共查询到20条相似文献，搜索用时 140 毫秒
1.
Beibei Zhang Yinbao Li Qidi He Jun Qin Yanyan Yu Xinchun Li Lin Zhang Meicun Yao Junshan Liu Zuanguang Chen 《Biomicrofluidics》2014,8(5)
We reported a new microfluidic system integrated with worm responders for evaluating the environmental manganese toxicity. The micro device consists of worm loading units, worm observing chambers, and a radial concentration gradient generator (CGG). Eight T-shape worm loading units of the micro device were used to load the exact number of worms into the corresponding eight chambers with the assistance of worm responders and doorsills. The worm responder, as a key component, was employed for performing automated worm-counting assay through electric impedance sensing. This label-free and non-invasive worm-counting technique was applied to the microsystem for the first time. In addition, the disk-shaped CGG can generate a range of stepwise concentrations of the appointed chemical automatically and simultaneously. Due to the scalable architecture of radial CGG, it has the potential to increase the throughput of the assay. Dopaminergic (DAergic) neurotoxicity of manganese on C. elegans was quantitatively assessed via the observation of green fluorescence protein-tagged DAergic neurons of the strain BZ555 on-chip. In addition, oxidative stress triggered by manganese was evaluated by the quantitative fluorescence intensity of the strain CL2166. By scoring the survival ratio and stroke frequency of worms, we characterized the dose- and time-dependent mobility defects of the manganese-exposed worms. Furthermore, we applied the microsystem to investigate the effect of natural antioxidants to protect manganese-induced toxicity. 相似文献
2.
The discovery of new drugs is often propelled by the increasing resistance of parasites to existing drugs and the availability of better technology platforms. The area of microfluidics has provided devices for faster screening of compounds, controlled sampling/sorting of whole animals, and automated behavioral pattern recognition. In most microfluidic devices, drug effects on small animals (e.g., Caenorhabditis elegans) are quantified by an end-point, dose response curve representing a single parameter (such as worm velocity or stroke frequency). Here, we present a multi-parameter extraction method to characterize modes of paralysis in C. elegans over an extended time period. A microfluidic device with real-time imaging is used to expose C. elegans to four anthelmintic drugs (i.e., pyrantel, levamisole, tribendimidine, and methyridine). We quantified worm behavior with parameters such as curls per second, types of paralyzation, mode frequency, and number/duration of active/immobilization periods. Each drug was chosen at EC75 where 75% of the worm population is responsive to the drug. At equipotent concentrations, we observed differences in the manner with which worms paralyzed in drug environments. Our study highlights the need for assaying drug effects on small animal models with multiple parameters quantified at regular time points over an extended period to adequately capture the resistance and adaptability in chemical environments. 相似文献
3.
Zhichang Qiu Long Tu Liang Huang Taoyuanmin Zhu Volker Nock Enchao Yu Xiao Liu Wenhui Wang 《Biomicrofluidics》2015,9(1)
Optogenetics has been recently applied to manipulate the neural circuits of Caenorhabditis elegans (C. elegans) to investigate its mechanosensation and locomotive behavior, which is a fundamental topic in model biology. In most neuron-related research, free C. elegans moves on an open area such as agar surface. However, this simple environment is different from the soil, in which C. elegans naturally dwells. To bridge up the gap, this paper presents integration of optogenetic illumination of C. elegans neural circuits and muscular force measurement in a structured microfluidic chip mimicking the C. elegans soil habitat. The microfluidic chip is essentially a ∼1 × 1 cm2 elastomeric polydimethylsiloxane micro-pillar array, configured in either form of lattice (LC) or honeycomb (HC) to mimic the environment in which the worm dwells. The integrated system has four key modules for illumination pattern generation, pattern projection, automatic tracking of the worm, and force measurement. Specifically, two optical pathways co-exist in an inverted microscope, including built-in bright-field illumination for worm tracking and pattern generation, and added-in optogenetic illumination for pattern projection onto the worm body segment. The behavior of a freely moving worm in the chip under optogenetic manipulation can be recorded for off-line force measurements. Using wild-type N2 C. elegans, we demonstrated optical illumination of C. elegans neurons by projecting light onto its head/tail segment at 14 Hz refresh frequency. We also measured the force and observed three representative locomotion patterns of forward movement, reversal, and omega turn for LC and HC configurations. Being capable of stimulating or inhibiting worm neurons and simultaneously measuring the thrust force, this enabling platform would offer new insights into the correlation between neurons and locomotive behaviors of the nematode under a complex environment. 相似文献
4.
Quantifying the motility of micro-organisms is beneficial in understanding their biomechanical properties. This paper presents a simple image-based algorithm to derive the kinetic power and propulsive force of the nematode Caenorhabditis elegans. To avoid unnecessary disturbance, each worm was confined in an aqueous droplet of 0.5 μl. The droplet was sandwiched between two glass slides and sealed with mineral oil to prevent evaporation. For motion visualization, 3-μm fluorescent particles were dispersed in the droplet. Since the droplet formed an isolated environment, the fluid drag and energy loss due to wall frictions were associated with the worm''s kinetic power and propulsion. A microparticle image velocimetry system was used to acquire consecutive particle images for fluid analysis. The short-time interval (Δt < 20 ms) between images enabled quasi real-time measurements. A numerical simulation of the flow in a straight channel showed that the relative error of this algorithm was significantly mitigated as the image was divided into small interrogation windows. The time-averaged power and propulsive force of a N2 adult worm over three swimming cycles were estimated to be 5.2 ± 3.1 pW and 1.0 ± 0.8 nN, respectively. In addition, a mutant, KG532 [kin-2(ce179) X], and a wild-type (N2) worm in a viscous medium were investigated. Both cases showed an increase in the kinetic power as compared with the N2 worm in the nematode growth medium due to the hyperactive nature of the kin-2 mutant and the high viscosity medium used. Overall, the technique deals with less sophisticated calculations and is automation possible. 相似文献
5.
Microfluidics offers unique ways of handling and manipulating microorganisms, which has particularly benefited Caenorhabditis elegans research. Optics plays a major role in these microfluidic platforms, not only as a read-out for the biological systems of interest but also as a vehicle for applying perturbations to biological systems. Here, we describe different areas of research in C. elegans developmental biology and behavior neuroscience enabled by microfluidics combined with the optical components. In particular, we highlight the diversity of optical tools and methods in use and the strategies implemented in microfluidics to make the devices compatible with optical techniques. We also offer some thoughts on future challenges in adapting advancements in optics to microfluidic platforms. 相似文献
6.
A microfluidic device combined with a light modulation system was developed to assess the inhibitory effect of carrageenan on Dengue virus (DENV) infection via real-time monitoring of cellular oxygen consumption rates (OCRs). Measuring cellular OCRs, which can reflect cellular metabolic activity, enabled us to monitor the process of viral infection in real time and to rapidly determine the antiviral activity of potential drugs/chemical compounds. The time variation of the cellular OCR of single cells that were infected in situ by DENV at different multiplicity of infection (m.o.i.) values was first successfully measured within a microfluidic device. The influence of the timing of carrageenan treatment on DENV infection was then examined by real-time monitoring of cellular OCRs in three groups. Cells that were pre-treated with carrageenan and then infected with DENV served as a pre-treatment group, cells to which carrageenan was added simultaneously with DENV served as a virucide group, and cells that were pre-infected with DENV and then treated with carrageenan served as a post-treatment group. By monitoring cellular OCRs, we could rapidly evaluate the inhibitory effect of carrageenan on DENV infection, obtaining a result within 7 h and showing that carrageenan had strong and effective anti-DENV activity in the three groups. In particular, a strong inhibitory effect was observed in the virucide group. Moreover, once the virus enters host cells in the post-treatment group, the immediate treatment with carrageenan for the infected cells has higher efficiency of antiviral activity. Our proposed platform enables to perform time-course or dose-response measurements of changes in cellular metabolic activity caused by diseases, chemical compounds, and drugs via monitoring of the cellular OCR, with rapid and real-time detection. This approach provides the potential to study a wide range of biological applications in cell-based biosensing, toxicology, and drug discovery. 相似文献
7.
针对网络蠕虫的快速传播特性,运用简单流行病学模型和从监控系统获得的非法扫描数据,通过检测非法扫描流量的增长趋势,在蠕虫病毒爆发初期对其进行实时预警,运用数据挖掘技术从扫描数据中自动获取扫描特征,据此特征对蠕虫扫描进行过滤和隔离,阻断蠕虫病毒的传播。 相似文献
8.
Measuring forces applied by multi-cellular organisms is valuable in investigating biomechanics of their locomotion. Several technologies have been developed to measure such forces, for example, strain gauges, micro-machined sensors, and calibrated cantilevers. We introduce an innovative combination of techniques as a high throughput screening tool to assess forces applied by multiple genetic model organisms. First, we fabricated colored Polydimethylsiloxane (PDMS) micropillars where the color enhances contrast making it easier to detect and track pillar displacement driven by the organism. Second, we developed a semi-automated graphical user interface to analyze the images for pillar displacement, thus reducing the analysis time for each animal to minutes. The addition of color reduced the Young''s modulus of PDMS. Therefore, the dye-PDMS composite was characterized using Yeoh''s hyperelastic model and the pillars were calibrated using a silicon based force sensor. We used our device to measure forces exerted by wild type and mutant Caenorhabditis elegans moving on an agarose surface. Wild type C. elegans exert an average force of ∼1 μN on an individual pillar and a total average force of ∼7.68 μN. We show that the middle of C. elegans exerts more force than its extremities. We find that C. elegans mutants with defective body wall muscles apply significantly lower force on individual pillars, while mutants defective in sensing externally applied mechanical forces still apply the same average force per pillar compared to wild type animals. Average forces applied per pillar are independent of the length, diameter, or cuticle stiffness of the animal. We also used the device to measure, for the first time, forces applied by Drosophila melanogaster larvae. Peristaltic waves occurred at 0.4 Hz applying an average force of ∼1.58 μN on a single pillar. Our colored microfluidic device along with its displacement tracking software allows us to measure forces applied by multiple model organisms that crawl or slither to travel through their environment. 相似文献
9.
We here present and characterize a programmable nanoliter scale droplet-on-demand device that can be used separately or readily integrated into low cost single layer rapid prototyping microfluidic systems for a wide range of user applications. The passive microfluidic device allows external (off-the-shelf) electronically controlled pinch valves to program the delivery of nanoliter scale aqueous droplets from up to 9 different inputs to a central outlet channel. The inputs can be either continuous aqueous fluid streams or microliter scale aqueous plugs embedded in a carrier fluid, in which case the number of effective input solutions that can be employed in an experiment is no longer strongly constrained (100 s–1000 s). Both nanoliter droplet sequencing output and nanoliter-scale droplet mixing are reported with this device. Optimization of the geometry and pressure relationships in the device was achieved in several hardware iterations with the support of open source microfluidic simulation software and equivalent circuit models. The requisite modular control of pressure relationships within the device is accomplished using hydrodynamic barriers and matched resistance channels with three different channel heights, custom parallel reversible microfluidic I/O connections, low dead-volume pinch valves, and a simply adjustable array of external screw valves. Programmable sequences of droplet mixes or chains of droplets can be achieved with the device at low Hz frequencies, limited by device elasticity, and could be further enhanced by valve integration. The chip has already found use in the characterization of droplet bunching during export and the synthesis of a DNA library. 相似文献
10.
In this paper, we study the role of temporal coordination in managing the early stages of innovation (aka fuzzy front-end) in the context of virtual teams. Following a comparative case study approach, we detail the role of temporal coordination through the study of two contrasting virtual teams—one with a 24-h lifespan, and one with a five-month lifespan—from two Industry-Academia collaboration projects. Our approach was longitudinal capturing virtual team activities from start to end of each project, and involved multiple data collection methods, including observations and interviews. The findings reveal that the virtual team lifespan influences the type of temporal coordination that emerges. In virtual teams with short lifespans, tight coordination with frequent communication can help to reduce the uncertainty characterizing the fuzzy front-end. On the other hand, in virtual teams with longer lifespans, loose coordination allows dispersed members to work simultaneously on different, complementary aspects of the task at hand. These findings extend scholarly understanding around how innovation activities are coordinated in technology-mediated environments, such as virtual teams. Finally, we discuss theoretical and managerial implications. 相似文献
11.
网络安全形势日渐严峻,病毒、特洛伊木马、网络蠕虫、恶意软件、间谍软件以及拒绝服务(DOS)攻击等各种安全威胁事件成指数级增长。本文针对校园网中蠕虫的防治提出了一套应用方案。 相似文献
12.
13.
Jiseok Lim Ouriel Caen Jérémy Vrignon Manfred Konrad Valérie Taly Jean-Christophe Baret 《Biomicrofluidics》2015,9(3)
Droplet-based microfluidic technologies are powerful tools for applications requiring high-throughput, for example, in biochemistry or material sciences. Several systems have been proposed for the high-throughput production of monodisperse emulsions by parallelizing multiple droplet makers. However, these systems have two main limitations: (1) they allow the use of only a single disperse phase; (2) they are based on multiple layer microfabrication techniques. We present here a pipette-and-play solution offering the possibility of manipulating simultaneously 10 different disperse phases on a single layer device. This system allows high-throughput emulsion production using aqueous flow rates of up to 26 ml/h (>110 000 drops/s) leading to emulsions with user-defined complex chemical composition. We demonstrate the multiplex capabilities of our system by measuring the kinetics of β-galactosidase in droplets using nine different concentrations of a fluorogenic substrate. 相似文献
14.
Francesca Sapuppo Andreu Llobera Florinda Schembri Marcos Intaglietta Victor J. Cadarso Maide Bucolo 《Biomicrofluidics》2010,4(2)
We describe design and miniaturization of a polymeric optical interface for flow monitoring in biomicrofluidics applications based on polydimethylsiloxane technology, providing optical transparency and compatibility with biological tissues. Design and ray tracing simulation are presented as well as device realization and optical analysis of flow dynamics in microscopic blood vessels. Optics characterization of this polymeric microinterface in dynamic experimental conditions provides a proof of concept for the application of the device to two-phase flow monitoring in both in vitro experiments and in vivo microcirculation investigations. This technology supports the study of in vitro and in vivo microfluidic systems. It yields simultaneous optical measurements, allowing for continuous monitoring of flow. This development, integrating a well-known and widely used optical flow monitoring systems, provides a disposable interface between live mammalian tissues and microfluidic devices making them accessible to detection∕processing technology, in support or replacing standard intravital microscopy. 相似文献
15.
Wei Zhou Lili Niu Feiyan Cai Fei Li Chen Wang Xiaowei Huang Jingjing Wang Junru Wu Long Meng Hairong Zheng 《Biomicrofluidics》2016,10(3)
A microfluidic device based on a pair of slant-finger interdigital transducers (SFITs) is developed to achieve a selective and flexible manipulation of microbubbles (MBs) by surface acoustic waves (SAWs). The resonance frequency of SAWs generated by the SFITs depends on the location of its parallel pathway; the particles at different locations of the SAWs'' pathway can be controlled selectively by choosing the frequency of the excitation signal applied on the SFITs. By adjusting the input signal continuously, MBs can be transported along the acoustic aperture precisely. The displacement of MBs has a linear relationship with the frequency shift. The resolution of transportation is 15.19 ± 2.65 μm when the shift of input signal frequency is at a step of 10 kHz. In addition, the MBs can be controlled in a two-dimensional plane by combining variations of the frequency and the relative phase of the excitation signal applied on the SFITs simultaneously. This technology may open up the possibility of selectively and flexibly manipulating MBs using a simple one-dimensional device. 相似文献
16.
We present a novel image-based method to measure the on-chip microfluidic pressure and flow rate simultaneously by using the integrated optofluidic membrane interferometers (OMIs). The device was constructed with two layers of structured polydimethylsiloxane (PDMS) on a glass substrate by multilayer soft lithography. The OMI consists of a flexible air-gap optical cavity which upon illumination by monochromatic light generates interference patterns that depends on the pressure. These interference patterns were captured with a microscope and analyzed by computer based on a pattern recognition algorithm. Compared with the previous techniques for pressure sensing, this method offers several advantages including low cost, simple fabrication, large dynamic range, and high sensitivity. For pressure sensing, we demonstrate a dynamic range of 0-10 psi with an accuracy of ±2% of full scale. Since multiple OMIs can be integrated into a single chip for detecting pressures at multiple locations simultaneously, we also demonstrated a microfluidic flow sensing by measuring the differential pressure along a channel. Thanks to the simple fabrication that is compatible with normal microfluidics, such OMIs can be easily integrated into other microfluidic systems for in situ fluid monitoring. 相似文献
17.
Pamela Green 《Journal of The Franklin Institute》2011,348(3):500-505
The discovery of small RNAs that can turn off genes has given us a new way to think about how genes are regulated. These molecules are present in all complex organisms and are thought to regulate upwards of 30% of human genes. Due to their small size, their discovery was surprisingly recent and was underappreciated initially. Beginning with two back-to-back papers published in 1993, the labs of Victor Ambros and Gary Ruvkun reported the first small RNA (now known as a microRNA or miRNA) and how it regulated a target mRNA in the roundworm Caenorhabditis elegans through base-pairing interactions. It took until 1999 for another report to document novel small RNAs in complex systems, when David Balcoumbe discovered similarly sized molecules, now known as small interfering RNAs or siRNAs, that were associated with shutting off or “silencing” genes in plants. A frenzy of reports on small RNAs and their roles in turning off genes ensued with many researchers including Ambros, Ruvkun, and Baulcombe prominently participating. Almost instantly it became clear that small RNAs were not a quaint oddity exclusive to the worm, and molecular biology was never the same. Now we know that these molecules are critical for normal growth and development, are associated with cancer and other diseases, and have tremendous applied potential to improve agriculture and human health. 相似文献
18.
This article describes a fabrication process for the generation of a leak proof paper based microfluidic device and a new design strategy for convenient incorporation of externally prepared test zones. Briefly, a negative photolithographic method was used to prepare the device with a partial photoresist layer on the rear of the device to block the leakage of sample. Microscopy and Field Emission Scanning Electron Microscopy data validated the formation of the photoresist layer. The partial layer of photoresist on the device channel limits sample volume to 7 ± 0.2 μl as compared to devices without the partial photoresist layer which requires a larger sample volume of 10 ± 0.1 μl. The design prototype with a customized external test zone exploits the channel protrusions on the UV exposed photoresist treated paper to bridge the externally applied test zone to the sample and absorbent zones. The partially laminated device with an external test zone has a comparatively low wicking speed of 1.8 ± 0.9 mm/min compared to the completely laminated device with an inbuilt test zone (3.3 ± 1.2 mm/min) which extends the reaction time between the analyte and reagents. The efficacy of the prepared device was studied with colorimetric assays for the non-specific detection of protein by tetrabromophenol blue, acid/base with phenolphthalein indicator, and specific detection of proteins using the HRP-DAB chemistry. The prepared device has the potential for leak proof detection of analyte, requires low sample volume, involves reduced cost of production (∼$0.03, excluding reagent and lamination cost), and enables the integration of customized test zones. 相似文献
19.
Hui Huang Lili Jiang Shu Li Jun Deng Yan Li Jie Yao Biyuan Li Junsong Zheng 《Biomicrofluidics》2014,8(1)
Molecular gradients play a significant role in regulating biological and pathological processes. Although conventional gradient-generators have been used for studying chemotaxis and axon guidance, there are still many limitations, including the inability to maintain stable tempo-spatial gradients and the lack of the cell monitoring in a real-time manner. To overcome these shortcomings, microfluidic devices have been developed. In this study, we developed a microfluidic gradient device for regulating neuron axon guidance. A microfluidic device enables the generation of Brain-derived neurotrophic factor (BDNF) gradient profiles in a temporal and spatial manner. We test the effect of the gradient profiles on axon guidance, in the BDNF concentration gradient axon towards the high concentration gradient. This microfluidic gradient device could be used as a powerful tool for cell biology research. 相似文献
20.
Sara Baratchi Francisco J. Tovar-Lopez Khashayar Khoshmanesh Megan S. Grace William Darby Juhura Almazi Arnan Mitchell Peter McIntyre 《Biomicrofluidics》2014,8(4)
Shear stress is the major mechanical force applied on vascular endothelial cells by blood flow, and is a crucial factor in normal vascular physiology and in the development of some vascular pathologies. The exact mechanisms of cellular mechano-transduction in mammalian cells and tissues have not yet been elucidated, but it is known that mechanically sensitive receptors and ion channels play a crucial role. This paper describes the use of a novel and efficient microfluidic device to study mechanically-sensitive receptors and ion channels in vitro, which has three independent channels from which recordings can be made and has a small surface area such that fewer cells are required than for conventional flow chambers. The contoured channels of the device enabled examination of a range of shear stresses in one field of view, which is not possible with parallel plate flow chambers and other previously used devices, where one level of flow-induced shear stress is produced per fixed flow-rate. We exposed bovine aortic endothelial cells to different levels of shear stress, and measured the resulting change in intracellular calcium levels ([Ca2+]i) using the fluorescent calcium sensitive dye Fluo-4AM. Shear stress caused an elevation of [Ca2+]i that was proportional to the level of shear experienced. The response was temperature dependant such that at lower temperatures more shear stress was required to elicit a given level of calcium signal and the magnitude of influx was reduced. We demonstrated that shear stress-induced elevations in [Ca2+]i are largely due to calcium influx through the transient receptor potential vanilloid type 4 ion channel. 相似文献