Caenorhabditis elegans is an important genetic model for neuroscience studies, used for analyses of how genes control connectivity, neuronal function, and behavior. To date, however, most studies of neuronal function...
Regular physical exercise has been shown to delay and alleviate neurodegenerative diseases. Yet, optimum physical exercise conditions that provide neuronal protection and exercise-related factors remain poorly understood. Here, we create an Acoustic Gym on a chip through the surface acoustic wave (SAW) microfluidic technology to precisely control the duration and intensity of swimming exercise of model organisms. We find that precisely dosed swimming exercise enabled by acoustic streaming decreases neuronal loss in two different neurodegenerative disease models of Caenorhabditis elegans , a Parkinson’s disease model and a tauopathy model. These findings highlight the importance of optimum exercise conditions for effective neuronal protection, a key characteristic of healthy aging in the elderly population. This SAW device also paves avenues for screening for compounds that can enhance or replace the beneficial effects of exercise and for identifying drug targets for treating neurodegenerative diseases.
In recent years, microfluidic devices have become an important tool for use in lab-on-a-chip processes, including drug screening and delivery, bio-chemical reactions, sample preparation and analysis, chemotaxis, and separations. In many such processes, a flat cross-sectional concentration profile with uniform flow velocity across the channel is desired to achieve controlled and precise solute transport. This is often accommodated by the use of electroosmotic flow, however, it is not an ideal for many applications, particularly biomicrofluidics. Meanwhile, pressure-driven systems generally exhibit a parabolic cross-sectional concentration profile through a channel. We draw inspiration from finite element fluid dynamics simulations to design and fabricate a practical solution to achieving a flat solute concentration profile in a two-dimensional (2D) microfluidic channel. The channel possesses geometric features to passively flatten the solute profile before entering the defined region of interest in the microfluidic channel. An obviously flat solute profile across the channel is demonstrated in both simulation and experiment. This technology readily lends itself to many microfluidic applications which require controlled solute transport in pressure driven systems.2 of 11 channel [13][14][15]. However, EOF heavily relies on the electrical properties of the medium and surface, for instance, imperfections or chemical coatings on the channel surface can distort the concentration profile [16,17]. Moreover, the application of an electric field can potentially be incompatible with nonhomogeneous solutes/buffers used in the device and may have negative effects on biological samples [18,19]. It can also be difficult to use electroosmotic flows for particular processes, such as mixing particles, due to the irrotational nature of the flow [20,21]. Recently, flat concentration profiles could be generated through magnetohydrodynamic (MHD) pumping [22]. To allow for effective MHD, the introduction of redox species to the fluid element is necessary. Thus, controlling the concentration profile in a microfluidics device without dependency on the liquid composition remains a challenge.Pressure-driven flows introduced with a mechanical syringe pump provide a simple and inexpensive alternative when EOF is not compatible with a device or the sample [13,23]. However, it is well known that a pressure gradient through a channel will introduce a parabolic flow profile in the axial direction. This is due to the no-slip condition found at the channel wall, which causes a non-uniform velocity gradient along the cross section of the channel [24]. Considering a two-dimensional (2D) cross-section of a rectangular channel, this effect is proportional to channel dimensions and much more significant in the axial dimension of a typical device. Accordingly, the introduction of such a parabolic profile prevents precise solute transport within the device.Related literature on the topic of Taylor dispersion in microfluidic channels has suggested that pa...
Caenorhabditis elegans is an important genetic model for neuroscience studies due to its unique combination of genetics, transparency, complete synaptic connectome, and well-characterized behaviors. These factors, in turn, enable analyses of how genes control connectivity, neuronal function, and behavior. To date, however, most studies of neuronal function in C. elegans are incapable of performing microscopy imaging with subcellular resolution and behavior analysis in the same set of animals. This constraint stems from the immobilization requirement for high-resolution imaging that is incompatible with behavioral analysis. In particular, conventional immobilization methods often lead to either irreversible, partial, or slowly reversible immobilization of animals preventing a multiplexed approach. Here, we present a novel microfluidic device that uses surface acoustic waves (SAW) as a non-contact method to temporarily immobilize worms for a short period (40 seconds). This device allows non-invasive analysis of swimming behavior and high-resolution synaptic imaging in the same animal. In addition, because of the low impact of this SAW approach, the device enables fast, repeated imaging of single neurons and behavior in the same animals for three to four days. We anticipate that this device will enable longitudinal analysis of animal motility and subcellular morphological changes during development and ageing in C. elegans.
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