Hsueh-Chia Chang

Microfluidic devices for bioapplications.

Harnessing the ability to precisely and reproducibly actuate fluids and manipulate bioparticles such as DNA, cells, and molecules at the microscale, microfluidics is a powerful tool that is currently revolutionizing chemical and biological analysis by replicating laboratory bench-top technology on a miniature chip-scale device, thus allowing assays to be carried out at a fraction of the time and cost while affording portability and field-use capability. Emerging from a decade of research and development in microfluidic technology are a wide range of promising laboratory and consumer biotechnological applications from microscale genetic and proteomic analysis kits, cell culture and manipulation platforms, biosensors, and pathogen detection systems to point-of-care diagnostic devices, high-throughput combinatorial drug screening platforms, schemes for targeted drug delivery and advanced therapeutics, and novel biomaterials synthesis for tissue engineering. The developments associated with these technological advances along with their respective applications to date are reviewed from a broad perspective and possible future directions that could arise from the current state of the art are discussed.

An integrated dielectrophoretic chip for continuous bioparticle filtering, focusing, sorting, trapping, and detecting

Multi-target pathogen detection using heterogeneous medical samples require continuous filtering, sorting, and trapping of debris, bioparticles, and immunocolloids within a diagnostic chip. We present an integrated AC dielectrophoretic (DEP) microfluidic platform based on planar electrodes that form three-dimensional (3D) DEP gates. This platform can continuously perform these tasks with a throughput of 3 muLmin. Mixtures of latex particles, Escherichia coli Nissle, Lactobacillus, and Candida albicans are sorted and concentrated by these 3D DEP gates. Surface enhanced Raman scattering is used as an on-chip detection method on the concentrated bacteria. A processing rate of 500 bacteria was estimated when 100 mul of a heterogeneous colony of 10(7) colony forming units ml was processed in a single pass within 30 min.

Marangoni effects of trace impurities on the motion of long gas bubbles in capillaries

When a viscous liquid is displaced by a long air bubble in a capillary, it leaves behind a wetting liquid film. A lubrication analysis by Bretherton (1961), which assumes a mobile surface, underpredicts the film thickness at low bubble speeds. In this investigation, the Marangoni effect of small amounts of impurities is shown to be capable of explaining this discrepancy. We carry out an asymptotic analysis for different convective, diffusive and kinetic timescales and show that, if transport in the film is mass-transfer limited such that a bulk concentration gradient exists in the film, the film thickness increases by a maximum factor of 4 2/3; over Brethertons mobile result at low bubble speeds. Moreover, at large bubble speeds, Brethertons mobile prediction is approached for all ranges of timescales. For intermediate bubble speeds, the film thickness varies with respect to the bubble speed with an exponent smaller than 2/3 of the mobile theory. These results are favourably compared to literature data on film thickness.

Transport of gas bubbles in capillaries

The pressure drop and wetting film thickness for isolated bubbles and bubble trains moving in circular and square capillaries are computed. An arclength‐angle formulation of a composite lubrication equation allows for the numerical matching of the lubrication solution of the transition region to the static profiles away from the channel wall. This technique is shown to extend the classical matched asymptotic analysis of Bretherton for circular capillaries to higher capillary numbers Ca. More importantly, it allows the study of finite bubbles, which are shown to resemble infinitely long bubbles in film thickness and pressure drop if their lengths exceed the channel width. The numerical study of bubble trains, verified by a matched asymptotic analysis, shows a surprising result that the pressure drop across one member bubble is identical to that of an isolated bubble at low capillary numbers. This analysis of square capillaries neglects azimuthal flow and is only valid for Ca>3.0×10−3. Nevertheless the film...

NONLINEAR EVOLUTION OF WAVES ON A VERTICALLY FALLING FILM

Wave formation on a falling film is an intriguing hydrodynamic phenomenon involving transitions among a rich variety of spatial and temporal structures. Immediately beyond an inception region, short, near-sinusoidal capillary waves are observed. Further downstream, long, near-solitary waves with large tear-drop humps preceded by short, front-running capillary waves appear. Both kinds of waves evolve slowly downstream such that over about ten wavelengths, they resemble stationary waves which propagate at constant speeds and shapes. We exploit this quasi-steady property here to study wave evolution and selection on a vertically falling film. All finite-amplitude stationary waves with the same average thickness as the Nusselt flat film are constructed numerically from a boundary-layer approximation of the equations of motion. As is consistent with earlier near-critical analyses, two travelling wave families are found, each parameterized by the wavelength or the speed. One family γ 1 travels slower than infinitesimally small waves of the same wavelength while the other family γ 2 and its hybrids travel faster. Stability analyses of these waves involving three-dimensional disturbances of arbitrary wavelength indicate that there exists a unique nearly sinusoidal wave on the slow family γ 1 with wavenumber α s (or α 2 ) that has the lowest growth rate. This wave is slightly shorter than the fastest growing linear mode with wavenumber α m and approaches the wave on γ 1 with the highest flow rate at low Reynolds numbers. On the fast γ 2 family, however, multiple bands of near-solitary waves bounded below by α f are found to be stable to two-dimensional disturbances. This multiplicity of stable bands can be interpreted as a result of favourable interaction among solitary-wave-like coherent structures to form a periodic train. (All waves are unstable to three-dimensional disturbances with small growth rates.) The suggested selection mechanism is consistent with literature data and our numerical experiments that indicate waves slow down immediately beyond inception as they approach the short capillary wave with wavenumber α 2 of the slow γ 1 family. They then approach the long stable waves on the γ 2 family further downstream and hence accelerate and develop into the unique solitary wave shapes, before they succumb to the slowly evolving transverse disturbances.

A critical comparison of equilibrium, non-equilibrium and boundary-driven molecular dynamics techniques for studying transport in microporous materials

Transport in an idealized model with variable pore diameter as well as an AlPO4-5 zeolite is examined using three different molecular dynamics techniques: (1) equilibrium molecular dynamics (EMD); (2) external field nonequilibrium molecular dynamics (EF–NEMD); and (3) dual control volume grand canonical molecular dynamics (DCV–GCMD). The EMD and EF–NEMD methods yield identical transport coefficients for all the systems studied. The transport coefficients calculated using the DCV–GCMD method, however, tend to be lower than those obtained from the EMD and EF–NEMD methods unless a large ratio of stochastic to dynamic moves is used for each control volume, and a streaming velocity is added to all inserted molecules. Through development and application of a combined reaction–diffusion–convection model, this discrepancy is shown to be due to spurious mass and momentum transfers caused by the control volume equilibration procedure. This shortcoming can be remedied with a proper choice of streaming velocity in co...

Electrokinetic micropump and micromixer design based on ac faradaic polarization

A microfluidic pump and mixer design based on ac faradaic polarization is proposed. Unlike ac electrokinetic devices based on capacitive charging of the electrodes, the design yields a net electro-osmotic flow for high-conductivity electrolytes at high voltages and frequencies without producing gas bubbles or generating pH gradients. The average velocity, which can be more than an order of magnitude higher than that generated by the capacitive mechanism, has an exponential dependence on the voltage and increases monotonically at low frequencies. Vortices and net flows with linear velocities in excess of 1mm∕s are generated with orthogonal microfabricated planar electrodes based on the unique flow and polarization features of this new ac charging mechanism.

LONG WAVES ON INCLINED FILMS AT HIGH REYNOLDS NUMBER

At large Reynolds number (Re>10), waves on inclined films grow rapidly downstream in both amplitude and wavelength to the extent that linear stability theory cannot adequately describe their velocity-wavenumber relationship. We develop a second-order integral boundary-layer approximation for long waves at intermediate Re of O(e −1 ), where e is the dimensionless wavenumber scaled with respect to the film thickness

A continuous high-throughput bioparticle sorter based on 3D traveling-wave dielectrophoresis

We present a high throughput (maximum flow rate approximately 10 microl/min or linear velocity approximately 3 mm/s) continuous bio-particle sorter based on 3D traveling-wave dielectrophoresis (twDEP) at an optimum AC frequency of 500 kHz. The high throughput sorting is achieved with a sustained twDEP particle force normal to the continuous through-flow, which is applied over the entire chip by a single 3D electrode array. The design allows continuous fractionation of micron-sized particles into different downstream sub-channels based on differences in their twDEP mobility on both sides of the cross-over. Conventional DEP is integrated upstream to focus the particles into a single levitated queue to allow twDEP sorting by mobility difference and to minimize sedimentation and field-induced lysis. The 3D electrode array design minimizes the offsetting effect of nDEP (negative DEP with particle force towards regions with weak fields) on twDEP such that both forces increase monotonically with voltage to further increase the throughput. Effective focusing and separation of red blood cells from debris-filled heterogeneous samples are demonstrated, as well as size-based separation of poly-dispersed liposome suspensions into two distinct bands at 2.3 to 4.6 microm and 1.5 to 2.7 microm, at the highest throughput recorded in hand-held chips of 6 microl/min.

Nonlinear electrokinetic ejection and entrainment due to polarization at nearly insulated wedges

We examine a singular electrokinetic flow around a corner or a wedge in micro-channels constructed from dielectric materials whose permittivity is small but finite compared to that of the electrolyte. When the wedge angle is less than 180°, the applied electric field, which is tangential far from the corner, develops a normal surface component that becomes singular at the corner. This normal field leakage causes opposite polarization at the two sides of the wedge and produces a converging singular tangential electrokinetic flow that ejects liquid from the tip. By expanding in cylindrical harmonics, we estimate this ejecting flow as a function of the permittivity ratio, applied electric field, angle of the wedge and the microscopic corner curvature that suppresses the singularity. The ejecting flow entrains tangential flow on the front side of the wedge and produces a vortex on the downstream side. This entrainment offers a long-range attractive hydrodynamic force that complements short-range electrostatic...