Jae Hyun Chung

Bio-mimetic silicone cilia for microfluidic manipulation

This paper presents a bio-mimetic microfluidic device that mimics the high compliance and the beating frequency of biological cilia in order to achieve bio-compatible manipulation of microfluidics. Because the highly compliant cilia can easily collapse due to interaction energy and surface tension, the major challenge in developing a bio-mimetic device is the manufacturing of highly compliant cilia. An underwater fabrication method is developed to avoid the cilia collapse by lowering the surface energy of the cilia. Another challenge is to mimic the low beating frequency (10-100 Hz) of biological cilia. The proposed microfluidic device is excited by a piezo actuator to resonate the cilia in water. Due to the highly compliant nature of the silicone cilia, the resulting actuation frequency is in the beating frequency range of biological cilia. Simulations and experiments are presented to demonstrate microfluidic manipulation by resonance of the assembled cilia array.

Multi-walled carbon nanotubes experiencing electrical breakdown as gas sensors

This paper presents a new approach to gas sensing using a multi-walled carbon nanotube (MWCNT) subject to electrical breakdown. The electrical resistances of large-diameter MWCNTs were found to decrease in the presence of air after experiencing electrical breakdown, while pristine MWCNTs were not appreciably sensitive. The sensitivity could be controlled by manipulating the level of the electrical breakdown, and larger-diameter MWCNTs showed better sensitivity because they possess more damaged shells that can create more adsorption sites for oxygen molecules. It was suggested by theoretical calculations that the oxygen sensitivity might be associated with an oxidized junction that exists between the outer and inner shells of the nanotubes.

Nanoscale gap fabrication and integration of carbon nanotubes by micromachining

This paper presents new techniques for fabricating nanoscale gaps based on microlithography and the assembly of a carbon nanotube (CNT) across a gap. A sharp nanoscale gap was fabricated by the controlled over-etching of an Al thin film. The etching process was monitored by measured resistance, and a nanoscale gap (∼20 nm) was fabricated. A rounded gap was also created by using a lift-off process on a bridge pattern with a metal layer. The smallest gap created by this method was 150 nm. An ac electric field was used to deposit single-walled carbon nanotubes (SWCNTs) dispersed in a liquid across the prepared gaps. A highly oriented assembly was obtained for the deposition across this round gap. It was also demonstrated that a single multi-walled carbon nanotube (MWCNT) could be directionally deposited across a microscale gap when guided by a biased ac electric field. Compared with chemical vapor deposition (CVD) methods, suggested assembly procedure can be performed at a room temperature, thus providing more process freedom. Various configurations for device application and fundamental experiments can be conceived using the proposed method.

Immunosensor towards low-cost, rapid diagnosis of tuberculosis

A rapid, accurate tuberculosis diagnostic tool that is compatible with the needs of tuberculosis-endemic settings is a long-sought goal. An immunofluorescence microtip sensor is described that detects Mycobacterium tuberculosis complex cells in sputum in 25 minutes. Concentration mechanisms based on flow circulation and electric field are combined at different scales to concentrate target bacteria in 1 mL samples onto the surfaces of microscale tips. Specificity is conferred by genus-specific antibodies on the microtip surface. Immunofluorescence is then used to detect the captured cells on the microtip. The detection limit in sputum is 200 CFU mL(-1) with a success rate of 96%, which is comparable to PCR.

Size-specific concentration of DNA to a nanostructured tip using dielectrophoresis and capillary action.

One of the critical challenges in the fields of disease diagnostics and environmental monitoring is to concentrate extracellular DNA from a sample mixture rapidly. Unlike genomic DNA in normal cells, extracellular DNA dissolved in a biological sample can potentially offer crucial information about pathogens and toxins. The current concentration methods, however, are not able to directly concentrate extracellular DNA due to aggressive sample preparation steps. This paper presents a concentration mechanism of extracellular DNA onto a nanostructured tip using dielectrophoresis (DEP) in conjunction with capillary action. DNA immersed in a solution is captured onto a nanotip by two sequential actions: (1) attraction of DNA and other bioparticles in the vicinity of a nanotip by DEP and (2) size-specific capture of DNA onto the nanotip by capillary action. To investigate the size-specific capturing mechanism, an analytical model for the capillary action on a nanotip is presented, which is compared to the experiment for capturing polystyrene nanospheres. This analysis predicts the capture of a spherical particle smaller than 0.39 times a nanotip diameter, whereas our experiment shows that polystyrene spheres smaller than 0.84 times a nanotip diameter are captured. This discrepancy can be caused by the increase of the capturing force due to attractive DEP force. In addition, the diameter of the captured spheres can be increased by other experimental conditions including the tip geometry, the multiple particle interaction, and the contact angles. When a nanotip is used for concentrating lambda-DNA, 6.7 pg/mL (210 aM) of DNA is selectively extracted from a sample mixture containing lambda-DNA and Drosophila cells in one minute. The captured DNA is investigated by fluorescence microscopy, scanning electron microscopy (SEM), and X-ray analysis. This nanotip-based DNA concentrating method is a rapid and highly sensitive technique to detect extracellular DNA from a sample mixture.

Microfluidic one-step synthesis of alginate microspheres immobilized with antibodies.

Micrometre- and submicrometre-size functionalized beads are frequently used to capture targets of interest from a biological sample for biological characterizations and disease diagnosis. The main challenge of the microbead-based assay is in the immobilization of probe molecules onto the microbead surfaces. In this paper, we report a versatile droplet microfluidics method to fabricate alginate microspheres while simultaneously immobilizing anti-Mycobacterium tuberculosis complex IgY and anti-Escherichia coli IgG antibodies primarily on the porous alginate carriers for specific binding and binding affinity tests. The binding affinity of antibodies is directly measured by fluorescence intensity of stained target bacteria on the microspheres. We demonstrate that the functionalized alginate microspheres yield specificity comparable with an enzyme-linked immunosorbent assay. The high surface area-to-volume ratio of the functionalized porous alginate microspheres improves the detection limit. By using the droplet microfluidics, we can easily modify the size and shape of alginate microspheres, and increase the concentration of functionalized alginate microspheres to further enhance binding kinetics and enable multiplexing.

USNCTAM perspectives on mechanics in medicine

Over decades, the theoretical and applied mechanics community has developed sophisticated approaches for analysing the behaviour of complex engineering systems. Most of these approaches have targeted systems in the transportation, materials, defence and energy industries. Applying and further developing engineering approaches for understanding, predicting and modulating the response of complicated biomedical processes not only holds great promise in meeting societal needs, but also poses serious challenges. This report, prepared for the US National Committee on Theoretical and Applied Mechanics, aims to identify the most pressing challenges in biological sciences and medicine that can be tackled within the broad field of mechanics. This echoes and complements a number of national and international initiatives aiming at fostering interdisciplinary biomedical research. This report also comments on cultural/educational challenges. Specifically, this report focuses on three major thrusts in which we believe mechanics has and will continue to have a substantial impact. (i) Rationally engineering injectable nano/microdevices for imaging and therapy of disease. Within this context, we discuss nanoparticle carrier design, vascular transport and adhesion, endocytosis and tumour growth in response to therapy, as well as uncertainty quantification techniques to better connect models and experiments. (ii) Design of biomedical devices, including point-of-care diagnostic systems, model organ and multi-organ microdevices, and pulsatile ventricular assistant devices. (iii) Mechanics of cellular processes, including mechanosensing and mechanotransduction, improved characterization of cellular constitutive behaviour, and microfluidic systems for single-cell studies.

A Dilution-Filtration System for Removing Cryoprotective Agents

In most cryopreservation applications, the final concentrations of cryoprotective agents (CPAs) must be reduced to biocompatible levels. However, traditional methods for removing CPAs usually have disadvantages of operation complexity, time consumption, and ease of contamination, especially for the applications involving large volumes of cell suspensions. A dilution-filtration system, which involves pure ultrafiltration for separation, was developed for continuous, automatic, and closed process of removing CPAs. To predict the optimal protocols under given experimental conditions, a theoretical model was established first. Cell-free experiments were then conducted to investigate the variation in CPA concentration during the process, and the experimental data were compared with the theoretical values for the validation of the model. Finally, ten units (212.9 ml/unit±9.5 ml/unit) of thawed human red blood cells (cryopreserved with 40% (w/v) glycerol) were deglycerolized using the theoretically optimal operation protocols to further validate the effectiveness and advantage of the system. In the cell-free experiments, glycerol was continuously removed and the concentration variations fitted the simulated results quite well. In the in-vitro experiments, glycerol concentration in RBC suspension was reduced to 5.57 g/l±2.81 g/l within an hour, and the cell count recovery rate was 91.19%±3.57%, (n=10), which proves that the system is not only safe for removing CPAs, but also particularly efficient for processing large-scale samples. However, the operation parameters must be carefully controlled and the optimal protocols should be specialized and various from case to case. The presented theoretical model provides an effective approach to find out the optimal operation protocols under given experimental conditions and constrains.

Size-selective immunofluorescence of Mycobacterium tuberculosis cells by capillary- and viscous forces

Rapid, low cost screening of tuberculosis requires an effective enrichment method of Mycobacterium tuberculosis (MTB) cells. Currently, microfiltration and centrifugation steps are frequently used for sample preparation, which are cumbersome and time-consuming. In this study, the size-selective capturing mechanism of a microtip-sensor is presented to directly enrich MTB cells from a sample mixture. When a microtip is withdrawn from a spherical suspension in the radial direction, the cells that are concentrated by AC electroosmosis are selectively enriched to the tip due to capillary- and viscous forces. The size-selectivity is characterized by using polystyrene microspheres, which is then applied to size-selective capture of MTB from a sample mixture. Our approach yields a detection limit of 800 cells mL(-1), one of the highest-sensitivity immunosensors to date.

Hardware-in-the-loop simulation for ABS based on PC

The prevalence of microprocessor-based controllers in automotive systems has greatly increased the need for tools which can be used to validate and tune the control systems over their full range of operation. The objective of this paper is to develop a real time simulator for an anti-lock brake system (ABS) based on the methodology of hardware-in-the-loop simulation using a personal computer. By use of this simulator, the analysis of a commercial electronic control unit as well as the validation of the developed control logic for ABS was performed successfully. The idea of the simulator can be applied to the development of more advanced control systems, such as traction control system, vehicle dynamic control system and so forth.