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Oscillatory flows have become an indispensable tool in microfluidics, inducing inertial effects for displacing and manipulating fluid-borne objects in a reliable, controllable and label-free fashion. However, the quantitative description of such effects has been confined to limit cases and specialized scenarios. Here we develop an analytical formalism yielding the equation of motion of density-mismatched spherical particles in oscillatory background flows, generalizing previous work. Inertial force terms are systematically derived from the geometry of the flow field together with analytically known Stokes number dependences. Supported by independent, first-principles direct numerical simulations, we find that these forces are important even for nearly density-matched objects such as cells or bacteria, enabling their fast displacement and separation. Our formalism thus consistently incorporates particle inertia into the Maxey–Riley equation, and in doing so provides a generalization of Auton's modification to added mass, as well as recovering the description of acoustic radiation forces on particles as a limiting case.more » « less
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Myokines and exosomes, originating from skeletal muscle, are shown to play a significant role in maintaining brain homeostasis. While exercise has been reported to promote muscle secretion, little is known about the effects of neuronal innervation and activity on the yield and molecular composition of biologically active molecules from muscle. As neuromuscular diseases and disabilities associated with denervation impact muscle metabolism, we hypothesize that neuronal innervation and firing may play a pivotal role in regulating secretion activities of skeletal muscles. We examined this hypothesis using an engineered neuromuscular tissue model consisting of skeletal muscles innervated by motor neurons. The innervated muscles displayed elevated expression of mRNAs encoding neurotrophic myokines, such as interleukin-6, brain-derived neurotrophic factor, and FDNC5, as well as the mRNA of peroxisome-proliferator-activated receptor γ coactivator 1α, a key regulator of muscle metabolism. Upon glutamate stimulation, the innervated muscles secreted higher levels of irisin and exosomes containing more diverse neurotrophic microRNAs than neuron-free muscles. Consequently, biological factors secreted by innervated muscles enhanced branching, axonal transport, and, ultimately, spontaneous network activities of primary hippocampal neurons in vitro. Overall, these results reveal the importance of neuronal innervation in modulating muscle-derived factors that promote neuronal function and suggest that the engineered neuromuscular tissue model holds significant promise as a platform for producing neurotrophic molecules.more » « less
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Viscous streaming refers to the rectified, steady flows that emerge when a liquid oscillates around an immersed microfeature. Relevant to microfluidics, the resulting local, strong inertial effects allow manipulation of fluid and particles effectively, within short time scales and compact footprints. Nonetheless, practically, viscous streaming has been stymied by a narrow set of achievable flow topologies, limiting scope and application. Here, by moving away from classically employed microfeatures of uniform curvature, we experimentally show how multicurvature designs, computationally obtained, give rise, instead, to rich flow repertoires. The potential utility of these flows is then illustrated in compact, robust, and tunable devices for enhanced manipulation, filtering, and separation of both synthetic and biological particles. Overall, our mixed computational/experimental approach expands the scope of viscous streaming application, with opportunities in manufacturing, environment, health, and medicine, from particle self-assembly to microplastics removal.more » « less
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Abstract Motivated by the unexplored potential of in vitro neural systems for computing and by the corresponding need of versatile, scalable interfaces for multimodal interaction, an accurate, modular, fully customizable, and portable recording/stimulation solution that can be easily fabricated, robustly operated, and broadly disseminated is presented. This approach entails a reconfigurable platform that works across multiple industry standards and that enables a complete signal chain, from neural substrates sampled through micro‐electrode arrays (MEAs) to data acquisition, downstream analysis, and cloud storage. Built‐in modularity supports the seamless integration of electrical/optical stimulation and fluidic interfaces. Custom MEA fabrication leverages maskless photolithography, favoring the rapid prototyping of a variety of configurations, spatial topologies, and constitutive materials. Through a dedicated analysis and management software suite, the utility and robustness of this system are demonstrated across neural cultures and applications, including embryonic stem cell‐derived and primary neurons, organotypic brain slices, 3D engineered tissue mimics, concurrent calcium imaging, and long‐term recording. Overall, this technology, termed “mind in vitro” to underscore the computing inspiration, provides an end‐to‐end solution that can be widely deployed due to its affordable (>10× cost reduction) and open‐source nature, catering to the expanding needs of both conventional and unconventional electrophysiology.more » « less
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