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1.
Nat Commun ; 11(1): 1466, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32193428

RESUMO

The positive or negative value (valence) of past experiences is normally integrated into neuronal circuits that encode episodic memories and plays an important role in guiding behavior. Here, we show, using mouse behavioral models, that glutamatergic afferents from the ventral tegmental area to the dorsal hippocampus (VTA→DH) signal negative valence to memory circuits, leading to the formation of fear-inducing context memories and to context-specific reinstatement of fear. To a lesser extent, these projections also contributed to opioid-induced place preference, suggesting a role in signaling positive valence as well, and thus a lack of dedicated polarity. Manipulations of VTA terminal activity were more effective in females and paralleled by sex differences in glutamatergic signaling. By prioritizing retrieval of negative and positive over neutral memories, the VTA→DH circuit can facilitate the selection of adaptive behaviors when current and past experiences are valence congruent.

2.
Cell ; 181(1): 115-135, 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32220309

RESUMO

Techniques for neuromodulation serve as effective routes to care of patients with many types of challenging conditions. Continued progress in this field of medicine will require (1) improvements in our understanding of the mechanisms of neural control over organ function and (2) advances in technologies for precisely modulating these functions in a programmable manner. This review presents recent research on devices that are relevant to both of these goals, with an emphasis on multimodal operation, miniaturized dimensions, biocompatible designs, advanced neural interface schemes, and battery-free, wireless capabilities. A future that involves recording and modulating neural activity with such systems, including those that exploit closed-loop strategies and/or bioresorbable designs, seems increasingly within reach.

3.
Adv Mater ; : e1908424, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32100406

RESUMO

Deterministic transformations of 2D patterns of materials into well-controlled 3D mesostructures serve as the basis for manufacturing methods that can bypass limitations of conventional 3D micro/nanofabrication. Here, guided mechanical buckling processes provide access to a rich range of complex 3D mesostructures in high-performance materials, from inorganic and organic semiconductors, metals and dielectrics, to ceramics and even 2D materials (e.g., graphene, MoS2 ). Previous studies demonstrate that iterative computational procedures can define design parameters for certain targeted 3D configurations, but without the ability to address complex shapes. A technical need is in efficient, generalized inverse design algorithms that directly yield sets of optimized parameters. Here, such schemes are introduced, where the distributions of thicknesses across arrays of separated or interconnected ribbons provide scalable routes to 3D surfaces with a broad range of targeted shapes. Specifically, discretizing desired shapes into 2D ribbon components allows for analytic solutions to the inverse design of centrally symmetric and even general surfaces, in an approximate manner. Combined theoretical, numerical, and experimental studies of ≈20 different 3D structures with characteristic sizes (e.g., ribbon width) ranging from ≈200 µm to ≈2 cm and with geometries that resemble hemispheres, fire balloons, flowers, concave lenses, saddle surfaces, waterdrops, and rodents, illustrate the essential ideas.

4.
Proc Natl Acad Sci U S A ; 117(6): 2835-2845, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-31974306

RESUMO

Recording cell-specific neuronal activity while monitoring behaviors of freely moving subjects can provide some of the most significant insights into brain function. Current means for monitoring calcium dynamics in genetically targeted populations of neurons rely on delivery of light and recording of fluorescent signals through optical fibers that can reduce subject mobility, induce motion artifacts, and limit experimental paradigms to isolated subjects in open, two-dimensional (2D) spaces. Wireless alternatives eliminate constraints associated with optical fibers, but their use of head stages with batteries adds bulk and weight that can affect behaviors, with limited operational lifetimes. The systems introduced here avoid drawbacks of both types of technologies, by combining highly miniaturized electronics and energy harvesters with injectable photometric modules in a class of fully wireless, battery-free photometer that is fully implantable subdermally to allow for the interrogation of neural dynamics in freely behaving subjects, without limitations set by fiber optic tethers or operational lifetimes constrained by traditional power supplies. The unique capabilities of these systems, their compatibility with magnetic resonant imaging and computed tomography and the ability to manufacture them with techniques in widespread use for consumer electronics, suggest a potential for broad adoption in neuroscience research.

5.
Nat Biomed Eng ; 4(2): 148-158, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31768002

RESUMO

Skin-mounted soft electronics that incorporate high-bandwidth triaxial accelerometers can capture broad classes of physiologically relevant information, including mechano-acoustic signatures of underlying body processes (such as those measured by a stethoscope) and precision kinematics of core-body motions. Here, we describe a wireless device designed to be conformally placed on the suprasternal notch for the continuous measurement of mechano-acoustic signals, from subtle vibrations of the skin at accelerations of around 10-3 m s-2 to large motions of the entire body at about 10 m s-2, and at frequencies up to around 800 Hz. Because the measurements are a complex superposition of signals that arise from locomotion, body orientation, swallowing, respiration, cardiac activity, vocal-fold vibrations and other sources, we exploited frequency-domain analysis and machine learning to obtain-from human subjects during natural daily activities and exercise-real-time recordings of heart rate, respiration rate, energy intensity and other essential vital signs, as well as talking time and cadence, swallow counts and patterns, and other unconventional biomarkers. We also used the device in sleep laboratories and validated the measurements using polysomnography.

6.
Lab Chip ; 20(1): 84-92, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31776526

RESUMO

Eccrine sweat is a rich and largely unexplored biofluid that contains a range of important biomarkers, from electrolytes, metabolites, micronutrients and hormones to exogenous agents, each of which can change in concentration with diet, stress level, hydration status and physiologic or metabolic state. Traditionally, clinicians and researchers have used absorbent pads and benchtop analyzers to collect and analyze the biochemical constituents of sweat in controlled, laboratory settings. Recently reported wearable microfluidic and electrochemical sensing devices represent significant advances in this context, with capabilities for rapid, in situ evaluations, in many cases with improved repeatability and accuracy. A limitation is that assays performed in these platforms offer limited control of reaction kinetics and mixing of different reagents and samples. Here, we present a multi-layered microfluidic device platform with designs that eliminate these constraints, to enable integrated enzymatic assays with demonstrations of in situ analysis of the concentrations of ammonia and ethanol in microliter volumes of sweat. Careful characterization of the reaction kinetics and their optimization using statistical techniques yield robust analysis protocols. Human subject studies with sweat initiated by warm-water bathing highlight the operational features of these systems.

7.
ACS Sens ; 5(1): 13-18, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31833351

RESUMO

Environmental hazards typically are encountered in the gaseous phase; however, selective sensing modalities for identifying and quantitating compounds of interest in an inexpensive, pseudo-real-time format are severely lacking. Here, we present a novel proof-of-concept that combines an Air2Liquid sampler in conjunction with an oil-in-water microfluidic assay for detection of organophosphates. We believe this proof-of-concept will enable development of a new platform technology for semivolatile detection that we have demonstrated to detect 50 pmoles (2 ppb) of neurotoxic organophosphates.

8.
Nat Commun ; 10(1): 5513, 2019 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-31797921

RESUMO

Recently introduced classes of thin, soft, skin-mounted microfluidic systems offer powerful capabilities for continuous, real-time monitoring of total sweat loss, sweat rate and sweat biomarkers. Although these technologies operate without the cost, complexity, size, and weight associated with active components or power sources, rehydration events can render previous measurements irrelevant and detection of anomalous physiological events, such as high sweat loss, requires user engagement to observe colorimetric responses. Here we address these limitations through monolithic systems of pinch valves and suction pumps for purging of sweat as a reset mechanism to coincide with hydration events, microstructural optics for reversible readout of sweat loss, and effervescent pumps and chemesthetic agents for automated delivery of sensory warnings of excessive sweat loss. Human subject trials demonstrate the ability of these systems to alert users to the potential for dehydration via skin sensations initiated by sweat-triggered ejection of menthol and capsaicin.

9.
Sci Adv ; 5(12): eaay2462, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31853499

RESUMO

Exposure to electromagnetic radiation (EMR) from the sun and from artificial lighting systems represents a modifiable risk factor for a broad range of health conditions including skin cancer, skin aging, sleep and mood disorders, and retinal damage. Technologies for personalized EMR dosimetry could guide lifestyles toward behaviors that ensure healthy levels of exposure. Here, we report a millimeter-scale, ultralow-power digital dosimeter platform that provides continuous EMR dosimetry in an autonomous mode at one or multiple wavelengths simultaneously, with time-managed wireless, long-range communication to standard consumer devices. A single, small button cell battery supports a multiyear life span, enabled by the combined use of a light-powered, accumulation mode of detection and a light-adaptive, ultralow-power circuit design. Field studies demonstrate single- and multimodal dosimetry platforms of this type, with a focus on monitoring short-wavelength blue light from indoor lighting and display systems and ultraviolet/visible/infrared radiation from the sun.

10.
Nat Commun ; 10(1): 5742, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31848334

RESUMO

Small animals support a wide range of pathological phenotypes and genotypes as versatile, affordable models for pathogenesis of cardiovascular diseases and for exploration of strategies in electrotherapy, gene therapy, and optogenetics. Pacing tools in such contexts are currently limited to tethered embodiments that constrain animal behaviors and experimental designs. Here, we introduce a highly miniaturized wireless energy-harvesting and digital communication electronics for thin, miniaturized pacing platforms weighing 110 mg with capabilities for subdermal implantation and tolerance to over 200,000 multiaxial cycles of strain without degradation in electrical or optical performance. Multimodal and multisite pacing in ex vivo and in vivo studies over many days demonstrate chronic stability and excellent biocompatibility. Optogenetic stimulation of cardiac cycles with in-animal control and induction of heart failure through chronic pacing serve as examples of modes of operation relevant to fundamental and applied cardiovascular research and biomedical technology.

11.
Opt Express ; 27(20): A1467-A1480, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31684499

RESUMO

Optical concentration can improve the efficiency and reduce the cost of photovoltaic power but has traditionally been too bulky, massive, and unreliable for use in space. Here, we explore a new ultra-compact and low-mass microcell concentrating photovoltaic (µCPV) paradigm for space based on the monolithic integration of transfer-printed microscale solar cells and molded microconcentrator optics. We derive basic bounds on the compactness as a function of geometric concentration ratio and angular acceptance, and show that a simple reflective parabolic concentrator provides the best combination of specific power, angular acceptance, and overall fabrication simplicity. This architecture is simulated in detail and validated experimentally with a µCPV prototype that is less than 1.7 mm thick and operates with six, 650 µm square triple-junction microcells at a geometric concentration ratio of 18.4×. In outdoor testing, the system achieves a terrestrial power conversion efficiency of 25.8 ± 0.2% over a ±9.5° angular range, resulting in a specific power of approximately 111 W/kg. These results lay the groundwork for future space µCPV systems and establish a realistic path to exceed 350 W/kg specific power at >33% power conversion efficiency by scaling down to even smaller microcells.

12.
Adv Mater ; 31(52): e1905715, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31721341

RESUMO

3D structures that incorporate high-performance electronic materials and allow for remote, on-demand 3D shape reconfiguration are of interest for applications that range from ingestible medical devices and microrobotics to tunable optoelectronics. Here, materials and design approaches are introduced for assembly of such systems via controlled mechanical buckling of 2D precursors built on shape-memory polymer (SMP) substrates. The temporary shape fixing and recovery of SMPs, governed by thermomechanical loading, provide deterministic control over the assembly and reconfiguration processes, including a range of mechanical manipulations facilitated by the elastic and highly stretchable properties of the materials. Experimental demonstrations include 3D mesostructures of various geometries and length scales, as well as 3D aquatic platforms that can change trajectories and release small objects on demand. The results create many opportunities for advanced, programmable 3D microsystem technologies.

13.
Nature ; 575(7783): 473-479, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31748722

RESUMO

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.

14.
Sensors (Basel) ; 19(20)2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31635375

RESUMO

Gait and balance impairments are linked with reduced mobility and increased risk of falling. Wearable sensing technologies, such as inertial measurement units (IMUs), may augment clinical assessments by providing continuous, high-resolution data. This study tested and validated the utility of a single IMU to quantify gait and balance features during routine clinical outcome tests, and evaluated changes in sensor-derived measurements with age, sex, height, and weight. Age-ranged, healthy individuals (N = 49, 20-70 years) wore a lower back IMU during the 10 m walk test (10MWT), Timed Up and Go (TUG), and Berg Balance Scale (BBS). Spatiotemporal gait parameters computed from the sensor data were validated against gold standard measures, demonstrating excellent agreement for stance time, step time, gait velocity, and step count (intraclass correlation (ICC) > 0.90). There was good agreement for swing time (ICC = 0.78) and moderate agreement for step length (ICC = 0.68). A total of 184 features were calculated from the acceleration and angular velocity signals across these tests, 36 of which had significant correlations with age. This approach was also demonstrated for an individual with stroke, providing higher resolution information about balance, gait, and mobility than the clinical test scores alone. Leveraging mobility data from wireless, wearable sensors can help clinicians and patients more objectively pinpoint impairments, track progression, and set personalized goals during and after rehabilitation.

15.
Adv Mater ; 31(48): e1905405, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31595583

RESUMO

Most natural materials expand uniformly in all directions upon heating. Artificial, engineered systems offer opportunities to tune thermal expansion properties in interesting ways. Previous reports exploit diverse design principles and fabrication techniques to achieve a negative or ultralow coefficient of thermal expansion, but very few demonstrate tunability over different behaviors. This work presents a collection of 2D material structures that exploit bimaterial serpentine lattices with micrometer feature sizes as the basis of a mechanical metamaterials system capable of supporting positive/negative, isotropic/anisotropic, and homogeneous/heterogeneous thermal expansion properties, with additional features in unusual shearing, bending, and gradient modes of thermal expansion. Control over the thermal expansion tensor achieved in this way provides a continuum-mechanics platform for advanced strain-field engineering, including examples of 2D metamaterials that transform into 3D surfaces upon heating. Integrated electrical and optical sources of thermal actuation provide capabilities for reversible shape reconfiguration with response times of less than 1 s, as the basis of dynamically responsive metamaterials.

16.
Proc Natl Acad Sci U S A ; 116(43): 21427-21437, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31601737

RESUMO

Pharmacology and optogenetics are widely used in neuroscience research to study the central and peripheral nervous systems. While both approaches allow for sophisticated studies of neural circuitry, continued advances are, in part, hampered by technology limitations associated with requirements for physical tethers that connect external equipment to rigid probes inserted into delicate regions of the brain. The results can lead to tissue damage and alterations in behavioral tasks and natural movements, with additional difficulties in use for studies that involve social interactions and/or motions in complex 3-dimensional environments. These disadvantages are particularly pronounced in research that demands combined optogenetic and pharmacological functions in a single experiment. Here, we present a lightweight, wireless, battery-free injectable microsystem that combines soft microfluidic and microscale inorganic light-emitting diode probes for programmable pharmacology and optogenetics, designed to offer the features of drug refillability and adjustable flow rates, together with programmable control over the temporal profiles. The technology has potential for large-scale manufacturing and broad distribution to the neuroscience community, with capabilities in targeting specific neuronal populations in freely moving animals. In addition, the same platform can easily be adapted for a wide range of other types of passive or active electronic functions, including electrical stimulation.

17.
Adv Mater ; 31(42): e1902739, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31489737

RESUMO

Transient forms of electronics, systems that disintegrate, dissolve, resorb, or sublime in a controlled manner after a well-defined operating lifetime, are of interest for applications in hardware secure technologies, temporary biomedical implants, "green" consumer devices and other areas that cannot be addressed with conventional approaches. Broad sets of materials now exist for a range of transient electronic components, including transistors, diodes, antennas, sensors, and even batteries. This work reports the first examples of transient light-emitting diodes (LEDs) that can completely dissolve in aqueous solutions to biologically and environmentally benign end products. Thin films of highly textured ZnO and polycrystalline Mo serve as semiconductors for light generation and conductors for transparent electrodes, respectively. The emitted light spans a range of visible wavelengths, where nanomembranes of monocrystalline silicon can serve as transient filters to yield red, green, and blue LEDs. Detailed characterization of the material chemistries and morphologies of the constituent layers, assessments of their performance properties, and studies of their dissolution processes define the underlying aspects. These results establish an electroluminescent light source technology for unique classes of optoelectronic systems that vanish into benign forms when exposed to aqueous conditions in the environment or in living organisms.


Assuntos
Semicondutores , Molibdênio/química , Fenômenos Ópticos , Solubilidade , Água/química , Óxido de Zinco/química
18.
Adv Mater ; : e1902767, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31490582

RESUMO

Combined advances in material science, mechanical engineering, and electrical engineering form the foundations of thin, soft electronic/optoelectronic platforms that have unique capabilities in wireless monitoring and control of various biological processes in cells, tissues, and organs. Miniaturized, stretchable antennas represent an essential link between such devices and external systems for control, power delivery, data processing, and/or communication. Applications typically involve a demanding set of considerations in performance, size, and stretchability. Some of the most effective strategies rely on unusual materials such as liquid metals, nanowires, and woven textiles or on optimally configured 2D/3D structures such as serpentines and helical coils of conventional materials. In the best cases, the performance metrics of small, stretchable, radio frequency (RF) antennas realized using these strategies compare favorably to those of traditional devices. Examples range from dipole, monopole, and patch antennas for far-field RF operation, to magnetic loop antennas for near-field communication (NFC), where the key parameters include operating frequency, Q factor, radiation pattern, and reflection coefficient S11 across a range of mechanical deformations and cyclic loads. Despite significant progress over the last several years, many challenges and associated research opportunities remain in the development of high-efficiency antennas for biointegrated electronic/optoelectronic systems.

19.
Nat Biomed Eng ; 3(8): 644-654, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31391594

RESUMO

Capabilities in real-time monitoring of internal physiological processes could inform pharmacological drug-delivery schedules, surgical intervention procedures and the management of recovery and rehabilitation. Current methods rely on external imaging techniques or implantable sensors, without the ability to provide continuous information over clinically relevant timescales, and/or with requirements in surgical procedures with associated costs and risks. Here, we describe injectable classes of photonic devices, made entirely of materials that naturally resorb and undergo clearance from the body after a controlled operational lifetime, for the spectroscopic characterization of targeted tissues and biofluids. As an example application, we show that the devices can be used for the continuous monitoring of cerebral temperature, oxygenation and neural activity in freely moving mice. These types of devices should prove useful in fundamental studies of disease pathology, in neuroscience research, in surgical procedures and in monitoring of recovery from injury or illness.

20.
ACS Nano ; 13(10): 11572-11581, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31433939

RESUMO

Implantable electronics are of great interest owing to their capability for real-time and continuous recording of cellular-electrical activity. Nevertheless, as such systems involve direct interfaces with surrounding biofluidic environments, maintaining their long-term sustainable operation, without leakage currents or corrosion, is a daunting challenge. Herein, we present a thin, flexible semiconducting material system that offers attractive attributes in this context. The material consists of crystalline cubic silicon carbide nanomembranes grown on silicon wafers, released and then physically transferred to a final device substrate (e.g., polyimide). The experimental results demonstrate that SiC nanomembranes with thicknesses of 230 nm do not experience the hydrolysis process (i.e., the etching rate is 0 nm/day at 96 °C in phosphate-buffered saline (PBS)). There is no observable water permeability for at least 60 days in PBS at 96 °C and non-Na+ ion diffusion detected at a thickness of 50 nm after being soaked in 1× PBS for 12 days. These properties enable Faradaic interfaces between active electronics and biological tissues, as well as multimodal sensing of temperature, strain, and other properties without the need for additional encapsulating layers. These findings create important opportunities for use of flexible, wide band gap materials as essential components of long-lived neurological and cardiac electrophysiological device interfaces.

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