Papers by Hsueh-Chia Chang
Biomicrofluidics, Mar 1, 2007
Rapid concentration and detection of bacteria in integrated chips and microfluidic devices is nee... more Rapid concentration and detection of bacteria in integrated chips and microfluidic devices is needed for the advancement of lab-on-a-chip devices because current detection methods require high concentrations of bacteria which render them impractical. We present a new chip-scale rapid bacteria concentration technique combined with surface-enhanced Raman scattering ͑SERS͒ to enhance the detection of low bacteria count samples. This concentration technique relies on convection by a long-range converging vortex to concentrate the bacteria into a packed mound of 200 m in diameter within 15 min. Concentration of bioparticle samples as low as 10 4 colony forming units ͑CFU͒/ml are presented using batch volumes as large as 150 l. Mixtures of silver nanoparticles with Saccharomyces cerevisiae, Escherichia coli F-amp, and Bacillus subtilis produce distinct and noticeably different Raman spectra, illustrating that this technique can be used as a detection and identification tool.
Nature Communications
Cardiovascular disease-related deaths (one-third of global deaths) can be reduced with a simple s... more Cardiovascular disease-related deaths (one-third of global deaths) can be reduced with a simple screening test for better biomarkers than the current lipid and lipoprotein profiles. We propose using a highly atheroprotective subset of HDL with colocalized PON1 (PON1-HDL) for superior cardiovascular risk assessment. However, direct quantification of HDL proteomic subclasses are complicated by the peroxides/antioxidants associated with HDL interfering with redox reactions in enzymatic calorimetric and electrochemical immunoassays. Hence, we developed an enzyme-free Nanoparticle-Gated Electrokinetic Membrane Sensor (NGEMS) platform for quantification of PON1-HDL in plasma within 60 min, with a sub-picomolar limit of detection, 3–4 log dynamic range and without needing sample pretreatment or individual-sample calibration. Using NGEMS, we report our study on human plasma PON1-HDL as a cardiovascular risk marker with AUC~0.99 significantly outperforming others (AUC~0.6–0.8), including cho...
Communications Biology
Superparamagnetic nanobeads offer several advantages over microbeads for immunocapture of nanocar... more Superparamagnetic nanobeads offer several advantages over microbeads for immunocapture of nanocarriers (extracellular vesicles, lipoproteins, and viruses) in a bioassay: high-yield capture, reduction in incubation time, and higher capture capacity. However, nanobeads are difficult to “pull-down” because their superparamagnetic feature requires high nanoscale magnetic field gradients. Here, an electrodeposited track-etched membrane is shown to produce a unique superparamagnetic nano-edge ring with multiple edges around nanopores. With a uniform external magnetic field, the induced monopole and dipole of this nano edge junction combine to produce a 10× higher nanobead trapping force. A dense nanobead suspension can be filtered through the magnetic nanoporous membrane (MNM) at high throughput with a 99% bead capture rate. The yield of specific nanocarriers in heterogeneous media by nanobeads/MNM exceeds 80%. Reproducibility, low loss, and concentration-independent capture rates are als...
Applied Physics Letters, 2006
We report a free-surface electrohydrodynamic flow phenomenon driven by an ionic wind mechanism in... more We report a free-surface electrohydrodynamic flow phenomenon driven by an ionic wind mechanism induced by a high frequency gas-phase ac field ͑Ͼ10 kHz͒. Intense vortices Ͼ1 cm/s are generated above a critical voltage, beyond which the vortices break down to spawn off new vortex pairs leading to a cascade of vortices over a continuum of length scales; the mixing efficiency approaches a turbulent-like state. Colloidal particles are attracted and aggregated into planar crystal structures within the vortices by a combination of dielectrophoresis and shear-induced diffusion.
SIAM Journal on Applied Mathematics, 1998
The description of the spatio-temporal dynamics of an extended active/dispersive medium, such as ... more The description of the spatio-temporal dynamics of an extended active/dispersive medium, such as wave dynamics on a falling film, can be simplified considerably if the dynamics is dominated by a fixed number of solitary pulses separated by radiation-free flat substrates. Radiation is generated in a noise-free environment when excess mass drains out of a nonequilibrium (excited) pulse in the form of a spreading shelf and the radiation grows rapidly by feeding on the active substrate. However, this growth can be suppressed if the localized radiation packet is absorbed by a second pulse. It is shown that both the generation and suppression mechanisms can be quantitatively understood by analyzing the essential spectrum of the equilibrium pulse that determines how it attenuates an absorbed radiation wavepacket and a peculiar resonance pole that captures the drainage dynamics of an excited pulse. The instantaneous speed of a decaying pulse is shown to scale linearly with respect to its instantaneous amplitude and the length of the spreading shelf is shown to increase linearly. An approximate stability criterion is then developed for pulse trains to radiation disturbances and verified numerically by both direct simulation and a Floquet analysis for the generalized Kuramoto-Sivashinsky (gKS) equation.
Lab on a Chip, 2009
We present an analysis of the results of in situ surface-enhanced Raman scattering ͑SERS͒ of bact... more We present an analysis of the results of in situ surface-enhanced Raman scattering ͑SERS͒ of bacteria using a microfluidic chip capable of continuously sorting and concentrating bacteria via three-dimensional dielectrophoresis ͑DEP͒. Microchannels were made by sandwiching DEP microelectrodes between two glass slides. Avoiding the use of a metal nanoparticle suspension, a roughened metal surface is integrated into the DEP-based microfluidic chip for on-chip SERS detection of bacteria. On the upper surface of the slide, a roughened metal shelter was settled in front of the DEP concentrator to enhance Raman scattering. Similarly, an electrodepatterned bottom layer fabricated on a thin cover-slip was used to reduce fluorescence noise from the glass substrate. Gram positive ͑Staphylococcus aureus͒ and Gram negative ͑Pseudomonas aeruginosa͒ bacteria were effectively distinguished in the SERS spectral data. Staphylococcus aureus ͑concentration of 10 6 CFU/ ml͒ was continuously separated and concentrated via DEP out of a sample of blood cells. At a flow rate of 1 l / min, the bacteria were highly concentrated at the roughened surface and ready for on-chip SERS analysis within 3 min. The SERS data were successfully amplified by one order of magnitude and analyzed within a few minutes, resulting in the detection of signature peaks of the respective bacteria.
Journal of Applied Physics, 2007
Positive ac dielectrophoresis ͑DEP͒ is used to rapidly align ensembles of CdSe semiconductor nano... more Positive ac dielectrophoresis ͑DEP͒ is used to rapidly align ensembles of CdSe semiconductor nanowires ͑NWs͒ near patterned microelectrodes. Due to their large geometric aspect ratio, the induced dipole of the wires is proportional to their conductivity, which can be drastically enhanced under super-band-gap illumination by several orders of magnitude, with a corresponding increase in the wire DEP mobility. This optical enhancement of conductivity occurs because of the generation of mobile electrons and holes and is verified by a photocurrent measurement. The linear nanowire alignment exhibits a high degree of fluorescent polarization anisotropy in both absorption and emission. An unexpected observation is a reversible, factor of ϳ4, electric-field-induced, and frequency-dependent enhancement of the nanowire emission near 10 Hz. Such illumination-sensitive, field-enhanced, and frequency-dependent alignment and emission phenomena of NWs suggest an electrical-optical platform for fabricating CdSe nanowire devices for polarization-sensitive photodetection and biosensing applications.
Biomicrofluidics, 2007
Rapid concentration and detection of bacteria in integrated chips and microfluidic devices is nee... more Rapid concentration and detection of bacteria in integrated chips and microfluidic devices is needed for the advancement of lab-on-a-chip devices because current detection methods require high concentrations of bacteria which render them impractical. We present a new chip-scale rapid bacteria concentration technique combined with surface-enhanced Raman scattering ͑SERS͒ to enhance the detection of low bacteria count samples. This concentration technique relies on convection by a long-range converging vortex to concentrate the bacteria into a packed mound of 200 m in diameter within 15 min. Concentration of bioparticle samples as low as 10 4 colony forming units ͑CFU͒/ml are presented using batch volumes as large as 150 l. Mixtures of silver nanoparticles with Saccharomyces cerevisiae, Escherichia coli F-amp, and Bacillus subtilis produce distinct and noticeably different Raman spectra, illustrating that this technique can be used as a detection and identification tool.
Annual Review of Fluid Mechanics, 1994
Key Engineering Materials, 2011
ABSTRACT Micro/nanochannel is of great importance due to its wide applications in micro total ana... more ABSTRACT Micro/nanochannel is of great importance due to its wide applications in micro total analysis system. In a given micro/nanofluidic device, the nanochannel and microchannel can works as function provider and reagent delivering passage, respectively. The easiest way to fabricate micro/nanochannel is depositing material onto a predefined microchannel until nanometer-sized pattern is obtained. Although the deposition process inside the microchannel has been studied before, the filling performance at the side-opening, the connection between microchannels with different widths, is limited studied. The different filling performance at side-opening will lead to a distinct geometrical size. In this work, side-opening filling process during a low pressure chemical vapor deposition of silicon dioxide onto pre-etched microchannels with patterns of straight, triangle and rhombus shapes was preliminarily studied. A filling factor was defined to describe the side-opening filling performance. The present results indicated that the side-opening filling will be affected by the side-opening width, the depth of the microchannel and the microchannel shape.
Vaccine, 2001
The objective of the present study was to investigate the feasibility of a DNA vaccine to protect... more The objective of the present study was to investigate the feasibility of a DNA vaccine to protect chickens against infectious bursal disease virus (IBDV) infection. A plasmid DNA carrying VP2, VP4, and VP3 genes of the standard challenge (STC) strain of IBDV was constructed and designated as pCR3.1-VP243-STC. One-day-old chickens were intramuscularly injected with the plasmid pCR3.1-VP243-STC once (group D1), twice (group D2), or three times (group D3) at weekly intervals. Chickens at 3 weeks old were orally inoculated with IBDV strain STC and observed for 10 days after challenge. Immunization twice (group D2) or three times (group D3) with the plasmid pCR3.1-VP243-STC conferred protection for 50-100 or 80-100% of chickens, respectively, as evidenced by the absence of clinical signs, mortality, and bursal atrophy. Although chickens vaccinated once (group D1) with the plasmid pCR3.1-VP243-STC did not have clinical signs, they exhibited varying degree of bursal atrophy after challenge. Enzyme-linked immunosorbent assay (ELISA) antibody titers in chickens protected by the plasmid pCR3.1-VP243-STC were significantly lower (P < 0.05) than those not protected 10 days after challenge. IBDV antigen was not detected in the bursae of chickens that were protected by receiving the plasmid pCR3.1-VP243-STC twice or three times. The results indicate that the constructed plasmid pCR3.1-VP243-STC as a DNA vaccine provided efficacious protection for chickens against IBDV infection.
Solid-state nanopores allow high-throughput single-molecule detection but identifying and even re... more Solid-state nanopores allow high-throughput single-molecule detection but identifying and even registering all translocating small molecules remain key challenges due to their high translocation speeds. We show here the same electric field that drives the molecules into the pore can selectively pin and delay their transport. A thin high-permittivity dielectric coating on slender bullet-shaped polymer nanopores permits electric field leakage at the pore tip to produce a voltage-dependent surface field on the upper periphery of the pore that can reversibly edge-pin entering molecules that can absorb conformally to the tip corner. This localized tip field renders molecular entry an activated process with sensitive exponential dependence on the bias voltage and molecular rigidity. The exponential sensitivity allows us to selectively prolong the translocation time of short single-stranded DNA molecules by up to 5 orders of magnitude, allowing discrimination against their double-stranded duplexes with 97% confidence. We show evidence that the leak-field pinned single-stranded DNA actually absorbs onto the edge before entering the pore, yielding translocation times as long as minutes. Solid-state and protein nanopores are an emerging class of single-molecule sensors for DNA sequencing 1-3 , protein detection 1,4,5 , and DNA-protein complex analyses 6. The Achilles heel of nanopores has been the inability to control the motion of biomolecules during voltage-driven translocation through the pore 1,3,7-9. With the development of enzyme-based methods that ratchet polynucleotides through the pore, the first nanopore-sequencer has been realized using protein nanopores 3. Despite the progress that has been made with biological nanopores, solid-state nanopores with high stability and tunable pore diameters still offer several advantages. They facilitate integration with compact electronic/optical sensor modalities and allow higher throughput than their protein counterparts. However, developing solid-state nanopore sensors capable of complete characterization of the translocating biomolecules has been challenging 1,7,9 , primarily because of the fast electrophoretic translocation by highly focused electric fields at the pore. The high fields are due to the nanoscale pore dimensions necessary for resistive current signals above thermal noise, and the minimum bias voltage (20-60 mV) 10 necessary to overcome barriers due to conformation entropy, electrostatic repulsion, and electro-osmotic flow 11,12. Typical electrophoretic velocities of nucleic acids across solid-state nanopores are 10-1000 ns per base 1. At these high velocities, short nucleic acids (<100 nt) as well as small protein molecules are often undetected, much less identified 13. Thus, a high signal bandwidth (> 1 MHz) is needed to fully resolve the resistive pulses 14,15. High signal bandwidth, however, also strongly amplifies thermal noise in the current recordings; this noise makes the signal resistive pulses become undetectable 16. This limitation hence prevents accurate profiling of promising cancer biomarkers like proteins, short mRNA fragments, and microRNAs (19-22 nt) by solid-state nanopores 13,17,18. For the proposed sequencing applications by quantum tunneling, speed control is also a key issue for realizing practical
apid and highly sensitive RNA/DNA hybridization assays have attracted enormous attention in a wid... more apid and highly sensitive RNA/DNA hybridization assays have attracted enormous attention in a wide variety of applications ranging from genotyping to molecular diagnosis.1,2 Conventional lab-based optical detectionmethods for hybrid-ization assays, such as microarray and real-time PCR, involve expensive detection protocols based on fluorescent tagging, thus requiring qualified professionals and limiting their potential use. Furthermore, DNA hybridization reactions in microarray analyses are time-consuming due to rate-limiting diffusion kinetics, making the tech-nique difficult for point-of-need and high-
We motivate the need for a rapid and portable genetic identification kit whose design must be fun... more We motivate the need for a rapid and portable genetic identification kit whose design must be fundamentally different from the DNA micro-arrays used in laboratories because of speed, detection sensitivity and facility concerns. A micro/nano bead platform developed in our laboratory with modified PCR and hybridization steps and with tailor-designed microfluidic fabrication techniques is then introduced as a first single-target prototype for rapid field-use genetic diagnostic kit.
Positive AC dielectrophoresis (DEP) is used to align ensembles of CdSe nanowires (NWs) near patte... more Positive AC dielectrophoresis (DEP) is used to align ensembles of CdSe nanowires (NWs) near patterned micro-electrodes. Such wires, with the same crystal structure as CdSe quantum dots (QDs) and nanorods (NRs) but with significantly larger aspect ratios and sizable induced and intrinsic dipole moments, have a DEP mobility 10~100 times higher than other materials of the same dimension. As a consequence, they rapidly selfassemble in an AC electric field. The alignment also affects the fluorescence properties of the nanowires, revealing a high degree of polarization anisotropy in both the absorption and emission. An unexpected outcome of our work is the reversible, factor of
In this study, an ion depleted zone created by an ion-selective membrane was used to impose a hig... more In this study, an ion depleted zone created by an ion-selective membrane was used to impose a high and uniform constant extracellular potential over an entire ∼1000 cell rat cardiomyocyte (rCM) colony on-a-chip to trigger synchronized voltage-gated ion channel activities while preserving cell viability, thus extending single-cell voltage-clamp ion channel studies to an entire normalized colony. Image analysis indicated that rCM beating was strengthened and accelerated (by a factor of ∼2) within minutes of ion depletion and the duration of contraction and relaxation phases was significantly reduced. After the initial synchronization, the entire colony responds collectively to external potential changes such that beating over the entire colony can be activated or deactivated within 0.1 s. These newly observed collective dynamic responses, due to simultaneous ion channel activation/deactivation by a uniform constant-potential extracellular environment, suggest that perm-selective membr...
Conference Record of the 1993 IEEE Industry Applications Conference Twenty-Eighth IAS Annual Meeting
A method for finding the grain margins and phase margins of nonlinear control systems for asympto... more A method for finding the grain margins and phase margins of nonlinear control systems for asymptotic stability is presented. The effects of adjustable parameters are analyzed. The systems considered are first linearized by the describing function method and modified by adding a gain-phase margin tester. Then the characteristic equations are formulated and factored into stability equations, and the parameter-plane method
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Papers by Hsueh-Chia Chang
new methods for production of internal microfluidic channels within the bulk of glass and polymer materials by direct internal 3D laser writing. This review critically summarizes the latest advances in the production of microfluidic 3D structures by using 3D printing technologies and direct internal 3D laser writing fabrication methods. Current applications of these rapid prototyped microfluidic platforms in biology will be also discussed. These include imaging of cells and living organisms, electrochemical detection of viruses and neurotransmitters, and
studies in drug transport and induced-release of adenosine triphosphate from erythrocytes.