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1.
Nano Lett ; 21(18): 7505-7511, 2021 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-34496209

RESUMO

The rapid spread of viral infections demands early detection strategies to minimize proliferation of the disease. Here, we demonstrate a plasmonic biosensor to detect Dengue virus, which was chosen as a model, via its nonstructural protein NS1 biomarker. The sensor is functionalized with a synthetic single-stranded DNA oligonucleotide and provides high affinity toward NS1 protein present in the virus genome. We demonstrate the detection of NS1 protein at a concentration of 0.1-10 µg/mL in bovine blood using an on-chip microfluidic plasma separator integrated with the plasmonic sensor which covers the clinical threshold of 0.6 µg/mL of high risk of developing Dengue hemorrhagic fever. The conceptual and practical demonstration shows the translation feasibility of these microfluidic optical biosensors for early detection of a wide range of viral infections, providing a rapid clinical diagnosis of infectious diseases directly from minimally processed biological samples at point of care locations.


Assuntos
Vírus da Dengue , Dengue , Animais , Biomarcadores , Bovinos , DNA , Vírus da Dengue/genética , Proteínas não Estruturais Virais
2.
Nat Commun ; 12(1): 5008, 2021 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34429436

RESUMO

Capabilities for continuous monitoring of pressures and temperatures at critical skin interfaces can help to guide care strategies that minimize the potential for pressure injuries in hospitalized patients or in individuals confined to the bed. This paper introduces a soft, skin-mountable class of sensor system for this purpose. The design includes a pressure-responsive element based on membrane deflection and a battery-free, wireless mode of operation capable of multi-site measurements at strategic locations across the body. Such devices yield continuous, simultaneous readings of pressure and temperature in a sequential readout scheme from a pair of primary antennas mounted under the bedding and connected to a wireless reader and a multiplexer located at the bedside. Experimental evaluation of the sensor and the complete system includes benchtop measurements and numerical simulations of the key features. Clinical trials involving two hemiplegic patients and a tetraplegic patient demonstrate the feasibility, functionality and long-term stability of this technology in operating hospital settings.


Assuntos
Técnicas Biossensoriais/métodos , Fontes de Energia Elétrica , Pressão , Temperatura , Tecnologia sem Fio , Adulto , Idoso , Idoso de 80 Anos ou mais , Técnicas Biossensoriais/instrumentação , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Pele , Termografia/instrumentação , Termografia/métodos
3.
Proc Natl Acad Sci U S A ; 118(30)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34301889

RESUMO

Wireless, battery-free, and fully subdermally implantable optogenetic tools are poised to transform neurobiological research in freely moving animals. Current-generation wireless devices are sufficiently small, thin, and light for subdermal implantation, offering some advantages over tethered methods for naturalistic behavior. Yet current devices using wireless power delivery require invasive stimulus delivery, penetrating the skull and disrupting the blood-brain barrier. This can cause tissue displacement, neuronal damage, and scarring. Power delivery constraints also sharply curtail operational arena size. Here, we implement highly miniaturized, capacitive power storage on the platform of wireless subdermal implants. With approaches to digitally manage power delivery to optoelectronic components, we enable two classes of applications: transcranial optogenetic activation millimeters into the brain (validated using motor cortex stimulation to induce turning behaviors) and wireless optogenetics in arenas of more than 1 m2 in size. This methodology allows for previously impossible behavioral experiments leveraging the modern optogenetic toolkit.

4.
Nat Neurosci ; 24(7): 1035-1045, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33972800

RESUMO

Advanced technologies for controlled delivery of light to targeted locations in biological tissues are essential to neuroscience research that applies optogenetics in animal models. Fully implantable, miniaturized devices with wireless control and power-harvesting strategies offer an appealing set of attributes in this context, particularly for studies that are incompatible with conventional fiber-optic approaches or battery-powered head stages. Limited programmable control and narrow options in illumination profiles constrain the use of existing devices. The results reported here overcome these drawbacks via two platforms, both with real-time user programmability over multiple independent light sources, in head-mounted and back-mounted designs. Engineering studies of the optoelectronic and thermal properties of these systems define their capabilities and key design considerations. Neuroscience applications demonstrate that induction of interbrain neuronal synchrony in the medial prefrontal cortex shapes social interaction within groups of mice, highlighting the power of real-time subject-specific programmability of the wireless optogenetic platforms introduced here.


Assuntos
Optogenética/instrumentação , Comportamento Social , Tecnologia sem Fio/instrumentação , Animais , Camundongos
5.
Sci Adv ; 7(12)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33731359

RESUMO

Three-dimensional (3D), submillimeter-scale constructs of neural cells, known as cortical spheroids, are of rapidly growing importance in biological research because these systems reproduce complex features of the brain in vitro. Despite their great potential for studies of neurodevelopment and neurological disease modeling, 3D living objects cannot be studied easily using conventional approaches to neuromodulation, sensing, and manipulation. Here, we introduce classes of microfabricated 3D frameworks as compliant, multifunctional neural interfaces to spheroids and to assembloids. Electrical, optical, chemical, and thermal interfaces to cortical spheroids demonstrate some of the capabilities. Complex architectures and high-resolution features highlight the design versatility. Detailed studies of the spreading of coordinated bursting events across the surface of an isolated cortical spheroid and of the cascade of processes associated with formation and regrowth of bridging tissues across a pair of such spheroids represent two of the many opportunities in basic neuroscience research enabled by these platforms.

6.
Sci Adv ; 7(7)2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33568482

RESUMO

Accurate, real-time monitoring of intravascular oxygen levels is important in tracking the cardiopulmonary health of patients after cardiothoracic surgery. Existing technologies use intravascular placement of glass fiber-optic catheters that pose risks of blood vessel damage, thrombosis, and infection. In addition, physical tethers to power supply systems and data acquisition hardware limit freedom of movement and add clutter to the intensive care unit. This report introduces a wireless, miniaturized, implantable optoelectronic catheter system incorporating optical components on the probe, encapsulated by soft biocompatible materials, as alternative technology that avoids these disadvantages. The absence of physical tethers and the flexible, biocompatible construction of the probe represent key defining features, resulting in a high-performance, patient-friendly implantable oximeter that can monitor localized tissue oxygenation, heart rate, and respiratory activity with wireless, real-time, continuous operation. In vitro and in vivo testing shows that this platform offers measurement accuracy and precision equivalent to those of existing clinical standards.

8.
Nat Commun ; 11(1): 5990, 2020 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-33239608

RESUMO

Bioresorbable electronic stimulators are of rapidly growing interest as unusual therapeutic platforms, i.e., bioelectronic medicines, for treating disease states, accelerating wound healing processes and eliminating infections. Here, we present advanced materials that support operation in these systems over clinically relevant timeframes, ultimately bioresorbing harmlessly to benign products without residues, to eliminate the need for surgical extraction. Our findings overcome key challenges of bioresorbable electronic devices by realizing lifetimes that match clinical needs. The devices exploit a bioresorbable dynamic covalent polymer that facilitates tight bonding to itself and other surfaces, as a soft, elastic substrate and encapsulation coating for wireless electronic components. We describe the underlying features and chemical design considerations for this polymer, and the biocompatibility of its constituent materials. In devices with optimized, wireless designs, these polymers enable stable, long-lived operation as distal stimulators in a rat model of peripheral nerve injuries, thereby demonstrating the potential of programmable long-term electrical stimulation for maintaining muscle receptivity and enhancing functional recovery.


Assuntos
Implantes Absorvíveis , Terapia por Estimulação Elétrica/instrumentação , Traumatismos dos Nervos Periféricos/terapia , Poliuretanos/química , Tecnologia sem Fio/instrumentação , Animais , Modelos Animais de Doenças , Terapia por Estimulação Elétrica/métodos , Feminino , Humanos , Teste de Materiais , Músculo Esquelético/inervação , Músculo Esquelético/fisiologia , Ratos , Regeneração , Nervo Isquiático/lesões , Nervo Isquiático/fisiologia
9.
Nat Neurosci ; 23(12): 1522-1536, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33199897

RESUMO

Interest in deciphering the fundamental mechanisms and processes of the human mind represents a central driving force in modern neuroscience research. Activities in support of this goal rely on advanced methodologies and engineering systems that are capable of interrogating and stimulating neural pathways, from single cells in small networks to interconnections that span the entire brain. Recent research establishes the foundations for a broad range of creative neurotechnologies that enable unique modes of operation in this context. This review focuses on those systems with proven utility in animal model studies and with levels of technical maturity that suggest a potential for broad deployment to the neuroscience community in the relatively near future. We include a brief summary of existing and emerging neuroscience techniques, as background for a primary focus on device technologies that address associated opportunities in electrical, optical and microfluidic neural interfaces, some with multimodal capabilities. Examples of the use of these technologies in recent neuroscience studies illustrate their practical value. The vibrancy of the engineering science associated with these platforms, the interdisciplinary nature of this field of research and its relevance to grand challenges in the treatment of neurological disorders motivate continued growth of this area of study.


Assuntos
Neurociências/tendências , Tecnologia/tendências , Animais , Encéfalo/fisiologia , Estimulação Elétrica/instrumentação , Estimulação Elétrica/métodos , Humanos , Neurociências/métodos , Optogenética/tendências , Farmacologia/métodos , Pesquisa
10.
Proc Natl Acad Sci U S A ; 117(6): 2835-2845, 2020 02 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.


Assuntos
Encéfalo/fisiologia , Fotometria/métodos , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/cirurgia , Desenho de Equipamento , Imageamento por Ressonância Magnética , Camundongos , Camundongos Endogâmicos C57BL , Fotometria/instrumentação , Próteses e Implantes , Tecnologia sem Fio/instrumentação
11.
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.


Assuntos
Realidade Aumentada , Desenho de Equipamento , Pele , Tato , Interface Usuário-Computador , Realidade Virtual , Tecnologia sem Fio/instrumentação , Comunicação , Epiderme , Retroalimentação , Feminino , Humanos , Masculino , Próteses e Implantes , Robótica , Mídias Sociais , Vibração , Jogos de Vídeo
12.
Proc Natl Acad Sci U S A ; 116(43): 21427-21437, 2019 10 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.


Assuntos
Optogenética/métodos , Farmacologia/métodos , Animais , Encéfalo/metabolismo , Química Encefálica , Channelrhodopsins/metabolismo , Estimulação Elétrica , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Optogenética/instrumentação , Farmacologia/instrumentação , Próteses e Implantes , Tecnologia sem Fio/instrumentação
13.
Proc Natl Acad Sci U S A ; 116(27): 13239-13248, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31217291

RESUMO

Recently developed methods in mechanically guided assembly provide deterministic access to wide-ranging classes of complex, 3D structures in high-performance functional materials, with characteristic length scales that can range from nanometers to centimeters. These processes exploit stress relaxation in prestretched elastomeric platforms to affect transformation of 2D precursors into 3D shapes by in- and out-of-plane translational displacements. This paper introduces a scheme for introducing local twisting deformations into this process, thereby providing access to 3D mesostructures that have strong, local levels of chirality and other previously inaccessible geometrical features. Here, elastomeric assembly platforms segmented into interconnected, rotatable units generate in-plane torques imposed through bonding sites at engineered locations across the 2D precursors during the process of stress relaxation. Nearly 2 dozen examples illustrate the ideas through a diverse variety of 3D structures, including those with designs inspired by the ancient arts of origami/kirigami and with layouts that can morph into different shapes. A mechanically tunable, multilayered chiral 3D metamaterial configured for operation in the terahertz regime serves as an application example guided by finite-element analysis and electromagnetic modeling.

14.
Sci Adv ; 5(3): eaaw0873, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30873435

RESUMO

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.


Assuntos
Fontes de Energia Elétrica , Oximetria/instrumentação , Próteses e Implantes , Tecnologia sem Fio/instrumentação , Animais , Substitutos Sanguíneos/análise , Corpo Estriado/metabolismo , Corpo Estriado/cirurgia , Hipóxia/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Oxigênio/análise , Ratos , Ratos Sprague-Dawley , Materiais Inteligentes
15.
Nano Lett ; 19(1): 449-454, 2019 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-30525676

RESUMO

Complex biological fluids without pretreatment, separation, or purification impose stringent limitations on the practical deployment of label-free plasmonic biosensors for advanced assays needed in point of care applications. In this work, we present an enzyme-free plasmonic neurotransmitter dopamine biosensor integrated with a microfluidic plasma separator. This integrated device allows the in-line separation of plasma directly from the bloodstream and channels it to the active detection area, where inorganic cerium oxide nanoparticles function as local selective dopamine binding sites through strong surface redox reaction. A thorough understanding and engineering of the nanoparticles is carried out to maximize its dopamine sensitivity and selectivity. We obtain detection of dopamine at 100 fM concentration in simulated body fluid and 1 nM directly from blood without any prior sample preparation. The detection selectivity is found to be at least five-times higher compared to the common interfering species. This demonstration shows the feasibility of the practical implementation of the proposed plasmonic system in detection of variety of biomarkers directly from the complex biological fluids.


Assuntos
Técnicas Biossensoriais , Dopamina/isolamento & purificação , Nanopartículas/química , Neurotransmissores/isolamento & purificação , Ácido 3,4-Di-Hidroxifenilacético/química , Cério/química , Dopamina/sangue , Humanos , Neurotransmissores/sangue
16.
Opt Lett ; 43(24): 6001-6004, 2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-30547990

RESUMO

Photonic microcavity coupling of a subwavelength hole-disk array, a two-element metal/dielectric composite structure with enhanced extraordinary transmission, leads to 100% coupling of incident light to the cavity system and subsequent absorption. This light-funneling process arises from the temporal and spatial coupling of the broadband localized surface plasmon resonance on the coupled hole-disk array and the photonic modes of the optical cavity, which induces spectral narrowing of the perfect absorption of light. A simple nanoimprint lithography-based large-area fabrication process paves the path towards practical implementation of plasmonic cavity-based devices and sensors.

17.
Light Sci Appl ; 7: 93, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30479759

RESUMO

Functional surfaces that can control light across the electromagnetic spectrum are highly desirable. Plasmonic nanostructures can assume this role by exhibiting dimension-tunable resonances that span multiple electromagnetic regimes. However, changing these structural parameters often impacts the higher-order resonances and spectral features in lower-wavelength domains. In this study, we discuss a cavity-coupled plasmonic system with resonances that are tunable across the 3-5 or 8-14 µm infrared bands while retaining near-invariant spectral properties in the visible domain. This result is accomplished by regime-dependent resonance mechanisms and their dependence on independent structural parameters. Through the identification and constraint of key parameters, we demonstrate multispectral data encoding, where images, viewable in the infrared spectral domain, appear as uniform areas of color in the visible domain-effectively hiding the information. Fabricated by large area nanoimprint lithography and compatible with flexible surfaces, the proposed system can produce multifunctional coatings for thermal management, camouflage, and anti-counterfeiting.

18.
Phys Rev Lett ; 120(13): 137601, 2018 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-29694216

RESUMO

A novel route of superchiral near-field generation is demonstrated based on geometrically achiral systems supporting degenerate and spatially superimposed plasmonic modes. Such systems generate a single-handed chiral near field with simultaneous zero far-field circular dichroism. The phenomenon is theoretically elucidated with a rotating dipole model, which predicts a uniform single-handed chiral near field that flips handedness solely by reversing the handedness of the source. This property allows detection of pure background free molecular chirality through near-field light-matter interaction, which is experimentally demonstrated in the precise identification of both handedness of a chiral molecule on a single substrate with about four orders of magnitude enhancement in detection sensitivity compared to its conventional volumetric counterpart.

19.
Proc Natl Acad Sci U S A ; 115(7): E1374-E1383, 2018 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-29378934

RESUMO

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.


Assuntos
Encéfalo/fisiologia , Estimulação Encefálica Profunda/métodos , Neurônios/fisiologia , Optogenética/instrumentação , Estimulação Luminosa/instrumentação , Tecnologia sem Fio , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fibras Ópticas
20.
Opt Express ; 26(25): 32931-32940, 2018 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-30645453

RESUMO

Frequency selective detection of low energy photons is a scientific challenge using natural materials. A hypothetical surface which functions like a light funnel with very low thermal mass in order to enhance photon collection and suppress background thermal noise is the ideal solution to address both low temperature and frequency selective detection limitations of present detection systems. Here, we present a cavity-coupled quasi-three dimensional plasmonic crystal which induces impedance matching to the free space giving rise to extraordinary transmission through the sub-wavelength aperture array like a "light funnel" in coupling low energy incident photons resulting in frequency selective perfect (~100%) absorption of the incident radiation and zero back reflection. The peak wavelength of absorption of the incident light is almost independent of the angle of incidence and remains within 20% of its maximum (100%) up to θi≤45˚. This perfect absorption results from the incident light-driven localized edge "micro-plasma" currents on the lossy metallic surfaces. The wide-angle light funneling is validated with experimental measurements. Further, a super-lattice based electronic biasing circuit converts the absorbed narrow linewidth (Δλ/λ0< 0.075) photon energy inside the sub-wavelength thick film (< λ/100) to voltage output with high signal to noise ratio close to the theoretical limit. Such artificial plasmonic surfaces enable flexible scaling of light funneling response to any wavelength range by simple dimensional changes paving the path towards room temperature frequency selective low energy photon detection.

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