PubMed Health⌕ Search

Biomedical subjects

Patrick S Doyle

Publications and source records attributed to Patrick S Doyle.

13 recordsLinked to original sources

A Brownian dynamics-finite element method for simulating DNA electrophoresis in nonhomogeneous electric fields.

The objective of this work is to develop a numerical method to simulate DNA electrophoresis in complicated geometries. The proposed numerical scheme is composed of three parts: (1) a bead-spring Brownian dynamics (BD) simulation, (2) an iterative solver-enhanced finite element method (FEM) for the electric field, and (3) the connection algorithm between FEM and BD. A target-induced searching algorithm is developed to quickly address the electric field in the complex geometry which is discretized into unstructured finite element meshes. We also develop a method to use the hard-sphere interaction algorithm proposed by Heyes and Melrose [J. Non-Newtonian Fluid Mech. 46, 1 (1993)] in FEM. To verify the accuracy of our numerical schemes, our method is applied to the problem of lambda-DNA deformation around an isolated cylindrical obstacle for which the analytical solution of the electric field is available and experimental data exist. We compare our schemes with an analytical approach and there is a good agreement between the two. We expect that the present numerical method will be useful for the design of future microfluidic devices to stretch and/or separate DNA.

Algorithms↗

Magnetically and biologically active bead-patterned hydrogels.

We present a new approach to the direct patterning of biologically and magnetically active microbeads in nonbiofouling polymer scaffolds for use in microfluidic devices. Briefly, the process involves treatment of a glass substrate, conformal contact bonding of a PDMS microchannel on the substrate, filling of the channel with beads and prepolymer solution, and UV-initiated photopolymerization of a mask-defined pattern using a standard inverted microscope. This versatile and simple method allows for the rapid fabrication of dispersed or packed bead patterns in poly(ethylene glycol) (PEG) hydrogels that are covalently linked to glass surfaces. By exploiting the relative opacity of the microbeads used, we are able to create both partially exposed and fully encapsulated bead patterns. To demonstrate the utility of this new technology, we separated magnetic bead-bound B lymphocytes from T lymphocytes on a PEG-encapsulated magnetic filtration platform and also captured B cells directly on patterned, protein-decorated beads in a flow-through microfluidic device. Beyond cell sorting, the accurate patterning of industrially standardized, chemically diverse microbeads may have significant implications for microchip-based analyte detection.

B-Lymphocytes↗

Experimental study of structure and dynamics in a monolayer of paramagnetic colloids confined by parallel hard walls.

We study the structural and dynamical properties of paramagnetic colloidal spheres interacting as repulsive dipoles in two dimensions and confined between parallel hard walls. We observed that the structure and dynamics of the self-assembled colloids are strongly dependent upon the width of the confining channel. The system exhibits re-entrant behavior as a function of the channel width, transitioning from solid-like to liquid-like repeatedly in excellent agreement with simulation results. For large channels, an ordered layered structure self-assembles near the walls, but this local structure is not commensurate with the bulk structure, leading to localized stable defects.

Journal Article↗

Continuous-flow lithography for high-throughput microparticle synthesis.

Precisely shaped polymeric particles and structures are widely used for applications in photonic materials, MEMS, biomaterials and self-assembly. Current approaches for particle synthesis are either batch processes or flow-through microfluidic schemes that are based on two-phase systems, limiting the throughput, shape and functionality of the particles. We report a one-phase method that combines the advantages of microscope projection photolithography and microfluidics to continuously form morphologically complex or multifunctional particles down to the colloidal length scale. Exploiting the inhibition of free-radical polymerization near PDMS surfaces, we are able to repeatedly pattern and flow rows of particles in less than 0.1 s, affording a throughput of near 100 particles per second using the simplest of device designs. Polymerization was also carried out across laminar, co-flowing streams to generate Janus particles containing different chemistries, whose relative proportions could be easily tuned. This new high-throughput technique offers unprecedented control over particle size, shape and anisotropy.

Journal Article↗

Methods to electrophoretically stretch DNA: microcontractions, gels, and hybrid gel-microcontraction devices.

The ability to controllably and continuously stretch large DNA molecules in a microfluidic format is important for gene mapping technologies such as Direct Linear Analysis (DLA). We have recently shown that electric field gradients can be readily generated in a microfluidic device and the resulting field is purely elongational. We present a single molecule fluorescence microscopy analysis of T4 DNA (169 kbp) stretching in the electric field gradients in a hyperbolic contraction microchannel. In addition, we are able to selectively pattern a crosslinked gel anywhere inside the microchannel. With an applied electric field, DNA molecules are forced to reptate through the gel and they moderately stretch as they exit the gel. By placing a gel immediately in front of the hyperbolic contraction, we bypass "molecular individualism" and achieve highly uniform and complete stretching of T4 DNA.

Bacteriophage T4↗

Permeation-driven flow in poly(dimethylsiloxane) microfluidic devices.

Poly(dimethylsiloxane) is currently the material of choice for rapidly fabricating microfluidic devices. As the size of these devices decreases, a significant hydrodynamic flow is generated due to permeation of fluid through the channel walls. We develop a theoretical model verified by single bead tracking experiments, which demonstrates that large flow rates (>10 microm/s) can be passively generated in a straight microchannel filled with water. Realizing that this flow may be unwanted in some applications, we present a method to eliminate it by inhibiting mass transfer of water into the poly(dimethylsiloxane) walls. Furthermore, we explore applications to harness this passively generated flow inside a microfluidic device such as bead stacking, chemical concentration, and passive pumping.

Journal Article↗

Structure and dynamics of repulsive magnetorheological colloids in two-dimensional channels.

We study a system of colloidal spheres with induced magnetic dipoles confined in two-dimensional (2D) hard-wall channels using Brownian dynamics simulations. The external magnetic field is directed normal to the 2D plane and therefore the colloids interact with a purely repulsive r(-3) potential. The effects of confinement between parallel walls are determined by analyzing the structure and dynamics of these confined systems and comparing to the unbounded (infinite) 2D plane limit. The bond-order correlation function is analyzed as a function of time and exhibits unique characteristics associated with the channel-like confinement. The existence of a plateau in this correlation function is observed over an intermediate time scale and the fate of the plateau (decay or persistence) depends upon the channel width, the strength of the external magnetic field, and the number density. The plateau is analyzed in further detail and an explanation is put forth for its existence and subsequent long time behavior. Additionally, re-entrant behavior with respect to dimensionless channel width is observed in the structural properties and an associated state-diagram is presented for these systems.

Journal Article↗

Role of a finite exposure time on measuring an elastic modulus using microrheology.

The role of a finite exposure time sigma on measuring rheological properties using microrheology techniques is theoretically investigated. We concentrate on studying fluid models displaying a plateau in the mean-squared displacement (MSD) of the embedded probe particle. A model is developed to compare the resulting experimentally measured MSD of the particle to its expected value in the fluid model. A plateau MSD is greatly modified in a measurement when sigma is greater than the plateau onset time. Moreover, apparent dynamics drastically differ from the true dynamics at frequencies omega less than or approximately equal sigma(-1) . These results quantify when and how a finite exposure time effects the measured MSD of a probe particle which can then alter the extracted rheological properties and physical interpretations.

Journal Article↗

Controlled synthesis of nonspherical microparticles using microfluidics.

The controlled synthesis of nonspherical microparticles using microfluidics processing is described. Polymer droplets, formed by shearing a photopolymer using a continuous water phase at a T-junction, were constrained to adopt nonspherical shapes by confining them using appropriate microchannel geometries. Plugs were obtained by shearing the polymer phase at low shear rates, while disks were obtained by flattening droplets using a channel of low height. The nonspherical shapes formed were permanently preserved by photopolymerizing the constrained droplets in situ using ultraviolet light. Monodisperse plugs and disks of different lengths and diameters were obtained by varying the flow rates of the two phases.

Journal Article↗

Structural analysis of a dipole system in two-dimensional channels.

A system of magnetic dipoles in two-dimensional (2D) channels was studied using Brownian dynamics simulations. The dipoles interact with a purely repulsive r(-3) potential and are confined by two hard walls in one of the dimensions. Solid crystals were annealed in the 2D channels and the structural properties of the crystals were investigated. The long-ranged nature of the purely repulsive dipoles combined with the presence of hard walls led to structural deviations from the unbounded (infinite) 2D dipolar crystal. The structures in the channels were characterized by a high density of particles along the walls. The particles along the wall became increasingly localized as the channel width was increased. The spacing of the walls was important in determining the properties of the structures formed in the channel. Small changes in the width of the channel induced significant structural changes in the crystal. These structural changes were manifested in the density profiles, defect concentrations, and local bond-orientation order of the system. Oscillations in the structural properties were observed as the channel width was increased, indicating the existence of magic-number channel widths for this system. As the channel width was increased the properties of the confined system approached those of the unbounded system surprisingly slowly.

Journal Article↗

Static and dynamic errors in particle tracking microrheology.

Particle tracking techniques are often used to assess the local mechanical properties of cells and biological fluids. The extracted trajectories are exploited to compute the mean-squared displacement that characterizes the dynamics of the probe particles. Limited spatial resolution and statistical uncertainty are the limiting factors that alter the accuracy of the mean-squared displacement estimation. We precisely quantified the effect of localization errors in the determination of the mean-squared displacement by separating the sources of these errors into two separate contributions. A "static error" arises in the position measurements of immobilized particles. A "dynamic error" comes from the particle motion during the finite exposure time that is required for visualization. We calculated the propagation of these errors on the mean-squared displacement. We examined the impact of our error analysis on theoretical model fluids used in biorheology. These theoretical predictions were verified for purely viscous fluids using simulations and a multiple-particle tracking technique performed with video microscopy. We showed that the static contribution can be confidently corrected in dynamics studies by using static experiments performed at a similar noise-to-signal ratio. This groundwork allowed us to achieve higher resolution in the mean-squared displacement, and thus to increase the accuracy of microrheology studies.

Algorithms↗

Electrophoretic collision of a DNA molecule with an insulating post.

We study the dynamics of single DNA molecules driven by an electric field into a stationary obstacle. These collisions are broadly classified as "hook" and "roll-off" events. We show that obstacle-induced electric field gradients stretch impacting DNA and thus greatly influence the hooking probability. Consequently, in addition to collision geometry, determination of the hooking probability depends on the Deborah number (De) for 0.5<De<40. Individual DNA impact dynamics are highly configuration sensitive, characteristic of polymers in elongational flows and fields.

DNA↗