Session Z19: Micro/Nano Particles: Biological/Assembly

Inertial migration of spherical particles in curved microfluidic ducts

Finite size particles suspended in flow through micro-scale ducts are known to migrate across streamlines and focus towards stable equilibria whose location depends on a variety of factors. This has a several practical applications involving the separation and isolation of cells. I will describe some of our work on modelling inertial migration of spherical particles at low Reynolds numbers in curved ducts having rectangular and trapezoidal cross-sections. Via a careful analysis of the coupled particle fluid motion we have been able to separate the effects of inertial lift and drag due to secondary fluid motion. By computing these forces and subsequently reconstructing particle motion we have been able to demonstrate some clear relationships between the lateral focusing location and three physical length scales. Moreover we have been able to identify a number of interesting dynamical changes that take place over the device design parameter space.   

Computational modeling of adhesion-based cell sorting in label-free microfluidic platform

Identifying and isolating cells that express desired molecular surface markers is required in a variety of applications in the biological sciences, cell therapy, and medical diagnostics. We develop a biophysical approach for high-throughput and label-free sorting of cells by their affinity for target ligands by molecular surface markers. Our approach consists of a microchannel decorated with periodic skewed ridges and coated with adhesive molecules. To examine the effects of specific and non-specific adhesion on cell trajectories, we conduct small scale experiments in conjunction with computer simulations. We perform both systematic simulations, to find parameters that best align with experimental results, and simulations with new layouts, to explore alternative configurations without the need to conduct a physical experiment. Our specific adhesion model captures the adhesion kinetics and accounts for the molecular binding/unbinding events due to specific interactions of adhesive molecules and corresponding ligands. We find that specific and non-specific adhesion lead to distinct parameters of cells trajectories such as cell interaction time with the ridge, which can be used to identify different types of cell interaction. Furthermore, cell trajectories are sensitive to adhesion level and therefore can be used to sort cells with different ligand expression.   

Stiffness-based cell sorting using power-law fluids in ridged microchannels

Sorting biological cells in heterogeneous populations is a critical task required in a variety of biomedical applications and therapeutics. Microfluidic methods are a promising pathway towards establishing label-free sorting based on cell intrinsic biophysical properties, such as cell deformability. Experiments and numerical studies show that microchannels decorated with diagonal ridges can be used to separate cell by stiffness in a Newtonian fluid. In an effort to increase the throughput and enhance sorting resolution, we leverage the shear dependent viscosity of non-Newtonian fluids. Using numerical simulations, we probe the stiffness-based sorting of compliant cells in ridged microchannels filled with a shear-thinning power-law fluid. We consider compliant cells with a range of capillary numbers and examine the effect of ridge geometry on cell trajectories in microchannel. Results reveal shear-thinning fluids can be used to enhance sorting resolution of deformable cells.

    

Modelling Microparticle Manufacture

Microparticles - 1 to 100 micrometer sized capsules - will enable cheap and precise single-cell analysis. Current research uses temperature-induced phase separation to efficiently fabricate polymer gel microparticles of desired shapes and sizes. To better understand this process, we develop several models of microscale phase separation of ternary fluids. A simple surface energy minimisation model describes possible equilibrium microparticle shapes. We then interrogate the dynamics of microparticle manufacture by combining a ternary Cahn-Hilliard model with surface tension- and buoyancy-driven Stokes flow. By simulating the model in three dimensions using the efficient Dedalus spectral code, we show that all physical effects - surface tension, fluid flow, and buoyancy - are necessary for microparticles to attain crescent configurations. Without fluid flow or buoyancy, microparticles consistently settle on spherical shell equilibria, in contrast to experiments. We then outline how varying surface energies, densities, viscosities, and concentrations can each influence microparticle manufacture, before concluding with a discussion of how fluid stresses drive microparticle evolution.   

Synchronous oscillatory electro-inertial focusing of biological particles

Manipulation of microparticles and living cells using active and passive techniques in microfluidic devices is useful for a variety of applications including filtration of contaminants, flow cytometry, and microfluidic mixing. Here, we present experimental results on the focusing of biological particles including bacteria and epithelial cells using synchronous oscillatory electro-inertial flow in a microfluidic device. By varying the phase difference between an oscillatory flow and AC electric field, we show that the focusing efficiency and the focusing positions of bioparticles can be controlled. Specifically, we are able to focus E. coli bacteria (1 μm) in a short channel of only 2 cm in length. Furthermore, this technique is suitable for preserving the viability of bioparticles, including epithelial cells (70 μm), due to the low shear stress experienced in the device. These results show that synchronous oscillatory electro-inertial microfluidics offers novel capabilities for manipulating microscale biological particles based on their size and surface properties, such as zeta potential.   

A Topology-Motivated Approach to Identifying Topological Defects in Liquid Crystals

Current computational techniques for identifying topological defects in particle-based simulations of liquid crystalline materials rest upon Q-tensor theory, which is premised upon violations of local ordering but is ultimately insensitive to global topological features of the system. Here, we describe a novel defect-detection algorithm suitable for use with molecular-scale particle trajectory data, which assigns a unique vector to each mesogen, thereby defining the director field at the mesogen level. This algorithm is sensitive to the topology of the system and can identify the presence of defect cores by systematically searching for discontinuities in this vector field. For a variety of liquid crystalline assemblies obtained from molecular-dynamics simulations, we show that defects identified using this approach compare favorably to defects identified using a commonplace technique based upon the scalar order parameter.   

Dynamics of spheroids in pressure driven flows of shear thinning fluids.

Particles in inertialess flows of shear thinning fluids are a model representation of several systems in biology, ecology, and microfluidics.  In this research , we delineate  the orientational kinematics of spheroids in pressure driven flows of shear thinning fluids. The shear thinning rheology is rendered by the Carreau model. We employ  a combination of perturbative techniques and the reciprocal theorem to analyse the motion of both prolate and oblate spheroids. There are two perturbative strategies adopted, one near the zero shear Newtonian plateau and the other near the infinite shear Newtonian plateau of the Carreau model. In both limits, we find that a reduction in effective viscosity decreases the spheroid’s rotational time period in pressure driven flows, which is contrary to the observations reported in earlier publications for linear flows. The extent to which shear thinning alters the kinematics is a function of the particle shape. For a prolate particle, the effect of shear thinning is most prominent when the spheroid projector is aligned in the direction of the velocity gradient, while for an oblate particle the effect is most prominent when the projector is aligned along the flow direction.  Shear thinning does not resolve the degeneracy of Jefferey's orbits.

This work was supported by the American Chemical Society Petroleum Research Fund under grant ACS PRF 61266-DNI9.   

Author not Attending

Active drops swim at the micron scale by utilizing the non-linear coupling between the advective transport of a chemical solute they emit, and the Marangoni flows generated by this solute's distribution. This self-propulsion is well studied in an unbounded fluid, where it occurs above a critical advective-to-diffusive transport ratio (i.e., Péclet number). However, the influence of a confining rigid wall on the propulsion of an active drop has remained essentially unexplored, despite its prevalence in experiments. We therefore investigate the steady state propulsion of a model active droplet parallel to a passive rigid wall, to which it is confined by a constant external force (e.g., gravity). Using a numerical framework based on a non-axisymmetric bi-spherical decomposition, we provide critical physical insights on the drop's long-time propulsion as a function of its confinement and the Péclet number.   

Rapid Screening of Diabetic Retinopathy from Tear Fluid-Proteins Using a SAW-based Acoustofluidic System

This study aims to enhance the fluorescent signal of trace tear fluid proteins by surface acoustic wave (SAW). Due to various acoustic radiation forces exerted on particles and complexes of different sizes and properties, rapid mixing, separation, and concentration of particles and complexes in liquid medium using SAW have been powerful manipulations used in various biomedical applications.

A lab-on-chip system features many advantages, such as a significant reduction of reagents and sample volume, short reaction and analysis time, high throughput, and portability. The fluorescent signal after the immunoassay implies a successful sandwiched immunocomplex. Our results showed that SAW can mix, separate, and concentrate two different sizes of PS particles. Thus, we can further infer that SAW can do the rapid diagnosis on bead-based sandwiched immunocomplex without washing. Using this SAW-based enhancement technic, we can rapidly concentrate PS particles within ~10 s, it strongly shortens the processing time of the analysis.   

Particle trapping using axial primary acoustic radiation force

Development in bio-particle handling microfluidic systems is subject to advancements in efficient techniques of trapping them. Contactless and gentle trapping platform offered by the ultrasonic standing wave technology makes it an attractive tool for widespread biotechnological applications. In the present study, we demonstrate an acoustofluidic trapping technique based on the standing bulk acoustic waves (S-BAW) generated inside a uniquely designed chamber – the ‘shaped trap’ that enables the particle to experience the axial primary radiation force (A-PRF) along the flow direction as the main trapping force. The study of particle dynamics reveals that the competition between A-PRF and viscous drag force governs particle trajectory. The ratio of the acoustic energy to the viscous work (β) provides a general criterion for particle trapping at a distinctive off-node site that is spatially controllable through variations in particle size, flow velocity, and acoustic energy density, creating a zone of trapping sites. Particles get trapped for β > β_cr at some distance away from the pressure nodal plane and the distance varies as β^c (c = 0.6 –1.0). Our study highlights the importance of utilizing the A-PRF as the main retention force (which originates from the more dominant potential energy gradients present away from the pressure nodal plane) against the flow unlike the conventional S-BAW trapping systems relying on lateral acoustic energy density gradient (which relies on the smaller lateral acoustic velocity field gradients effective only near the pressure nodal plane), consequently achieving an improved control over the trapping sites and higher retention force which could potentially bring in significant throughput advancements to the existing bioparticle trapping technology, thus opening up new avenues for biochemical applications.