Young-Hyun Jin

Lab-on-a-chip for multiplexed biosensing of residual antibiotics in milk

A multiplexed immunoassay-based antibiotic sensing device integrated in a lab-on-a-chip format is described. The approach is multidisciplinary and involves the convergent development of a multi-antibiotic competitive immunoassay based on sensitive wavelength interrogated optical sensor (WIOS) technology and a polymer-based self-contained microfluidic cartridge. Immunoassay solutions are pressure-driven through external and concerted actuation of a single syringe pump and multiposition valve. Moreover, the use of a novel photosensitive material in a one step fabrication process allowed the rapid fabrication of microfluidic components and interconnection port simultaneously. Pre-filled microfluidic cartridges were used as binary response rapid tests for the simultaneous detection of three antibiotic families - sulfonamides, fluoroquinolones and tetracyclines - in raw milk. For test interpretation, any signal lower than the threshold value obtained for the corresponding Maximum Residue Limit (MRL) concentration (100 microg L(-1)) was considered negative for a given antibiotic. The reliability of the multiplexed detection system was assessed by way of a validation test carried out on a series of six blind milk samples. A test accuracy of 95% was calculated from this experiment. The whole immunoassay procedure is fast (less than 10 minutes) and easy to handle (automated actuation).

Acrylated hyperbranched polymer photoresist for ultra-thick and low-stress high aspect ratio micropatterns

Different photocurable acrylates, including two hyperbranched monomers, are compared with an epoxy negative-tone photoresist (SU-8) with respect to their suitability for the fabrication of ultra-thick polymer microstructures in a photolithographic process. To this end, a resolution pattern was used and key parameters, such as the maximum attainable thickness and aspect ratio, the minimum resolution and the processing time were determined. Compared to SU-8, all acrylate materials allowed the fabrication of thicker layers with a fast single layer fabrication procedure. Microstructures with thicknesses of up to 850 µm, an aspect ratio of up to 7.7, a 5.5-fold reduction in internal stress and a 6-fold reduction in processing time compared to SU-8 were demonstrated using an acrylated hyperbranched polyether. The specific development process of the hyperbranched polymer combined with channel design moreover enabled us to produce a high-performance valve for micro-battery devices.

A fast low-temperature micromolding process for hydrophilic microfluidic devices using UV-curable acrylated hyperbranched polymers

A novel UV-curable low-stress hyperbranched polymer (HBP) micromolding process is presented for the fast and low-temperature fabrication of hydrophilic microfluidic devices. Process, material and surface properties of the acrylated polyether HBP are also characterized and compared to those of polydimethylsiloxane (PDMS) and cyclic olefin copolymers (COC). The HBP dispensed on a PDMS master was cured at room temperature using a 3 min UV exposure at the intensity of 22.2 mW cm−2. Thermal, mechanical and surface properties of the micromolded HBP structures have been characterized and resulted in a glass transition temperature of 55 °C, Youngs modulus of 770 MPa and hydrophilic surface having a water contact angle of 54°. Micromolding of 33 µm thick HBP microstructures has been demonstrated. We achieved 14.5 µm wide vertical walls, 14.7 µm wide fluidic channels, 24.1 µm wide square pillars and 53.4 µm wide square holes. A microfluidic network device, composed of microfluidic channels and reservoirs, was fabricated and its microfluidic performance has been verified by a fluidic test.

An SOI optical microswitch integrated with silicon waveguides and touch-down micromirror actuators

We present an SOI optical microswitch for applications to an integrated optical transceiver module, connected with optical I/O ports, source (LD) and receiver (PD). The optical microswitch consists of the waveguides and the micromirror actuators, all fabricated by the silicon layer on an SOI wafer. In the normally off-state, the micromirrors bypass the input signal to the output port. In the on-state, however, the actuated micromirrors provide optical interconnections between I/O ports and PD/LD, respectively. The present waveguide switch uses actuated micromirrors, thus providing more reliable optical path change than the conventional electro-optic or thermo-optic waveguide switches. In addition, we simplify the structure and the process of the microswitch by using the silicon waveguides and the silicon mirror-actuators, all fabricated by the ICP etching of an identical SOI wafer.

Nonlinearly modulated digital microactuators for nano-precision digital motion generation

This paper presents a nonlinearly modulated digital actuator (NMDA) for producing nano-precision digital stroke. The NMDA, composed of a digital microactuator and a nonlinear micromechanical modulator, purifies the stroke of the digital actuator in order to generate the high-precision displacement output required for nano-positioning devices. The function and concept of the nonlinear micromechanical modulator are equivalent to those of nonlinear electrical limiters, such as Zener diodes. We design and fabricate both linear and nonlinear modulators, having identical input and output strokes of 15.2 /spl mu/m and 5.4 /spl mu/m, respectively. We compare the characteristics of the linear and nonlinear modulators linked to identical digital actuators. The NMDA shows a repeatability of 12.3 /spl plusmn/ 2.9 nm, superior to the 27.8 /spl plusmn/ 2.9 nm achieved by the linearly modulated digital actuator (LMDA). We experimentally verify the displacement purifying capability of the nonlinear mechanical modulator, applicable to nano-precision positioning devices and systems.

A Multi-Channel SPR Biomolecule Detection System using an Integrated PDMS Nano-Scale Grating Chip

The paper presents a simple multi-channel SPR (surface plasmon resonance) biomolecule detection system using a grating-integrated SPR sensor chip. The present system is composed of a grating-integrated SPR sensor chip for SPR coupling and an external mirror for sequential reflection on each channel in the SPR sensor chip. Compared to the previous multi-channel SPR sensing systems, the present system eliminates bulky and expensive optical components, resulting in the smaller and the simpler system. The SPR sensor chip integrated with nano-scale pitch grating and fluidic channels is fabricated by micromolding technique to reduce the cost of the SPR sensor chip. In the experimental study, the presence of target biomolecule (streptavidin) shifts the SPR dip by 1.0nm; while the SPR dip for reference signal monitoring remains at the same position. From the experimental results, we verify the biomolecule detection performance of the present multi-channel SPR sensing system using a grating- integrated SPR sensor chip.

Electrical and Fluidic Characterization of Microelectrofluidic Bench Fabricated Using UV-curable Polymer

We present a novel polymer fabrication process involving direct UV patterning of a hyperbranched polymer, AEO3000. Compared to PDMS, which is the most widely used polymer in bioMEMS devices, the present polymer has advantages with regard to electrode integration and fast fabrication. We designed a four-chip microelectrofluidic bench having three electrical pads and two fluidic I/O ports. We integrated a microfluidic mixer and a cell separator on the bench to characterize the interconnection performance and sample manipulation. Electrical and fluidic characterization of the microfluidic bench was performed. The measured electrical contact resistance was , which is small enough for electrical applications, and the pressure drop was 8.3 kPa, which was 39.3% of the value in the tubing method. By performing yeast mixing and a separation test in the integrated module on the bench, we successfully showed that the interconnected chips could be used for bio-sample manipulation.

Lab-on-a-chip for Analysis and Diagnostics: Application to Multiplexed Detection of Antibiotics in Milk

The concern for “food safety” surely emerged very early in human history, contributing to the establishment of certain rules and customs. In today’s technologically developed countries, food safety is subject to strict laws that regulate the presence of undesired substances in food. In particular, in the milk industry, levels of residues of veterinary medicinal products, of which antibiotics represent a significant part, are regulated by European Council (EC) Regulation no. 2377/90. More precisely, a series of four antibiotic families are found to be of particular interest due to their routine use for treatment in bacterial infection and/or prophylactic purposes: fluoroquinolones, sulfonamides, β-lactams, and tetracyclines. Their excessive use in dairy diet in recent decades gave rise to stronger bacterial resistance, which consequently represents a serious problem in the efficiency of classic antibacterial treatment in humans [1]. In this context, there is a considerable need for developing sensing devices able to detect a series of antibiotic families simultaneously. A few dipstick format tests [1] commercially available that are cheap, fast, and reliable currently offer an interesting alternative to expensive conventional chromatographic techniques. However, those systems are not fully automated and are unable to detect more than two antibiotic families per single test. The present work reports the development of a lab-on-a-chip (LOC) test system for multiplexed detection of four antibiotic families in raw milk. A fabricated microfluidic cartridge is prefilled with the solutions necessary for immunoassays, and the whole detection sequence is operated automatically by external pump-and-valve combinations. The immunoassay principle is based on a competitive assay format, and the resulting refractive index changes at the sensor surface are probed using the wavelength interrogated optical sensing (WIOS) method. The multiplexed sensing system that was consequently developed was adapted for the simultaneous detection of sulfonamides, fluoroquinolones, β-lactams, and tetracyclines. The whole test procedure is fast (less than 10 min), easy to handle (automated actuation), and cost-effective due to the use of novel photosensitive materials in a “one-step” fabrication process.

A Disposable Grating-integrated Multi-channel SPR Sensor Chip for Real-time Monitoring of Biomolecule Binding

The paper presents a multi-channel real-time monitoring of biomolecule binding using a disposable SPR (Surface Plasmon Resonance) sensor chip integrated with nano-scale pitch grating. The sensor chip has two fluidic channels for sample delivery and gratings in each fluidic channel for SPR sensing. An external mirror makes an incidence of light at different angles on each sensing channel, thus generating two SPR dip at different spectral band. The gratings on the SPR sensor chip are fabricated by micromolding process for disposable application. We monitor the biotin-streptavidin binding reaction in real-time. The binding reaction using 0.2 muM streptavidin solution on the biotinylated surface is saturated in 30 min. The refractive index sensitivity of the SPR sensor chip is also characterized as 321.78 nm/RI at the sensing wavelength of 607 nm and 512.26 nm/RI at 704 nm.

An optical microswitch chip integrated with silicon waveguides and touch-down electrostatic micromirrors

We present an silicon-on-insulator (SOI) optical microswitch, composed of silicon waveguides and electrostatically actuated gold-coated silicon micromirrors integrated with laser diode (LD) receivers and photo diode (PD) transmitters. For a low switching voltage, we modify the conventional curved electrode microactuator into a new microactuator with touch-down beams. We fabricate the waveguides and the actuated micromirror using the inductively coupled plasma (ICP) etching process of SOI wafers. The fabricated microswitch operates at the switching voltage of 31.7 ± 4 V with the resonant frequency of 6.89 kHz. Compared to the conventional microactuator, the touch-down beam microactuator achieves 77.4% reduction of the switching voltage. We observe the single mode wave propagation through the silicon waveguide with the measured micromirror loss of 4.18 ± 0.25 dB. We discuss a feasible method to achieve the switching voltage lower than 10 V by reducing the residual stress in the insulation layers of touch-down beams to the level of 30 MPa. We also analyze the major source of micromirror loss, thereby presenting design guidelines for low-loss micromirror switches.