Machine Learning Identification Framework of Hemodynamics of Blood Flow in Patient-Specific Coronary Arteries with Abnormality.

In this study, we put forth a new deep neural network framework to predict flow behavior in a coronary arterial network with different properties in the presence of any abnormality like stenosis. An artificial neural network (ANN) model is trained using synthetic data so that it can predict the pressure and velocity within the arterial network. The data required to train the neural network were obtained from the CFD analysis of several geometries of arteries with specific features in ABAQUS software. The proposed approach precisely predicts the hemodynamic behavior of the blood flow. The average accuracy of the pressure prediction was 98.7%, and the average velocity magnitude accuracy was 93.2%. Our model can also be used to predict fractional flow reserve (FFR), which is one of the main indices to determine the severity of stenosis, and our model predicts this index successfully based on the artery features.

Continuous Submicron Particle Separation Via Vortex-Enhanced Ionic Concentration Polarization: A Numerical Investigation.

Separation and isolation of suspended submicron particles is fundamental to a wide range of applications, including desalination, chemical processing, and medical diagnostics. Ion concentration polarization (ICP), an electrokinetic phenomenon in micro-nano interfaces, has gained attention due to its unique ability to manipulate molecules or particles in suspension and solution. Less well understood, though, is the ability of this phenomenon to generate circulatory fluid flow, and how this enables and enhances continuous particle capture. Here, we perform a comprehensive study of a low-voltage ICP, demonstrating a new electrokinetic method for extracting submicron particles via flow-enhanced particle redirection. To do so, a 2D-FEM model solves the Poisson-Nernst-Planck equation coupled with the Navier-Stokes and continuity equations. Four distinct operational modes (Allowed, Blocked, Captured, and Dodged) were recognized as a function of the particle's charges and sizes, resulting in the capture or release from ICP-induced vortices, with the critical particle dimensions determined by appropriately tuning inlet flow rates (200-800 [µm/s]) and applied voltages (0-2.5 [V]). It is found that vortices are generated above a non-dimensional ICP-induced velocity of U*=1, which represents an equilibrium between ICP velocity and lateral flow velocity. It was also found that in the case of multi-target separation, the surface charge of the particle, rather than a particle's size, is the primary determinant of particle trajectory. These findings contribute to a better understanding of ICP-based particle separation and isolation, as well as laying the foundations for the rational design and optimization of ICP-based sorting systems.

Zigzag microchannel for rigid inertial separation and enrichment (Z-RISE) of cells and particles.

Separation and enrichment of target cells prior to downstream analyses is an essential pre-treatment step in many biomedical and clinical assays. Separation techniques utilizing simple, cost-effective, and user-friendly devices are highly desirable, both in the lab and at the point of need. Passive microfluidic approaches, especially inertial microfluidics, fit this brief perfectly and are highly desired. Using an optimized additive manufacturing technique, we developed a zigzag microchannel for rigid inertial separation and enrichment, hereafter referred to as Z-RISE. We empirically showed that the Z-RISE device outperforms equivalent devices based on curvilinear (sinusoidal), asymmetric curvilinear, zigzag with round corners, or square-wave formats and modelled this behavior to gain a better understanding of the physics underpinning the improved focusing and separation performance. The comparison between rigid and soft zigzag microchannels reveals that channel rigidity significantly affects and enhances the focusing performance of the microchannel. Compared to other serpentine microchannels, zigzag microfluidics demonstrates superior separation and purity efficiency due to the sudden channel cross-section expansion at the corners. Within Z-RISE, particles are aligned in either double-side or single-line focusing positions. The transition of particles from a double-focusing line to a single focusing line introduced a new phenomenon referred to as the plus focusing position. We experimentally demonstrated that Z-RISE could enrich leukocytes and their subtypes from diluted and RBC lysed blood while depleting dead cells, debris, and RBCs. Z-RISE was also shown to yield outstanding particle or cell concentration with a concentration efficiency of more than 99.99%. Our data support the great potential of Z-RISE for applications that involve particle and cell manipulations and pave the way for commercialization perspective in the near future.

Rapid and Continuous Cryopreservation of Stem Cells with a 3D Micromixer.

Cryopreservation is the final step of stem cell production before the cryostorage of the product. Conventional methods of adding cryoprotecting agents (CPA) into the cells can be manual or automated with robotic arms. However, challenging issues with these methods at industrial-scale production are the insufficient mixing of cells and CPA, leading to damage of cells, discontinuous feeding, the batch-to-batch difference in products, and, occasionally, cross-contamination. Therefore, the current study proposes an alternative way to overcome the abovementioned challenges; a highly efficient micromixer for low-cost, continuous, labour-free, and automated mixing of stem cells with CPA solutions. Our results show that our micromixer provides a more homogenous mixing of cells and CPA compared to the manual mixing method, while the cell properties, including surface markers, differentiation potential, proliferation, morphology, and therapeutic potential, are well preserved.

Numerical and Experimental Study of Cross-Sectional Effects on the Mixing Performance of the Spiral Microfluidics.

Mixing at the microscale is of great importance for various applications ranging from biological and chemical synthesis to drug delivery. Among the numerous types of micromixers that have been developed, planar passive spiral micromixers have gained considerable interest due to their ease of fabrication and integration into complex miniaturized systems. However, less attention has been paid to non-planar spiral micromixers with various cross-sections and the effects of these cross-sections on the total performance of the micromixer. Here, mixing performance in a spiral micromixer with different channel cross-sections is evaluated experimentally and numerically in the Re range of 0.001 to 50. The accuracy of the 3D-finite element model was first verified at different flow rates by tracking the mixing index across the loops, which were directly proportional to the spiral radius and were hence also proportional to the Dean flow. It is shown that higher flow rates induce stronger vortices compared to lower flow rates; thus, fewer loops are required for efficient mixing. The numerical study revealed that a large-angle outward trapezoidal cross-section provides the highest mixing performance, reaching efficiencies of up to 95%. Moreover, the velocity/vorticity along the channel length was analyzed and discussed to evaluate channel mixing performance. A relatively low pressure drop (<130 kPa) makes these passive spiral micromixers ideal candidates for various lab-on-chip applications.

Periodic Rayleigh streaming vortices and Eckart flow arising from traveling-wave-based diffractive acoustic fields.

Recent studies have demonstrated that periodic time-averaged acoustic fields can be produced from traveling surface acoustic waves (SAWs) in microfluidic devices. This is caused by diffractive effects arising from a spatially limited transducer. This permits the generation of acoustic patterns evocative of those produced from standing waves, but instead with the application of a traveling wave. While acoustic pressure fields in such systems have been investigated, acoustic streaming from diffractive fields has not. In this work we examine this phenomenon and demonstrate the appearance of geometry-dependent acoustic vortices, and demonstrate that periodic, identically rotating Rayleigh streaming vortices result from the imposition of a traveling SAW. This is also characterized by a channel-spanning flow that bridges between adjacent vortices along the channel top and bottom. We find that the channel dimensions determine the types of streaming that develops; while Eckart streaming has been previously presumed to be a distinguishing feature of traveling-wave actuation, we show that Rayleigh streaming vortices also results. This has implications for microfluidic actuation, where traveling acoustic waves have applications in microscale mixing, separation, and patterning.

Inducing Mild Traumatic Brain Injury in C. elegans via Cavitation-Free Surface Acoustic Wave-Driven Ultrasonic Irradiation.

Mild traumatic brain injury is an all-too-common outcome from modern warfare and sport, and lacks a reproducible model for assessment of potential treatments and protection against it. Here we consider the use of surface acoustic wave (SAW) irradiation of C. elegans worms-without cavitation-as a potential, ethically reasonable animal-on-a-chip model for inducing traumatic brain injury in an animal, producing significant effects on memory and learning that could prove useful in a model that progress from youth to old age in but a few weeks. We show a significant effect by SAW on the ability of worms to learn post-exposure through associative learning chemotaxis. At higher SAW intensity, we find immediate, thorough, but temporary paralysis of the worms. We further explore the importance of homogeneous exposure of the worms to the SAW-driven ultrasound, an aspect poorly controlled in past efforts, if at all, and demonstrate the absence of cavitation through a change in fluids from a standard media for the worms to the exceedingly viscous polyvinyl alcohol. Likewise, we demonstrate that acoustic streaming, when present, is not directly responsible for paralysis nor learning disabilities induced in the worm, but is beneficial at low amplitudes to ensuring homogeneous ultrasound exposure.

A Novel On-Chip Method for Differential Extraction of Sperm in Forensic Cases.

One out of every six American women has been the victim of a sexual assault in their lifetime. However, the DNA casework backlog continues to increase outpacing the nation's capacity since DNA evidence processing in sexual assault casework remains a bottleneck due to laborious and time-consuming differential extraction of victim's and perpetrator's cells. Additionally, a significant amount (60-90%) of male DNA evidence may be lost with existing procedures. Here, a microfluidic method is developed that selectively captures sperm using a unique oligosaccharide sequence (Sialyl-LewisX), a major carbohydrate ligand for sperm-egg binding. This method is validated with forensic mock samples dating back to 2003, resulting in 70-92% sperm capture efficiency and a 60-92% reduction in epithelial fraction. Captured sperm are then lysed on-chip and sperm DNA is isolated. This method reduces assay-time from 8 h to 80 min, providing an inexpensive alternative to current differential extraction techniques, accelerating identification of suspects and advancing public safety.

Enhanced Ion Current Rectification in 2D Graphene-Based Nanofluidic Devices.

Furthering the promise of graphene-based planar nanofluidic devices as flexible, robust, low cost, and facile large-scale alternatives to conventional nanochannels for ion transport, we show how the nonlinear current-voltage (I-V) characteristics and ion current rectification in these platforms can be enhanced by increasing the system asymmetry. Asymmetric cuts made to the 2D multilayered graphene oxide film, for example, introduces further asymmetry to that natively inherent in the structurally symmetric system, which was recently shown to be responsible for its rectification behavior due to diffusion boundary layer fore-aft asymmetry. Supported by good agreement with theory, we attribute the enhancement to the decrease in the limiting current in the positive bias state in which counter-ion trapping occurs within the negatively charged graphene oxide sheets due to increased film permselectivity as its cross-section and surface charge distribution is altered on one end; these effects being shown to be sensitive to the electrolyte pH. Further, we show that an imbalance in the pH or concentration in the microreservoirs flanking the film can also increase asymmetry and hence rectification, in addition to displaying a host of other phenomena associated with the I-V characteristics of typical nanochannel electrokinetic systems.

pH dependent isotropic to nematic phase transitions in graphene oxide dispersions reveal droplet liquid crystalline phases.

Size fractionation, amplified by the surface charge density of graphene oxide (GO) sheets, broadens the pH dependent isotropic (I) to nematic (N) phase transition in aqueous dispersions of graphene oxide (GO). In this biphasic region, a highly organized droplet nematic phase of uniform size (20 ± 2.8 µm diameter) with an isotropic interior is observed.