Hanseup Kim

Characterization of a microfluidic in vitro model of the blood-brain barrier (μBBB)

The blood-brain barrier (BBB), a unique selective barrier for the central nervous system (CNS), hinders the passage of most compounds to the CNS, complicating drug development. Innovative in vitro models of the BBB can provide useful insights into its role in CNS disease progression and drug delivery. Static transwell models lack fluidic shear stress, while the conventional dynamic in vitro BBB lacks a thin dual cell layer interface. To address both limitations, we developed a microfluidic blood-brain barrier (μBBB) which closely mimics the in vivo BBB with a dynamic environment and a comparatively thin culture membrane (10 μm). To test validity of the fabricated BBB model, μBBBs were cultured with b.End3 endothelial cells, both with and without co-cultured C8-D1A astrocytes, and their key properties were tested with optical imaging, trans-endothelial electrical resistance (TEER), and permeability assays. The resultant imaging of ZO-1 revealed clearly expressed tight junctions in b.End3 cells, Live/Dead assays indicated high cell viability, and astrocytic morphology of C8-D1A cells were confirmed by ESEM and GFAP immunostains. By day 3 of endothelial culture, TEER levels typically exceeded 250 Ω cm(2) in μBBB co-cultures, and 25 Ω cm(2) for transwell co-cultures. Instantaneous transient drop in TEER in response to histamine exposure was observed in real-time, followed by recovery, implying stability of the fabricated μBBB model. Resultant permeability coefficients were comparable to previous BBB models, and were significantly increased at higher pH (>10). These results demonstrate that the developed μBBB system is a valid model for some studies of BBB function and drug delivery.

Micro Power Generator for Harvesting Low-Frequency and Nonperiodic Vibrations

This paper presents a new inertial power generator for scavenging low-frequency nonperiodic vibrations called the Parametric Frequency-Increased Generator (PFIG). The PFIG utilizes three magnetically coupled mechanical structures to initiate high-frequency mechanical oscillations in an electromechanical transducer. The fixed internal displacement and dynamics of the PFIG allow it to operate more effectively than resonant generators when the ambient vibration amplitude is higher than the internal displacement limit of the device. The design, fabrication, and testing of an electromagnetic PFIG are discussed. The developed PFIG can generate a peak power of 163 μW and an average power of 13.6 μW from an input acceleration of 9.8 m/s2 at 10 Hz, and it can operate at frequencies up to 65 Hz, giving it an unprecedented operating bandwidth and versatility. The internal volume of the generator is 2.12 cm3 (3.75 cm3 including the casing). The harvester has a volume figure of merit of 0.068% and a bandwidth figure of merit of 0.375%. These values, although seemingly low, are the highest reported in the literature for a device of this size and operating in the difficult frequency range of ≤ 20 Hz.

Characterization of low-temperature wafer bonding using thin-film parylene

This paper presents detailed experimental data on wafer bonding using a thin Parylene layer, and reports results on: 1) bond strength and its dependence on bonding temperature, bonding force, ambient pressure (vacuum), and time, 2) bond strength variation and stability up to two years post bond, and 3) bond strength variation after exposure to process chemicals. Wafer bonding using thin (<381 nm) Parylene intermediate layers on each wafer in a standard commercial bonder and aligner has been successfully developed. The Parylene bond strength is optimized at 230/spl deg/C, although Parylene bonding is possible at as low as 130/spl deg/C. The optimized bonding conditions are a low-temperature of /spl sim/230/spl deg/C, a vacuum of /spl sim/ 0.153 mbar, and 800 N force on a 100 mm wafer. The resultant Parylene bond strength is 3.60 MPa, and the strength for wafers bonded at or above 210/spl deg/C is maintained within 93% of its original value after two years. The bond strength is also measured after exposure to several process chemicals. The bond strength was reduced most in undiluted AZ400K (base) by 69% after one week, then in BHF (acid), MF319 (base), Acetone (solvent), and IPA (solvent) by 56%, 33%, 20%, and 8%, respectively, although less than one hour exposure to these chemicals did not cause a significant bond strength change (less than 11%). [1487].

Low-temperature characterization and micropatterning of coevaporated Bi2Te3 and Sb2Te3 films

Thermoelectric (TE) properties of the coevaporated Bi2Te3 and Sb2Te3 films are measured from 100 to 300 K for Seebeck coefficient αS and from 5 to 300 K for electrical resistivity ρe, mobility μe, and Hall coefficient RH. For the low-temperature characterization of TE films, the conditions for coevaporation deposition of Bi, Te, and Sb to form Bi2Te3 and Sb2Te3 films are also investigated, including substrate material, substrate temperature Tsub, and elemental flux ratio (FR). The resublimation of Te occurring above 473 K significantly affects the film composition and quality. Our optimal deposition conditions for Bi2Te3 films are Tsub=533 K and FR=2.4, and those for Sb2Te3 films are Tsub=503 K and FR=3.0. The TE properties of both films are strongly temperature dependent, while Bi2Te3 films show a stronger temperature dependence than Sb2Te3 films due to different major scattering mechanisms. αS of both the coevaporated films are close to or higher than those of bulk materials, but ρe is much higher (due ...

A piezoelectric frequency-increased power generator for scavenging low-frequency ambient vibration

This paper presents the design, fabrication, and testing of a piezoelectric inertial micro power generator for scavenging low-frequency non-periodic vibrations. A mechanism up-converts the ambient vibration frequency to a higher internal operation frequency, in order to achieve better electromechanical coupling and efficiency: enhancing the generators performance at very low frequencies (≪30Hz). The generator incorporates a bulk piezoelectric ceramic machined using ultrafast laser ablation. The fabricated device generated a peak power of 100µW and an average power of 3.25µW from an input acceleration of 9.8m/s2 at 10Hz. The device operates over a frequency range of 24Hz. The internal volume of the generator is 1.2cm3.

An Integrated Micro-Analytical System for Complex Vapor Mixtures

A micro gas chromatograph (muGC) capable of quantitatively analyzing the components of complex vapor mixtures at trace concentrations is described. The muGC features a micro- preconcentrator/focuser (muPCF), dual-column pressure- and temperature-programmed separation module, and an integrated array of nanoparticle-coated chemiresistors. The latest design modifications and performance data are presented. Highlights include a 4-min separation of a 30-component mixture with a 3-m DRIE Si/glass microcolumn, a 14-sec separation of an 11-component mixture on a 25-cm microcolumn, a complete multi-vapor analysis from a hybrid microsystem that combines analytical, rf- wireless, and microcontroller modules, and a rapid analysis driven by a 4-stage peristaltic micropump.

A fully integrated high-efficiency peristaltic 18-stage gas micropump with active microvalves

We report the design, fabrication, and test results of a fully integrated peristaltic 18-stage gas micropump consisting of 18 serially-connected pumping chambers and 19 microvalves. The peristaltic micropump achieves (1) high-pressure differentials by accumulating small pressure differentials that are evenly distributed across the individual stages using a low-compression multi-stage design, (2) high flow rate by operating pumping membranes at fluidic resonance and high frequency (>10 kHz), and (3) gas flow regulation by actively controlling the open/close timing of microvalves for either high flow or high pressure. The 18-stage micropump includes several new innovations, such as checkerboard microvalves, dual drive electrodes, and dual pumping chambers to achieve efficient electrostatic pumping. The fabricated 18-statge pump has produced an air flow rate of ~4.0 seem and maximum pressure differential of-17.5 kPa with a total power of only ~57 mW. It has a total package volume of 25.1 x 19.1 x 1 mm3 and each individual membrane is only 2x2 mm2.

A Micropump-Driven High-Speed MEMS Gas Chromatography System

We report (1) the integration of the first functioning MEMS gas chromatography system ( muGC) featuring a micropump, a micro-column, and a micro-chemiresistor sensor array; and (2) experimental demonstration of the state-of-the-art multi-vapor gas separation and detection. In particular, we report the best GC analysis data from the first micropump-driven muGC system to date: the separation and detection of 11 volatile organic compounds (VOC)s within only 78 seconds while consuming only 15.1 mW of power within a small volume of 0.5 cc. We also report the use of temperature programming (TP) of the separation column for fast analysis, which shortened the analysis time from 78 seconds to 24 seconds while maintaining gas analysis resolution.

Two-dimensional position deteciton system with MEMS accelerometer for MOUSE applications

A hybrid two-dimensional position sensing system is designed for mouse applications. The system measures the acceleration of hand-movements which are converted into two-dimensional location coor-dinates. The system consists of four major components: 1) MEMS accelerometers, 2) CMOS analog read-out circuitry, 3) an accelera-tion magnitude extraction module, and 4) a 16-bit RISC micropro-cessor. Mechanical and analog circuit simulation shows that the designed padless mouse system can detect accelerations as small as 5.3 mg and operate up to 18MHz.

A multiple-channel, multiple-assay platform for characterization of full-range shear stress effects on vascular endothelial cells.

Vascular endothelial cells (VECs), which line blood vessels and are key to understanding pathologies and treatments of various diseases, experience highly variable wall shear stress (WSS) in vivo (1-60 dyn cm(-2)), imposing numerous effects on physiological and morphological functions. Previous flow-based systems for studying these effects have been limited in range, and comprehensive information on VEC functions at the full spectrum of WSS has not been available yet. To allow rapid characterization of WSS effects, we developed the first multiple channel microfluidic platform that enables a wide range (~15×) of homogeneous WSS conditions while simultaneously allowing trans-monolayer assays, such as permeability and trans-endothelial electrical resistance (TEER) assays, as well as cell morphometry and protein expression assays. Flow velocity/WSS distributions between channels were predicted with COMSOL simulations and verified by measurement using an integrated microflow sensor array. Biomechanical responses of the brain microvascular endothelial cell line bEnd.3 to the full natural spectrum of WSS were investigated with the platform. Under increasing WSS conditions ranging from 0 to 86 dyn cm(-2), (1) permeabilities of FITC-conjugated dextran and propidium iodide decreased, respectively, at rates of 4.06 × 10(-8) and 6.04 × 10(-8) cm s(-1) per dyn cm(-2); (2) TEER increased at a rate of 0.8 Ω cm(2) per dyn cm(-2); (3) increased alignment of cells along the flow direction under increasing WSS conditions; and finally (4) increased protein expression of both the tight junction component ZO-1 (~5×) and the efflux transporter P-gp (~6×) was observed at 86 dyn cm(-2) compared to static controls via western blot. We conclude that the presented microfluidic platform is a valid approach for comprehensively assaying cell responses to fluidic WSS.