Fluid Propulsion Research Articles

NINL and DZANK1 Co-function in Vesicle Transport and Are Essential for Photoreceptor Development in Zebrafish.

Ciliopathies are Mendelian disorders caused by dysfunction of cilia, ubiquitous organelles involved in fluid propulsion (motile cilia) or signal transduction (primary cilia). Retinal dystrophy is a common phenotypic characteristic of ciliopathies since photoreceptor outer segments are specialized primary cilia. These ciliary structures heavily rely on intracellular minus-end directed transport of cargo, mediated at least in part by the cytoplasmic dynein 1 motor complex, for their formation, maintenance and function. Ninein-like protein (NINL) is known to associate with this motor complex and is an important interaction partner of the ciliopathy-associated proteins lebercilin, USH2A and CC2D2A. Here, we scrutinize the function of NINL with combined proteomic and zebrafish in vivo approaches. We identify Double Zinc Ribbon and Ankyrin Repeat domains 1 (DZANK1) as a novel interaction partner of NINL and show that loss of Ninl, Dzank1 or both synergistically leads to dysmorphic photoreceptor outer segments, accumulation of trans-Golgi-derived vesicles and mislocalization of Rhodopsin and Ush2a in zebrafish. In addition, retrograde melanosome transport is severely impaired in zebrafish lacking Ninl or Dzank1. We further demonstrate that NINL and DZANK1 are essential for intracellular dynein-based transport by associating with complementary subunits of the cytoplasmic dynein 1 motor complex, thus shedding light on the structure and stoichiometry of this important motor complex. Altogether, our results support a model in which the NINL-DZANK1 protein module is involved in the proper assembly and folding of the cytoplasmic dynein 1 motor complex in photoreceptor cells, a process essential for outer segment formation and function.

MiR-34/449 control apical actin network formation during multiciliogenesis through small GTPase pathways.

Vertebrate multiciliated cells (MCCs) contribute to fluid propulsion in several biological processes. We previously showed that microRNAs of the miR-34/449 family trigger MCC differentiation by repressing cell cycle genes and the Notch pathway. Here, using human and Xenopus MCCs, we show that beyond this initial step, miR-34/449 later promote the assembly of an apical actin network, required for proper basal bodies anchoring. Identification of miR-34/449 targets related to small GTPase pathways led us to characterize R-Ras as a key regulator of this process. Protection of RRAS messenger RNA against miR-34/449 binding impairs actin cap formation and multiciliogenesis, despite a still active RhoA. We propose that miR-34/449 also promote relocalization of the actin binding protein Filamin-A, a known RRAS interactor, near basal bodies in MCCs. Our study illustrates the intricate role played by miR-34/449 in coordinating several steps of a complex differentiation programme by regulating distinct signalling pathways.

Microscale flow propulsion through bioinspired and magnetically actuated artificial cilia.

Recent advances in microscale flow propulsion through bioinspired artificial cilia provide a promising alternative for lab-on-a-chip applications. However, the ability of actuating artificial cilia to achieve a time-dependent local flow control with high accuracy together with the elegance of full integration into the biocompatible microfluidic platforms remains remote. Driven by this motive, the current work has constructed a series of artificial cilia inside a microchannel to facilitate the time-dependent flow propulsion through artificial cilia actuation with high-speed (>40 Hz) circular beating behavior. The generated flow was quantified using micro-particle image velocimetry and particle tracking with instantaneous net flow velocity of up to 10(1 ) μm/s. Induced flow patterns caused by the tilted conical motion of artificial cilia constitutes efficient fluid propulsion at microscale. This flow phenomenon was further measured and illustrated by examining the induced flow behavior across the depth of the microchannel to provide a global view of the underlying flow propulsion mechanism. The presented analytic paradigms and substantial flow evidence present novel insights into the area of flow manipulation at microscale.

Lymph formation, composition and circulation: a proteomics perspective.

During the last 20 years a deeper understanding of the lymphatic circulatory system, lymph formation and composition has emerged. This review will examine the current knowledge on the organization of the lymphatic vascular tree, the formation of lymph from the extracellular fluid, lymph circulation and the lymph proteomic composition during physiological and pathological conditions. Formation of the lymph fluid is dependent on pressure gradients in the capillary beds and the composition of the endothelial cell glycocalyx, which acts as a molecular sieve. Fluid propulsion toward the draining node is dependent on the intrinsic pumping mechanism of the lymphangions and their unidirectional valves. The lymph 'omics' composition is dependent on the ultrafiltration of plasma proteins as well as proteins and molecules derived from the metabolic and catabolic activities of each parenchymal organ from which the lymph drains. Altogether, these new insights have brought about a new awareness of the importance of the lymphatic system in human physiology and pathology.

Microfluidic-assisted fabrication of flexible and location traceable organo-motor.

In this paper, we fabricate a flexible and location traceable micromotor, called organo-motor, assisted by microfluidic devices and with high throughput. The organo-motors are composed of organic hydrogel material, poly (ethylene glycol) diacrylate (PEGDA), which can provide the flexibility of their structure. For spatial and temporal traceability of the organo-motors under magnetic resonance imaging (MRI), superparamagnetic iron oxide nanoparticles (SPION; Fe3O4) were incorporated into the PEGDA microhydrogels. Furthermore, a thin layer of platinum (Pt) was deposited onto one side of the SPION-PEGDA microhydrogels providing geometrical asymmetry and catalytic propulsion in aqueous fluids containing hydrogen peroxide solution, H2O2. Furthermore, the motion of the organo-motor was controlled by a small external magnet enabled by the presence of SPION in the motor architecture.

Pneumatically-actuated artificial cilia array for biomimetic fluid propulsion.

Arrays of beating cilia emerged in nature as one of the most efficient propulsion mechanisms at a small scale, and are omnipresent in microorganisms. Previous attempts at mimicking these systems have foundered against the complexity of fabricating small-scale cilia exhibiting complex beating motions. In this paper, we propose for the first time arrays of pneumatically-actuated artificial cilia that are able to address some of these issues. These artificial cilia arrays consist of six highly flexible silicone rubber actuators with a diameter of 1 mm and a length of 8 mm that can be actuated independently from each other. In an experimental setup, the effects of the driving frequency, phase difference and duty cycle on the net flow in a closed-loop channel have been studied. Net fluid speeds of up to 19 mm s(-1) have been measured. Further, it is possible to invert the flow direction by simply changing the driving frequency or by changing the duty cycle of the driving block pulse pressure wave without changing the bending direction of the cilia. Using PIV measurements, we corroborate for the first time existing mathematical models of cilia arrays to measurements on prototypes.

Turning erythrocytes into functional micromotors.

Attempts to apply artificial nano/micromotors for diverse biomedical applications have inspired a variety of strategies for designing motors with diverse propulsion mechanisms and functions. However, existing artificial motors are made exclusively of synthetic materials, which are subject to serious immune attack and clearance upon entering the bloodstream. Herein we report an elegant approach that turns natural red blood cells (RBCs) into functional micromotors with the aid of ultrasound propulsion and magnetic guidance. Iron oxide nanoparticles are loaded into the RBCs, where their asymmetric distribution within the cells results in a net magnetization, thus enabling magnetic alignment and guidance under acoustic propulsion. The RBC motors display efficient guided and prolonged propulsion in various biological fluids, including undiluted whole blood. The stability and functionality of the RBC motors, as well as the tolerability of regular RBCs to the ultrasound operation, are carefully examined. Since the RBC motors preserve the biological and structural features of regular RBCs, these motors possess a wide range of antigenic, transport, and mechanical properties that common synthetic motors cannot achieve and thus hold considerable promise for a number of practical biomedical uses.

Swimming by reciprocal motion at low Reynolds number.

Biological microorganisms swim with flagella and cilia that execute nonreciprocal motions for low Reynolds number (Re) propulsion in viscous fluids. This symmetry requirement is a consequence of Purcell’s scallop theorem, which complicates the actuation scheme needed by microswimmers. However, most biomedically important fluids are non-Newtonian where the scallop theorem no longer holds. It should therefore be possible to realize a microswimmer that moves with reciprocal periodic body-shape changes in non-Newtonian fluids. Here we report a symmetric ‘micro-scallop’, a single-hinge microswimmer that can propel in shear thickening and shear thinning (non-Newtonian) fluids by reciprocal motion at low Re. Excellent agreement between our measurements and both numerical and analytical theoretical predictions indicates that the net propulsion is caused by modulation of the fluid viscosity upon varying the shear rate. This reciprocal swimming mechanism opens new possibilities in designing biomedical microdevices that can propel by a simple actuation scheme in non-Newtonian biological fluids.

Locomotion of microorganisms near a no-slip boundary in a viscoelastic fluid.

Locomotion of microorganisms plays a vital role in most of their biological processes. In many of these processes, microorganisms are exposed to complex fluids while swimming in confined domains, such as spermatozoa in mucus of mammalian reproduction tracts or bacteria in extracellular polymeric matrices during biofilm formation. Thus, it is important to understand the kinematics of propulsion in a viscoelastic fluid near a no-slip boundary. We use a squirmer model with a time-reversible body motion to analytically investigate the swimming kinematics in an Oldroyd-B fluid near a wall. Analysis of the time-averaged motion of the swimmer shows that both pullers and pushers in a viscoelastic fluid swim towards the no-slip boundary if they are initially located within a small domain of "attraction" in the vicinity of the wall. In contrast, neutral swimmers always move towards the wall regardless of their initial distance from the wall. Outside the domain of attraction, pullers and pushers are both repelled from the no-slip boundary. Time-averaged locomotion is most pronounced at a Deborah number of unity. We examine the swimming trajectories of different types of swimmers as a function of their initial orientation and distance from the no-slip boundary.

Continuously distributed magnetization profile for millimeter-scale elastomeric undulatory swimming

We have developed a millimeter-scale magnetically driven swimming robot for untethered motion at mid to low Reynolds numbers. The robot is propelled by continuous undulatory deformation, which is enabled by the distributed magnetization profile of a flexible sheet. We demonstrate control of a prototype device and measure deformation and speed as a function of magnetic field strength and frequency. Experimental results are compared with simple magnetoelastic and fluid propulsion models. The presented mechanism provides an efficient remote actuation method at the millimeter scale that may be suitable for further scaling down in size for micro-robotics applications in biotechnology and healthcare.

Hemingwayis required for sperm flagella assembly and ciliary motility inDrosophila

Cilia play major functions in physiology and development, and ciliary dysfunctions are responsible for several diseases in humans called ciliopathies. Cilia motility is required for cell and fluid propulsion in organisms. In humans, cilia motility deficiencies lead to primary ciliary dyskinesia, with upper-airways recurrent infections, left-right asymmetry perturbations, and fertility defects. In Drosophila, we identified hemingway (hmw) as a novel component required for motile cilia function. hmw encodes a 604-amino acid protein characterized by a highly conserved coiled-coil domain also found in the human orthologue, KIAA1430. We show that HMW is conserved in species with motile cilia and that, in Drosophila, hmw is expressed in ciliated sensory neurons and spermatozoa. We created hmw-knockout flies and found that they are hearing impaired and male sterile. hmw is implicated in the motility of ciliated auditory sensory neurons and, in the testis, is required for elongation and maintenance of sperm flagella. Because HMW is absent from mature flagella, we propose that HMW is not a structural component of the motile axoneme but is required for proper acquisition of motile properties. This identifies HMW as a novel, evolutionarily conserved component necessary for motile cilium function and flagella assembly.

DEVELOPMENT OF A FLOW INJECTION ANALYSIS SYSTEM EMPLOYNG ALTERNATIVE AND LOW-COST MATERIALS FOR DIDACTIC PURPOSES

This work describes a simple and inexpensive flow injection analysis system in which gravity force provides fluid propulsion while needles for insulin administration or metallic wires act as electrodes for amperometric detection. The proposed system was able to demonstrate the influence of several operational parameters on the transient signals. Moreover, this system was successfully used to evaluate both the stoichiometry of Cu2+-EDTA complex and the effect of pH on the kinetics of the reaction between ferricyanide and ascorbic acid. Therefore, the proposed system can be regarded as an efficient and accessible didactic tool for the teaching of FIA principles.

Ferromagnetic shape memory flapper for remotely actuated propulsion systems

Generating propulsion with small-scale devices is a major challenge due to both the domination of viscous forces at low Reynolds numbers as well as the small relative stroke length of traditional actuators. Ferromagnetic shape memory materials are good candidates for such devices as they exhibit a unique combination of large strains and fast responses, and can be remotely activated by magnetic fields. This paper presents the design, analysis, and realization of a novel NiMnGa shear actuation method, which is especially suitable for small-scale fluid propulsion. A fluid mechanics analysis shows that the two key parameters for powerful propulsion are the engineering shear strain and twin boundary velocity. Using high-speed photography, we directly measure both parameters under an alternating magnetic field. Reynolds numbers in the inertial flow regime (>700) are evaluated. Measurements of the transient thrust show values up to 40 mN, significantly higher than biological equivalents. This work paves the way for new remotely activated and controlled propulsion for untethered micro-scale robots.

The cilium in lights: new views of an ancient organelle

Nearly all cells have cilia, microtubule based projections from the apical cell surface, and nearly all cells use them in essential and unique ways. How mammalian cilia function in vivo as mechanosensors, signal transducers, or in fluid propulsion has been difficult to study due to lack of tools for live imaging of cilia. A new transgenic mouse that enables tissue-specific GFP labeling of cilia creates new opportunities for using live imaging to understand cilium function and to better characterize the many genetic models of ciliopathies.See research article: http://www.ciliajournal.com/content/2/1/8

Fluid propulsion using magnetically-actuated artificial cilia – experiments and simulations

We conducted a combined modelling and experimental approach to explore the underlying physical mechanisms responsible for fluid flow caused by magnetically-actuated plate-like artificial cilia. After independently calibrating the elastic and magnetic properties of the cilia, the model predictions are observed to be in excellent agreement with the experimental results. We show that the fluid propelled is due to a combination of asymmetric motion and fluid inertia forces. The asymmetric motion of the cilia and inertial forces contribute equally to the total fluid flow. We have performed a parametric study and found the cilia thickness and magnetic field that should be applied in order to maximise the fluid transport.

Integration of multiple components in polystyrene-based microfluidic devices part I: fabrication and characterization

In Part I of a two-part series, we describe a simple and inexpensive approach to fabricate polystyrene devices that is based upon melting polystyrene (from either a Petri dish or powder form) against PDMS molds or around electrode materials. The ability to incorporate microchannels in polystyrene and integrate the resulting device with standard laboratory equipment such as an optical plate reader for analyte readout and pipets for fluid propulsion is first described. A simple approach for sample and reagent delivery to the device channels using a standard, multi-channel micropipette and a PDMS-based injection block is detailed. Integration of the microfluidic device with these off-chip functions (sample delivery and readout) enables high-throughput screens and analyses. An approach to fabricate polystyrene-based devices with embedded electrodes is also demonstrated, thereby enabling the integration of microchip electrophoresis with electrochemical detection through the use of a palladium electrode (for a decoupler) and carbon-fiber bundle (for detection). The device was sealed against a PDMS-based microchannel and used for the electrophoretic separation and amperometric detection of dopamine, epinephrine, catechol, and 3,4-dihydroxyphenylacetic acid. Finally, these devices were compared against PDMS-based microchips in terms of their optical transparency and absorption of an anti-platelet drug, clopidogrel. Part I of this series lays the foundation for Part II, where these devices were utilized for various on-chip cellular analysis.

A MAGNETOHYDRODYNAMIC STUDY OF BEHAVIOR IN AN ELECTROLYTE FLUID USING NUMERICAL AND EXPERIMENTAL SOLUTIONS

This article examines a rectangular closed circuit filled with an electrolyte fluid, known as macro pumps, where a permanent magnet generates a magnetic field and electrodes generate the electric field in the flow. The fluid conductor moves inside the circuit under magnetohydrodynamic effect (MHD). The MHD model has been derived from the Navier Stokes equation and coupled with the Maxwell equations for Newtonian incompressible fluid. Electric and magnetic components engaged in the test chamber assist in creating the propulsion of the electrolyte fluid. The electromagnetic forces that arise are due to the cross product between the vector density of induced current and the vector density of magnetic field applied. This is the Lorentz force. Results are present of 3D numerical MHD simulation for newtonian fluid as well as experimental data. The goal is to relate the magnetic field with the electric field and the amounts of movement produced, and calculate de current density and fluid velocity. An u-shaped and m-shaped velocity profile is expected in the flows. The flow analysis is performed with the magnetic field fixed, while the electric field is changed. Observing the interaction between the fields strengths, and density of the electrolyte fluid, an optimal configuration for the flow velocity isdetermined and compared with others publications.

Kirigami artificial muscles with complex biologically inspired morphologies

In this paper we present bio-inspired smart structures which exploit the actuation of flexible ionic polymer composites and the kirigami design principle. Kirigami design is used to convert planar actuators into active 3D structures capable of large out-of-plane displacement and that replicate biological mechanisms. Here we present the burstbot, a fluid control and propulsion mechanism based on the atrioventricular cuspid valve, and the vortibot, a spiral actuator based on Vorticella campanula, a ciliate protozoa. Models derived from biological counterparts are used as a platform for design optimization and actuator performance measurement. The symmetric and asymmetric fluid interactions of the burstbot are investigated and the effectiveness in fluid transport applications is demonstrated. The vortibot actuator is geometrically optimized as a camera positioner capable of 360° scanning. Experimental results for a one-turn spiral actuator show complex actuation derived from a single degree of freedom control signal.

Thermodynamics of Angular Propulsion in Fluids

The presented study examines the energetics of confined fluid flow in a rotating reference frame. Parallels are drawn to the corresponding scenario of rectilinear motion, where ejection of fluid results in linear propulsion of the frame. Absorption of flow energy into the frame motion leads to cooling of the ejected fluid. Relevance of the observed energetics to the temperature separation phenomenon in Ranque-Hilsch vortex tubes is discussed.

Bio-Inspired Omnidirectional Multilink Propulsion Mechanism in Fluid

Since most organisms are fairly autonomic, functional and efficient, the study of machines modeled on the movements of organisms has become significant in the engineering field. From this point of view, we observed organisms that swim in water by bending motions and noticed that the direction in which polychaetes swim differs from that of nematodes. This is explained by fleshy protrusions, called parapodia, that increase the worm’s tangential drag component during its movement in water. In this study, we have developed a bio-inspired omnidirectional in fluid propulsion mechanism that changes the angle of these protrusions.