An integrated platform enabling optogenetic illumination of Caenorhabditis elegans neurons and muscular force measurement in microstructured environments     

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   

A programmable microvalve-based microfluidic array for characterization of neurotoxin-induced responses of individual C. elegans     

Hui Ma  Lei Jiang  Weiwei Shi  Jianhua Qin    Bingcheng Lin 《Biomicrofluidics》2009,3(4)

The soil dwelling nematode Caenorhabditis elegans (C. elegans) is an excellent model organism for the study of numerous disease including neurodegenerative disease. In this study, a programmable microvalve-based microfluidic array for real-time and long-term monitoring of the neurotoxin-induced responses of the individual C. elegans was developed. The device consisted of a flow layer and a control layer, which were used for worm manipulation. By activating the programmable microvalves in the control layer, mutiple worms could be individually captured and intermittently immobilized in parallel channels. Thus the mobility behavior, together with the corresponding dopaminergic neuron features of the worms in response to neurotoxin, could be investigated simultaneously. It was found that the neurotoxin MPP+ enabled to induce mobility defects and dopaminergic neurons loss in worms. The established system is easy and fast to operate, which offers not only the controllable microenvironment for analyzing the individual worms in parallel, monitoring the same worm over time, but also the capability to characterize the mobility behavior and neuron features in response to stimuli simultaneously. In addition, the device enabled to sustain the worm culture over most of their adult lifespan without any harm to worm, providing a potential platform for lifespan and aging research.  相似文献   

A perspective on optical developments in microfluidic platforms for Caenorhabditis elegans research     

Guillaume Aubry  Hang Lu 《Biomicrofluidics》2014,8(1)

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   

Microfluidic platform integrated with worm-counting setup for assessing manganese toxicity     

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   

Modeling and validation of autoinducer-mediated bacterial gene expression in microfluidic environments     

Caitlin M. Austin  William Stoy  Peter Su  Marie C. Harber  J. Patrick Bardill  Brian K. Hammer  Craig R. Forest 《Biomicrofluidics》2014,8(3)

Biosensors exploiting communication within genetically engineered bacteria are becoming increasingly important for monitoring environmental changes. Currently, there are a variety of mathematical models for understanding and predicting how genetically engineered bacteria respond to molecular stimuli in these environments, but as sensors have miniaturized towards microfluidics and are subjected to complex time-varying inputs, the shortcomings of these models have become apparent. The effects of microfluidic environments such as low oxygen concentration, increased biofilm encapsulation, diffusion limited molecular distribution, and higher population densities strongly affect rate constants for gene expression not accounted for in previous models. We report a mathematical model that accurately predicts the biological response of the autoinducer N-acyl homoserine lactone-mediated green fluorescent protein expression in reporter bacteria in microfluidic environments by accommodating these rate constants. This generalized mass action model considers a chain of biomolecular events from input autoinducer chemical to fluorescent protein expression through a series of six chemical species. We have validated this model against experimental data from our own apparatus as well as prior published experimental results. Results indicate accurate prediction of dynamics (e.g., 14% peak time error from a pulse input) and with reduced mean-squared error with pulse or step inputs for a range of concentrations (10 μM–30 μM). This model can help advance the design of genetically engineered bacteria sensors and molecular communication devices.  相似文献   

Real-time detection, control, and sorting of microfluidic droplets   总被引：1，自引：0，他引：1  

Xize Niu  Mengying Zhang  Suili Peng  Weijia Wen    Ping Sheng 《Biomicrofluidics》2007,1(4)

We report the design and implementation of capacitive detection and control of microfluidic droplets in microfluidic devices. Integrated microfluidic chip(s) with detection∕control circuit enables us to monitor in situ the individual volume of droplets, ranging from nanoliter to picoliter, velocity and even composition, with an operation frequency of several kilohertz. Through electronic feedback, we are able to easily count, sort, and direct the microfluidic droplets. Potential applications of this approach can be employed in the areas of biomicrofluidic processing, microchemical reactions as well as digital microfluidics.  相似文献   

Preface to Special Topic: Microfluidics in Drug Delivery     

Brigitte Stadler 《Biomicrofluidics》2015,9(5)

In this special topic of Biomicrofluidics, the importance of microfluidics in the field of drug delivery is highlighted. Different aspects from cell-drug carrier interactions, delivery vehicle assembly to novel drug delivery devices are considered. The contributing reviews and original articles illustrate the synergistic outcomes between these two areas of research with the aim to have a positive impact on biomedical applications.Microfluidics is certainly one of the huge success stories when it comes to anticipated impact and fulfilled promises in academic research environments. Microfluidic approaches are game changers in many disciplines in natural science, including (bio)medical science. In the latter case, the fields of biosensing/diagnostics, tissue engineering, and drug discovery/delivery have benefited from concepts which allow for the fast throughput manipulation of fluids at the submillimeter length scale.A key aim in microfluidic-assisted drug discovery is the development of strategies which will facilitate the identification of potential “hits”—new drugs with the anticipated therapeutic benefit. In this context, “organ(disease)-on-chips” are considered as highly sophisticated in vitro models with lower cost and less ethical issues compared to extensive testing in animals. This technology is still very young with countless research challenges to be addressed and eventually overcome, but the few current reports are promising, and include “gut-on-chip,” “cancer-on-chip,” or “blood vessel-on-chip.” Additionally, intravenously injected drug delivery vehicles are exposed to the blood stream and the induced mechanical forces which are likely to affect their interaction with cells and tissue. Therefore, understanding the diffusion phenomena of biomolecules in microfluidic devices as reviewed by Yesil-Celiktas and coworkers in the current special content is crucial.¹ What is more, the contribution by Hosta-Rigau and colleagues provides a comprehensive overview over the interaction of drug carriers and cells in microfluidic-based systems which deliver a simple, but yet more realistic model of the dynamic in vivo situation.² Further, to illustrate the relevance of shear stress when assessing the potential of nanocarriers for drug delivery applications, we assembled novel block copolymers consisting of poly(cholesteryl acrylate) as the hydrophobic core and poly(N-isopropylacrylamide) as the hydrophilic extensions together with lipids into vesicles using the evaporation-rehydration method.³ Following on, we biologically evaluated the assemblies with applied shear stress using macrophages. In a related report by the Chakraborty group, a biocompatible acoustic microfluidic system was outlined including the effect of microbubbles with the applied acoustic field on biological cells.⁴From a different perspective, droplet microfluidics has become a popular method to assemble a huge diversity of particles of different size, shape, and morphology equipped with options for active or passive drug release. Microfluidics provides unique opportunities and flexibility to fabricate decent amounts of mono-disperse drug carriers using monomers, polymers, lipids, or inorganic precursor materials as building blocks. The assembly of size-tunable polymer/lipid particles by Sun et al.,⁵ and the fabrication of poly (lactic-co-glycolic acid) nanoparticles incorporated within poly (ethylene glycol) (PEG) microgels by the Chen group,⁶ provide interesting examples in this context. Further, artefacts associated with this technique have to be addressed and understood to avoid inaccurate and misleading data as reported by Litten et al.⁷ Microfluidic techniques can also be employed for cell encapsulation. Fan et al. demonstrated the trapping of human colon cancer cells in hydrogel particles with preserved viability and response to inflammatory stimuli.⁸Novel drug delivery devices which consider microfluidic concepts and set-ups are an interesting addition to traditional approaches. Implantable drug delivery systems provide an alternative to ensure constant drug level in blood without relying on the compliance of the patient while circumventing challenges involved in oral drug delivery coming from drug instability or limited absorbance among others. Yi and coworkers propose a reservoir approach in combination with a heat responsive valve towards the long term delivery of solid drugs.⁹ What is more, nebulizers, as alternative to inhalers for pulmonary drug delivery, suffer from miniaturization and drug degradation issues. Cortez-Jugo et al. report on a novel portable acoustomicrofluidic device, which successfully nebulized monoclonal antibodies into a fine aerosol mist including the first positive biological evaluation.¹⁰Further, combining microfluidics with sensing concepts as illustrated by Knoll and coworker¹¹ is of importance, since the design of drug delivery vehicles strongly relies on the fundamental understanding of the interaction between biomolecules, cells, and tissue.Taken together, these articles give an overview over the use of microfluidics in the area of drug delivery, which goes beyond the assembly of drug carries, but also provides a platform for their biological evaluation or the design of entirely new drug delivery devices. I hope that this collection of articles will stimulate new ideas and future collaborations between engineers/chemists/physicist and biologists towards the common goal to provide solutions for biomedical challenges. Finally, I would like to thank Professor Leslie Yeo for the invitation to be the guest editor for this special topic, and Christine Urso and other editorial and production staffs of Biomicrofluidics for making it a reality.  相似文献   

A multichannel acoustically driven microfluidic chip to study particle-cell interactions     

Xue-Yan Wang  Christian Fillafer  Clara Pichl  Stephanie Deinhammer  Renate Hofer-Warbinek  Michael Wirth  Franz Gabor 《Biomicrofluidics》2013,7(4)

Microfluidic devices have emerged as important tools for experimental physiology. They allow to study the effects of hydrodynamic flow on physiological and pathophysiological processes, e.g., in the circulatory system of the body. Such dynamic in vitro test systems are essential in order to address fundamental problems in drug delivery and targeted imaging, such as the binding of particles to cells under flow. In the present work an acoustically driven microfluidic platform is presented in which four miniature flow channels can be operated in parallel at distinct flow velocities with only slight inter-experimental variations. The device can accommodate various channel architectures and is fully compatible with cell culture as well as microscopy. Moreover, the flow channels can be readily separated from the surface acoustic wave pumps and subsequently channel-associated luminescence, absorbance, and/or fluorescence can be determined with a standard microplate reader. In order to create artificial blood vessels, different coatings were evaluated for the cultivation of endothelial cells in the microchannels. It was found that 0.01% fibronectin is the most suitable coating for growth of endothelial monolayers. Finally, the microfluidic system was used to study the binding of 1 μm polystyrene microspheres to three different types of endothelial cell monolayers (HUVEC, HUVECtert, HMEC-1) at different average shear rates. It demonstrated that average shear rates between 0.5 s⁻¹ and 2.25 s⁻¹ exert no significant effect on cytoadhesion of particles to all three types of endothelial monolayers. In conclusion, the multichannel microfluidic platform is a promising device to study the impact of hydrodynamic forces on cell physiology and binding of drug carriers to endothelium.  相似文献   

Label-free viscosity measurement of complex fluids using reversal flow switching manipulation in a microfluidic channel     

Yang Jun Kang  Jeongeun Ryu  Sang-Joon Lee 《Biomicrofluidics》2013,7(4)

The accurate viscosity measurement of complex fluids is essential for characterizing fluidic behaviors in blood vessels and in microfluidic channels of lab-on-a-chip devices. A microfluidic platform that accurately identifies biophysical properties of blood can be used as a promising tool for the early detections of cardiovascular and microcirculation diseases. In this study, a flow-switching phenomenon depending on hydrodynamic balancing in a microfluidic channel was adopted to conduct viscosity measurement of complex fluids with label-free operation. A microfluidic device for demonstrating this proposed method was designed to have two inlets for supplying the test and reference fluids, two side channels in parallel, and a junction channel connected to the midpoint of the two side channels. According to this proposed method, viscosities of various fluids with different phases (aqueous, oil, and blood) in relation to that of reference fluid were accurately determined by measuring the switching flow-rate ratio between the test and reference fluids, when a reverse flow of the test or reference fluid occurs in the junction channel. An analytical viscosity formula was derived to measure the viscosity of a test fluid in relation to that of the corresponding reference fluid using a discrete circuit model for the microfluidic device. The experimental analysis for evaluating the effects of various parameters on the performance of the proposed method revealed that the fluidic resistance ratio (R_JL/R_L, fluidic resistance in the junction channel (R_JL) to fluidic resistance in the side channel (R_L)) strongly affects the measurement accuracy. The microfluidic device with smaller R_JL/R_L values is helpful to measure accurately the viscosity of the test fluid. The proposed method accurately measured the viscosities of various fluids, including single-phase (Glycerin and plasma) and oil-water phase (oil vs. deionized water) fluids, compared with conventional methods. The proposed method was also successfully applied to measure viscosities of blood with varying hematocrits, chemically fixed RBC_S, and channel sizes. Based on these experimental results, the proposed method can be effectively used to measure the viscosities of various fluids easily, without any fluorescent labeling and tedious calibration procedures.  相似文献   

3D printed microfluidic devices with integrated valves     

Chad I. Rogers  Kamran Qaderi  Adam T. Woolley  Gregory P. Nordin 《Biomicrofluidics》2015,9(1)

We report the successful fabrication and testing of 3D printed microfluidic devices with integrated membrane-based valves. Fabrication is performed with a low-cost commercially available stereolithographic 3D printer. Horizontal microfluidic channels with designed rectangular cross sectional dimensions as small as 350 μm wide and 250 μm tall are printed with 100% yield, as are cylindrical vertical microfluidic channels with 350 μm designed (210 μm actual) diameters. Based on our previous work [Rogers et al., Anal. Chem. 83, 6418 (2011)], we use a custom resin formulation tailored for low non-specific protein adsorption. Valves are fabricated with a membrane consisting of a single build layer. The fluid pressure required to open a closed valve is the same as the control pressure holding the valve closed. 3D printed valves are successfully demonstrated for up to 800 actuations.  相似文献   

Smartphone-interfaced lab-on-a-chip devices for field-deployable enzyme-linked immunosorbent assay     

Arnold Chen  Royal Wang  Candace R. S. Bever  Siyuan Xing  Bruce D. Hammock  Tingrui Pan 《Biomicrofluidics》2014,8(6)

The emerging technologies on mobile-based diagnosis and bioanalytical detection have enabled powerful laboratory assays such as enzyme-linked immunosorbent assay (ELISA) to be conducted in field-use lab-on-a-chip devices. In this paper, we present a low-cost universal serial bus (USB)-interfaced mobile platform to perform microfluidic ELISA operations in detecting the presence and concentrations of BDE-47 (2,2′,4,4′-tetrabromodiphenyl ether), an environmental contaminant found in our food supply with adverse health impact. Our point-of-care diagnostic device utilizes flexible interdigitated carbon black electrodes to convert electric current into a microfluidic pump via gas bubble expansion during electrolytic reaction. The micropump receives power from a mobile phone and transports BDE-47 analytes through the microfluidic device conducting competitive ELISA. Using variable domain of heavy chain antibodies (commonly referred to as single domain antibodies or Nanobodies), the proposed device is sensitive for a BDE-47 concentration range of 10⁻³–10⁴μg/l, with a comparable performance to that uses a standard competitive ELISA protocol. It is anticipated that the potential impact in mobile detection of health and environmental contaminants will prove beneficial to our community and low-resource environments.  相似文献   

Implementation of tetra-poly(ethylene glycol) hydrogel with high mechanical strength into microfluidic device technology     

Hiroaki Takehara  Akira Nagaoka  Jun Noguchi  Takanori Akagi  Takamasa Sakai  Ung-il Chung  Haruo Kasai  Takanori Ichiki 《Biomicrofluidics》2013,7(5)

Hydrogels have several excellent characteristics suitable for biomedical use such as softness, biological inertness and solute permeability. Hence, integrating hydrogels into microfluidic devices is a promising approach for providing additional functions such as biocompatibility and porosity, to microfluidic devices. However, the poor mechanical strength of hydrogels has severely limited device design and fabrication. A tetra-poly(ethylene glycol) (tetra-PEG) hydrogel synthesized recently has high mechanical strength and is expected to overcome such a limitation. In this research, we have comprehensively studied the implementation of tetra-PEG gel into microfluidic device technology. First, the fabrication of tetra-PEG gel/PDMS hybrid microchannels was established by developing a simple and robust bonding technique. Second, some fundamental features of tetra-PEG gel/PDMS hybrid microchannels, particularly fluid flow and mass transfer, were studied. Finally, to demonstrate the unique application of tetra-PEG-gel-integrated microfluidic devices, the generation of patterned chemical modulation with the maximum concentration gradient: 10% per 20 μm in a hydrogel was performed. The techniques developed in this study are expected to provide fundamental and beneficial methods of developing various microfluidic devices for life science and biomedical applications.  相似文献   

Microfluidics based on ZnO/nanocrystalline diamond surface acoustic wave devices   总被引：1，自引：0，他引：1  

Fu YQ  Garcia-Gancedo L  Pang HF  Porro S  Gu YW  Luo JK  Zu XT  Placido F  Wilson JI  Flewitt AJ  Milne WI 《Biomicrofluidics》2012,6(2):24105-2410511

Surface acoustic wave (SAW) devices with 64 μm wavelength were fabricated on a zinc oxide (ZnO) film deposited on top of an ultra-smooth nanocrystalline diamond (UNCD) layer. The smooth surface of the UNCD film allowed the growth of the ZnO film with excellent c-axis orientation and low surface roughness, suitable for SAW fabrication, and could restrain the wave from significantly dissipating into the substrate. The frequency response of the fabricated devices was characterized and a Rayleigh mode was observed at ∼65.4 MHz. This mode was utilised to demonstrate that the ZnO/UNCD SAW device can be successfully used for microfluidic applications. Streaming, pumping, and jetting using microdroplets of 0.5 and 20 μl were achieved and characterized under different powers applied to the SAW device, focusing more on the jetting behaviors induced by the ZnO SAW.  相似文献   

Single nanopore transport of synthetic and biological polyelectrolytes in three-dimensional hybrid microfluidic∕nanofluidic devices     

Travis L. King  Enid N. Gatimu  Paul W. Bohn 《Biomicrofluidics》2009,3(1)

This paper presents a study of electrokinetic transport in single nanopores integrated into vertically stacked three-dimensional hybrid microfluidic∕nanofluidic structures. In these devices, single nanopores, created by focused ion beam (FIB) milling in thin polymer films, provide fluidic connection between two vertically separated, perpendicular microfluidic channels. Experiments address both systems in which the nanoporous membrane is composed of the same (homojunction) or different (heterojunction) polymer as the microfluidic channels. These devices are then used to study the electrokinetic transport properties of synthetic (i.e., polystyrene sulfonate and polyallylamine) and biological (i.e., DNA) polyelectrolytes across these nanopores using both electrical current measurements and confocal microscopy. Both optical and electrical measurements indicate that electro-osmotic transport is predominant over electrophoresis in single nanopores with d>180 nm, consistent with results obtained under similar conditions for nanocapillary array membranes.  相似文献   

Bistability in droplet traffic at asymmetric microfluidic junctions   总被引：1，自引：0，他引：1  

Pravien Parthiban  Saif A. Khan 《Biomicrofluidics》2013,7(4)

We present the first experimental demonstration of confined microfluidic droplets acting as discrete negative resistors, wherein the effective hydrodynamic resistance to flow in a microchannel is reduced by the presence of a droplet. The implications of this hitherto unexplored regime in the traffic of droplets in microfluidic networks are highlighted by demonstrating bistable filtering into either arm of symmetric and asymmetric microfluidic loops, and programming oscillatory droplet routing therein.  相似文献   

Three-dimensional fit-to-flow microfluidic assembly     

Chen A  Pan T 《Biomicrofluidics》2011,5(4):46505-465059

Three-dimensional microfluidics holds great promise for large-scale integration of versatile, digitalized, and multitasking fluidic manipulations for biological and clinical applications. Successful translation of microfluidic toolsets to these purposes faces persistent technical challenges, such as reliable system-level packaging, device assembly and alignment, and world-to-chip interface. In this paper, we extended our previously established fit-to-flow (F2F) world-to-chip interconnection scheme to a complete system-level assembly strategy that addresses the three-dimensional microfluidic integration on demand. The modular F2F assembly consists of an interfacial chip, pluggable alignment modules, and multiple monolithic layers of microfluidic channels, through which convoluted three-dimensional microfluidic networks can be easily assembled and readily sealed with the capability of reconfigurable fluid flow. The monolithic laser-micromachining process simplifies and standardizes the fabrication of single-layer pluggable polymeric modules, which can be mass-produced as the renowned Lego^® building blocks. In addition, interlocking features are implemented between the plug-and-play microfluidic chips and the complementary alignment modules through the F2F assembly, resulting in facile and secure alignment with average misalignment of 45 μm. Importantly, the 3D multilayer microfluidic assembly has a comparable sealing performance as the conventional single-layer devices, providing an average leakage pressure of 38.47 kPa. The modular reconfigurability of the system-level reversible packaging concept has been demonstrated by re-routing microfluidic flows through interchangeable modular microchannel layers.  相似文献   

Colored polydimethylsiloxane micropillar arrays for high throughput measurements of forces applied by genetic model organisms     

Siddharth M. Khare  Anjali Awasthi  V. Venkataraman  Sandhya P. Koushika 《Biomicrofluidics》2015,9(1)

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   

A microfluidic chip for controlled release of drugs from microcapsules     

Wen-Chuan Cheng  Yuan He  An-Yi Chang  Long Que 《Biomicrofluidics》2013,7(6)

A new microfluidic device with liquid-droplet merging and droplet storage functions for the controlled release of drugs from microcapsules is reported. A switching channel is designed and integrated within the microfluidic device, facilitating the generation and capturing of uniform droplets by the storage chambers. The drug model is the MnCO₃ microparticle, which is encapsulated by a microcapsule and fabricated using a simple layer-by-layer nanoassembly process. The merging function is used for dynamically adding the control solution into the droplets, which contain drugs within the microcapsules (DWμCs) and water. The storage chambers are used for collecting DWμCs-laden droplets so that the controlled-drug release in specific droplets can be monitored for an extended period of time, which has been experimentally implemented successfully. This technology could offer a promising technical platform for the long-term observation and studies of drug effects on specific cells in a controlled manner, which is especially useful for single cell analysis.  相似文献   

A standalone perfusion platform for drug testing and target validation in micro-vessel networks     

Boyang Zhang  Carlotta Peticone  Shashi K. Murthy  Milica Radisic 《Biomicrofluidics》2013,7(4)

Studying the effects of pharmacological agents on human endothelium includes the routine use of cell monolayers cultivated in multi-well plates. This configuration fails to recapitulate the complex architecture of vascular networks in vivo and does not capture the relationship between shear stress (i.e. flow) experienced by the cells and dose of the applied pharmacological agents. Microfluidic platforms have been applied extensively to create vascular systems in vitro; however, they rely on bulky external hardware to operate, which hinders the wide application of microfluidic chips by non-microfluidic experts. Here, we have developed a standalone perfusion platform where multiple devices were perfused at a time with a single miniaturized peristaltic pump. Using the platform, multiple micro-vessel networks, that contained three levels of branching structures, were created by culturing endothelial cells within circular micro-channel networks mimicking the geometrical configuration of natural blood vessels. To demonstrate the feasibility of our platform for drug testing and validation assays, a drug induced nitric oxide assay was performed on the engineered micro-vessel network using a panel of vaso-active drugs (acetylcholine, phenylephrine, atorvastatin, and sildenafil), showing both flow and drug dose dependent responses. The interactive effects between flow and drug dose for sildenafil could not be captured by a simple straight rectangular channel coated with endothelial cells, but it was captured in a more physiological branching circular network. A monocyte adhesion assay was also demonstrated with and without stimulation by an inflammatory cytokine, tumor necrosis factor-α.  相似文献   

Quantitative characterization of micromixing simulation     

Zhiyi Zhang  ChaeHo Yim  Min Lin    Xudong Cao 《Biomicrofluidics》2008,2(3)

Micromixers with floor-grooved microfluidic channels have been successfully demonstrated in experiment. In this work, we numerically simulated the mixing within the devices and used the obtained concentration versus channel length profiles to quantitatively characterize the process. It was found that the concentration at any given cross-section location of the microfluidic channel periodically oscillates along the channel length, in coordination with the groove-caused helical flow during the mixing, and eventually converges to the neutral concentration value of two the mixing fluids. With these data, the specific channel length required for each helical flow to complete, the mixing efficiency of the devices, and the total channel length required to complete a mixing were easily defined and quantified, and were used to directly and comprehensively characterize the micromixing. This concentration versus channel length profile-based characterization method was also demonstrated in quantitatively analyzing the micromixing within a classic T mixer. It has clear advantages over the traditional concentration image-based characterization method that is only able to provide qualitative or semiquantitative information about a micromixing, and is expected to find an increasing use in studying mixing and optimizing device structure through numerical simulations.  相似文献