- Notre Dame, Indiana, United States
Hsueh-Chia Chang
University of Notre Dame, Chemical and Biomolecular Engineering, Department Member
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... 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...
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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... 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...
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Research Interests: Mechanical Engineering, Materials Science, Biomedical Engineering, Sensors and Sensing, Microfluidics, and 12 moreBiomechanics, Cell Biology, Nanotechnology, PRODUCTION ENGINEERING, Medicine, Additive Manufacturing, Rapid Prototyping, Biological Sciences, Biomicrofluidics, Classical Physics, 3-D printing, and Interdisciplinary Engineering
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Research Interests: Engineering, Physics, Chemistry, Fluorescence, Applied Physics, and 15 moreDielectrophoresis, Nanowires, Mathematical Sciences, Applied, Physical sciences, Band Gap, Polarisation, Dep, Frequency Dependence, Electrophoresis, Quantum Wires, Fluorescence polarization, Electric Field, Aspect Ratio, and Photoconductivity
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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... 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.
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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... 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 fundamentally different from the DNA micro-arrays used in laboratories because of speed, detection sensitivity and facility concerns. A... 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 patterned micro-electrodes. Such wires, with the same crystal structure as CdSe quantum dots (QDs) and nanorods (NRs) but with significantly... 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 high and uniform constant extracellular potential over an entire ∼1000 cell rat cardiomyocyte (rCM) colony on-a-chip to trigger synchronized... 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...
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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... 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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We report a high-throughput single-cell encapsulation method based on the “tip streaming” mode of alternating current (AC) electrospray, which can be universally applied to many types of hydrogels and stem cells toward a range of... more
We report a high-throughput single-cell encapsulation method based on the “tip streaming” mode of alternating current (AC) electrospray, which can be universally applied to many types of hydrogels and stem cells toward a range of approaches in regenerative medicine.
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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... 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 be redirected to selectively pin and delay their transport. A thin high-permittivity dielectric coating on bullet-shaped polymer nanopores permits electric field leakage at the pore tip to produce a voltage-dependent surface field on the entry side that can reversibly edge-pin molecules. This mechanism renders molecular entry an activated process with sensitive exponential dependence on the bias voltage and molecular rigidity. This sensitivity allows us to selectively prolong the translocation time of short single-stranded DNA molecules by up to 5 orders of magnitude, to as long as minutes, allowing discrimination against their double-stranded duplexes with 97% confidence.
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We report a bifurcated continuous field-flow fractionation (BCFFF) chip for high-yield and high-throughput (20 min) extraction of nucleic acids from physiological samples. The design uses a membrane ionic transistor to...
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We report a theory for biphasic ionic current signals during DNA and nanoparticles translocation through a solid-state nanopore that produces scaling results consistent with finite element simulations (FEM), molecular dynamics...
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Exosomes carry microRNA biomarkers, occur in higher abundance in cancerous patients than in healthy ones, and because they are present in most biofluids, including blood and urine, these can be obtained noninvasively. Standard laboratory... more
Exosomes carry microRNA biomarkers, occur in higher abundance in cancerous patients than in healthy ones, and because they are present in most biofluids, including blood and urine, these can be obtained noninvasively. Standard laboratory techniques to isolate exosomes are expensive, time consuming, provide poor purity, and recover on the order of 25% of the available exosomes. We present a new microfluidic technique to simultaneously isolate exosomes and preconcentrate them by electrophoresis using a high transverse local electric field generated by ion-depleting ion-selective membrane. We use pressure-driven flow to deliver an exosome sample to a microfluidic chip such that the transverse electric field forces them out of the cross flow and into an agarose gel which filters out unwanted cellular debris while the ion-selective membrane concentrates the exosomes through an enrichment effect. We efficiently isolated exosomes from 1× PBS buffer, cell culture media, and blood serum. Usi...
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By treating DNA as a vibrating nonlinear lattice, an activated kinetic theory for DNA melting is developed to capture the breakage of the hydrogen bonds and subsequent softening of torsional and bending vibration modes. With a... more
By treating DNA as a vibrating nonlinear lattice, an activated kinetic theory for DNA melting is developed to capture the breakage of the hydrogen bonds and subsequent softening of torsional and bending vibration modes. With a coarse-grained lattice model, we identify a key bending mode with GHz frequency that replaces the hydrogen vibration modes as the dominant out-of-phase phonon vibration at the transition state. By associating its bending modulus to a universal in-phase bending vibration modulus at equilibrium, we can hence estimate the entropic change in the out-of-phase vibration from near-equilibrium all-atom simulations. This and estimates of torsional and bending entropy changes lead to the first predictive and sequence-dependent theory with good quantitative agreement with experimental data for the activation energy of melting of short DNA molecules without intermediate hairpin structures.
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Surface acoustic wave sensors and microfluidic platforms enable effective chemical detection and sample manipulation.
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Steady waves on a thin liquid film flowing down an inclined plane are analyzed near the critical Reynolds number. A second‐order bifurcation analysis of an interface equation, which is valid to third order in the long‐wave expansion,... more
Steady waves on a thin liquid film flowing down an inclined plane are analyzed near the critical Reynolds number. A second‐order bifurcation analysis of an interface equation, which is valid to third order in the long‐wave expansion, reveals two sets of waves near criticality. One set travels faster than twice the interfacial velocity, while the other set is symmetrically slower for the vertical film. Each set contains two families of shocks, one family of periodic waves, and a single solitary wave. Local analytical estimates of the velocity, amplitude, and wavelength are obtained for all waves. These estimates are favorably compared to numerical solutions of the steady waves and to experimental data near criticality. An interesting result is that naturally excited waves with wavelengths close to the maximum growing linear mode should not be studied with a local analysis near the neutral curve. Instead, they are better approximated by a Melnikov perturbation of the solitary wave solution.
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A stable nanoscale thermal hot spot, with temperature approaching 100 °C, is shown to be sustained by localized Ohmic heating of a focused electric field at the tip of a slender conic nanopore. The self-similar (length-independent) conic... more
A stable nanoscale thermal hot spot, with temperature approaching 100 °C, is shown to be sustained by localized Ohmic heating of a focused electric field at the tip of a slender conic nanopore. The self-similar (length-independent) conic geometry allows us to match the singular heat source at the tip to the singular radial heat loss from the slender cone to obtain a self-similar steady temperature profile along the cone and the resulting ionic current conductance enhancement due to viscosity reduction. The universal scaling, which depends only on a single dimensionless parameter Z, collapses the measured conductance data and computed temperature profiles in ion-track conic nanopores and conic nanopipettes. The collapsed numerical data reveal universal values for the hot-spot location and temperature in an aqueous electrolyte.
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Mucosal infection by the human papillomavirus (HPV) is responsible for a growing number of malignancies, predominantly represented by cervical cancer and oropharyngeal squamous cell carcinoma. Because of the prevalence of the virus,... more
Mucosal infection by the human papillomavirus (HPV) is responsible for a growing number of malignancies, predominantly represented by cervical cancer and oropharyngeal squamous cell carcinoma. Because of the prevalence of the virus, persistence of infection, and long latency period, novel and low-cost methods are needed for effective population level screening and monitoring. We review established methods for screening of cervical and oral cancer as well as commercially-available techniques for detection of HPV DNA. We then describe the ongoing development of microfluidic nucleic acid-based biosensors to evaluate circulating host microRNAs that are produced in response to an oncogenic HPV infection. The goal is to develop an ideal screening platform that is low-cost, portable, and easy to use, with appropriate signal stability, sensitivity and specificity. Advances in technologies for sample lysis, pre-treatment and concentration, and multiplexed nucleic acid detection are provided....
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A microfluidic ion exchange membrane hybrid ionic circuit chip is designed to achieve high-flux ionic diode, transistor and amplifier functionalities.
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Electric field focusing into charged nano-channels can concentrate and filter charged biological molecules. This transport specificity is further enhanced with sequence or receptor specific DNA probes and antibodies functionalized onto... more
Electric field focusing into charged nano-channels can concentrate and filter charged biological molecules. This transport specificity is further enhanced with sequence or receptor specific DNA probes and antibodies functionalized onto the channel wall or nano-colloids. Our theoretical and experimental studies show, however, the same field-focusing phenomenon can discharge mobile ions from the channel and produce a growing polarized layer outside
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We have designed and tested nanochannel impedance sensors for biomolecular detection based on fundamental analyses of the underlying electrokinetic phenomena. Probe-functionalized nanocolloids (macroions) with specific hybridized and... more
We have designed and tested nanochannel impedance sensors for biomolecular detection based on fundamental analyses of the underlying electrokinetic phenomena. Probe-functionalized nanocolloids (macroions) with specific hybridized and unhybridized impedance signals are used to capture multiple molecular targets. These nanocolloids are driven electrophoretically, electro-osmotically or dielectrophoretically by a slow (and high-amplitude) AC field into the nanochannels, where field focusing amplifies their
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The conducting Taylor cone can activate specified harmonics of Laplace equation near the cone and can generate field maxima at multiple discrete polar angles. As the nanocolloids are ejected out from the cone tip, the difference of... more
The conducting Taylor cone can activate specified harmonics of Laplace equation near the cone and can generate field maxima at multiple discrete polar angles. As the nanocolloids are ejected out from the cone tip, the difference of dominating forces in axial and transverse direction defines size-dependent initial angle before the colloids are trapped by the field maxima of the harmonics at the closest polar angle. This size-dependent selection of harmonics governs the different size colloids to travel along different trajectories and form separated deposition in the downstream of the electrospray. This electrospray-based separation of nanocolloids is successfully used to detect DNA hybridization. A family of cone shape is generated by changing voltage in a finite range. Variation of Taylor cone angle changes the harmonics and the trajectory of colloid is found to shift to a larger polar angle under higher voltage.
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We report the first nanofluidic inductor (L) to complement the known nanofluidic capacitors (C), resistors (R), and diodes for ion currents. Under negative bias, the nanopore behaves like a parallel RC circuit at low frequencies; however,... more
We report the first nanofluidic inductor (L) to complement the known nanofluidic capacitors (C), resistors (R), and diodes for ion currents. Under negative bias, the nanopore behaves like a parallel RC circuit at low frequencies; however, under positive bias, the asymptotic dynamics is that of a serial RL circuit. This new ionic circuit element can lead to nanofluidic RLC or diode-inductor oscillator circuits and new intrapore biosensing/rapid sequencing strategies. A universal theory, with explicit estimates for the capacitance and inductance at opposite biases, is derived to collapse the rectified dynamics of all conic nanopores to facilitate design of this new nanofluidic circuit.
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The capability of 3D printing technologies for direct production of complex 3D structures in a single step has recently attracted an ever increasing interest within the field of microfluidics. Recently, ultrafast lasers have also allowed... more
The capability of 3D printing technologies for direct production of complex 3D structures in a single step has recently attracted an ever increasing interest within the field of microfluidics. Recently, ultrafast lasers have also allowed developing
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.
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.