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1.
Sci Rep ; 11(1): 20258, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34642363

RESUMO

Direct-current generators, especially those based on the Schottky contacts between conductive polymers and metal electrodes, are efficient in converting mechanical stimuli into electrical energy. In contrast to triboelectric and piezoelectric generators, direct-current generators readily produce direct-current outputs and high currents that are crucial for integrating multiple energy-harvesting units in large scale and driving some types of devices. We are focusing on the relationship between Schottky barrier height and performance, systematically investigating the effects of various conductive polymers and electrodes on the outputs by both theoretical simulation and experiments. Tailoring the Schottky barrier height between conductive polymers and metal electrodes is demonstrated a significant approach to design the new DC generators. The preparation method of electrochemical deposition endows the generators flexibility, the linear relationship of current/voltage output vs. strain applied on the generators, combined with the large outputs offer advantages for the generator to work as flexible sensors. Furthermore, a mechanosensation-active matrix array based on direct-current generator for the strain monitoring demonstrated its promising prospects in flexible electronics. The direct-current generators with improved performance could serve as a stream new blood for versatile sensory systems and human-machine interactive interfaces.

3.
Int J Mol Sci ; 22(13)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201700

RESUMO

DNA repair ensures genomic stability to achieve healthy ageing, including cognitive maintenance. Mutations on genes encoding key DNA repair proteins can lead to diseases with accelerated ageing phenotypes. Some of these diseases are xeroderma pigmentosum group A (XPA, caused by mutation of XPA), Cockayne syndrome group A and group B (CSA, CSB, and are caused by mutations of CSA and CSB, respectively), ataxia-telangiectasia (A-T, caused by mutation of ATM), and Werner syndrome (WS, with most cases caused by mutations in WRN). Except for WS, a common trait of the aforementioned progerias is neurodegeneration. Evidence from studies using animal models and patient tissues suggests that the associated DNA repair deficiencies lead to depletion of cellular nicotinamide adenine dinucleotide (NAD+), resulting in impaired mitophagy, accumulation of damaged mitochondria, metabolic derailment, energy deprivation, and finally leading to neuronal dysfunction and loss. Intriguingly, these features are also observed in Alzheimer's disease (AD), the most common type of dementia affecting more than 50 million individuals worldwide. Further studies on the mechanisms of the DNA repair deficient premature ageing diseases will help to unveil the mystery of ageing and may provide novel therapeutic strategies for AD.


Assuntos
Envelhecimento/patologia , Doença de Alzheimer/complicações , Dano ao DNA , Instabilidade Genômica , Doenças Neurodegenerativas/patologia , Animais , Reparo do DNA , Humanos , Mutação , Doenças Neurodegenerativas/etiologia
4.
Proc Natl Acad Sci U S A ; 118(19)2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33941674

RESUMO

Tissue-on-chip systems represent promising platforms for monitoring and controlling tissue functions in vitro for various purposes in biomedical research. The two-dimensional (2D) layouts of these constructs constrain the types of interactions that can be studied and limit their relevance to three-dimensional (3D) tissues. The development of 3D electronic scaffolds and microphysiological devices with geometries and functions tailored to realistic 3D tissues has the potential to create important possibilities in advanced sensing and control. This study presents classes of compliant 3D frameworks that incorporate microscale strain sensors for high-sensitivity measurements of contractile forces of engineered optogenetic muscle tissue rings, supported by quantitative simulations. Compared with traditional approaches based on optical microscopy, these 3D mechanical frameworks and sensing systems can measure not only motions but also contractile forces with high accuracy and high temporal resolution. Results of active tension force measurements of engineered muscle rings under different stimulation conditions in long-term monitoring settings for over 5 wk and in response to various chemical and drug doses demonstrate the utility of such platforms in sensing and modulation of muscle and other tissues. Possibilities for applications range from drug screening and disease modeling to biohybrid robotic engineering.

5.
Proc Natl Acad Sci U S A ; 118(11)2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33836614

RESUMO

Structures that significantly and rapidly change their shapes and sizes upon external stimuli have widespread applications in a diversity of areas. The ability to miniaturize these deployable and morphable structures is essential for applications in fields that require high-spatial resolution or minimal invasiveness, such as biomechanics sensing, surgery, and biopsy. Despite intensive studies on the actuation mechanisms and material/structure strategies, it remains challenging to realize deployable and morphable structures in high-performance inorganic materials at small scales (e.g., several millimeters, comparable to the feature size of many biological tissues). The difficulty in integrating actuation materials increases as the size scales down, and many types of actuation forces become too small compared to the structure rigidity at millimeter scales. Here, we present schemes of electromagnetic actuation and design strategies to overcome this challenge, by exploiting the mechanics-guided three-dimensional (3D) assembly to enable integration of current-carrying metallic or magnetic films into millimeter-scale structures that generate controlled Lorentz forces or magnetic forces under an external magnetic field. Tailored designs guided by quantitative modeling and developed scaling laws allow formation of low-rigidity 3D architectures that deform significantly, reversibly, and rapidly by remotely controlled electromagnetic actuation. Reconfigurable mesostructures with multiple stable states can be also achieved, in which distinct 3D configurations are maintained after removal of the magnetic field. Demonstration of a functional device that combines the deep and shallow sensing for simultaneous measurements of thermal conductivities in bilayer films suggests the promising potential of the proposed strategy toward multimodal sensing of biomedical signals.

6.
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.

7.
Biofouling ; 37(2): 222-234, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33682548

RESUMO

Porphyromonas gingivalis biofilms are implicated in the pathology of peri-implantitis and periodontitis. In this study, D-arginine (R), D-methionine (M), D-histidine (H), and a mixture of these D-amino acids (D-AAs) were investigated as an effective therapeutic strategy against P. gingivalis biofilms. The bacterial growth activity and minimum inhibitory concentrations were determined for each D-AA, along with the effects of the D-AAs mixture on biofilm development, morphology, structure, extracellular polysaccharides (EPS), cytotoxicity towards commensals, and bacterial structure. The D-AA mixture delayed the proliferation of P. gingivalis, changed its membrane structure, and decreased biofilm thickness and integrity, as compared with individual D-AAs. The EPS content increased with the concentration of D-AAs. The present study shows that a 4 mM RMH, triple D-AA mixture, enhanced deleterious effects on P. gingivalis biofilms without any cytotoxicity compared with individual D-AAs, thus providing a new strategy for the treatment of peri-implantitis and periodontitis.


Assuntos
Histidina , Porphyromonas gingivalis , Arginina , Biofilmes , Metionina
8.
Proc Natl Acad Sci U S A ; 118(5)2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33468630

RESUMO

Precise, quantitative measurements of the hydration status of skin can yield important insights into dermatological health and skin structure and function, with additional relevance to essential processes of thermoregulation and other features of basic physiology. Existing tools for determining skin water content exploit surrogate electrical assessments performed with bulky, rigid, and expensive instruments that are difficult to use in a repeatable manner. Recent alternatives exploit thermal measurements using soft wireless devices that adhere gently and noninvasively to the surface of the skin, but with limited operating range (∼1 cm) and high sensitivity to subtle environmental fluctuations. This paper introduces a set of ideas and technologies that overcome these drawbacks to enable high-speed, robust, long-range automated measurements of thermal transport properties via a miniaturized, multisensor module controlled by a long-range (∼10 m) Bluetooth Low Energy system on a chip, with a graphical user interface to standard smartphones. Soft contact to the surface of the skin, with almost zero user burden, yields recordings that can be quantitatively connected to hydration levels of both the epidermis and dermis, using computational modeling techniques, with high levels of repeatability and insensitivity to ambient fluctuations in temperature. Systematic studies of polymers in layered configurations similar to those of human skin, of porcine skin with known levels of hydration, and of human subjects with benchmarks against clinical devices validate the measurement approach and associated sensor hardware. The results support capabilities in characterizing skin barrier function, assessing severity of skin diseases, and evaluating cosmetic and medication efficacy, for use in the clinic or in the home.


Assuntos
Eletrônica , Pele/patologia , Água , Tecnologia sem Fio , Adolescente , Adulto , Pré-Escolar , Análise de Elementos Finitos , Humanos , Temperatura
9.
Expert Rev Anticancer Ther ; 21(2): 165-176, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33115280

RESUMO

Introduction: The microbiota is recognized for its impact on both human health and disease. The human microbiota is made up of trillions of cells, including bacteria, viruses, and fungi. The largest population of microbes reside in the gut, prompting research for better understanding of the impact of gastrointestinal microbiota in different diseases. Evidence from numerous studies has pointed out the role of commensal microbes as key determinants of cancer pathogenesis. Moreover, gut microbiota may play an important role in chemoresistance; consequently, this knowledge might be important for novel strategies to improve anticancer treatment efficacy.Areas covered: We describe the role of microbiota in different gastrointestinal cancer types (esophageal, gastric, colorectal, hepatocellular and pancreatic-biliary tract cancers). Moreover, we analyzed the impact of the microbiota on resistance to anticancer therapies, and, lastly, we focused on possibilities of microbiota modulation to enhance anticancer therapy efficacy.Expert opinion: Increasing evidence shows that gut microbiota might influence resistance to anticancer treatment, including conventional chemotherapy, immunotherapy, radiotherapy, and surgery. Therefore, a better knowledge of gut microbiota and its interactions with anticancer drugs will enable us to develop novel anticancer treatment strategies and subsequently improve the cancer patients' outcome.

10.
Sci Adv ; 6(49)2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33277260

RESUMO

Present-day dermatological diagnostic tools are expensive, time-consuming, require substantial operational expertise, and typically probe only the superficial layers of skin (~15 µm). We introduce a soft, battery-free, noninvasive, reusable skin hydration sensor (SHS) adherable to most of the body surface. The platform measures volumetric water content (up to ~1 mm in depth) and wirelessly transmits data to any near-field communication-compatible smartphone. The SHS is readily manufacturable, comprises unique powering and encapsulation strategies, and achieves high measurement precision (±5% volumetric water content) and resolution (±0.015°C skin surface temperature). Validation on n = 16 healthy/normal human participants reveals an average skin water content of ~63% across multiple body locations. Pilot studies on patients with atopic dermatitis (AD), psoriasis, urticaria, xerosis cutis, and rosacea highlight the diagnostic capability of the SHS (P AD = 0.0034) and its ability to study impact of topical treatments on skin diseases.

12.
Sci Adv ; 6(35): eabb1093, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32923633

RESUMO

Implantable drug release platforms that offer wirelessly programmable control over pharmacokinetics have potential in advanced treatment protocols for hormone imbalances, malignant cancers, diabetic conditions, and others. We present a system with this type of functionality in which the constituent materials undergo complete bioresorption to eliminate device load from the patient after completing the final stage of the release process. Here, bioresorbable polyanhydride reservoirs store drugs in defined reservoirs without leakage until wirelessly triggered valve structures open to allow release. These valves operate through an electrochemical mechanism of geometrically accelerated corrosion induced by passage of electrical current from a wireless, bioresorbable power-harvesting unit. Evaluations in cell cultures demonstrate the efficacy of this technology for the treatment of cancerous tissues by release of the drug doxorubicin. Complete in vivo studies of platforms with multiple, independently controlled release events in live-animal models illustrate capabilities for control of blood glucose levels by timed delivery of insulin.

13.
NPJ Digit Med ; 3: 29, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32195364

RESUMO

Hydrocephalus is a common disorder caused by the buildup of cerebrospinal fluid (CSF) in the brain. Treatment typically involves the surgical implantation of a pressure-regulated silicone tube assembly, known as a shunt. Unfortunately, shunts have extremely high failure rates and diagnosing shunt malfunction is challenging due to a combination of vague symptoms and a lack of a convenient means to monitor flow. Here, we introduce a wireless, wearable device that enables precise measurements of CSF flow, continuously or intermittently, in hospitals, laboratories or even in home settings. The technology exploits measurements of thermal transport through near-surface layers of skin to assess flow, with a soft, flexible, and skin-conformal device that can be constructed using commercially available components. Systematic benchtop studies and numerical simulations highlight all of the key considerations. Measurements on 7 patients establish high levels of functionality, with data that reveal time dependent changes in flow associated with positional and inertial effects on the body. Taken together, the results suggest a significant advance in monitoring capabilities for patients with shunted hydrocephalus, with potential for practical use across a range of settings and circumstances, and additional utility for research purposes in studies of CSF hydrodynamics.

14.
NPJ Digit Med ; 3(1): 29, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33594221

RESUMO

Hydrocephalus is a common disorder caused by the buildup of cerebrospinal fluid (CSF) in the brain. Treatment typically involves the surgical implantation of a pressure-regulated silicone tube assembly, known as a shunt. Unfortunately, shunts have extremely high failure rates and diagnosing shunt malfunction is challenging due to a combination of vague symptoms and a lack of a convenient means to monitor flow. Here, we introduce a wireless, wearable device that enables precise measurements of CSF flow, continuously or intermittently, in hospitals, laboratories or even in home settings. The technology exploits measurements of thermal transport through near-surface layers of skin to assess flow, with a soft, flexible, and skin-conformal device that can be constructed using commercially available components. Systematic benchtop studies and numerical simulations highlight all of the key considerations. Measurements on 7 patients establish high levels of functionality, with data that reveal time dependent changes in flow associated with positional and inertial effects on the body. Taken together, the results suggest a significant advance in monitoring capabilities for patients with shunted hydrocephalus, with potential for practical use across a range of settings and circumstances, and additional utility for research purposes in studies of CSF hydrodynamics.

15.
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.

16.
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.

17.
ACS Nano ; 13(10): 10972-10979, 2019 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-31124670

RESUMO

Sensors that reproduce the complex characteristics of cutaneous receptors in the skin have important potential in the context of artificial systems for controlled interactions with the physical environment. Multimodal responses with high sensitivity and wide dynamic range are essential for many such applications. This report introduces a simple, three-dimensional type of microelectromechanical sensor that incorporates monocrystalline silicon nanomembranes as piezoresistive elements in a configuration that enables separate, simultaneous measurements of multiple mechanical stimuli, such as normal force, shear force, and bending, along with temperature. The technology provides high sensitivity measurements with millisecond response times, as supported by quantitative simulations. The fabrication and assembly processes allow scalable production of interconnected arrays of such devices with capabilities in spatiotemporal mapping. Integration with wireless data recording and transmission electronics allows operation with standard consumer devices.


Assuntos
Técnicas Biossensoriais , Fenômenos Físicos , Pele/metabolismo , Tato/fisiologia , Eletrônica , Fenômenos Mecânicos , Pele/química , Temperatura , Tato/genética
18.
ACS Appl Mater Interfaces ; 11(3): 3482-3492, 2019 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-30584766

RESUMO

Development of schemes to form complex three-dimensional (3D) mesostructures in functional materials is a topic of broad interest, thanks to the ubiquitous applications across a diversity of technologies. Recently established schemes in the mechanically guided 3D assembly allow deterministic transformation of two-dimensional structures into sophisticated 3D architectures by controlled compressive buckling resulted from strain release of prestretched elastomer substrates. Existing studies mostly exploited supporting substrates made of homogeneous elastomeric material with uniform thickness, which produces relatively uniform strain field to drive the 3D assembly, thus posing limitations to the geometric diversity of resultant 3D mesostructures. To offer nonuniform strains with desired spatial distributions in the 3D assembly, this paper introduces a versatile set of concepts in the design of engineered substrates with heterogeneous integration of materials of different moduli. Such heterogeneous, deformable substrates can achieve large strain gradients and efficient strain isolation/magnification, which are difficult to realize using the previously reported strategies. Theoretical and experimental studies on the underlying mechanics offer a viable route to the design of heterogeneous, deformable substrates to yield favorable strain fields. A broad collection of 3D mesostructures and associated heterogeneous substrates is fabricated and demonstrated, including examples that resemble windmills, scorpions, and manta rays and those that have application potentials in tunable inductors and vibrational microsystems.

19.
ACS Nano ; 13(1): 449-457, 2019 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-30457837

RESUMO

Vibrational resonances of microelectromechanical systems (MEMS) can serve as means for assessing physical properties of ultrathin coatings in sensors and analytical platforms. Most such technologies exist in largely two-dimensional configurations with a limited total number of accessible vibration modes and modal displacements, thereby placing constraints on design options and operational capabilities. This study presents a set of concepts in three-dimensional (3D) microscale platforms with vibrational resonances excited by Lorentz-force actuation for purposes of measuring properties of thin-film coatings. Nanoscale films including photodefinable epoxy, cresol novolak resin, and polymer brush with thicknesses as small as 270 nm serve as the test vehicles for demonstrating the advantages of these 3D MEMS for detection of multiple physical properties, such as modulus and density, within a single polymer sample. The stability and reusability of the structure are demonstrated through multiple measurements of polymer samples using a single platform, and via integration with thermal actuators, the temperature-dependent physical properties of polymer films are assessed. Numerical modeling also suggests the potential for characterization of anisotropic mechanical properties in single or multilayer films. The findings establish unusual opportunities for interrogation of the physical properties of polymers through advanced MEMS design.

20.
Sci Adv ; 4(11): eaau5849, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30406207

RESUMO

With accelerating trends in miniaturization of semiconductor devices, techniques for energy harvesting become increasingly important, especially in wearable technologies and sensors for the internet of things. Although thermoelectric systems have many attractive attributes in this context, maintaining large temperature differences across the device terminals and achieving low-thermal impedance interfaces to the surrounding environment become increasingly difficult to achieve as the characteristic dimensions decrease. Here, we propose and demonstrate an architectural solution to this problem, where thin-film active materials integrate into compliant, open three-dimensional (3D) forms. This approach not only enables efficient thermal impedance matching but also multiplies the heat flow through the harvester, thereby increasing the efficiencies for power conversion. Interconnected arrays of 3D thermoelectric coils built using microscale ribbons of monocrystalline silicon as the active material demonstrate these concepts. Quantitative measurements and simulations establish the basic operating principles and the key design features. The results suggest a scalable strategy for deploying hard thermoelectric thin-film materials in harvesters that can integrate effectively with soft materials systems, including those of the human body.

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