Yoomin Ahn

On-chip immunoassay using surface-enhanced Raman scattering of hollow gold nanospheres.

A surface-enhanced Raman scattering (SERS)-based gradient optofluidic sensor has been developed for a fast and sensitive immunoassay. In this work, a novel microfluidic sensor with functional internal structures has been designed and fabricated. This sensor is composed of three compartments consisting of the gradient channel that serially dilutes the target marker, the injection and mixing area of antibody-conjugated hollow gold nanospheres and magnetic beads, and the trapping area of sandwich immunocomplexes using multiple solenoids. Quantitative analysis of a specific target marker is performed by analyzing its characteristic SERS signals. This SERS-based gradient optofluidic sensor can replace the set of microwells or microtubes used in manual serial dilutions that have been traditionally used in enzyme-linked immunosorbent assay (ELISA)-type assays. The limit of detection for rabbit immunoglobin (IgG) is estimated to be 1-10 ng/mL. This novel SERS-based optofluidic immunoassay system is expected to be a powerful clinical tool for the fast and sensitive medical diagnosis of a disease.

A novel microfluidic biosensor based on an electrical detection system for alpha-fetoprotein

Conventional immunoassays are labor intensive, expensive and time consuming and require large pieces of equipment for detection. Therefore, we have developed and characterized a novel immunoassay methodology comprised of microbeads and microbiochips. In this method, microbeads are used to filter and immobilize antibodies and an immuno-gold silver staining (IGSS) method is then used to amplify electrical signals that correspond to the bound antibodies. The chip used for this system is composed of an inexpensive and biocompatible polydimethylsiloxane (PDMS) layer over a Pyrex glass substrate that contains a platinum (Pt) microelectrode, which is used to detect the electrical signal in this system, the microelectrode is fabricated on the substrate and a microchannel and pillar-type microfilter is formed in the PDMS layer. A sandwich immunoassay approach was applied to detect alpha-fetoprotein (AFP), a cancer biomarker, using this system. The results of this study showed that the time required for a complete assay was reduced by 1h and a detection limit as low as 1 ng/mL was attained when this system used, which indicates that similar bead-based electrical detection systems could be used for the diagnosis of many forms of cancer.

Microchip-based multiplex electro-immunosensing system for the detection of cancer biomarkers

Microfluidic‐based microchips have become the focus of research interest for immunoassays and biomarker diagnostics. This is due to their aptitude for high‐throughput processing, small sample volume, and short analysis times. In this paper, we describe the development of a microchip‐based multiplex electro‐immunosensing system for simultaneous detection of cancer biomarkers using gold nanoparticles and silver enhancer. Our microchip is composed of biocompatible poly(PDMS) and glass substrates. To fix the antibody‐immobilized microbeads, we used pillar‐type microfilters within a reaction chamber. An immunogold silver staining (IGSS) method was used to amplify the electrical signal that corresponded to the immunecomplex. To demonstrate this approach, we simultaneously assayed three cancer biomarkers, alpha‐fetoprotein (AFP), carcinoembryonic antigen (CEA), and prostate‐specific antigen (PSA) on the microchip. The electrical signal generated from the result of the immunoreaction was measured and monitored by a PC‐based system. The overall assay time was reduced from 3–8 h to about 55 min when compared to conventional immunoassays. The working range of the proposed microchip was from 10−3 to 10−1 μg/mL of the target antigen.

Hydrodynamic analysis of chemical mechanical polishing process

Chemical Mechanical Polishing (CMP) refers to a material removal process done by rubbing a work piece against a polishing pad under load in the presence of chemically active abrasive containing slurry. The CMP process is a combination of chemical dissolution and mechanical action. The mechanical action of CMP involves hydrodynamic lubrication. The liquid slurry is trapped between the work piece (wafer) and pad (tooling) forming a lubricating film. For the first step to understand the mechanism of the CMP process, hydrodynamic analysis is done with a semiconductor wafer. Slurry pressure distribution, resultant forces and moments acting on the wafer are calculated in typical conditions of the wafer polishing, and then nominal clearance of the slurry film, roll and pitch angles at the steady state are obtained.

Three-dimensional wafer scale hydrodynamic modeling for chemical mechanical polishing

Chemical mechanical polishing (CMP) refers to a surface removal process done by rubbing a work piece against a polishing pad under load in the presence of chemically active slurry containing an abrasive. The CMP process is a combination of mechanical action and chemical dissolution. The mechanical action of CMP includes hydrodynamic behavior. The slurry fluid trapped between the work piece and the polishing pad forms a hydrodynamic film. Firstly, to understand the surface removal mechanism of the CMP process, hydrodynamic analysis was carried out on full-scale semiconductor wafers. The three-dimensional Reynolds equation was applied to obtain distributions of thickness and pressure of the slurry fluid on the wafer surface. The distribution of contact shear stress of the slurry was also analyzed.

PDMS–glass serpentine microchannel chip for time domain PCR with bubble suppression in sample injection

This paper reports on the development of a low-cost microreactor (10 µl) biochip for DNA polymerase chain reaction (PCR). The microbiochip (20 mm × 28 mm) is a hybrid type that is composed of a polydimethylsiloxane (PDMS) layer with a serpentine microchannel (360 µm × 100 µm) chamber and glass substrate integrated with a microheater and thermal microsensor. Because of the hydrophobic chip surface, bubbles are usually created during sample loading in the PMDS-based microchip. These bubbles disrupt the stable biochemical reaction. An improved microreactor chamber was designed using microfluidic simulation. The reactor has a rounded-corner serpentine channel architecture, which enables stable injection into the hydrophobic surface using only a micropipette. The reactor temperature needed for the PCR reaction is controlled within ±0.5 °C by the LabVIEW software proportional-integrative-derivative (PID) controller. PCR analyses of the sex-determining Y chromosome (SRY) gene and mouse GAPDH gene were successfully performed in less than 54 min by the fabricated microreactor chip.

Effect of mechanical process parameters on chemical mechanical polishing of al thin films

The effects of polishing pressure and abrasive on the chemical mechanical polishing of blanket and patterned aluminum thin films were investigated. The CMP process experiments were conducted using a soft pad and slurry mainly composed of acid solution and Al2O3 abrasive. The result of the blanket film showed that, as the concentration of abrasive in the slurry increased, surface roughness deteriorated but waviness improved. The planarity of the patterned Al films was slowly improved by the CMP when the widths of the gaps between the patterns were relatively small. An attempt was made to find the optimum CMP process conditions by which the patterned Al thin film could be planarized with a fine surface. The most satisfactory film surface was obtained when the applied pressure was low (10 kPa) and the abrasive concentration was relatively high (5 wt.%).

Si multiprobes integrated with lateral actuators for independent scanning probe applications

Silicon SPM multiprobes having lateral actuators with a very small pitch were microfabricated and evaluated for independent parallel operations and nanomaterial characterizations. Two types of 1 × 4 probe array were developed. In order to treat smaller objects, the distance between each cantilever tip was produced to be as small as possible. The inter-tip distance is about 7 µm. In addition, the cantilevers of the multiprobes had comb drive actuators that enable individual probes to move horizontally. More flexibility in SPM operation was obtained with these individual self-movement probes possibly opening up new applications in nanotechnology. Using the microfabricated multiprobes, the characterization of the electric properties of a carbon nanotube by a two-probe measurement and the manipulation of a microlens were demonstrated.

Microfabricated, continuous-flow, microbial three-electrode cell for potential toxicity detection

Bioelectrochemical microfluidic devices are developed based on the continuous flow mode of membrane-less, microbial three-electrode cells (M3Cs). These novel devices are the miniaturized microfluidic-based three-electrode cells for the first time, and these are composed of an Ag/AgCl reference electrode, indium tin oxide anode and cathode electrodes. The basic performance of the devices is tested using biofilms grown from wastewater inoculum in an experiment that senses for toxic materials. The toxic materials used are: sodium cyanide, imidazole, and sodium azide in concentrations of 0.02–0.8 mM, with lactate and sodium acetate functioning as substrates. While a constant potential of 0.2 V is applied to the working electrodes of the device, the bioelectrocatalytic oxidation current is monitored at 35°C. When the biocides are introduced, the response current from the cell decreases. The sensor can detect imidazole at the range of 0.02–0.4 mM. The experimental results show the potential of using microfluidic-based microbial electrolysis cells not only as biocide sensors, but also as investigative tools for microbial electrochemical assays.

Separation-Type Multiplex Polymerase Chain Reaction Chip for Detecting Male Infertility

A novel polymerase chain reaction (PCR) biochip is presented in this paper. In this PCR chip, the glass substrate integrated with the microheater and microsensor is separable from the reaction chamber where the sample is injected, which now makes repeated reuse of the glass substrate possible. The heat transfer efficiency and target gene amplification of the proposed separable PCR chip was compared with that of the conventional united PCR chip. The results showed that the sex-determining Y chromosome (SRY) gene PCR for detecting male infertility was successfully performed in the separable chip. However, repeated multiplex PCR was successful for only two genes, SPGY1 and SRY, but not for gene SY586. Future work is needed for a multiplex PCR with more than three genes.