Yaw-Jen Chang

Dividable membrane with multi-reaction wells for microarray biochips.

This paper presents a multi-well membrane fabricated using polydimethylsiloxane (PDMS) as a part of a microarray biochip that allows dividable incubation chambers to be provided on a single chip. The conditions of the forming temperature, time, and mixing proportion of the materials were investigated to obtain optimal physical absorption with the surface of the chip substrate. To verify the properties of the multi-well chip, immunoassays were performed by the alpha-1-fetoprotein (AFP) antigen sandwich experiment. The results showed that the detection limit reached to the concentration of 10 ng/ml AFP antigen, and that the dynamic range was 30-3000 ng/ml. Attaining excellent physical absorption helps in avoiding cross-contamination or interference between different samples on the same biochip. The merits of dividable multi-well chips include promoting effective use of surface and multiple-sample experiments.

Fabrication of Protein Chip with Ni-Co Alloy Coated Surface

In this study, a Ni-Co alloy coated protein chip was fabricated by means of electrodepositing nickel and cobalt on the substrate surface. The protein was immobilized on the coated surface by the affinity mechanism of nickel and cobalt which belong to the intermediate metal group. Then, the immunoreaction can be performed on the chip. The results show that the alloy coating belongs to abnormal codeposition of Ni-Co alloy. The proportion of Ni-Co composition will affect the affinity of electroplated layer with protein and, consequentially, influence the results of immunoassay. Thus, in this paper the Taguchi method was adopted to determine the optimal fabrication process of the Ni-Co alloy coated chip using L18 orthogonal array. The experimental factors that affect the performance of abnormal codeposition include the quantity of cobalt, current density of electroplating, operation temperature, and pH of electroplating buffer. The major purpose of this research is the planarization of IMAC technique so that biological molecular can be absorbed on protein chip for further analysis. The advantages of this novel protein chip include good performance, high repeatability, and less cost.

Immunoassay chip for URICASE protein using histidine-immobilization technique

This paper presents a nickel-coated immunoassay chip fabricated by electroplating technology for Uricase protein. The Taguchi method was adopted to determine the optimal electroplating condition. The considered factors that affect the performance of nickel-coated chip included current density of electroplating, operation temperature, and pH of electroplating buffer, etc. As a result of systematic electroplating approach, a stable and optimal chip surface was obtained. Due to the physical adsorption between intermediate metal and protein, this chip provides specific binding with His-tagged Uricase. In addition, it offers self-assembling and directional molecule immobilization on the surface of chip. The immunoassay was performed for verification. This nickel-coated chip can be used not only for His-tagged Uricase but for any His-tagged proteins in the pathological analyses with inexpensive microarray chip design.

Temperature Control in Mini-Bioreactor and Its Impact to Immunoassay

In this paper, the precise temperature control incorporated in the mini-bioreactor for biochemical reaction was developed. The temperature control system can be operated from computer. The variation of temperature is within  0.2C using fuzzy control algorithm. Compared with conventional oven, it has 10-fold precision. It also has better heating efficiency with rapid rising time to reach the desired temperature. The experimental results of immunoassays show that the temperature control has a great impact to immnuoreaction. Under a stable temperature environment, the variation of fluorescence intensities scanned after immunoassays is smaller for all titration concentrations. The temperature control system in mini-bioreactor can promote better experimental results of immunoassay.

Applying Technique of Sacrificial Layer for the Fabrication of Microfilter

Biochip plays an important role in biotechnology and many scientists also pay a lot of attention on this product. Thus, in this study we used MEMS and sacrificial layer techniques to manufacture the microfilter. It only depends on different development properties of the positive and negative photoresists. The feature size of filtration can be precisely controlled by the thickness of sacrificial layer. The main materials for this study are just photoresists, such as negative photoresist SU-8 and positive photoresists AZ4620 and RP4000. The fabrication process was carried out in the yellow room. Compared with the traditional micromachining methods such as bulk micromanufacturing, surface micromachining and the LIGA process, this proposed design and fabrication of microfilter have many advantages including economical fabrication cost and high yield.

Measurement of the Biotin Concentration Using QCM Biosensors

This paper presents a novel Ni-Co alloy coated QCM biosensor fabricated by electroplating nickel and cobalt on the surface of 10-MHz AT-cut QCM. The biotin was immobilized on the coated surface by the affinity mechanism of Ni-Co alloy. Then, the immunoreactions can be performed on the QCM biosensors. The results show that the Ni-Co alloy coated QCM biosensor can provide specific binding with His-tagged biotin. For different biotin concentrations, the QCM produced different frequency shifts. In addition, fluorescent detection was also performed to show that the coated Ni-Co film has better nonspecific binding ability than nitrocellulose film to immobilize His-tagged proteins for target analyses. The advantages of this biosensor include: (1) label-free detection based on the principle of QCM resonator; (2) minimal sample consumption (0.5 mul of biotin each drop used in this study); (3) inexpensive fabrication process using the well-developed electroplating technique.

Design and Fabrication of Micromixer With Piezoceramic Buzzer

Micromixer is an important bioMEMS device for mixing samples. In this study, we developed a novel active micromixer using SU-8 to form the microstructure and piezoceramic buzzer to produce the agitation. This device consists of a mixing chamber, inlets and an outlet. It is tolerant of gas bubbles so that the priming process can be achieved. Under the agitation of piezoceramic buzzer, the samples can be well mixed. The advantages of this proposed micromixer include: (1) simple fabrication process; (2) low cost; (3) disposable; and (4) mass-production available.

Long Term Sensibility of the Ni-Co Protein Chip

For the metal ion affinity chromatography, the nickel is used to capture the histidines(his)-tagged protein to make up a rapid purification system from the organism lysate. In this study, based on the optimization approach of Taguchi method, we developed a Ni-Co protein chip whose intermediate metal surface could capture the recombinant protein successfully. Thus, the proposed Ni-Co chip can provide specific binding with His-tagged biotin and His-tagged Uricase. In addition, under the constant humidity and temperature, the immobilization capability of Ni-Co chip with specific binding of immuno- reaction was tested every week. Finally, we obtained the long term performance of Ni-Co chip with 6timesHis-Uricase of concentration of 20 mug/ml.