RESUMO
Surface modification is a promising method to solve the tribological problems in microsystems. To modify the surface, we fabricated hierarchical patterns with different pitches of nano-scale features and different surface chemistries. Micro- and nano-patterns with similar geometrical configurations were also fabricated for comparison. The nano-tribological behavior of the patterns was investigated using an atomic force microscope at different relative humidity levels (5% to 80%) and applied normal loads (40 nN to 120 nN) under a constant sliding velocity. The results showed significant enhancement in the de-wetting and tribological performance of the hierarchical patterns compared with those of flat and micro- and nano-patterned surfaces. The PTFE-coated hierarchical patterns showed similar dynamic contact angles (advancing and receding) to those of the real lotus leaf. The influence of relative humidity on adhesion and friction behavior was found to be significant for all the tested surfaces. The tribological performance was improved as the pitch of the nano-scale geometry of the hierarchical pattern increased, even though the wetting property was not influenced significantly. A model was proposed based on the role of intermolecular force to explain the effect of the pitch of the hierarchical patterns on the adhesion and friction behavior. According to the model based on the molecular force, the contact between a ball and the patterned surface was a multi-asperity contact, contrary to the single-asperity contact predicted by the Johnson-Kendall-Roberts (JKR) and Maugis-Dugdale (MD) models. The strong intermolecular forces, which are activated in the confined spaces between the adjacent nano-pillars and the ball, contributed to the contact area and hence the adhesion and friction forces.
Assuntos
Nanoestruturas/química , Polimetil Metacrilato/química , Politetrafluoretileno/química , Molhabilidade , Adesividade , Fricção , Umidade , Microscopia de Força Atômica , Nanoestruturas/ultraestruturaRESUMO
During the last several years, legged locomotive mechanism has been considered as one of the main self-propelling mechanisms for future endoscopic microrobots due to its superior propulsion efficiency of an endoscopic microrobot inside the intestinal track. Nevertheless, its clinical application has been largely limited since the legged locomotive mechanism utilizes an end effector which has a sharp tip to generate sufficient traction by physically penetrating and interlocking with the intestinal tissue. This can cause excessive physical tissue damage or even complete perforation of the intestinal wall that can lead to abdominal inflammation. Hence, in this work two types of new end effectors, penetration-limited end effector (PLEE) and bi-material structured end effector (BMEE) were specially designed to acquire high medical safety as well as effective traction generation performance. The microscopic end effector specimens were fabricated with micro-wire electric discharge machining process. Traction generation performance of the end effectors was evaluated by direct measurement of resistance forces during contact-sliding tests using a custom-built contact-sliding tester. The safety of the end effector design was evaluated by examination of microscopic intestinal tissue damage using a scanning electron microscope (SEM). Physical damage characteristics of the intestinal tissue and related contact physics of the end effectors were discussed. From the results, the end effectors were evaluated with respect to their prospects in future medical applications as safe end effectors as well as micro-surgical tools.
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Endoscopia/efeitos adversos , Endoscopia/instrumentação , Intestino Grosso/citologia , Microtecnologia/instrumentação , Robótica/instrumentação , Segurança , Animais , Desenho de Equipamento , Fenômenos Mecânicos , Mucosa/citologia , SuínosRESUMO
Anisotropically organized neural networks are indispensable routes for functional connectivity in the brain, which remains largely unknown. While prevailing animal models require additional preparation and stimulation-applying devices and have exhibited limited capabilities regarding localized stimulation, no in vitro platform exists that permits spatiotemporal control of chemo-stimulation in anisotropic three-dimensional (3D) neural networks. We present the integration of microchannels seamlessly into a fibril-aligned 3D scaffold by adapting a single fabrication principle. We investigated the underlying physics of elastic microchannels' ridges and interfacial sol-gel transition of collagen under compression to determine a critical window of geometry and strain. We demonstrated the spatiotemporally resolved neuromodulation in an aligned 3D neural network by local deliveries of KCl and Ca2+ signal inhibitors, such as tetrodotoxin, nifedipine, and mibefradil, and also visualized Ca2+ signal propagation with a speed of ~3.7 µm/s. We anticipate that our technology will pave the way to elucidate functional connectivity and neurological diseases associated with transsynaptic propagation.
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Encéfalo , Colágeno , Animais , Encéfalo/fisiologiaRESUMO
BACKGROUND: Capsule endoscopy that could actively move and approach a specific site might be more valuable for the diagnosis or treatment of GI diseases. OBJECTIVE: We tested the performance of active locomotion of a novel wired capsule endoscope with a paddling-based locomotion mechanism, using 3 models: a silicone tube, an extracted porcine colon, and a living pig. DESIGN: In vitro, ex vivo, and in vivo experiments in a pig model. SETTING: Study in an animal laboratory. INTERVENTIONS: For the in vitro test, the locomotive capsule was controlled to actively move from one side of a silicone tube to the other by a controller-operated automatic traveling program. The velocity was calculated by following a video recording. We performed ex vivo tests by using an extracted porcine colon in the same manner we performed the in vitro test. In in vivo experiments, the capsule was inserted into the rectum of a living pig under anesthesia, and was controlled to move automatically forward. After 8 consecutive trials, the velocity was calculated. MAIN OUTCOME MEASUREMENTS: Elapsed time, velocity, and mucosal damage. RESULTS: The locomotive capsule showed stable and active movement inside the lumen both in vitro and ex vivo. The velocity was 60 cm/min in the silicone tube, and 36.8 and 37.5 cm/min in the extracted porcine colon. In the in vivo experiments, the capsule stably moved forward inside the colon of a living pig without any serious complications. The mean velocity was 17 cm/min over 40 cm length. We noted pinpoint erythematous mucosal injuries in the colon. LIMITATION: Porcine model experiments, wired capsule endoscope. CONCLUSIONS: The novel paddling-based locomotive capsule endoscope performed fast and stable movement in a living pig colon with consistent velocity. Further investigation is necessary for practical use in humans.
Assuntos
Biomimética/instrumentação , Cápsulas Endoscópicas , Endoscopia por Cápsula/métodos , Doenças do Colo/diagnóstico , Animais , Modelos Animais de Doenças , Desenho de Equipamento , Suínos , Gravação em VídeoRESUMO
The mechanical properties of a small fragment (30 bp) of an individual double-stranded deoxyribonucleic acid (dsDNA) in water have been investigated by atomic force microscopy (AFM). We have stretched three systems including ssDNA, double-fixed dsDNA (one strand of the dsDNA molecules was biotinylated at the 3'-end and thiolated at the 5'-end, this was reversed for the other complementary strand) and single-fixed dsDNA (one strand of the dsDNA molecules was biotinylated at the 3'-end and thiolated at the 5'-end, whereas the other complementary strand was biotinylated at only the 5'-end). The achieved thiolation and biotinylation were to bind ds- or ssDNA to the gold surface and streptavidin-coated AFM tip, respectively. Analysis of the force versus displacement (F-D) curves from tip-DNA-substrate systems shows that the pull-off length (L(o)) and stretch length (delta) from the double-fixed system were shorter than those observed in the ssDNA and the single-fixed system. The obtained stretch force (F(st)) from the single-fixed dsDNA was much greater than that from the ssDNA even though it was about 10 pN greater than the one obtained in the double-fixed system. As a result, the Young's modulus of the double-fixed dsDNA was greater than that of the single-fixed dsDNA and the ssDNA. A more reliable stiffness of the dsDNA was observed via the double-fixed system, since there is no effect of the unpaired molecules during stretching, which always occurred in the single-fixed system. The unpaired molecules were also observed by comparing the stiffness of ssDNA and single-fixed dsDNA in which the end of one strand was left free.
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DNA/química , Módulo de Elasticidade , Microscopia de Força Atômica/métodos , Biotina/química , DNA de Cadeia Simples/química , Ouro/química , Distribuição Normal , Estreptavidina/química , Compostos de Sulfidrila/químicaRESUMO
We report the surface-energy-dependent wetting transition characteristics of an evaporating water droplet on surface-energy-controlled microcavity structures with functional nanocoatings. The droplet wetting scenarios were categorized into four types depending on the synergistic effect of surface energy and pattern size. The silicon (Si) microcavity surfaces (γSi = 69.8 mJ/m2) and the polytetrafluoroethylene (PTFE)-coated microcavity surfaces (γPTFE = 15.0 mJ/m2) displayed stable Wenzel and Cassie wetting states, respectively, irrespective of time. In contrast, diamond-like carbon (DLC)-coated (γDLC = 55.5 mJ/m2) and fluorinated diamond-like carbon (FDLC)-coated (γFDLC = 36.2 mJ/m2) surfaces demonstrated a time-dependent transition of wetting states. In particular, the DLC-coated surface showed random filling of microcavities at the earlier time point, while the FDLC-coated surface displayed directional filling of microcavities at the late stage of drop evaporation. Such dynamic wetting scenarios based on surface energy, in particular, the random and directional wetting transitions related to surface energy of nanocoatings have not been explored previously. Furthermore, the microscopic role of nanocoating in the wetting scenarios was analyzed by monitoring the time-dependent deformation and movement of the air-water interface (AWI) at individual cavities using the fluorescence interference-contrast (FLIC) technique. A coating-dependent depinning mechanism of the AWI was responsible for variable filling of cavities leading to time-dependent wetting scenarios. A capillary wetting model was used to relate this depinning event to the evaporation-induced internal flow within the droplet. Interestingly, FLIC analysis revealed that a hydrophilic nanocoating can induce microscopic hydrophobicity near the cavity edges leading to delayed and variable cavity filling. The surface energy-dependent classification of the wetting scenarios may help the design of novel evaporation-assisted thermodynamic and mass-transfer processes.
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Novel drug delivery systems based on microtechnology have advanced tremendously, but yet face some technological and societal hurdles to fully achieve their potential. The novel drug delivery systems aim to deliver drugs in a spatiotemporal- and dosage-controlled manner with a goal to address the unmet medical needs from oral delivery and hypodermic injection. The unmet needs include effective delivery of new types of drug candidates that are otherwise insoluble and unstable, targeted delivery to areas protected by barriers (e.g. brain and posterior eye segment), localized delivery of potent drugs, and improved patient compliance. After scrutinizing the design considerations and challenges associated with delivery to areas that cannot be efficiently targeted through standard drug delivery (e.g. brain, posterior eye segment, and gastrointestinal tract), this review provides a summary of recent advances that addressed these challenges and summarizes yet unresolved problems in each target area. The opportunities for innovation in devising the novel drug delivery systems are still high; with integration of advanced microtechnology, advanced fabrication of biomaterials, and biotechnology, the novel drug delivery is poised to be a promising alternative to the oral administration and hypodermic injection for a large spectrum of drug candidates.
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Sistemas de Liberação de Medicamentos/instrumentação , Sistemas Microeletromecânicos , Administração Oral , Humanos , Sistemas Microeletromecânicos/instrumentação , Preparações Farmacêuticas/administração & dosagemRESUMO
We developed a novel method to fabricate a crab-like microrobot that can actuate for a long period in a physiological condition. The microrobot backbone was built with a biocompatible and elastic material-polydimethylsiloxane (PDMS)-by using a specially designed 3D molding aligner, and consisted of three strips of PDMS "legs" connected across a "body." Cardiomyocytes were then plated on the grooved top surface of the backbone, resulting in a high concentration of pulsating cells. These key techniques enabled the microrobot to walk continuously for over ten days. The performance of our crab-like microrobot was measured at an average velocity of 100 microm s(-1), and the estimated total distance it travelled was 50 m over a one-week period. Thus, we have demonstrated for the first time a walking robot that exhibited reliable and long-term actuation performances.
Assuntos
Miocárdio/citologia , Robótica , Animais , Células Cultivadas , Desenho de Equipamento , Ratos , Ratos Sprague-DawleyRESUMO
In native tissues, cellular and acellular components are anisotropically organized and often aligned in specific directions, providing structural and mechanical properties for actuating biological functions. Thus, engineering alignment not only allows for emulation of native tissue structures but might also enable implementation of specific functionalities. However, achieving desired alignment is challenging, especially in three-dimensional constructs. By exploiting the elastomeric property of polydimethylsiloxane and fibrillogenesis kinetics of collagen, here we introduce a simple yet effective method to assemble and align fibrous structures in a multi-modular three-dimensional conglomerate. Applying this method, we have reconstructed the CA3-CA1 hippocampal neural circuit three-dimensionally in a monolithic gel, in which CA3 neurons extend parallel axons to and synapse with CA1 neurons. Furthermore, we show that alignment of the fibrous scaffold facilitates the establishment of functional connectivity. This method can be applied for reconstructing other neural circuits or tissue units where anisotropic organization in a multi-modular structure is desired.
Assuntos
Técnicas de Cultura de Células/métodos , Hipocampo/fisiologia , Rede Nervosa/fisiologia , Neurônios/fisiologia , Alicerces Teciduais/química , Animais , Anisotropia , Células Cultivadas , Colágeno/química , Hipocampo/citologia , Camundongos Endogâmicos ICR , Microscopia Confocal , Rede Nervosa/citologia , Neurônios/citologia , Ratos Sprague-Dawley , Sinapses/fisiologia , Imagem com Lapso de Tempo/métodos , Engenharia Tecidual/métodosRESUMO
Nanoscale patterns have dimensions that are comparable to the length scales affected by intermolecular and surface forces. In this study, we systematically investigated the individual roles of curvature, surface energy, lateral stiffness, material, and pattern density in the adhesion and friction of nanopatterns. We fabricated cylindrical and mushroom-shaped polymer pattern geometries containing flat- and round-topped morphologies using capillary force lithography and nanodrawing techniques. We showed that the curvature, surface energy, and density of the patterns predominantly influenced the adhesive interactions, whereas lateral stiffness dominated friction by controlling the geometrical interaction between the indenter and pillar during sliding. Interestingly, in contrast to previous studies, cylindrical and mushroom-shaped pillars showed similar adhesion characteristics but very different frictional properties. Using fracture mechanics analysis, we showed that this phenomenon is due to a larger ratio of the mushroom flange thickness (t) to the radius of the pillar stem (ρ), and we proposed a design criterion for mushroom patterns to exhibit a geckolike effect. The most important result of our work is the discovery of a linear master curve in the graph of adhesion versus friction for pillars with similar lateral stiffness values that is independent of curvature, material, surface energy, and pattern density. These results will aid in the identification of simple pattern parameters that can be scaled to tune adhesion and friction and will help broaden the understanding of nanoscale topographical interactions.
RESUMO
Superhydrophobicity facilitates the development of self-cleaning, anti-biofouling, and anti-corrosion surfaces. The leaves of the lotus (Nelumbo nucifera) and taro (Colocasia esculenta) plants are well known for their self-cleaning properties. A hierarchical structure comprising papillae epidermal cells superimposed with epicuticular wax crystalloids of varying shapes, sizes, and orientations is an important aspect of the surface of these plant leaves. We fabricated two types of hierarchical structures biomimicking the surface topography of the lotus leaf. The hierarchical patterns successfully demonstrated the superhydrophobic state in comparison with nano and micro patterns. We used the finite element method (FEM) to simulate and understand the wetting process. The FEM simulations showed good correlation with the experimental results. FEM was helpful in understanding the wetting of enormously complex biological surfaces with relative ease, and it qualifies as a potential tool for designing superhydrophobic surfaces. Using the FEM framework, we further designed surfaces to optimize the order of the shapes in hierarchy. The results showed that the superhydrophobic surface with the lowest wetted area was obtained by placing shapes with smaller geometric angles at the top of the hierarchy. This arrangement of shapes provides the optimum combination of superhydrophobicity and surface integrity. This observation explains why the hierarchical structure of many superhydrophobic leaves follows this order. We also investigated the complex hierarchical structure of Salvinia minima. Owing to its remarkable ability to entrap air and pin the contact line, it exhibits superhydrophobicity along with the much-required Cassie state. These properties of Salvinia minima make it an excellent candidate for developing omniphobic surfaces.
Assuntos
Materiais Biomiméticos/síntese química , Modelos Químicos , Nelumbo/química , Folhas de Planta/química , Água/química , Molhabilidade , Simulação por Computador , Interações Hidrofóbicas e Hidrofílicas , Teste de Materiais , Modelos Biológicos , Nelumbo/ultraestrutura , Folhas de Planta/ultraestruturaRESUMO
Multi-functional neural probes integrated with various stimulation modalities are becoming essential tools in neuroscience to study the brain more effectively. In this paper, we present a new multi-functional neural probe that allows chemical stimulation through drug delivery and simultaneous recording of individual neuron signals through a microelectrode array. By embedding microchannels in silicon using a proposed glass reflow process, we successfully fabricated 40 µm thick silicon neural probes suitable for small animal experiments. The electrochemical impedance spectroscopy confirms that impedance of iridium microelectrodes is low enough (<1 MΩ at 1 kHz) to measure neural signals. Flow rate characterization in a 0.9% w/v agarose gel shows the capability to deliver a small volume of drugs (<1 µl) at a controlled flow rate. We demonstrate the viability and potential of this new probe by conducting in vivo experiments on mice. Because of the proposed compact structure, both action potentials of individual neurons and local field potentials (LFP) at the thalamus region of a mouse brain were successfully detected with a noise level of ~30 µVpp. Furthermore, we successfully induced absence seizure by injecting seizure-inducing drugs (baclofen) at a local target region and observed distinctive changes in neural signal patterns. Specifically, spike-wave discharge (SWD), which is an indicative signal pattern of absence seizure, was successfully recorded. These signals were also directly compared to SWD detected after inducing absence seizure through direct injection of baclofen through the abdomen. This work demonstrates the potential of our multi-functional neural probes for use in effective investigation of brain functions and disorders by using widely available mouse models.
Assuntos
Encéfalo/citologia , Sistemas de Liberação de Medicamentos/instrumentação , Sistemas Microeletromecânicos/instrumentação , Microfluídica , Potenciais de Ação/efeitos dos fármacos , Animais , Baclofeno/administração & dosagem , Baclofeno/efeitos adversos , Encéfalo/metabolismo , Encéfalo/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microeletrodos , Neurônios/citologia , Neurônios/efeitos dos fármacos , Convulsões/induzido quimicamente , Convulsões/patologia , Convulsões/fisiopatologiaRESUMO
We investigate the role of viscous forces on the wetting of hydrophobic, semi-hydrophobic, and hydrophilic textured surfaces as second-order effects. We show that during the initial contact, the transition from inertia- to viscous-dominant regime occurs regardless of their surface topography and chemistry. Furthermore, we demonstrate the effect of viscosity on the apparent contact angle under quasi-static conditions by modulating the ratio of a water/glycerol mixture and show the effect of viscosity, especially on the semi-hydrophobic and hydrophobic textured substrates. The reason why the viscous force does not affect the apparent contact angle of the hydrophilic surface is explained based on the relationship between the disjoining pressure and surface chemistry. We further propose a wetting model that can predict the apparent contact angle of a liquid drop on a textured substrate by incorporating a viscous force component in the force balance equation. This model can predict apparent contact angles on semi-hydrophobic and hydrophobic textured surfaces exhibiting Wenzel state more accurately than the Wenzel model, indicating the importance of viscous forces in determining the apparent contact angle. The modified model can be applied for estimating the wetting properties of arbitrary engineered surfaces.
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Astrocytes are known to serve as scaffolding cells that shape the brain. The physical properties of astrocytes, such as stiffness, are important for their scaffolding function. These properties may be altered in certain pathological conditions, such as in brain cancer. However, actual stiffness of astrocytes is not yet well understood. Here, we report that the astrocyte stiffness is positively correlated with the density of cytoskeletal proteins, such as actin filaments, microtubules, and intermediate filaments. The value of the stiffness of astrocytes as measured by atomic force microscopy (AFM) increases 38-fold in five-week-old rats compared to postnatal-day zero pups. Using multicolor confocal microscopy, we found that the complexity of cytoskeletal proteins, such as actin filaments, microtubules, and intermediate filaments, increase as the animal gets older. Our findings indicate that the change of stiffness positively correlates with the maturation of cytoskeletal proteins, and suggest that AFM can be useful as an analytical and diagnostic tool for neuroscience.
Assuntos
Astrócitos/citologia , Citoesqueleto/metabolismo , Nanotecnologia , Animais , Animais Recém-Nascidos , Imunofluorescência , Microscopia de Força Atômica , Ratos , Ratos Sprague-DawleyRESUMO
Multi-functional neural probes are promising platforms to conduct efficient and effective in-depth studies of brain by recording neural signals as well as modulating the signals with various stimuli. Here we present a neural probe with an embedded microfluidic channel (chemtrode) with multi-drug delivery capability suitable for small animal experiments. We integrated a staggered herringbone mixer (SHM) in a 3-inlet microfluidic chip directly into our chemtrode. This chip, which also serves as a compact interface for the chemtrode, allows for efficient delivery of small volumes of multiple or concentration-modulated drugs via chaotic mixing. We demonstrated the successful infusion of combinatorial inputs of three chemicals with a low flow rate (170 nl min(-1)). By sequentially delivering red, green, and blue inks from each inlet and conducting visual inspections at the tip of the chemtrode, we measured a short residence time of 14 s which corresponds to a small swept volume of 66 nl. Finally, we demonstrated the potential of our proposed chemtrode as an enabling tool through extensive in vivo mice experiments. Through simultaneous infusions of a chemical (pilocarpine or tetrodotoxin (TTX) at inlet 1), a buffer solution (saline at inlet 2), and 4',6-diamidino-2-phenylindole (DAPI at inlet 3) locally into a mouse brain, we not only modulated the neural activities by varying the concentration of the chemical but also locally stained the cells at our target region (CA1 in hippocampus). More specifically, infusion of pilocarpine with a higher concentration resulted in an increase in neural activities while infusion of TTX with a higher concentration resulted in a distinctive reduction. For each chemical, we acquired multiple sets of data using only one mouse through a single implantation of the chemtrode. Our proposed chemtrode offers 1) multiplexed delivery of three drugs through a compact packaging with a small swept volume and 2) simultaneous recording to monitor near real-time effects on neural signals, which allows for more versatile in vivo experiments with a minimum number of animals to be sacrificed.
Assuntos
Sistemas de Liberação de Medicamentos , Dispositivos Lab-On-A-Chip , Próteses Neurais , Animais , Região CA1 Hipocampal , Sistemas de Liberação de Medicamentos/instrumentação , Sistemas de Liberação de Medicamentos/métodos , Humanos , Indóis/farmacologia , Masculino , Camundongos , Pilocarpina/farmacologia , Tetrodotoxina/farmacologiaRESUMO
Integration of stimulation modalities (e.g. electrical, optical, and chemical) on a large array of neural probes can enable an investigation of important underlying mechanisms of brain disorders that is not possible through neural recordings alone. Furthermore, it is important to achieve this integration of multiple functionalities in a compact structure to utilize a large number of the mouse models. Here we present a successful optical modulation of in vivo neural signals of a transgenic mouse through our compact 2D MEMS neural array (optrodes). Using a novel fabrication method that embeds a lower cladding layer in a silicon substrate, we achieved a thin silicon 2D optrode array that is capable of delivering light to multiple sites using SU-8 as a waveguide core. Without additional modification to the microelectrodes, the measured impedance of the multiple microelectrodes was below 1 MΩ at 1 kHz. In addition, with a low background noise level (± 25 µV), neural spikes from different individual neurons were recorded on each microelectrode. Lastly, we successfully used our optrodes to modulate the neural activity of a transgenic mouse through optical stimulation. These results demonstrate the functionality of the 2D optrode array and its potential as a next-generation tool for optogenetic applications.
Assuntos
Potenciais de Ação , Animais , Hipocampo/fisiologia , Camundongos , Camundongos Transgênicos , Sondas MolecularesRESUMO
We investigated the influence of nanoscale pattern shapes, contours, and surface chemistry on wetting behavior using a combination of experimental and modeling approaches. Among the investigated topographical shapes, re-entrant geometries showed superior performance owing to their ability to restrain the liquid-air interface in accordance with Gibbs criteria. The wetting state is also controlled by the surface texture in addition to the surface chemistry. Topographies with smaller intrinsic angles are better able to support the liquid droplet. Based on these observations, two geometrical relationships for designing superhydrophobic patterns exhibiting the Cassie-Baxter state are proposed. A detailed analysis of the simulation results showed the presence of viscous forces during the initial transient phase of the droplet interaction with the solid surface even at negligible normal velocity, which was verified experimentally using a high-speed imaging technique. During this transient phase, for a polystyrene surface, the liquid front was observed to be moving with a radial velocity of 0.4 m s(-1), which gradually decreased to almost zero after 35 ms. We observed that the viscous energy dissipation density is influenced by the surface material and topography and the wetting state. The viscous energy dissipation density is minimal in the case of the Cassie-Baxter state, while it becomes quite significant for the Wenzel state. The viscous effects are reduced for topographies with smooth geometries and surfaces with high slip length.
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OBJECTIVE: Optogenetics promises exciting neuroscience research by offering optical stimulation of neurons with unprecedented temporal resolution, cell-type specificity and the ability to excite as well as to silence neurons. This work provides the technical solution to deliver light to local neurons and record neural potentials, facilitating local circuit analysis and bridging the gap between optogenetics and neurophysiology research. APPROACH: We have designed and obtained the first in vivo validation of a neural probe with monolithically integrated electrodes and waveguide. High spatial precision enables optical excitation of targeted neurons with minimal power and recording of single-units in dense cortical and subcortical regions. MAIN RESULTS: The total coupling and transmission loss through the dielectric waveguide at 473 nm was 10.5 ± 1.9 dB, corresponding to an average output intensity of 9400 mW mm(-2) when coupled to a 7 mW optical fiber. Spontaneous field potentials and spiking activities of multiple Channelrhodopsin-2 expressing neurons were recorded in the hippocampus CA1 region of an anesthetized rat. Blue light stimulation at intensity of 51 mW mm(-2) induced robust spiking activities in the physiologically identified local populations. SIGNIFICANCE: This minimally invasive, complete monolithic integration provides unmatched spatial precision and scalability for future optogenetics studies at deep brain regions with high neuronal density.
Assuntos
Eletrodos Implantados , Optogenética/instrumentação , Optogenética/métodos , Animais , Região CA1 Hipocampal/fisiologia , Channelrhodopsins , Eletrônica , Tecnologia de Fibra Óptica , Próteses Neurais , Neurônios/fisiologia , Estimulação Luminosa/instrumentação , Estimulação Luminosa/métodos , Desenho de Prótese , Células Piramidais/fisiologia , Ratos , Ratos Long-EvansRESUMO
The microdrive is one of the most essential tools for extracellular, single-unit recordings in freely behaving animals to detect and isolate the single-unit activities from brain regions of interest. Due to the increasing number of neuroscience research projects using genetically engineered mice, the demand for effective recording devices in freely moving mice is also increasing. Although manually and automatically operated microdrive devices are available, they are limited in terms of size, weight, accuracy, manipulability, and convenience for single-unit recording in mice. The present study proposed a novel microdrive that employs a small, lightweight piezo-motor and a magnetoresistive (MR) sensor with a closed-loop position feedback control system. The total weight of the device is 1.82 g, which is perfectly suitable for application to mice. Most importantly, the proposed microdrive is capable of monitoring and adjusting electrode movement on-line by integrating a closed-loop feedback control system, which enhances the accuracy of micro-advancement of the electrode by utilizing position feedback. The performance of this newly developed microdrive was extensively evaluated for both mechanical and physiological concerns at both free-loading and various-loading conditions, including agarose gel matrix and then the hippocampus and thalamus of mice. In summary, this proposed microdrive can enhance the quality of recording single unit activities in freely moving mice in terms of the size and weight of the device, the convenience and accuracy of manipulation, and, most of all, in isolating single neurons and recording stability by providing accurate positioning of an electrode.
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Potenciais de Ação/fisiologia , Eletrofisiologia/instrumentação , Retroalimentação Fisiológica/fisiologia , Microeletrodos , Neurônios/fisiologia , Vigília/fisiologia , Animais , Eletrofisiologia/métodos , Desenho de Equipamento , Hipocampo/citologia , Camundongos , Tálamo/citologiaRESUMO
Autonomous locomotion in gastrointestinal (GI) tracts is achieved with a paddling-based capsule endoscope. For this, a miniaturized encoder module was developed utilizing a MEMS fabrication technology to monitor the position of paddles. The integrated encoder module yielded the high resolution of 0.0025 mm in the linear motion of the paddles. In addition, a PID control method was implemented on a DSP to control the stroke of the paddles accurately. As a result, the average accuracy and the standard deviation were measured to be 0.037 mm and 0.025 mm by a laser position sensor for the repetitive measurements. The locomotive performance was evaluated via ex-vivo tests according to various strokes in paddling. In an in-vivo experiment with a living pig, the locomotion speed was improved by 58% compared with the previous control method relying on a given timer value for reciprocation of the paddles. Finally, the integrated encoder module and the control system allow consistent paddling during locomotion even under loads in GI tract. It provides the autonomous locomotion without intervention in monitoring and controlling the capsule endoscope.