Fluidic Drag Forces Research Articles

A coupled cell-based smoothed finite element method and discrete phase model for incompressible laminar flow with dilute solid particles

In this paper, the cell-based smoothed finite element method (CS-FEM) empowered by the discrete phase model (DPM) is developed to solve dilute solid particles movements induced by incompressible laminar flow. In the present method, the fluid phase is solved by CS-FEM in the Eulerian framework, while particles are treated as discrete phases traced using Newton's second law in the Lagrangian framework. Meanwhile, the fluidic drag force on particles is considered to realize the one-way coupling of fluid to particles. For the fluid phase, the semi-implicit characteristic-based split (CBS) method is employed to suppress the spatial and pressure oscillations arising from the numerical solution of the Navier-Stokes equations discretized by the CS-FEM. To accurately capture the fluid velocity at an arbitrary particle position inside quadrilateral elements, the mean value coordinates interpolation is introduced. Furthermore, the motion equations for particles are solved by the fourth-order Runge-Kutta method to ensure high accuracy on particle trajectories. Several numerical examples in this paper demonstrate that the proposed method can effectively predict the effect of fluid flow on particle trajectories and position distributions in the analysis of practical and complex flow problems.

Efficient recovery of potent tumour-infiltrating lymphocytes through quantitative immunomagnetic cell sorting.

Adoptive cell therapies require the recovery and expansion of highly potent tumour-infiltrating lymphocytes (TILs). However, TILs in tumours are rare and difficult to isolate efficiently, which hinders the optimization of therapeutic potency and dose. Here we show that a configurable microfluidic device can efficiently recover potent TILs from solid tumours by leveraging specific expression levels of target cell-surface markers. The device, which is sandwiched by permanent magnets, balances magnetic forces and fluidic drag forces to sort cells labelled with magnetic nanoparticles conjugated with antibodies for the target markers. Compared with conventional cell sorting, immunomagnetic cell sorting recovered up to 30-fold higher numbers of TILs, and the higher levels and diversity of the recovered TILs accelerated TIL expansion and enhanced their therapeutic potency. Immunomagnetic cell sorting also allowed us to identify and isolate potent TIL subpopulations, in particular TILs with moderate levels of CD39 (a marker of T-cell reactivity to tumours and T-cell exhaustion), which we found are tumour-specific, self-renewable and essential for the long-term success of adoptive cell therapies.

Automatically Controlled Microfluidic System for Continuous Separation of Rare Bacteria from Blood.

Bloodstream infection by microorganisms is a major public health concern worldwide. Millions of people per year suffer from microbial infections, and current blood culture-based diagnostic methods are time-consuming because of the low concentration of infectious microorganisms in the bloodstream. In this study, we introduce an efficient automated microfluidic system for the continuous isolation of rare infectious bacteria (Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa) from blood. Bacteria received a balanced force between a fluidic drag force and a periodically controlled dielectrophoretic (DEP) force from tilted electrodes to minimize cell adhesion to the electrodes, which prevented the loss of rare infectious bacteria. Target bacteria were efficiently segregated from the undesired blood cells to ensure that only the bacteria received the DEP force under the hypotonic condition, while the blood cells received no DEP force and exited the channel via a laminar flow. Thus, the bacteria were successfully extracted from the blood with a high recovery yield of 91.3%, and the limit of the bacteria concentration for isolation was 100 cfu/ml. We also developed an automated system that performed every step from blood-sample loading to application of electricity to the microfluidic chip for bacteria separation. It reduced the standard deviation of the bacteria recovery yield from 6.16 to 2.77 compared with the conventional batch process, providing stable bacteria-extraction performance and minimizing errors and bacteria loss caused by user mistakes. © 2019 International Society for Advancement of Cytometry.

Plasmofluidic Microlenses for Label-Free Optical Sorting of Exosomes

Optical chromatography is a powerful optofluidic technique enabling label-free fractionation of microscopic bioparticles from heterogenous mixtures. However, sophisticated instrumentation requirements for precise alignment of optical scattering and fluidic drag forces is a fundamental shortcoming of this technique. Here, we introduce a subwavelength thick (<200 nm) Optofluidic PlasmonIC (OPtIC) microlens that effortlessly achieves objective-free focusing and self-alignment of opposing optical scattering and fluidic drag forces for selective separation of exosome size bioparticles. Our optofluidic microlens provides a self-collimating mechanism for particle trajectories with a spatial dispersion that is inherently minimized by the optical gradient and radial fluidic drag forces working together to align the particles along the optical axis. We demonstrate that this facile platform facilitates complete separation of small size bioparticles (i.e., exosomes) from a heterogenous mixture through negative depletion and provides a robust selective separation capability for same size nanoparticles based on their differences in chemical composition. Unlike existing optical chromatography techniques that require complicated instrumentation (lasers, objectives and precise alignment stages), our OPtIC microlenses with a foot-print of 4 μm × 4 μm open up the possibility of multiplexed and high-throughput sorting of nanoparticles on a chip using low-cost broadband light sources.

Low concentration E. coli O157:H7 bacteria sensing using microfluidic MEMS biosensor.

This paper reports the design, fabrication, and testing of a microfluidic MEMS biosensor for rapid sensing of low concentration Escherichia coli O157:H7. It consists of a specially designed focusing and sensing region, which enables the biosensor to detect low concentration of bacterial cells. The focusing region consists of a ramped vertical electrode pair made of electroplated gold along with tilted thin film finger pairs (45°) embedded inside a microchannel. The focusing region generates positive dielectrophoresis force, which moves the cells towards the edges of the tilted thin film electrode fingers, located at the center of the microchannel. The fluidic drag force then carries the focused cells to the sensing region, where three interdigitated electrode arrays (IDEAs) with 30, 20, and 10 pairs, respectively, are embedded inside the microchannel. This technique resulted in highly concentrated samples in the sensing region. The sensing IDEAs are functionalized with the anti-E. coli antibody for specific sensing of E. coli 0157:H7. As E. coli binds to the antibody, it results in an impedance change, which is measured across a wide frequency range of 100 Hz-10 MHz. The biosensor was fabricated on a glass substrate using the SU8 epoxy resist to form the microchannel, gold electroplating to form the vertical focusing electrode pair, a thin gold film to form the sensing electrode, the finger electrodes, traces and bonding pads, and polydimethylsiloxane to seal the device. The microfluidic impedance biosensor was tested with various low concentration bacterial samples and was able to detect bacterial concentration, as low as 39 CFU/ml with a total sensing time of 2 h.

Simple methods for fluidic drag estimation during pipe installation via HDD

This paper proposes a series of simple methods for fluidic drag evaluation of non-Newtonian slurries flowing within a bore during Horizontal Directional Drilling (HDD) pipe installation operations. The methods are based on adapting the solutions of annular and planar Couette flow problems to the HDD pullback problem and are favorable for practical uses by the HDD industry. In comparison to the existing methods, the proposed method accounts for a wide range of parameters, including slurry rheology, bore geometry, and pullback rate. For verification purposes, verified fluidic drag forces for two actual HDD crossings have been used. Comparison of the forces obtained via different methods confirms the ability of the new simple methods to capture the fluidic drag changes accurately.

Label-Free Detection of Bacillus anthracis Spore Uptake in Macrophage Cells Using Analytical Optical Force Measurements.

Understanding the interaction between macrophage cells and Bacillus anthracis spores is of significant importance with respect to both anthrax disease progression, spore detection for biodefense, as well as understanding cell clearance in general. While most detection systems rely on specific molecules, such as nucleic acids or proteins and fluorescent labels to identify the target(s) of interest, label-free methods probe changes in intrinsic properties, such as size, refractive index, and morphology, for correlation with a particular biological event. Optical chromatography is a label free technique that uses the balance between optical and fluidic drag forces within a microfluidic channel to determine the optical force on cells or particles. Here we show an increase in the optical force experienced by RAW264.7 macrophage cells upon the uptake of both microparticles and B. anthracis Sterne 34F2 spores. In the case of spores, the exposure was detected in as little as 1 h without the use of antibodies or fluorescent labels of any kind. An increase in the optical force was also seen in macrophage cells treated with cytochalasin D, both with and without a subsequent exposure to spores, indicating that a portion of the increase in the optical force arises independent of phagocytosis. These results demonstrate the capability of optical chromatography to detect subtle biological differences in a rapid and sensitive manner and suggest future potential in a range of applications, including the detection of biological threat agents for biodefense and pathogens for the prevention of sepsis and other diseases.

Nanoscale Measurements of Biochemical Interactions at the Surface of Optically Trapped Particles

Molecular interactions at biological surfaces are central to numerous physiological functions, such as cell-cell communication, adhesion, or the immune response to pathogens. Most analyses of these interactions require the use of purified proteins, which are studied in suspension or after immobilization on artificial carrier objects. To characterize instead biomolecular dynamics directly at the surface of small biological particles, we have combined optical tweezers with a multi-channel microfluidics chamber. This instrument allows us to expose a laser-trapped particle to a series of microenvironments that are created without walls by laminar flow. We monitor biochemical reactions between the particle surface and supplied ligands by measuring minuscule changes in the particle's response to a well-defined fluidic drag force. Among others, this response is highly sensitive to the particle size. Once a particle is trapped in a typical experiment, the chamber is moved perpendicularly to the main flow direction in a sinusoidal wave to apply a periodic drag force. Using custom-developed software, the resulting particle motion is tracked with a resolution of ∼5 nm at a rate of up to 3,200 frames per second. A linear-systems analysis allows us to monitor the particle radius in different environments with a resolution of a few nanometers. In first measurements, we used this setup to examine the interaction between protein-A and human IgG. We found that at saturation, bound IgG added an apparent thickness of 12.6±1.4(SD) nm to protein-A-coated beads, in agreement with the expected size of human IgG of ∼12 nm. Moreover, we measured an equilibrium constant of KA = 0.115 nM−1 for the protein-A:IgG interaction, in excellent agreement with literature values.

Capture Efficiency of Magnetic Nanoparticles in a Tube under Magnetic Field

In this work, we have performed the computational simulation to calculate the capture efficiency of magnetic nanoparticles flowing within a fluid in a tube under magnetic field. The capture efficiency is calculated by considering the dominant magnetization and fluidic drag forces acting on the magnetic particles. Further, experiments are also performed to calculate the capture efficiency of magnetic particles experimentally in a tube of diameter 6mm under magnetic field. Iron oxide (Fe3O4) nanoparticles were synthesized via co-precipitation method and transported them in a tube with help of peristaltic pump. The value of capture efficiency, calculated through experimental data, is found to be 26 and 50%, which is slightly differ from its value (30 and 52%) calculated through mathematical model at 2 and 6 kOe magnetic field, respectively. Subsequently, the experimental results validate the mathematical model results.

Crawling microrobot actuated by a magnetic navigation system in tubular environments

This paper proposes a crawling microrobot that can effectively navigate and anchor in various tubular environments including human blood vessels and pipes. The microrobot is a multibody structure comprising independently rotatable magnetic bodies with flexible legs and connecting rods. It can resist gravity and fluidic drag forces due to the moving mechanism using asymmetric friction force at the contact point between the leg and wall of the tube. Since the oscillating magnetic field generated by a magnetic navigation system (MNS) can induce oscillating motion of the microrobot, forward and backward crawling motions of the microrobot can be generated by controlling the currents in the MNS. This paper also proposes a methodology to effectively generate a three-dimensional (3D) oscillating magnetic field for the precise manipulation of the microrobot in a 3D tubular environment. Experiments in various environments were performed to verify the proposed microrobot.

A Biophysical Solution to Prevent Hemolysis Interferences

In-vivo and in-vitro hemolysis, membrane rupture of red blood cells (RBCs) and release of their contents into blood plasma, is one of the major critical issues in medicine. For in-vitro blood-based molecular diagnostics, inhibitors (hemoglobin, potassium, mRNA etc.) released from RBCs due to hemolysis during blood plasma separation can cause serious difficulties in quantitative molecular analysis with sensitivity and selectivity. Here we describe an innovative biophysical solution to prevent hemolysis in blood plasma separation devices for precision molecular diagnostics. In order to avoid biochemical interferences, RBCs are exposed to both fluidic drag force and gravitational force after the computation of transition fluid velocity from vertical up-flow to sedimentation was in the range of 1.3 to 2.5 µm/sec in the design of microfluidic separation device. A membrane filter for filtration was positioned on top of a vertical up-flow channel to reduce clogging of RBCs by gravity-assisted cells sedimentation. As a result, separated plasma volume was increased about 4-fold (2.4 µL plasma after 20 min with 38 % hematocrit human whole blood) and hemoglobin concentration in separated plasma was decreased about 90 % due to the prevention of RBCs hemolysis in comparison to a filter-in-bottom configuration. On-chip plasma contains ∼90 % of protein and ∼100 % of nucleic acids compared to off-chip centrifuged plasma, showing comparable target molecules recovery. This simple and reliable blood plasma separation platform can be easily integrated with downstream detection module for sample-to-answer POC diagnostics.

Label free detection of pseudorabies virus infection in Vero cells using laser force analysis

The rapid and robust identification of viral infections has broad implications for a number of fields, including medicine, biotechnology and biodefense. Most detection systems rely on specific molecules, such as nucleic acids or proteins, to identify the target(s) of interest. These molecules afford great specificity, but are often expensive, labor-intensive, labile and limited in scope. Label free detection methods seek to overcome these limitations by instead using detection methods that rely on intrinsic properties as a basis for identifying and separating species of interest and thus do not rely on specific prior knowledge of the target. Optical chromatography, one such technique, uses the balance between optical and fluidic drag forces within a microfluidic channel to determine the optical force on cells or particles. Here we present the application of individual optical force measurements as a means of investigating pseudorabies virus infection in Vero cells. Optical force differences are seen between cells from uninfected and infected populations at a multiplicity of infection as low as 0.001 and as soon as 2 hours post infection, demonstrating the potential of this technique as a means of detecting viral infection. Through the application of a pattern recognition neural network, individual cell size data are combined with optical force as a means of classifying cell populations. Potential applications include the early detection of bloodborne pathogens for the prevention of sepsis and other diseases as well as the detection of biological threat agents.

Controllable High-Speed Rotation of Nanowires

We report a versatile method for executing controllable high-speed rotation of nanowires by AC voltages applied to multiple electrodes. The rotation of the nanowires can be instantly switched on or off with precisely controlled rotation speed (to at least 1800 rpm), definite chirality, and total angle of rotation. We have determined the torque due to the fluidic drag force on nanowire of different lengths. We also demonstrate a micromotor using a rotating nanowires driving a dust particle into circular motion. This method has been used to rotate magnetic and nonmagnetic nanowires as well as carbon nanotubes.