Parkinson’s disease (PD) is a progressive neurological disorder associated with the loss of dopaminergic neurons (DNs) in the substantia nigra and the widespread accumulation of α-synuclein (α-syn) protein, leading to motor impairments and eventual cognitive dysfunction. In-vitro cell cultures and in-vivo animal models have provided the opportunity to investigate the PD pathological hallmarks and identify different therapeutic compounds. However, PD pathogenesis and causes are still not well understood, and effective inhibitory drugs for PD are yet to be discovered. Biologically simple but pathologically relevant disease models and advanced screening technologies are needed to reveal the mechanisms underpinning protein aggregation and PD progression. For instance, Caenorhabditis elegans (C. elegans) offers many advantages for fundamental PD neurobehavioral studies including a simple, well-mapped, and accessible neuronal system, genetic homology to humans, body transparency and amenability to genetic manipulation. Several transgenic worm strains that exhibit multiple PD-related phenotypes have been developed to perform neuronal and behavioral assays and drug screening. However, in conventional worm-based assays, the commonly used techniques are equipment-intensive, slow and low in throughput. Over the past two decades, microfluidics technology has contributed significantly to automation and control of C. elegans assays. In this review, we focus on C. elegans PD models and the recent advancements in microfluidic platforms used for manipulation, handling and neurobehavioral screening of these models. Moreover, we highlight the potential of C. elegans to elucidate the in-vivo mechanisms of neuron-to-neuron protein transfer that may underlie spreading Lewy pathology in PD, and its suitability for in-vitro studies. Given the advantages of C. elegans and microfluidics technology, their integration has the potential to facilitate the investigation of disease pathology and discovery of potential chemical leads for PD.
Ocean waves are one of the cleanest and most abundant energy sources on earth, and wave energy has the potential for future power generation. Triboelectric nanogenerator (TENG) technology has recently been proposed as a promising technology to harvest wave energy. In this paper, a theoretical study is performed on a duck-shaped TENG wave harvester recently introduced in our work. To enhance the design of the duck-shaped TENG wave harvester, the mechanical and electrical characteristics of the harvester’s overall structure, as well as its inner configuration, are analyzed, respectively, under different wave conditions, to optimize parameters such as duck radius and mass. Furthermore, a comprehensive hybrid 3D model is introduced to quantify the performance of the TENG wave harvester. Finally, the influence of different TENG parameters is validated by comparing the performance of several existing TENG wave harvesters. This study can be applied as a guideline for enhancing the performance of TENG wave energy harvesters.
This work presents an innovative technique to enhance the performance of the Savonius wind turbine. The new technique is based on introducing an upstream deflector and downstream baffle. The shape and location of both devices are optimized using a genetic algorithm. The performance of the turbine with the optimized devices is compared with the single Savonius turbine performance. The study employs the finite volume solver (ANSYS-FLUENT) to solve unsteady Reynolds Averaged Navier–Stokes equations and turbulence model equations. The optimized configuration results in much higher power coefficient than the Savonius turbine. The average peak power coefficient using both deflector and baffle is 0.47 compared to 0.24 of the Savonius turbine. The peak power coefficient of the turbine corresponds to a speed ratio close to unity. This improved performance is attributed to the favorable aerodynamic interaction between the turbine and the downstream baffle which accelerates the flow around the rotor and generates larger turning torque. The baffle generates a jet effect on the advancing bucket and accelerates the flow behind the bucket creating a large zone of negative pressure and thereby increases the driving torque. Furthermore, the upstream deflector (also called shield or curtain) produces a shield for the returning bucket of the turbine which diminishes the adverse effect associated with the returning bucket on the aerodynamic torque of the turbine. This remarkable improvement of turbine performance will encourage the future application of the Savonius wind turbine in small power applications of wind energy.
Behavioral responses of zebrafish larvae to environmental cues are important functional readouts that should be evoked on-demand and studied phenotypically in behavioral, genetical and developmental investigations. Very recently, it was shown that zebrafish larvae execute a voluntary and oriented movement toward the positive electrode of an electric field along a microchannel. Phenotypic characterization of this response was not feasible due to larva’s rapid movement along the channel. To overcome this challenge, a microfluidic device was introduced to partially immobilize the larva’s head while leaving its mid-body and tail unrestrained in a chamber to image motor behaviors in response to electric stimulation, hence achieving quantitative phenotyping of the electrically evoked movement in zebrafish larvae. The effect of electric current on the tail-beat frequency and response duration of 5–7 days postfertilization zebrafish larvae was studied. Investigations were also performed on zebrafish exposed to neurotoxin 6-hydroxydopamine and larvae carrying a pannexin1a (panx1a) gene knockout, as a proof of principle applications to demonstrate on-demand movement behavior screening in chemical and mutant assays. We demonstrated for the first time that 6-hydroxydopamine leads to electric response impairment, levodopa treatment rescues the response and panx1a is involved in the electrically evoked movement of zebrafish larvae. We envision that our technique is broadly applicable as a screening tool to quantitatively examine zebrafish larvae’s movements in response to physical and chemical stimulations in investigations of Parkinson’s and other neurodegenerative diseases, and as a tool to combine recent advances in genome engineering of model organisms to uncover the biology of electric response.
In this paper, we report a novel microfluidic method to conduct a Caenorhabditis elegans electrotaxis movement assay and neuronal imaging on up to 16 worms in parallel. C. elegans is a model organism for neurodegenerative disease and movement disorders such as Parkinson’s disease (PD), and for screening chemicals that alleviate protein aggregation, neuronal death, and movement impairment in PD. Electrotaxis of C. elegans in microfluidic channels has led to the development of neurobehavioral screening platforms, but enhancing the throughput of the electrotactic behavioral assay has remained a challenge. Our device consisted of a hierarchy of tree-like channels for worm loading into 16 parallel electrotaxis screening channels with equivalent electric fields. Tapered channels at the ends of electrotaxis channels were used for worm immobilization and fluorescent imaging of neurons. Parallel electrotaxis of worms was first validated against established single-worm electrotaxis phenotypes. Then, mutant screening was demonstrated using the NL5901 strain, carrying human -synuclein in the muscle cells, by showing the associated electrotaxis defects in the average speed, body bend frequency (BBF), and electrotaxis time index (ETI). Moreover, chemical screening of a PD worm model was shown by exposing the BZ555 strain, expressing green fluorescence protein (GFP) in the dopaminergic neurons (DNs), to 6-hydroxydopamine neurotoxin. The neurotoxin-treated worms exhibited a reduction in electrotaxis swimming speed, BBF, ETI, and DNs fluorescence intensity. We envision our technique to be used widely in C. elegans-based movement disorder assays to accelerate behavioral and cellular phenotypic investigations.