Biomedical subjects

Hsueh-Chia Chang

Publications and source records attributed to Hsueh-Chia Chang.

At least 19 recordsLinked to original sources

PubMed2007

Open-tubular capillary electrochromatography-mass spectrometry with sheathless nanoflow electrospray ionization for analysis of amino acids and peptides.

A novel, rugged sheathless capillary electrochromatography-electrospray ionization (CEC-ESI) device, in which an open-tubular separation capillary and an electrospray tip are integrated with a Nafion tubing junction, is coupled to mass spectrometry (MS) for the analysis of amino acids and peptides. A stable electrospray was generated at nanoflow rates by applying a positive electrical potential at the Nafion membrane junction. To sustain the stable spray, an electroosmotic flow (EOF) to the spray was supported by coating the fused silica capillary with Lupamin, a high-molecular-weight linear positively charged polyvinylamine (PVAm) polymer, which also minimizes analyte adsorption. Electrochromatographic separation of amino acids and peptides was further enhanced by the chromatographic selectivity of Lupamin stationary phase for these molecules. The device was very reliable and reproducible for CEC-ESI-MS analyses of amino acids and peptides for over a hundred injections. The separation and detection behaviors of amino acids and peptides under different conditions including pH, concentration, and composition of mobile phases on Lupamin-coated and uncoated capillaries have been investigated. The relationship between nano electrospray stability and EOF is discussed.

Amino Acids↗

PubMed2006

AC electro-osmotic mixing induced by non-contact external electrodes.

We demonstrate efficient mixing in a micro-fluidic reservoir smaller than 10 microL using ac electro-osmosis driven by field-induced polarization. Our mixing device, of that electrodes are outside of the mixing unit, consists of three circular reservoirs (3mm in diameter) connected by a 1 mm x 1 mm channel. Unlike dc electro-osmosis, whose polarization is from charged substrate functional groups, this new mechanism uses the external field to capacitively charge the surface and the surface capacitance becomes the key factor in the electrokinetic mobility. The charging and mixing are enhanced at tailor-designed channel corners by exploiting the high normal fields at geometric singularities. The induced surface dielectric polarization and the resulting electric counter-ion double layer produce an effective Zeta potential in excess of 1 V, over one order of magnitude larger than the channel Zeta potential. The resulting ac electro-osmotic slip velocity scales quadratically with respect to the applied field, in contrast to the linear scaling of dc electro-osmosis and at 1cm/s and larger, exceeds the classical dc values by two orders of magnitude. The polarization is non-uniform at the corners due to field leakage to the dielectric substrate and the inhomogeneous slip velocity produces intense mixing vortices that effectively homogenize solutes in 30s in a 3mm reservoir, in contrast to hour-long mixing by pure diffusion.

Complex Mixtures↗

PubMed2006

Polyhedra formation and transient cone ejection of a resonant microdrop forced by an ac electric field.

New deformation or fission phenomena are reported for microdrops driven by an ac electric field at their resonant frequencies. The Maxwell forces that pull out the vertices from a drop can be enhanced when the ac frequency is comparable to both the drop resonant frequency and the inverse charge relaxation time of the diffuse layer. The selected polyhedra possess symmetries that ensure a global force balance of the Maxwell forces and a linear dimension consistent with a sphere whose nth harmonic (n is up to six in the observation) coincides with the applied ac frequency. At high voltages, the resonant focusing of charges by the vibration modes produces evenly distributed and transient Taylor cones that can eject charged nanodrops.

Acetonitriles↗

PubMed2006

A micro-scale multi-frequency reactance measurement technique to detect bacterial growth at low bio-particle concentrations.

The technique described enables the user to detect the presence and proliferation of bacteria through an increase in the bulk capacitance (C) of the suspension, which is proportional to the bacteria count, at practical frequencies less than 1 MHz. The geometry of the micro-capillary design employed increases the bulk resistance (R) of the medium, thus increasing its RC time. This makes the measured reactance sensitive to changes in the bulk capacitance, which is usually masked by the much larger surface capacitance. The sensitivity is further enhanced by the existence of a minimum in the value of the reactance at a frequency proportional to the inverse medium RC time. The value of this reactance minimum and the frequency at which the minimum is recorded are dependent on the bacteria count and permit the detection of an initial concentration of approximately 100 CFU ml(-1) of E. coli within 3 hours of incubation, in comparison with the previous reported values of about 8 hours, with an initial load of 1000 CFU ml(-1).

Bacteriological Techniques↗

PubMed2006

Role of erythrocyte deformability during capillary wetting.

Deformability of erythrocyte was found to fundamentally alter the wetting dynamics of red blood cell (RBC) suspensions during their invasion into capillaries. Normal RBC suspensions failed to penetrate more than 1 cm into a glass capillary when the capillary radius was smaller than a critical value that is dependent on the erythrocyte concentration (about 50 microm for whole blood). In contrast, suspensions of rigidified RBCs, after cross-linking with different concentrations of glutaraldehyde or incubating with 100 ng/mL of an endotoxin, could penetrate any capillary larger than the erythrocyte dimension. The effect of RBC deformability on penetration was attributed to the enhanced shear-induced migration of normal deformable RBCs toward the capillary centreline, which imparted a higher average velocity to the RBCs than the average plasma velocity. As a result, the erythrocytes advanced into the capillary faster than the wetting meniscus, packing behind it to form a concentrated slug. This tightly packed slug had a high hydrodynamic resistance that could arrest the penetrating flow of concentrated suspensions into the small capillaries.

Animals↗

PubMed2006

Electrowetting films on parallel line electrodes.

A lubrication analysis is presented for the spreading dynamics of a high permittivity polar dielectric liquid drop due to an electric field sustained by parallel line electrode pairs separated by a distance R(e). The normal Maxwell stress, concentrated at the tip region near the apparent three-phase contact line, produces a negative capillary pressure that is responsible for pulling out a thin finger of liquid film ahead of the macroscopic drop, analogous to that obtained in self-similar gravity spreading. This front-running electrowetting film maintains a constant contact angle and volume as its front position advances in time t by the universal law 0.43R(e)(t/T(cap))1/3, independent of the drop dimension, surface tension, and wettability. T(cap)=pi(2)mu(l)R(e)/8(epsilon0epsilonl)V2 is the electrocapillary time scale where mu(l) is the liquid viscosity, epsilon0epsilonl the liquid permittivity, and V the applied voltage. This spreading dynamics for the electrowetting film is much faster than the rest of the drop; after a short transient, the latter spreads over the electrowetting film by draining into it. By employing matched asymptotics, we are able to elucidate this unique mechanism, justified by the reasonable agreement with numerical and experimental results. Unlike the usual electrowetting-on-dielectric configuration where the field singularity at the contact line produces a static change in the contact angle consistent with the Lippmann equation, we show that the parallel electrode configuration produces a bulk negative Maxwell pressure within the drop. This Maxwell pressure increases in magnitude toward the contact line due to field confinement and is responsible for a bulk pressure gradient that gives rise to a front-running spontaneous electrowetting film.

Journal Article↗

PubMed2006

Bacteria capture, concentration and detection by alternating current dielectrophoresis and self-assembly of dispersed single-wall carbon nanotubes.

The high polarizability and dielectrophoretic mobility of single-walled carbon nanotubes (SWNT) are utilized to capture and detect low numbers of bacteria and submicron particles in milliliter-sized samples. Concentrated SWNT solutions are mixed with the sample and a high-frequency (>100 kHz) alternating current (AC) field is applied by a microelectrode array to enhance bulk absorption of the particles (bacteria and nanoparticle substitutes) by the SWNTs via dipole-dipole interaction. The same AC field then drives the SWNT-bacteria aggregates to the microelectrode array by positive-AC dielectrophoresis (DEP), with enhanced and reversed bacteria DEP mobility due to the attached SWNTs. Since the field frequency exceeds the inverse RC time of the electrode double layer, the AC field penetrates deeply into the bulk and across the electrode gap. Consequently, the SWNTs and absorbed bacteria assemble rapidly (<5 min) into conducting linear aggregates between the electrodes. Measured AC impedance spectra by the same trapping electrodes and fields show a detection threshold of 10(4) bacteria/mL with this pathogen trapping and concentration technique.

Bacteria↗

PubMed2006

An integrated micropump and electrospray emitter system based on porous silica monoliths.

The work presents the design of an integrated system consisting of a high-pressure electroosmotic (EO) micropump and a microporous monolithic emitter, which together generate a stable and robust electrospray. Both the micropump and electrospray emitter are fabricated using a sol-gel process. Upon application of an electric potential of sufficient amplitude (>2 kV), the pump delivers fluids with an electroosmotically induced high pressure (>1 atm). The same potential is also harnessed to electrostatically generate a stable electrospray at the porous emitter. Electrokinetic coupling between pump and spray produces spray features different from sprays pressurized by independent mechanical pumps. Four typical spray modes, each with different drop sizes and charge-to-mass ratios, are observed and have been characterized. Since the monolith is silica-based, this integrated device can be used for a variety of fluids, especially organic solvents, without the swelling and shrinking problems that are commonly encountered for polymer monoliths. The maximum pressure generated by a 100 microm id monolithic pump is 3 atm at an applied voltage of 5 kV. The flow rate can be adjusted in the range of 100 nL/min to 1 microL/min by changing the voltage. For a given applied voltage across the pump and emitter system, it is seen that there exists one unique flow rate for which flow balance is achieved between the delivery of liquid to the emitter by the pump and the liquid ejection from the emitter. Under such a condition, a stable Taylor cone is obtained. The principles that lead to these results are also discussed.

Electroosmosis↗

PubMed2005

Capillary penetration failure of blood suspensions.

Blood suspension fails to penetrate a capillary with radius R less than 50 microm even if the capillary is perfectly wettable. This invasion threshold is attributed to three red blood cells (RBCs) segregation mechanisms--corner deflection at the entrance, the intermediate deformation-induced radial migration and shear-induced diffusion within a packed slug at the meniscus. The shear-induced radial migration for deformable particles endows the blood cells with a higher velocity than the meniscus to form the concentrated slug behind the meniscus. This tightly packed slug has a higher resistance and arrests the flow. Rigid particles and rigidified blood cells result in wetting behavior similar to that seen for homogeneous liquids, with decreased RBC migration towards the capillary centerline and reduction of packing. Corner deflection with a radial drift velocity accelerates the radial migration for small capillaries. However, deformation-induced radial migration is the key mechanism responsible for penetration failure. This sequence of mechanisms is confirmed through videomicroscopy and scaling theories were applied to capture the dependence of the critical capillary radius as a function of RBC concentrations.

Algorithms↗

PubMed2005

An electro-osmotic micro-pump based on monolithic silica for micro-flow analyses and electro-sprays.

A high-pressure electro-osmotic micro-pump fabricated by a sol-gel process is reported as a fluid-driving unit in a flow-injection analysis (FIA) system. The micro FIA system consists of a monolithic micro-pump on a glass slide (2.5 x 7.5 cm), a micro-injector, and a micro-sensor (2.5 x 1.5 cm). The monolithic silica matrix has a continuous skeleton morphology with micrometer-sized through-pores. The micrometer-size pores with a large negative surface charge density build up a large pressure under a DC electric field to drive fluid through the downstream units. A novel Nafion joint for the downstream cathode eliminates flow into the electrode reservoir and further enhances pressure build-up. The measured pump-pressure curve indicated a maximum pressure of 0.4 MPa at flow rate of 0.4 microL min(-1) at 6 kV. Despite the large voltage, the small current transmission area through the monolith produced a negligible current (less than 100 microA) that did not generate bubbles or ion contaminants. The flow rate can be precisely controlled in the range 200 nL to 2.5 microL min(-1) by varying the voltage from 1 to 6 kV. The high pump pressure and the large current-free DC field also enabled the pump to act as an electro-spray interface with a downstream analytical instrument.

Journal Article↗

PubMed2005

Aligning fast alternating current electroosmotic flow fields and characteristic frequencies with dielectrophoretic traps to achieve rapid bacteria detection.

Tailor-designed alternating current electroosmotic (AC-EO) stagnation flows are used to convect bioparticles globally from a bulk solution to localized dielectrophoretic (DEP) traps that are aligned at the flow stagnation points. The multiscale trap, with a typical trapping time of seconds for a dilute 70 microL volume of 10(3) particles per cc sample, is several orders of magnitude faster than conventional DEP traps and earlier AC-EO traps with parallel, castellated, or finger electrodes. A novel serpentine wire capable of sustaining a high voltage, up to 2500 V(RMS), without causing excessive heat dissipation or Faradaic reaction in strong electrolytes is fabricated to produce the strong AC-EO flow with two separated stagnation lines, one aligned with the field minimum and one with the field maximum. The continuous wire design allows a large applied voltage without inducing Faradaic electrode reactions. Particles are trapped within seconds at one of the traps depending on whether they suffer negative or positive DEP. The particles can also be rapidly released from their respective traps by varying the frequency of the applied AC field below particle-distinct cross-over frequencies. Zwitterion addition to the buffer allows further geometric and frequency alignments of the AC-EO and DEP motions. The same device hence allows fast trapping, detection, sorting, and characterization on a sample with realistic conductivity, volume, and bacteria count.

Bacteria↗

PubMed2005

AC electrospray biomaterials synthesis.

A rapid, viable and safe fabrication method for biomaterials synthesis is reported using high-frequency AC electrospraying. We demonstrate its potential for polymeric nanoparticle fabrication, drug encapsulation in mono-dispersed micron-sized biodegradable polymer shells and the synthesis of 1microm biodegradable fibers with adjustable pore sizes as bioscaffolds for tissue/orthopaedic engineering and wound care therapy. The absence of charge in the ejected drops and fibers facilitates pulmonary drug delivery, polymer encapsulation and minimizes protein/DNA denaturing or compound ionization.

Biocompatible Materials↗

PubMed2004

Nonlinear electrokinetics and "superfast" electrophoresis.

Nonlinear and nonequilibrium electrophoresis of spherical particles of radius a is shown to be possible when the solid surface allows field or current penetration. At low particle Peclet numbers, transient capacitative charging occurs until the surface polarization completely screens the external field. For a DC applied field [see text], the resulting electrokinetic velocity reaches Dukhin's maximum value of [formula: see text], where [see text] and mu are the liquid permittivity and viscosity. At high Peclet numbers, electroosmotic convection of the electroneutral bulk stops the transient charging before complete field-line exclusion. For an ion-selective and conducting spherical granule, the polarization is then determined by the steady-state Ohmic current driven by the penetrated external field. The high-Peclet electrokinetic velocity is lower, diffusivity-dependent and scales as [see text].

Electrophoresis↗

PubMed2004

A new ac electrospray mechanism by Maxwell-Wagner polarization and capillary resonance.

We report a new high-frequency (>10 kHz) ac electrospray that is capable of generating micron-sized electroneutral drops. Unlike its dc counterpart, the drops are not ejected continuously from a sharp Taylor cone but intermittently from a resonating meniscus at the orifice. We attribute the resonant frequency to the capillary-inertia vibration time of the meniscus and the drop ejection to the Maxwell-Wagner electric stress at the drop tip, which is observed to reverse its direction across a crossover frequency. Above this frequency, the oppositely directed Maxwell-Wagner force causes the liquid to recede up the microneedle as an apparent electrowetting effect.

Journal Article↗

PubMed2003

Knudsen diffusivity of a hard sphere in a rough slit pore.

An analytic theory for the Knudsen self-diffusivity D(s) of hard spheres in an atomically rough slit-shaped pore is presented which quantitatively matches simulation results. The theory assumes that, due to chaotic molecular trajectories caused by surface morphology, collisions of gas molecules with the wall are partly diffuse and partly specular, the relative magnitude of each depending upon the magnitude of the tangential momentum accommodation coefficient f. The theory thus represents a universal Knudsen fluctuation-dissipation correlation between longitudinal momentum loss and diffusivity that can simplify efforts to estimate D(s). It is also found that D(s) computed using Maxwell's theory of slip, in which collisions with the walls are assumed to be purely diffuse or specular, overpredicts the simulated D(s) by a large margin.

Journal Article↗

PubMed2003

Electrokinetic mixing vortices due to electrolyte depletion at microchannel junctions.

Due to electric field leakage across sharp corners, the irrotational character of Ohmic electroosmotic flow is violated. Instead, we demonstrate experimentally and theoretically evidence of electrolyte depletion and vortex separation in electroosmotic flow around a junction between wide and narrow channels. When the penetration length of the electric field exceeds the width of the narrow channel and if the electric field is directed from the narrow to the wide channel, the electromigration of ions diminishes significantly at the junction end of the narrow channel due to this leakage. Concentration depletion then develops at that location to maintain current balance but it also increases the corner zeta potential and the local electroosmotic slip velocity. A back pressure gradient hence appears to maintain flow balance and, at a sufficient magnitude, generates a pair of vortices.

Journal Article↗

PubMed2003

Dynamic synchronization analysis of venous pressure-driven cardiac output in rainbow trout.

Measurement of venous function in vivo is inherently difficult. In this study, we used the Hilbert transform to examine the dynamic relationships between venous pressure and cardiac output (CO) in rainbow trout whose blood volume was continuously increased and decreased by ramp infusion and withdrawal (I/W). The dorsal aorta and ductus Cuvier were cannulated percutaneously and connected to pressure transducers; a flow probe was placed around the ventral aorta. Whole blood from a donor was then I/W via the dorsal aortic cannula at a rate of 10% of the estimated blood volume per minute, and the duration of I/W was varied from 40, 60, 80, 90, 120, 230, 240, 260, 300, and 340 s. Compliance [change in (delta) blood vol/deltavenous pressure] was 2.8 +/- 0.2 ml x mmHg-1x g-1 (N = 25 measurements; 6 fish with closed pericardium) and 2.8 +/- 0.3 ml. mmHg-1x kg-1 (N = 19 measurements, 4 fish with open pericardium). Compliance was positively correlated with the duration of I/W, indicative of cardiovascular reflex responses at longer I/W durations. In trout with closed pericardium, CO followed venous pressure oscillations with an average time lag of 4.2 +/- 1.0 s (N = 9); heart rate (HR) was inversely correlated with CO. These studies show that CO is entrained by modulation of venous pressure, not by HR. Thus, although trout have a rigid pericardium, venous pressure (vis-a-tergo), not cardiac suction (vis-a-fronte), appears to be the primary determinant of CO. Estimation of venous compliance by ramp-modulation of venous pressure is faster and less traumatic than classical capacitance measurements and appears applicable to a variety of vertebrate species, as does the Hilbert transform, which permits analysis of signals with disparate frequencies.

Animals↗

PubMed2003

Manipulation and characterization of red blood cells with alternating current fields in microdevices.

The motion of a suspension of erythrocytes (red blood cells, RBCs) in response to a high-frequency alternating current (AC) field in a microfluidic device is examined with parallel and orthogonal electrode configurations to delineate the various fundamental driving forces. Cell repulsion from the platinum electrodes due to electrode polarization interacting with cell membrane polarizations is observed to be the strongest force acting on the particles in the first few seconds of field application. We exploit this strong repulsion to concentrate the bioparticles between the microelectrodes to amplify multiparticle aggregation phenomenon and dielectrophoretic (DEP) manipulation in a small and well-characterized region within the microfluidic device. Secondary motions include RBC pearl chain formation along field lines due to particle polarization followed by classical dielectrophoretic motion of the chains across field lines to regions of weaker field. These are driven by far weaker dipole-dipole and field-dipole interactions than the preliminary electrode repulsions. RBC chain length and total aggregated cells are presented for a variety of AC frequencies and are significantly amplified by the electrode repulsion. Motion of particles away from the polarized electrode is found to be species- and age-sensitive and can stand by itself as a promising identification and separation mechanism. In a 0.1 S/m isotonic phosphate buffer saline medium, we observe the largest cell mobilities at an optimal frequency of approximately 1 MHz, corresponding to the inverse diffusion time across the double layer of the cell and across the electrode's polarized layer. This suggests that the dielectric responses of both particles and electrodes in the low MHz frequency range are mostly determined by normal electromigration of ions from the bulk to their interfaces. Sensitivity to RBC age and species suggests that the surface proteins and membrane ion channels can affect the capacitance of the interface to accommodate the ions from the bulk. Such surface ion accumulation and polarization mechanisms are different from the classical dielectric theories. The resonant frequency of electrode polarization at around 1 MHz falls between positive and negative dielectrophoretic resonant frequency peaks - suggesting that the double-layer polarization mechanism is a distinct and potentially important bioparticle manipulation tool.

Electrochemistry↗