiles by industrial rapier loom can wirelessly charge a cell phone or power a health management jacket integrated with fibre sensors and a textile display.
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Cobalto/química , Suministros de Energía Eléctrica , Electrónica , Litio/química , Óxidos/química , Textiles , Dispositivos Electrónicos Vestibles , Grafito/química , Humanos , Iones , Masculino , Tecnología InalámbricaRESUMEN
Skin-like intrinsically stretchable soft electronic devices are essential to realize next-generation remote and preventative medicine for advanced personal healthcare1-4. The recent development of intrinsically stretchable conductors and semiconductors has enabled highly mechanically robust and skin-conformable electronic circuits or optoelectronic devices2,5-10. However, their operating frequencies have been limited to less than 100 hertz, which is much lower than that required for many applications. Here we report intrinsically stretchable diodes-based on stretchable organic and nanomaterials-capable of operating at a frequency as high as 13.56 megahertz. This operating frequency is high enough for the wireless operation of soft sensors and electrochromic display pixels using radiofrequency identification in which the base-carrier frequency is 6.78 megahertz or 13.56 megahertz. This was achieved through a combination of rational material design and device engineering. Specifically, we developed a stretchable anode, cathode, semiconductor and current collector that can satisfy the strict requirements for high-frequency operation. Finally, we show the operational feasibility of our diode by integrating it with a stretchable sensor, electrochromic display pixel and antenna to realize a stretchable wireless tag. This work is an important step towards enabling enhanced functionalities and capabilities for skin-like wearable electronics.
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Electrodos , Polímeros/química , Dispositivos Electrónicos Vestibles , Electrónica/instrumentación , Humanos , Nanocables/química , Semiconductores , Plata/química , Piel , Tecnología Inalámbrica/instrumentaciónRESUMEN
Large, distributed collections of miniaturized, wireless electronic devices1,2 may form the basis of future systems for environmental monitoring3, population surveillance4, disease management5 and other applications that demand coverage over expansive spatial scales. Aerial schemes to distribute the components for such networks are required, and-inspired by wind-dispersed seeds6-we examined passive structures designed for controlled, unpowered flight across natural environments or city settings. Techniques in mechanically guided assembly of three-dimensional (3D) mesostructures7-9 provide access to miniature, 3D fliers optimized for such purposes, in processes that align with the most sophisticated production techniques for electronic, optoelectronic, microfluidic and microelectromechanical technologies. Here we demonstrate a range of 3D macro-, meso- and microscale fliers produced in this manner, including those that incorporate active electronic and colorimetric payloads. Analytical, computational and experimental studies of the aerodynamics of high-performance structures of this type establish a set of fundamental considerations in bio-inspired design, with a focus on 3D fliers that exhibit controlled rotational kinematics and low terminal velocities. An approach that represents these complex 3D structures as discrete numbers of blades captures the essential physics in simple, analytical scaling forms, validated by computational and experimental results. Battery-free, wireless devices and colorimetric sensors for environmental measurements provide simple examples of a wide spectrum of applications of these unusual concepts.
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Biomimética , Equipos y Suministros Eléctricos , Miniaturización/instrumentación , Semillas , Viento , Tecnología Inalámbrica/instrumentación , Colorimetría , Monitoreo del Ambiente/instrumentación , Monitoreo del Ambiente/métodos , Fenómenos Mecánicos , Microfluídica , Vigilancia de la Población/métodos , RotaciónRESUMEN
Sensations of heat and touch produced by receptors in the skin are of essential importance for perceptions of the physical environment, with a particularly powerful role in interpersonal interactions. Advances in technologies for replicating these sensations in a programmable manner have the potential not only to enhance virtual/augmented reality environments but they also hold promise in medical applications for individuals with amputations or impaired sensory function. Engineering challenges are in achieving interfaces with precise spatial resolution, power-efficient operation, wide dynamic range, and fast temporal responses in both thermal and in physical modulation, with forms that can extend over large regions of the body. This paper introduces a wireless, skin-compatible interface for thermo-haptic modulation designed to address some of these challenges, with the ability to deliver programmable patterns of enhanced vibrational displacement and high-speed thermal stimulation. Experimental and computational investigations quantify the thermal and mechanical efficiency of a vertically stacked design layout in the thermo-haptic stimulators that also supports real-time, closed-loop control mechanisms. The platform is effective in conveying thermal and physical information through the skin, as demonstrated in the control of robotic prosthetics and in interactions with pressure/temperature-sensitive touch displays.
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Tacto , Realidad Virtual , Tecnología Inalámbrica , Humanos , Tecnología Inalámbrica/instrumentación , Tacto/fisiología , Piel , Robótica/instrumentación , Robótica/métodosRESUMEN
Advances in soft materials, miniaturized electronics, sensors, stimulators, radios, and battery-free power supplies are resulting in a new generation of fully implantable organ interfaces that leverage volumetric reduction and soft mechanics by eliminating electrochemical power storage. This device class offers the ability to provide high-fidelity readouts of physiological processes, enables stimulation, and allows control over organs to realize new therapeutic and diagnostic paradigms. Driven by seamless integration with connected infrastructure, these devices enable personalized digital medicine. Key to advances are carefully designed material, electrophysical, electrochemical, and electromagnetic systems that form implantables with mechanical properties closely matched to the target organ to deliver functionality that supports high-fidelity sensors and stimulators. The elimination of electrochemical power supplies enables control over device operation, anywhere from acute, to lifetimes matching the target subject with physical dimensions that supports imperceptible operation. This review provides a comprehensive overview of the basic building blocks of battery-free organ interfaces and related topics such as implantation, delivery, sterilization, and user acceptance. State of the art examples categorized by organ system and an outlook of interconnection and advanced strategies for computation leveraging the consistent power influx to elevate functionality of this device class over current battery-powered strategies is highlighted.
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Suministros de Energía Eléctrica , Tecnología Inalámbrica , Prótesis e Implantes , ElectrónicaRESUMEN
Scientists around the world have long aimed to produce miniature robots that can be controlled inside the human body to aid doctors in identifying and treating diseases. Such microrobots hold the potential to access hard-to-reach areas of the body through the natural lumina. Wireless access has the potential to overcome drawbacks of systemic therapy, as well as to enable completely new minimally invasive procedures. The aim of this review is fourfold: first, to provide a collection of valuable anatomical and physiological information on the target working environments together with engineering tools for the design of medical microrobots; second, to provide a comprehensive updated survey of the technological state of the art in relevant classes of medical microrobots; third, to analyze currently available tracking and closed-loop control strategies compatible with the in-body environment; and fourth, to explore the challenges still in place, to steer and inspire future research.
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Diseño de Equipo , Robótica , Humanos , Robótica/instrumentación , Ingeniería Biomédica/métodos , Tecnología Inalámbrica , Procedimientos Quirúrgicos Robotizados/métodos , Procedimientos Quirúrgicos Robotizados/instrumentación , MiniaturizaciónRESUMEN
Evolution of implantable neural interfaces is critical in addressing the challenges in understanding the fundamental working principles and therapeutic applications for central and peripheral nervous systems. Traditional approaches utilizing hermetically sealed, rigid electronics and detached electrodes face challenges in power supply, encapsulation, channel count, dispersed application location, and modality. Employing thin-film, wirelessly powered devices is promising to expand capabilities. Devices that forego bulky power supplies, favoring a configuration where electronics are integrated directly onto thin films, reduce displacement volumes for seamless, fully implantable interfaces with high energy availability and soft mechanics to conform to the neuronal target. We discuss 3 device architectures: (1) Highly miniaturized devices that merge electronics and neural interfaces into a single, injectable format; (2) Interfaces that consolidate power, computation, and neural connectivity on a thin sheet applied directly to the target area; (3) A spatially dislocated approach where power and computation are situated subdermally, connected via a thin interconnect to the neural interface.Each has advantages and constraints in terms of implantation invasiveness, power capturing efficiency, and directional sensitivity of power delivery. In powering these devices, near-field power delivery emerges as the most implemented technique. Key parameters are size and volume of primary and secondary antennas, which determine coupling efficiency and power delivery. Based on application requirements, ranging from small to large animal models, subjects require system level designs. Material strategies play a crucial role; monolithic designs, with materials like polyimide substrates, enable scalability with high performance. This contrasts with established hermetic encapsulation approaches that use a stainless steel or titanium box with passthroughs that result in large tissue displacements and prohibit intimate integration with target organ systems. Encapsulation, particularly with parylene, enables longevity and effectiveness; more research is needed to enable human lifetime operation. Implant-to-ambient device communication, focusing on strategies compatible with well-established standards and off-the-shelf electronics, is discussed with the goal of enabling seamless system integration, reliability, and scalability. The interface with the central nervous system is explored through various wireless, battery-free devices capable of both stimulation (electrical and optogenetic) and recording (photometric and electrochemical). These devices show advanced capabilities for chronic studies and insights into neural dynamics. In the peripheral nervous system, stimulation devices for applications, such as spinal and muscle stimulation, are discussed. The challenges lie in the mechanical and electrochemical durability. Examples that successfully navigate these challenges offer solutions for chronic studies in this domain. The potential of wireless, fully implantable nervous system interfaces using near field resonant power transfer is characterized by monolithically defined device architecture, providing a significant leap toward seamless access to the central and peripheral nervous systems. New avenues for research and therapeutic applications supporting a multimodal and multisite approach to neuromodulation with a high degree of connectivity and a holistic approach toward deciphering and supplementing the nervous system may enable recovery and treatment of injury and chronic disease.
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Tecnología Inalámbrica , Tecnología Inalámbrica/instrumentación , Humanos , Electrodos Implantados , Animales , Suministros de Energía EléctricaRESUMEN
Traditional technologies for virtual reality (VR) and augmented reality (AR) create human experiences through visual and auditory stimuli that replicate sensations associated with the physical world. The most widespread VR and AR systems use head-mounted displays, accelerometers and loudspeakers as the basis for three-dimensional, computer-generated environments that can exist in isolation or as overlays on actual scenery. In comparison to the eyes and the ears, the skin is a relatively underexplored sensory interface for VR and AR technology that could, nevertheless, greatly enhance experiences at a qualitative level, with direct relevance in areas such as communications, entertainment and medicine1,2. Here we present a wireless, battery-free platform of electronic systems and haptic (that is, touch-based) interfaces capable of softly laminating onto the curved surfaces of the skin to communicate information via spatio-temporally programmable patterns of localized mechanical vibrations. We describe the materials, device structures, power delivery strategies and communication schemes that serve as the foundations for such platforms. The resulting technology creates many opportunities for use where the skin provides an electronically programmable communication and sensory input channel to the body, as demonstrated through applications in social media and personal engagement, prosthetic control and feedback, and gaming and entertainment.
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Realidad Aumentada , Diseño de Equipo , Piel , Tacto , Interfaz Usuario-Computador , Realidad Virtual , Tecnología Inalámbrica/instrumentación , Comunicación , Epidermis , Retroalimentación , Femenino , Humanos , Masculino , Prótesis e Implantes , Robótica , Medios de Comunicación Sociales , Vibración , Juegos de VideoRESUMEN
The fast-growing field of bioelectronic medicine aims to develop engineered systems that can relieve clinical conditions by stimulating the peripheral nervous system1-5. This type of technology relies largely on electrical stimulation to provide neuromodulation of organ function or pain. One example is sacral nerve stimulation to treat overactive bladder, urinary incontinence and interstitial cystitis (also known as bladder pain syndrome)4,6,7. Conventional, continuous stimulation protocols, however, can cause discomfort and pain, particularly when treating symptoms that can be intermittent (for example, sudden urinary urgency)8. Direct physical coupling of electrodes to the nerve can lead to injury and inflammation9-11. Furthermore, typical therapeutic stimulators target large nerve bundles that innervate multiple structures, resulting in a lack of organ specificity. Here we introduce a miniaturized bio-optoelectronic implant that avoids these limitations by using (1) an optical stimulation interface that exploits microscale inorganic light-emitting diodes to activate opsins; (2) a soft, high-precision biophysical sensor system that allows continuous measurements of organ function; and (3) a control module and data analytics approach that enables coordinated, closed-loop operation of the system to eliminate pathological behaviours as they occur in real-time. In the example reported here, a soft strain gauge yields real-time information on bladder function in a rat model. Data algorithms identify pathological behaviour, and automated, closed-loop optogenetic neuromodulation of bladder sensory afferents normalizes bladder function. This all-optical scheme for neuromodulation offers chronic stability and the potential to stimulate specific cell types.
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Neuronas/fisiología , Optogenética/instrumentación , Optogenética/métodos , Vejiga Urinaria/inervación , Vejiga Urinaria/fisiología , Tecnología Inalámbrica/instrumentación , Algoritmos , Animales , Células Cultivadas , Electrónica , Femenino , Ganglios Espinales/citología , Humanos , Neuronas/citología , Ratas , Ratas Sprague-Dawley , Raíces Nerviosas Espinales/citologíaRESUMEN
As nitric oxide (NO) plays significant roles in a variety of physiological processes, the capability for real-time and accurate detection of NO in live organisms is in great demand. Traditional assessments of NO rely on indirect colorimetric techniques or electrochemical sensors that often comprise rigid constituent materials and can hardly satisfy sensitivity and spatial resolution simultaneously. Here, we report a flexible and highly sensitive biosensor based on organic electrochemical transistors (OECTs) capable of continuous and wireless detection of NO in biological systems. By modifying the geometry of the active channel and the gate electrodes of OECTs, devices achieve optimum signal amplification of NO. The sensor exhibits a low response limit, a wide linear range, high sensitivity, and excellent selectivity, with a miniaturized active sensing region compared with a conventional electrochemical sensor. The device demonstrates continuous detection of the nanomolar range of NO in cultured cells for hours without significant signal drift. Real-time and wireless measurement of NO is accomplished for 8 d in the articular cavity of New Zealand White rabbits with anterior cruciate ligament (ACL) rupture injuries. The observed high level of NO is associated with the onset of osteoarthritis (OA) at the later stage. The proposed device platform could provide critical information for the early diagnosis of chronic diseases and timely medical intervention to optimize therapeutic efficacy.
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Técnicas Biosensibles , Óxido Nítrico , Osteoartritis , Tecnología Inalámbrica , Animales , Técnicas Biosensibles/métodos , Enfermedad Crónica , Diagnóstico Precoz , Técnicas Electroquímicas/métodos , Electrodos , Óxido Nítrico/análisis , Osteoartritis/diagnóstico , ConejosRESUMEN
We have developed a DNA aptamer-conjugated graphene field-effect transistor (GFET) biosensor platform to detect receptor-binding domain (RBD), nucleocapsid (N), and spike (S) proteins, as well as viral particles of original Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronavirus and its variants in saliva samples. The GFET biosensor is a label-free, rapid (≤20 min), ultrasensitive handheld wireless readout device. The limit of detection (LoD) and the limit of quantitation (LoQ) of the sensor are 1.28 and 3.89 plaque-forming units (PFU)/mL for S protein and 1.45 and 4.39 PFU/mL for N protein, respectively. Cognate spike proteins of major variants of concern (N501Y, D614G, Y453F, Omicron-B1.1.529) showed sensor response ≥40 mV from the control (aptamer alone) for fM to nM concentration range. The sensor response was significantly lower for viral particles and cognate proteins of Middle East Respiratory Syndrome (MERS) compared to SARS-CoV-2, indicating the specificity of the diagnostic platform for SARS-CoV-2 vs. MERS viral proteins. During the early phase of the pandemic, the GFET sensor response agreed with RT-PCR data for oral human samples, as determined by the negative percent agreement (NPA) and positive percent agreement (PPA). During the recent Delta/Omicron wave, the GFET sensor also reliably distinguished positive and negative clinical saliva samples. Although the sensitivity is lower during the later pandemic phase, the GFET-defined positivity rate is in statistically close alignment with the epidemiological population-scale data. Thus, the aptamer-based GFET biosensor has a high level of precision in clinically and epidemiologically significant SARS-CoV-2 variant detection. This universal pathogen-sensing platform is amenable for a broad range of public health applications and real-time environmental monitoring.
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Técnicas Biosensibles , COVID-19 , Grafito , SARS-CoV-2 , Tecnología Inalámbrica , COVID-19/diagnóstico , Humanos , SARS-CoV-2/aislamiento & purificación , Saliva/virología , AutoevaluaciónRESUMEN
Active sampling in the olfactory domain is a fundamental aspect of mouse behavior, and there is increasing evidence that respiration-entrained neural activity outside of the olfactory system sets an important global brain rhythm. It is therefore crucial to accurately measure breathing during natural behaviors. We develop a new approach to do this in freely moving animals, by implanting a telemetry-based pressure sensor into the right jugular vein, which allows for wireless monitoring of thoracic pressure. After verifying this technique against standard head-fixed respiration measurements, we combined it with EEG and EMG recording and used evolving partial coherence analysis to investigate the relationship between respiration and brain activity across a range of experiments in which the mice could move freely. During voluntary exploration of odors and objects, we found that the association between respiration and cortical activity in the delta and theta frequency range decreased, whereas the association between respiration and cortical activity in the alpha range increased. During sleep, however, the presentation of an odor was able to cause a transient increase in sniffing without changing dominant sleep rhythms (delta and theta) in the cortex. Our data align with the emerging idea that the respiration rhythm could act as a synchronizing scaffold for specific brain rhythms during wakefulness and exploration, but suggest that respiratory changes are less able to impact brain activity during sleep. Combining wireless respiration monitoring with different types of brain recording across a variety of behaviors will further increase our understanding of the important links between active sampling, passive respiration, and neural activity.NEW & NOTEWORTHY Animals can alter their respiration rate to actively sample their environment, and increasing evidence suggests that neurons across the brain align their firing to this changing rhythm. We developed a new approach to measure sniffing in freely moving mice while simultaneously recording brain activity, and uncovered how specific cortical rhythms changed their coherence with respiration rhythm during natural behaviors and across arousal states.
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Ratones Endogámicos C57BL , Respiración , Animales , Ratones , Masculino , Tecnología Inalámbrica/instrumentación , Electroencefalografía , Telemetría/instrumentación , Electromiografía , Vigilia/fisiología , Ondas Encefálicas/fisiología , Sueño/fisiologíaRESUMEN
The integration of electrochemistry with nuclear magnetic resonance (NMR) spectroscopy recently offers a powerful approach to understanding oxidative metabolism, detecting reactive intermediates, and predicting biological activities. This combination is particularly effective as electrochemical methods provide excellent mimics of metabolic processes, while NMR spectroscopy offers precise chemical analysis. NMR is already widely utilized in the quality control of pharmaceuticals, foods, and additives and in metabolomic studies. However, the introduction of additional and external connections into the magnet has posed challenges, leading to signal deterioration and limitations in routine measurements. Herein, we report an anti-interference compact in situ electrochemical NMR system (AICISENS). Through a wireless strategy, the compact design allows for the independent and stable operation of electrochemical NMR components with effective interference isolation. Thus, it opens an avenue toward easy integration into in situ platforms, applicable not only to laboratory settings but also to fieldwork. The operability, reliability, and versatility were validated with a series of biomimetic assessments, including measurements of microbial electrochemical systems, functional foods, and simulated drug metabolisms. The robust performance of AICISENS demonstrates its high potential as a powerful analytical tool across diverse applications.