Browsing by Author "Yang, Yuh-Shyong"

Now showing 1 - 20 of 83

A CMOS Capacitive Dopamine Sensor with Sub-nM Detection Resolution
(2009)
Wang, Shi-Wei
;
Lin, Chih-Heng
;
Yang, Yuh-Shyong
;
Lu, Michael S. -C.
;
生物科技學系
Interdigitated microelectrodes integrated with CMOS sensing circuitry are presented in this work for detection of the neurotransmitter dopamine and as an immunosensor with sensitivity enhanced by gold nanoparticles. Microelectrodes covered by the silicon dioxide layer are fabricated through a maskless post-CMOS process. Charged biomolecules bind to the functionalized oxide surface after immobilization, producing a capacitive change for the underlying electrodes. Three electrode designs with gaps from 0.5 mu m to 1 mu m and capacitance values from 13 fF to 925 IF are tested. The capacitance increases with respect to the concentrations of nanoparticle and dopamine. The minimum detectable concentration of dopamine is 540 pM at a 1-Hz bandwidth.
A CMOS-Based Phototransistor for High-Sensitivity Biochemical Detection Using Absorption Photometry
(2008)
Chang, Yu-Wei
;
Tai, Yu-Ting
;
Huang, Yang-Tung
;
Yang, Yuh-Shyong
;
電子工程學系及電子研究所
This paper proposes a high-sensitivity biosensing system on the basis of absorption photometry and a phototransistor. Manufactured in a standard 0.35-mu m CMOS technology, the phototransistor exhibits a responsivity higher than 1000 A/W for 650-nm light. The TMB/H(2)O(2)/HRP method is chosen as a useful platform to determine the amount of various interesting targets. For the biochemical detection, a sample volume of only 10 mu l is required to be dropped on the slide above the phototransistor. Experimental results demonstrate that a high sensitivity of 2.5 mu A/pM is achieved, and the minimum HRP concentration successfully detected is 2.7 pM. This detection limit is three orders of magnitude better than that of a reported silicon biosensor.
A CMOS-compatible optical biosensing system based on visible absorption spectroscopy
(2007)
Chang, Yu-Wei
;
Yu, Ping-Chun
;
Huang, Yang-Tung
;
Yang, Yuh-Shyong
;
電子工程學系及電子研究所
A CMOS-compatible optical biosensing system based on visible absorption spectroscopy is proposed. Within the compact prototype, the CMOS sensor consisting a P(+)/N(well) finger photodiode and a transimpedance amplifier (TIA) is implemented in a standard 0.35-mu m CMOS technology. The ABTS/H(2)O(2)/HRP method is adopted as the ground for medical diagnosis, Experimental results demonstrate that the minimum concentration successfully detected for H(2)O(2) is 1 mu M. The detection limit is one order of magnitude better than a traditional CMOS biosensor, and comparable to a commercial spectrophotometer.
A High-Sensitivity CMOS-Compatible Biosensing System Based on Absorption Photometry
(2009-01-01)
Chang, Yu-Wei
;
Yu, Ping-Chun
;
Huang, Yang-Tung
;
Yang, Yuh-Shyong
;
生物科技學系
An optical biosensing system based on a standard CMOS technology and absorption photometry is proposed. Within the compact prototype, a CMOS sensor consisting a P(+)/N(well) finger photodiode and a transimpedance amplifier was implemented in a standard 0.35-mu m CMOS technology. The ABTS/H(2)O(2)/HRP method was adopted to be coupled with various analytes of interest, such as glucose and histamine, which can serve as the basis for medical diagnosis. The experimental results demonstrate that the minimum concentrations successfully detected for H(2)O(2), glucose, and histamine are 1 mu M, 1 mu M, and 10 mu M, respectively. The detection limits are at least one order of magnitude better than those of reported CMOS biosensors, and are even comparable to those of a commercial spectrophotometer.
A High-Sensitivity CMOS-Compatible Immunosensor Based on the HRP/TMB/Streptavidin System
(2008)
Tai, Yu-Ting
;
Chang, Yu-Wei
;
Lin, Ming-Yu
;
Yang, Yuh-Shyong
;
Huang, Yang-Tung
In this report, a CMOS-compatible colorimetric biosensor based on HRP/TMB/streptavidin system is proposed. HRP activity is used for labelled target quantification by photometric detector. The modulation of light intensity due to enzyme reaction can easily be detected in 96-well microarray plate by providing 650nm light source (LED). There is good correlation between absorbance in 650nm and the concentration of HRP-streptavidin with detection limit in 1.33 pM. This device is reusable and suits for various targets by microarray plate modification rather than biochip. With the advantage of portable, low cost, and reusable, this new designed immunosensor could be widely used for both research and diagnostic purposes.
A Miniature CMOS Optoelectronic Biosensor for Screening Skin-Whitening Agents
(2009)
Chang, Yu-Wei
;
Lu, Yen-Pei
;
Lin, Ming-Yu
;
Huang, Yang-Tung
;
Yang, Yuh-Shyong
A miniature CMOS optoelectronic biosensor is proposed for screening whitening agents. Based on the principle of absorption photometry, this biosensor is mainly composed of a green LED, a CMOS phototransistor, and a slide for performing the biochemical reactions. The requirement of the sample volume is only 10 mu l, much less than those in commercial instruments. Melanin assay and MTT assay were performed to evaluate the whitening mechanisms. Experimental results demonstrated that the density of 5x10(4) cells/ml can be successfully detected for both assays. This portable biosensor has great potential toward personalized diagnostic kits for further applications.
A nano switch mechanism for the redox-responsive sulfotransferase
(2012-07-15)
Lin, Chih-Heng
;
Lin, En-Shyh
;
Su, Tian-Mu
;
Hung, Kuo-Sheng
;
Yang, Yuh-Shyong
Cellular redox signaling is important in diverse physiological and pathological processes. The activity of rat phenol sulfotransferase (rSULT1A1), which is important for the metabolism of hormone and drug, is subjected to redox regulation. Two cysteines, Cys232 and Cys66, nanometer away from each other and from the enzyme active site were proposed to form disulfide bond to regulate the activity of rSULT1A1. A nano switch, composed of a flexible loop from amino acid residues 59-70, explained how this long distance interaction between two cysteines can be achieved. The enzyme properties were investigated through site-directed muatagnesis, circular dichroism, enzyme kinetics and homologous modeling of the rSULT1A1 structures. We proposed that the formation of disulfide bond between Cys232 and Cys66 induced conformational changes of sulfotransferase, then in turn affected its nucleotide binding and enzyme activity. This discovery was extended to understand the possible redox regulation of other sulfotransferases from different organisms. The redox switch can be created in other redox-insensitive sulfotransferases, such as human phenol sulfotransferase (hSULT1A1) and human alcohol sulfotransferase (hSULT2A1), to produce mutant enzymes with redox regulation capacity. This study strongly suggested that redox regulation of drug and hormone metabolism can be significantly varied even though the sequence and structure of SULT1A1 of human and rat have a high degree of homology. (C) 2012 Elsevier Inc. All rights reserved.
A NOVEL FLUOROMETRIC ASSAY OF HUMAN 3'-PHOSPHOADENOSINE 5'-PHOSPHOSULFATE SYNTHETASE
(2008-09-01)
Liu, Tzu-An
;
Yang, Yuh-Shyong
;
生物科技學系
;
Department of Biological Science and Technology
A Phototransistor-Based High-Sensitivity Biosensing System Using 650-nm Light
(2009-05-01)
Chang, Yu-Wei
;
Tai, Yu-Ting
;
Huang, Yang-Tung
;
Yang, Yuh-Shyong
;
生物科技學系
A miniature optical biosensing system based on a PMOS phototransistor and absorption photometry is proposed. The phototransistor was manufactured in a standard 0.35-mu m CMOS process, and it exhibited a responsivity higher than 1000 A/W for 650-nm light. For biochemical applications, the TMB/H(2)O(2)/HRP method was adopted as a useful basis in our system. A sample volume of only 10 mu l was required to be dropped on the slide above the phototransistor. Experimental results demonstrated that a high sensitivity of 2.5 mu A/pM was achieved, and the minimum HRP concentration successfully detected was 2.7 pM. This detection limit is three orders of magnitude better than that of a lately reported silicon biosensor, and is even comparable to that of a commercial spectrophotometer.
A target-specific approach for the identification of tyrosine-sulfated hemostatic proteins
(2009-07-01)
Liu, Tzu-An
;
Yasuda, Shin
;
Williams, Frederick E.
;
Liu, Ming-Yih
;
Suiko, Masahito
A simple methodology for the identification of hemostatic proteins that are subjected to post translational tyrosine sulfation was developed. The procedure involves sequence analysis of members of the three hemostatic pathways using the Sulfinator prediction algorithm, followed by [(35)S]sulfate labeling of cultured HepG2 human hepatoma cells, immunoprecipitation of targeted [(35)S]sulfate-labeled hemostatic proteins, and tyrosine O-[(35)S]sulfate analysis of immunoprecipitated proteins. Three new tyrosine-sulfated hemostatic proteins-protein S. prekallikrein, and plasminogen-were identified. Such a target-specific approach will allow investigation of tyrosine-sulfated proteins of other biochemical/physiological pathways/processes and contribute to a better understanding of the functional role of post-translational tyrosine sulfation. (C) 2009 Elsevier Inc. All rights reserved.
Alignment of Stretchable Nanoparticle Chains with Tunable Optical Properties Formed from Molecular Machinery
(2013-01-01)
Lin, Ming-Yu
;
Lu, Yen-Pei
;
Yang, Yuh-Shyong
;
Chen, Hsuen-Li
;
Yang, Chih-Hui
Control orientation and interparticle spacing of self-assembled nanoparticles can provide versatile functional materials for optical and electronic applications. In this study, we have obtained a glass substratum with tunable optical properties using flowing control and bimolecular competition. The surface of glass was modified from immobilized stretchable gold nanoparticle chains. The long and periodic single-stranded DNA nanotemplates were prepared using Phi29 DNA polymerase molecular machinery according to precise molecular biology regulation. Gold nanoparticle (Au NP) docked at the default sites of the nanotemplates and optical anisotropic absorption were enhanced by approximately 55 % by using tunable, flexible, and oriented one-dimensional metallic nanostructures.
An electrochemical dopamine sensor with a CMOS detection circuit
(2008-07-01)
Chan, Feng-Lin
;
Chang, Wen-Ying
;
Kuo, Li-Min
;
Lin, Chih-Heng
;
Wang, Shi-Wei
This paper presents the integration of interdigitated microelectrodes and a CMOS circuit for electrochemical sensing of the neurotransmitter dopamine. Gold electrodes with a gap of 3 mu m are fabricated by the lift-off technique. The CMOS sensing circuit has a current gain of 10, an integrating capacitor of 4 pF, and a measured dynamic range of 60 dB. The applied reduction and oxidation potentials are determined by voltammetry at about -0.2 V and 0.6 V, respectively. The measured collection efficiency can reach up to 84%. The produced oxidation current with respect to dopamine concentration averages 0.44 nA mu M(-1).
An electrochemical dopamine sensor with CMOS detection circuit
(2007-01-01)
Zhan, Feng-Lin
;
Kuo, Li-Min
;
Wang, Shi-Wei
;
Lu, Michael S. -C.
;
Chang, Wen-Ying
This paper presents the use of interdigitated microelectrodes as the platform for electrochemical sensing of the neurotransmitter dopamine. Gold electrodes with gaps ranging between 3 gm to 7 gm are fabricated by the lift-off technique. The reduction and oxidation potentials for dopamine are determined by voltammetry using the fabricated microelectrodes. A CMOS sensing circuit is used to amplify the electrochemical current produced by the working electrodes. Experimental result shows that for a dopamine concentration of 10 mu M the measured current value is 11 pA.
An enzymatic kinetics investigation into the significantly enhanced activity of functionalized gold nanoparticles
(2008)
Wu, Chung-Shu
;
Wu, Chia-Tien
;
Yang, Yuh-Shyong
;
Ko, Fu-Hsiang
;
材料科學與工程學系
Kinetic and thermodynamic studies reveal that the property of significantly enhanced catalytic activity with colloidal stability is attributed to an efficacious means of tuning enzyme-substrate association by varying with the rate constants in the presence of functionalized gold nanoparticles.
Association of Interleukin-16 Polymorphisms with Graves' Disease in a Taiwanese Population
(2014-04-30)
Tsai, Kun-Hsi
;
Chang, Ching-Yao
;
Tsai, Fuu-Jen
;
Lin, Hui-Ju
;
Yang, Yuh-Shyong
Graves' disease (GD) is a complex, organ-specific autoimmune disease wherein the thyroid gland becomes enlarged and overactive. During GD progression, T cells secrete interleukin-16 (IL-16) to promote inflammation, act as chemoattractants that recruit more inflammatory cells, and activate target cells to enhance the development of GD. To investigate the role of IL-16 in GD, we genotyped 474 patients with GD at 8 single-nucleotide polymorphisms (SNPs) in the IL-16 gene. The IL-16 SNP rs8028364 was found to be associated with GD when compared with the control subjects (P = 2.93 x 10(-17); CG genotype: odds ratio [OR] = 0.2 [0.07, 0.59]; CC genotype: OR = 0.03 [0.01, 0.09]). The rs1131445 polymorphism was found to be associated with GD under the allelic model (P = 0.01; G allele: OR = 1.97 [1.17, 3.32]). Sliding-window haplotype analysis by the PLINK program showed that the most significant haplotype was provided by the 6-SNP haplotype window, consisting of rs7182786, rs8028364, rs12907134, rs4128767, rs4072111 and rs8031107 (P = 2.31 x 10(-51)). We found 2 protective haplotypes: GCAAGG (P = 8.69 x 10(-7); OR = 0.22 [0.12, 0.41]) and AGAAGG (P = 0.0012; OR = 0.26 [0.12, 0.6]). In addition, GGGGAA (P = 0.39; OR = 2.32 [1.08, 4.99]) and GGGAGA (P = 1.18 x 10(-5); OR = 5.54 [2.50, 12.31]) were found to be the two high-risk haplotypes. These results suggest that polymorphisms in IL-16 may be used as genetic markers for the diagnosis and prognosis of GD.
Biochemical sensing device
(2005-05-12)
Yang, Yuh-Shyong
;
Wu, Chung-Yu
;
Lu, Ude
;
Shih, Yu-Chuan
;
Hu, Ben C.-P.
The invention is a biochemical sensing device, including a photodiode capable of sensing the light generated by the reaction made by a specific compound, a specific enzyme, and a luminol as well as converting the optical signal into a current signal. Also, there is a current/voltage converting circuit capable of converting the current signal into an analog voltage signal. In turn, the analog voltage signal can be converted into a digital voltage signal through an analog/digital converter. Finally, by using an electronic device, the digital voltage signal can be received and analyzed, and through the analysis, the amount of the specific compound can be measured. The device of the invention can provide a simple real-time medical assay that can be performed in massive amount. For this reason, the drawbacks of a conventional spectrum analysis instrument of being bulky and expensive can be improved.
Catalytic Behaviors in Modulating Enzymatic Activity through Different-sized Gold Nanoparticles
(2010)
Wu, Chung-Shu
;
Wu, Chia-Tien
;
Chen, Chieh
;
Huang, Chung-Chih
;
Yeh, Yu-Lin
We have demonstrated that gold nanoparticles (AuNPs) can effectively associate with enzyme through spontaneous adsorption to afford supramolecular complexes, resulting in a significant increase of its enzymatic activity. In this work, we embarked on a study of the interactions between the different-sized AuNPs and the substrate through quantifying the kinetic parameters (K(cat) and K(m)). The diversity of size allows us to probe the role of catalytic behaviors in modulating enzymatic activity.
Crystal Structures of Vertebrate Dihydropyrimidinase and Complexes from Tetraodon nigroviridis with Lysine Carbamylation METAL AND STRUCTURAL REQUIREMENTS FOR POST-TRANSLATIONAL MODIFICATION AND FUNCTION
(2013-10-18)
Hsieh, Yin-Cheng
;
Chen, Mei-Chun
;
Hsu, Ching-Chen
;
Chan, Sunney I.
;
Yang, Yuh-Shyong
Lysine carbamylation, a post-translational modification, facilitates metal coordination for specific enzymatic activities. We have determined structures of the vertebrate dihydropyrimidinase from Tetraodon nigroviridis (TnDhp) in various states: the apoenzyme as well as two forms of the holoenzyme with one and two metals at the catalytic site. The essential active-site structural requirements have been identified for the possible existence of four metal-mediated stages of lysine carbamylation. Only one metal is sufficient for stabilizing lysine carbamylation; however, the post-translational lysine carbamylation facilitates additional metal coordination for the regulation of specific enzymatic activities through controlling the conformations of two dynamic loops, Ala(69)-Arg(74) and Met(158)-Met(165), located in the tunnel for the substrate entrance. The substrate/product tunnel is in the open form in the apo-TnDhp, in the intermediate state in the monometal TnDhp, and in the closed form in the dimetal TnDhp structure, respectively. Structural comparison also suggests that the C-terminal tail plays a role in the enzymatic function through interactions with the Ala(69)-Arg(74) dynamic loop. In addition, the structures of the dimetal TnDhp in complexes with hydantoin, N-carbamyl--alanine, and N-carbamyl--amino isobutyrate as well as apo-TnDhp in complex with a product analog, N-(2-acetamido)-iminodiacetic acid, have been determined. These structural results illustrate how a protein exploits unique lysines and the metal distribution to accomplish lysine carbamylation as well as subsequent enzymatic functions.
dbPTM: an information repository of protein post-translational modification
(2006-01-01)
Lee, Tzong-Yi
;
Huang, Hsien-Da
;
Hung, Jui-Hung
;
Huang, Hsi-Yuan
;
Yang, Yuh-Shyong
dbPTM is a database that compiles information on protein post-translational modifications (PTMs), such as the catalytic sites, solvent accessibility of amino acid residues, protein secondary and tertiary structures, protein domains and protein variations. The database includes all of the experimentally validated PTM sites from Swiss-Prot, PhosphoELM and O-GLYCBASE. Only a small fraction of SwissProt proteins are annotated with experimentally verified PTM. Although the Swiss-Prot provides rich information about the PTM, other structural properties and functional information of proteins are also essential for elucidating protein mechanisms. The dbPTM systematically identifies three major types of protein PTM (phosphorylation, glycosylation and sulfation) sites against Swiss-Prot proteins by refining our previously developed prediction tool, KinasePhos (http://kinasephos.mbc.nctu.edu.tw/). Solvent accessibility and secondary structure of residues are also computationally predicted and are mapped to the PTM sites. The resource is now freely available at http://dbPTM.mbc.nctu.edu.tw/.
DIELECTROPHORETIC CONCENTRATOR FOR ENHANCED PERFORMANCE OF POLY-SILICON NANOWIRE FIELD EFFECT TRANSISTOR FOR BIOSENSING APPLICATION
(2012)
Puttaswamy, Srinivasu Valagerahally
;
Su, Yi-, Jr.
;
Sivashankar, Shilpa
;
Yang, Shih-Mo
;
Yang, Yuh-Shyong
Biological and medical fields have authenticated stupendous advancement in the development of biosensors and biochips. The development of highly sensitive biological sensors is need of the hour. This research work utilizes the dielectrophoretic concentrator chip with titanium (Ti) electrodes to shape the electric field, to pre-concentrate deoxyribo nucleic acid (DNA) within microfluidic channel onto nanowire region of poly-silicon nanowire field effect transistor (poly-Si NWFET). Preconcentration of biomolecules at the constriction site was demonstrated by focusing the DNA with negative dielectrophoresis (nDEP) manipulation technique. After integrating the DEP device with poly-Si NWFET, the I-V-G curve was plotted to ensure n-type behavior.