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Inspired by the vibrations of aquatic plants such as seaweed in the unsteady flow fields generated by free-surface waves, we investigate a novel device based on piezoelectric plates to harvest energy from oscillatory cross flows. Towards this end, numerical studies are conducted using a flow-structure-electric interaction model to understand the underlying physical mechanisms involved in the dynamics and energy harvesting performance of one or a pair of piezoelectric plates in an oscillatory cross flow. In a single-plate configuration, both periodic and irregular responses have been observed depending on parameters such as normalized plate stiffness and Keulegan-Carpenter number. Large power harvesting is achieved with the excitation of natural modes. Besides, when the time scale of the motion and the intrinsic time scale of the circuit are close to each other the power extraction is enhanced. In a two-plate configuration with tandem formation, the hydrodynamic interaction between the two plates can induce irregularity in the response. In terms of energy harvesting, two counteracting mechanisms have been identified, shielding and energy recovery. The shielding effect reduces plate motion and energy harvesting, whereas with the energy recovery effect one plate is able to recovery energy from the wake of another for performance enhancement. The competition between these mechanisms leads to constructive or destructive interactions between the two plates. These results suggest that for better performance the system should be excited at its natural period, which should be close to the intrinsic time scale of the circuit. Moreover, using a pair of plates in a tandem formation can further improve the energy harvesting capacity when conditions for constructive interaction are satisfied.

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This paper aims to examine the ability to control Red Blood Cell (RBCs) dynamics and the associated extracellular flow patterns in microfluidic channels via oscillatory flows. Our computational approach employs a hybrid continuum-particle coupling, in which the cell membrane and cytosol fluid are modeled using the Dissipative Particle Dynamics (DPD) method. The blood plasma is modeled as an incompressible fluid via the Immersed Boundary Method (IBM). This coupling is novel because it provides an accurate description of RBC dynamics while the extracellular flow patterns around the RBCs are also captured in detail. Our coupling methodology is validated with available experimental and computational data in the literature and shows excellent agreement. We explore the controlling regimes by varying the shape of the oscillatory flow waveform at the channel inlet. Our simulation results show that a host of RBC morphological dynamics emerges depending on the channel geometry, the incoming flow waveform, and the RBC initial location. Complex dynamics of RBC are induced by the flow waveform. Our results show that the RBC shape is strongly dependent on its initial location. Our results suggest that the controlling of oscillatory flows can be used to induce specific morphological shapes of RBCs and the surrounding fluid patterns in bio-engineering applications.

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Hemodynamic shear stress is one of the major factors that are involved in the pathogenesis of many cardiovascular diseases including atherosclerosis and abdominal aortic aneurysm (AAA), through its modulatory effect on the endothelial cell's redox homeostasis and mechanosensitive gene expression. Among important mechanisms, oxidative stress, endoplasmic reticulum stress activation, and the subsequent endothelial dysfunction are attributed to disturbed blood flow and low shear stress in the vascular curvature and bifurcations which are considered atheroprone regions and aneurysm occurrence spots. Many pathways were shown to be involved in AAA progression. Of particular interest from recent findings is, the (Nrf2)/Keap-1 pathway, where Nrf2 is a transcription factor that has antioxidant properties and is strongly associated with several CVDs, yet, the exact mechanism by which Nrf2 alleviates CVDs still to be elucidated. Nrf2 expression is closely affected by shear stress and was shown to participate in AAA. In the current review paper, we discussed the link between disturbed hemodynamics and its effect on Nrf2 as a mechanosensitive gene and its role in the development of endothelial dysfunction which is linked to the progression of AAA.

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Coastal development and climate change are sparking growing concern about the vulnerability of the organic carbon (OC) stocks in marine sediments to remineralization, especially in high threaten coastal ecosystems like seagrass meadows. Uncertainties still exist regarding the role played by hydrodynamics, seagrass canopies and sediment properties in OC resuspension and remineralization. A set of laboratory experiments were conducted to assess, for the first time, the mechanisms by which the particulate and dissolved organic carbon (POC and DOC) may be released and remineralized under hydrodynamic conditions (i.e., unidirectional and oscillatory flows) in two eelgrass densities and sediments properties (i.e., grain size and OC content). After a gradually increase in hydrodynamic forces, our results demonstrated that the presence of eelgrass reduced sediment erosion and OC loss in high-density canopies, while low-density canopies promote OC resuspension (on average, 1.8-fold higher than high-density canopies). We also demonstrated that unidirectional and oscillatory flows released similar DOC from surface sediments (on average, 15.5 ± 1.4 and 18.4 ± 1.8 g m-2, respectively), whereas oscillatory flow released significantly more POC than unidirectional flows (from 10.8 ± 1.1 to 32.1 ± 5.6 g m-2 for unidirectional and oscillatory flows, respectively). POC and DOC released was strongly influenced by both seagrass meadow structure (i.e., lower eelgrass density and shoot area) and sediment properties (i.e., lower mud and higher sediment water content). We found that, although >74 % of OC in upper sediments was remineralized within 30 days, a relatively high amount of OC in high-density canopies is recalcitrant, highlighting its potential for the formation of blue carbon deposits. This study highlights the vulnerability of OC deposits in seagrass sediments to resuspension if the meadow is degraded and/or the climate change yield stronger storms, which could potentially weaken the seagrass meadows' service as blue carbon ecosystem in the future.

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The classical problem of secondary flow driven by a sinusoidally varying pressure gradient is extended here to address periodic pressure gradients of complex waveform, which are present in many oscillatory physiological flows. A slender two-dimensional wavy-walled channel is selected as a canonical model problem. Following standard steady-streaming analyses, valid for small values of the ratio ε of the stroke length of the pulsatile motion to the channel wavelength, the spatially periodic flow is described in terms of power-law expansions of ε, with the Womersley number assumed to be of order unity. The solution found at leading order involves a time-periodic velocity with a zero time-averaged value at any given point. As in the case of a sinusoidal pressure gradient, effects of inertia enter at the following order to induce a steady flow in the form of recirculating vortices with zero net flow rate. An improved two-term asymptotic description of this secondary flow is sought by carrying the analysis to the following order. It is found that, when the pressure gradient has a waveform with multiple harmonics, the resulting velocity corrections display a nonzero flow rate, not present in the single-frequency case, which enables stationary convective transport along the channel. Direct numerical simulations for values of ε of order unity are used to investigate effects of inertia and delineate the range of validity of the asymptotic limit ε≪1. The comparisons of the time-averaged velocity obtained numerically with the two-term asymptotic description reveals that the latter remains remarkably accurate for values of ε exceeding 0.5. As an illustrative example, the results of the model problem are used to investigate the cerebrospinal-fluid flow driven along the spinal canal by the cardiac and respiratory cycles, characterized by markedly non-sinusoidal waveforms.

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PCR is indispensable in basic science and biotechnology for in-orbit life science research. However, manpower and resources are limited in space. To address the constraints of in-orbit PCR, we proposed an oscillatory-flow PCR technique based on biaxial centrifugation. Oscillatory-flow PCR remarkably reduces the power requirements of the PCR process and has a relatively high ramp rate. A microfluidic chip that could perform dispensing, volume correction, and oscillatory-flow PCR of four samples simultaneously using biaxial centrifugation was designed. An automatic biaxial centrifugation device was designed and assembled to validate the biaxial centrifugation oscillatory-flow PCR. Simulation analysis and experimental tests indicated that the device could perform fully automated PCR amplification of four samples in one hour, with a ramp rate of 4.4 ∘C/s and average power consumption of less than 30 W. The PCR results were consistent with those obtained using conventional PCR equipment. Air bubbles generated during amplification were removed by oscillation. The chip and device realized a low-power, miniaturized, and fast PCR method under microgravity conditions, indicating good space application prospects and potential for higher throughput and extension to qPCR.

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An unsteady free convective flow of an electrically conducting viscous fluid due to accelerated inestimable inclined perpendicular shield has been presented in presence of heat and mass transfer phenomenon. The applications of thermos-diffusion and heat source are also incorporated. The chemical reaction consequences are considered in the concentration equation. The compelling meadow is considered to be homogeneous and practical perpendicular to the flow direction. Further, the oscillatory suction effects are also taken into observations for porous regime. The closed form expressions are resulted with implementation of perturbation approach. The non-dimensional expression for the proposed governing system is yield out with entertaining appropriate variables. The graphically influence of parameters is studied. Following to obtained observations, it is claimed that declining deviation in velocity is predicted with chemical reactive factor. Further, less thermal transport between container to fluid is noticed for radiative absorption parameter.

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The aortic valve facilitates unidirectional blood flow to the systemic circulation between the left cardiac ventricle and the aorta. The valve's biomechanical function relies on thin leaflets to adequately open and close over the cardiac cycle. A monolayer of valve endothelial cells (VECs) resides on the outer surface of the aortic valve leaflet. Deeper within the leaflet are sublayers of valve interstitial cells (VICs). Valve tissue remodeling involves paracrine signaling between VECs and VICs. Aortic valve calcification can result from abnormal paracrine communication between these two cell types. VECs are known to respond to hemodynamic stimuli, and, specifically, flow abnormalities can induce VEC dysfunction. This dysfunction can subsequently change the phenotype of VICs, leading to aortic valve calcification. However, the relation between VEC-exposed flow oscillations under pulsatile flow to the progression of aortic valve calcification by VICs remains unknown. In this study, we quantified the level of flow oscillations that VECs were exposed to under dynamic culture and then immersed VICs in VEC-conditioned media. We found that VIC-induced calcification was augmented under maximum flow oscillations, wherein the flow was fully forward for half the cardiac cycle period and fully reversed for the other half. We were able to computationally correlate this finding to specific regions of the aortic valve that experience relatively high flow oscillations and that have been shown to be associated with severe calcified deposits. These findings establish a basis for future investigations on engineering calcified human valve tissues and its potential for therapeutic discovery of aortic valve calcification.

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Calcium plays an important role in barrier function repair and skin homeostasis. In particular, calcium phosphates (CaPs) are well established materials for biomedical engineering due to their biocompatibility. To generate biomaterials with a more complete set of biological properties, previously discarded silk sericin (SS) has been recovered and used as a template to grow CaPs. Crucial characteristics for skin applications, such as antibacterial activity, can be further enhanced by doping CaPs with cerium (Ce) ions. The effectiveness of cell attachment and growth on the materials highly depends on their morphology, particle size distribution, and chemical composition. These characteristics can be tailored through the application of oscillatory flow technology, which provides precise mixing control of the reaction medium. Thus, in the present work, CaP/SS and CaP/SS/Ce particles were fabricated for the first time using a modular oscillatory flow plate reactor (MOFPR) in a continuous mode. Furthermore, the biological behavior of both these composites and of previously produced pure CaPs was assessed using human dermal fibroblasts (HDFs). It was demonstrated that both CaP based with plate-shaped nanoparticles and CaP-SS-based composites significantly improved cell viability and proliferation over time. The results obtained represent a first step towards the reinvention of CaPs for skin engineering.

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Low, oscillatory flow/shear patterns are associated with atherosclerotic lesion development. Increased expression of KCa3.1 has been found in Vascular Smooth Muscle (VSM), macrophages and T-cells in lesions from humans and mice. Increased expression of KCa3.1, is also required for VSM cell proliferation and migration. Previously, we showed that the specific KCa3.1 inhibitor, TRAM-34, could inhibit coronary neointimal development following balloon injury in swine. Atherosclerosis develops in regions with a low, oscillatory (i.e. atheroprone) flow pattern. Therefore, we used the Partial Carotid Ligation (PCL) model in high-fat fed, Apoe-/- mice to determine the role of KCa3.1 in atherosclerotic lesion composition and development. PCL was performed on 8-10 week old male Apoe-/- mice and subsequently placed on a Western diet (TD.88137, Teklad) for 4 weeks. Mice received daily s.c. injections of TRAM-34 (120 mg/kg) or equal volumes of vehicle (peanut oil, PO). 1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34) treatment reduced lesion size ~50% (p < 0.05). In addition, lesions from TRAM-34 treated mice contained less collagen (6% ± 1% vs. 15% ± 2%; p < 0.05), fibronectin (14% ± 3% vs. 32% ± 3%; p < 0.05) and smooth muscle content (19% ± 2% vs. 29% ± 3%; p < 0.05). Conversely, TRAM-34 had no effect on total cholesterol (1455 vs. 1334 mg/dl, PO and TRAM, resp.) or body weight (29.1 vs. 28.8 g, PO and TRAM, resp.). Medial smooth muscle of atherosclerotic carotids showed diminished RE1-Silencing Transcription Factor (REST)/Neural Restrictive Silencing Factor (NRSF) expression, while REST overexpression in vitro inhibited smooth muscle migration. Together, these data support a downregulation of REST/NRSF and upregulation of KCa3.1 in determining smooth muscle and matrix content of atherosclerotic lesions.

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Elastin (ELN) insufficiency leads to the cardiovascular hallmarks of the contiguous gene deletion disorder, Williams-Beuren syndrome, including hypertension and vascular stiffness. Previous studies showed that Williams-Beuren syndrome deletions, which extended to include the NCF1 gene, were associated with lower blood pressure (BP) and reduced vascular stiffness. NCF1 encodes for p47phox, the regulatory component of the NOX1 NADPH oxidase complex that generates reactive oxygen species (ROS) in the vascular wall. Dihydroethidium and 8-hydroxyguanosine staining of mouse aortas confirmed that Eln heterozygotes (Eln+/- ) had greater ROS levels than the wild-types (Eln+/+ ), a finding that was negated in vessels cultured without hemodynamic stressors. To analyze the Nox effect on ELN insufficiency, we used both genetic and chemical manipulations. Both Ncf1 haploinsufficiency (Ncf1+/- ) and Nox1 insufficiency (Nox1-/y ) decreased oxidative stress and systolic BP in Eln+/- without modifying vascular structure. Chronic treatment with apocynin, a p47phox inhibitor, lowered systolic BP in Eln+/- , but had no impact on Eln+/+ controls. In vivo dosing with phenylephrine (PE) produced an augmented BP response in Eln+/- relative to Eln+/+ , and genetic modifications or drug-based interventions that lower Nox1 expression reduced the hypercontractile response to PE in Eln+/- mice to Eln+/+ levels. These results indicate that the mechanical and structural differences caused by ELN insufficiency leading to oscillatory flow can perpetuate oxidative stress conditions, which are linked to hypertension, and that by lowering the Nox1-mediated capacity for vascular ROS production, BP differences can be normalized.

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Biological cells in vivo typically reside in a dynamic flowing microenvironment with extensive biomechanical and biochemical cues varying in time and space. These dynamic biomechanical and biochemical signals together act to regulate cellular behaviors and functions. Microfluidic technology is an important experimental platform for mimicking extracellular flowing microenvironment in vitro. However, most existing microfluidic chips for generating dynamic shear stress and biochemical signals require expensive, large peripheral pumps and external control systems, unsuitable for being placed inside cell incubators to conduct cell biology experiments. This study has developed a microfluidic generator of dynamic shear stress and biochemical signals based on autonomously oscillatory flow. Further, based on the lumped-parameter and distributed-parameter models of multiscale fluid dynamics, the oscillatory flow field and the concentration field of biochemical factors has been simulated at the cell culture region within the designed microfluidic chip. Using the constructed experimental system, the feasibility of the designed microfluidic chip has been validated by simulating biochemical factors with red dye. The simulation results demonstrate that dynamic shear stress and biochemical signals with adjustable period and amplitude can be generated at the cell culture chamber within the microfluidic chip. The amplitudes of dynamic shear stress and biochemical signals is proportional to the pressure difference and inversely proportional to the flow resistance, while their periods are correlated positively with the flow capacity and the flow resistance. The experimental results reveal the feasibility of the designed microfluidic chip. Conclusively, the proposed microfluidic generator based on autonomously oscillatory flow can generate dynamic shear stress and biochemical signals without peripheral pumps and external control systems. In addition to reducing the experimental cost, due to the tiny volume, it is beneficial to be integrated into cell incubators for cell biology experiments. Thus, the proposed microfluidic chip provides a novel experimental platform for cell biology investigations.

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Atherosclerosis is characterized by the plaque formation that restricts intraarterial blood flow. The disturbed blood flow with the associated oscillatory stress (OS) at the arterial curvatures and branch points can trigger endothelial activation and is one of the risk factors of atherosclerosis. Many studies reported the mechanotransduction related to OS and atherogenesis; however, the transcriptional and posttranscriptional regulatory mechanisms of atherosclerosis remain unclear. Herein, we investigated the role of N6-methyladenosine (m6A) RNA methylation in mechanotransduction in endothelial cells (ECs) because of its important role in epitranscriptome regulation. We have identified m6A methyltransferase METTL3 as a responsive hub to hemodynamic forces and atherogenic stimuli in ECs. OS led to an up-regulation of METTL3 expression, accompanied by m6A RNA hypermethylation, increased NF-κB p65 Ser536 phosphorylation, and enhanced monocyte adhesion. Knockdown of METTL3 abrogated this OS-induced m6A RNA hypermethylation and other manifestations, while METTL3 overexpression led to changes resembling the OS effects. RNA-sequencing and m6A-enhanced cross-linking and immunoprecipitation (eCLIP) experiments revealed NLRP1 and KLF4 as two hemodynamics-related downstream targets of METTL3-mediated hypermethylation. The METTL3-mediated RNA hypermethylation up-regulated NLRP1 transcript and down-regulated KLF4 transcript through YTHDF1 and YTHDF2 m6A reader proteins, respectively. In the in vivo atherosclerosis model, partial ligation of the carotid artery led to plaque formation and up-regulation of METTL3 and NLRP1, with down-regulation of KLF4; knockdown of METTL3 via repetitive shRNA administration prevented the atherogenic process, NLRP3 up-regulation, and KLF4 down-regulation. Collectively, we have demonstrated that METTL3 serves a central role in the atherogenesis induced by OS and disturbed blood flow.

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This paper presents the design, theoretical analysis, simulation verification, fabrication and prototype characterization of a novel biaxial bionic hair flow sensor based on resonant sensing. Firstly, the device architecture, mainly consists of a polymer hair post, a silicon micro signal transducer and a glass substrate, is described, the theoretical simplified model is established and the mechanical sensitivity to air flow is deducted. Then, the structure simulations based on Ansys software are implemented to preliminarily verify the feasibility of the proposed sensor conception and optimize the structure parameters simultaneously. Subsequently, a closed-loop control scheme based on digital phase-locked loop and an amplitude demodulation algorithm of oscillatory flow velocity based on the least mean square method are proposed to transform and extract the air flow signal, and then verify it by circuit simulations based on SIMULINK. Finally, the fabricated prototype is illustrated and comprehensively tested. The tested prototype possesses an x-axis scale factor of 1.56 Hz/(m/s)2 and a y-axis scale factor of 1.81 Hz/(m/s)2 for the steady air flow and an x-axis detection threshold of 43.27 mm/s and a y-axis detection threshold of 41.85 mm/s for the oscillatory air flow.

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Support of somatic growth is a fundamental requirement of tissue-engineered valves. However, efforts thus far have been unable to maintain this support long term. A key event that will determine the valve's long-term success is the extent to which healthy host tissue remodeling can occur on the valve soon after implantation. The construct's phenotypic-status plays a critical role in accelerating tissue remodeling and engineered valve integration with the host via chemotaxis. In the current study, human bone-marrow-derived mesenchymal stem cells were utilized to seed synthetic, biodegradable scaffolds for a period of 8 days in rotisserie culture. Subsequently, cell-seeded scaffolds were exposed to physiologically relevant oscillatory shear stresses (overall mean, time-averaged shear stress, ~7.9 dynes/cm2; overall mean, oscillatory shear index, ~0.18) for an additional 2 weeks. The constructs were found to exhibit relatively augmented endothelial cell expression (CD31; compared to static controls) but concomitantly served to restrict the level of the activated smooth muscle phenotype (α-SMA) and also produced very low stem cell secretion levels of fibronectin (p < 0.05 compared to static and rotisserie controls). These findings suggest that fluid-induced oscillatory shear stresses alone are important in regulating a healthy valve phenotype of the engineered tissue matrix. Moreover, as solid stresses could lead to increased α-SMA levels, they should be excluded from conditioning during the culture process owing to their associated potential risks with pathological tissue remodeling. In conclusion, engineered valve tissues derived from mesenchymal stem cells revealed both a relatively robust valvular phenotype after exposure to physiologically relevant scales of oscillatory shear stress and may thereby serve to accelerate healthy valve tissue remodeling in the host post-implantation.

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The ability to precisely control particle migration within microfluidic systems is essential for focusing, separating, counting, and detecting a wide range of biological species. To date, viscoelastic microfluidic systems have primarily been applied to the focusing, separation, and isolation of micrometer-sized species, with their use in nanoparticle manipulations being underdeveloped and underexplored, due to issues related to nanoparticle diffusivity and a need for extended channel lengths. To overcome such issues, we herein present sheathless oscillatory viscoelastic microfluidics as a method for focusing and separating both micrometer and sub-micrometer species. To highlight the efficacy of our approach, we segment our study into three size regimes, namely, micrometer (where characteristic particle dimensions are above 1 µm), sub-micrometer (where characteristic dimensions are between 1 µm and 100 nm), and nano (where characteristic dimensions are below 100 nm) regimes. Based on the ability to successfully manipulate particles in all these regimes, we demonstrate the successful isolation of p-bodies from biofluids (in the micrometer regime), the focusing of λ-DNA (in the sub-micrometer regime), and the focusing of extracellular vesicles (in the nanoregime). Finally, we characterize the physics underlying viscoelastic microflows using a dimensionless number that relates the lateral velocity (due to elastic effects) to the diffusion constant of the species within the viscoelastic carrier fluid. Based on the ability to precisely manipulate species in all three regimes, we expect that sheathless oscillatory viscoelastic microfluidics may be used to good effect in a range of biological and life science applications.

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The one-dimensional viscoelastic fluid flow between two infinite parallel plates with oscillatory inlet condition is examined using the Johnson-Segalman model. The symmetric and antisymmetric Chandrasekhar functions in space are utilized to represent the velocity and stress fields. The non-dimensional form of the conservation laws in addition to the constitutive equations are solved numerically based on the Galerkin projection method. Two critical Weissenberg numbers (We) for various Reynolds numbers (Re) and viscosity ratios (ε) are obtained to determine the stable range of nonlinear system behavior. Moreover, for the unsteady case, the effects of Re, viscosity ratio of solvent to solution as well as We are investigated. According to the obtained results, increasing of oscillations frequency in subcritical zone, the same as low frequency case, has almost no effect on the velocity and its gradient. Nevertheless, the normal stress amplitude of oscillations is reduced. The Re number determines the number of oscillations and the needed time prior to the steady condition. For lower Re, due to higher effect of viscosity, the initial fluctuations are intensely occurred in a short time period in contrary to the high Re case.

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In the study, we describe an oscillatory flow-assisted efficient target enrichment method by using a particle-based microarray device. Periodic oscillating flow effectively increased the mixing and binding performance between the target molecules in the sample solution and surface functionalized microparticles. Particles were trapped, secured, and released with an elastic microvalve structure operated via differences in the flow conditions. Single particle (20-µm diameter) trapping efficiency exceeded 95%. Secured particles can freely move inside each array element based on oscillating sample flow. Furthermore, the particles can be released from the array and collected at the outlet of the device, and this provides an opportunity for further off-chip analysis. As a proof-of-concept, we used the interaction between streptavidin-coated microparticles and fluorescence labeled biotin solution and demonstrated that target enrichment and detection based on oscillatory flow were significantly more efficient than that based on unidirectional or static flow. The applicability of the method was further examined by conducting an on-chip immunoassay to detect the presence of anti-Zika nonstructural protein 1 (NS1) monoclonal antibody. The limit of detection (LOD) was as low as 1 ng/mL with an assay time of only 10 min and less than 10 µL of sample consumption.

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We demonstrate that erythrocyte deformations, specifically of a type as occur in splenic flow (Zhu et al., 2017), and of the type that promote vesiculation can be caused by simple, yet tailored, oscillatory shear flow. We show that such oscillatory shear flow provides an ideal environment to explore a wide variety of metabolic and biochemical effects that promote erythrocyte vesiculation. Deformation details, typical of splenic flow, such as in-folding and implications for membrane/skeleton interaction are demonstrated and quantitatively analyzed. We introduce a theoretical, essentially analytical, vesiculation model that directly couples to our more complex numerical, multilevel, model that clearly delineates various fundamental elements, i.e., sub-processes, that are involved and mediate the vesiculation process. This analytical model highlights particulary important vesiculation precursors such as areas of membrane/skeleton disruptions that trigger the vesiculation process. We demonstrate, using flow cytometry, that the deformations we experimentally induce on cells, and numerically simulate, do not induce lethal forms of cell damage but do induce vesiculation as theoretically forecasted. This, we demonstrate, provides a direct link to cell membrane/skeletal damage such as is associated with metabolic and aging damage. An additional noteworthy feature of this approach is the avoidance of artificial devices, e.g., micro-fluidic chambers, in which deformations and their time scales are often unrepresentative of physiological processes such as splenic flow.

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Inertial microfluidics (i.e., migration and focusing of particles in finite Reynolds number microchannel flows) is a passive, precise, and high-throughput method for microparticle manipulation and sorting. Therefore, it has been utilized in numerous biomedical applications including phenotypic cell screening, blood fractionation, and rare-cell isolation. Nonetheless, the applications of this technology have been limited to larger bioparticles such as blood cells, circulating tumor cells, and stem cells, because smaller particles require drastically longer channels for inertial focusing, which increases the pressure requirement and the footprint of the device to the extent that the system becomes unfeasible. Inertial manipulation of smaller bioparticles such as fungi, bacteria, viruses, and other pathogens or blood components such as platelets and exosomes is of significant interest. Here, we show that using oscillatory microfluidics, inertial focusing in practically "infinite channels" can be achieved, allowing for focusing of micron-scale (i.e. hundreds of nanometers) particles. This method enables manipulation of particles at extremely low particle Reynolds number (Rep < 0.005) flows that are otherwise unattainable by steady-flow inertial microfluidics (which has been limited to Rep > ∼10-1). Using this technique, we demonstrated that synthetic particles as small as 500 nm and a submicron bacterium, Staphylococcus aureus, can be inertially focused. Furthermore, we characterized the physics of inertial microfluidics in this newly enabled particle size and Rep range using a Peclet-like dimensionless number (α). We experimentally observed that α >> 1 is required to overcome diffusion and be able to inertially manipulate particles.

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