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Amperometric Electrochemical Microsystem for a Miniaturized Protein biosensor array

IEEE TRANSACTIONS ON BIOMEDICAL CIRCUITS AND SYSTEMS 2009年第3期3卷 160-168页

作者： Yang, Chao Huang, Yue Hassler, Brian L. Worden, R. Mark Mason, Andrew J. Marvell Semicond Inc Santa Clara CA 95054 USA Michigan State Univ E Lansing MI 48824 USA

Protein-based bioelectrochemical interfaces offer great potential for rapid detection, continuous use, and miniaturized sensor arrays. This paper introduces a microsystem platform that enables multiple bioelectrochemical interfaces to be interrogated simultaneously by an onchip amperometric readout system. A post-complementary metal-oxide semiconductor (CMOS) fabrication procedure is described that permits the formation of planar electrode arrays and self assembly of biosensor interfaces on the electrodes. The onchip, 0.5-mu m CMOS readout electronics include a compact potentiostat that supports a very broad range of input currents-6 pA to 10 mu A-to accommodate diverse biosensor interfaces. The 2.3 x 2.2-mm chip operates from a 5-V supply at 0.6 mA. A prototype electrochemical sensor platform, including an onchip potentiostat and miniaturized biosensor array, was characterized by using cyclic voltammetry. The linear relationship between the oxidization peak values and the concentrations of target analytes in the solution verifies functionality of the system and demonstrates the potential for future implementations of this platform in high sensitivity, low cost, and onchip protein-based sensor arrays.

关键词： Amperometric readout bioelectronic sensor biosensor array complementary metal-oxide semiconductor (CMOS) potentiostat electrochemical sensor

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Bioelectronic tongue and multivariate analysis: A next step in BOD measurements

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WATER RESEARCH 2013年第7期47卷 2555-2562页

作者： Raud, Merlin Kikas, Timo Univ Tartu Inst Chem EE-50411 Tartu Estonia Estonian Univ Life Sci Inst Technol Tartu Estonia

Seven biosensors based on different semi-specific and universal microorganisms were constructed for biochemical oxygen demand (BOD) measurements in various synthetic industrial wastewaters. All biosensors were calibrated using OECD synthetic wastewater and the resulting calibration curves were used in the calculations of the sensor-BOD values for all biosensors. In addition, the output signals of all biosensors were analyzed as a bioelectronic tongue and comprehensive multivariate data analysis was applied to extract qualitative and quantitative information from the samples. In the case of individual biosensor measurements, most accurate result was gained when semi-specific biosensor was applied to analyze sample specific to that biosensor. Universal biosensors or biosensors semi-specific to other samples underestimated the BOD7 of the sample 10-25%. PLS regression method was used for the multivariate calibration of the biosensor array. The calculated sensor-BOD values differed from BOD7 less than 5.6% in all types of samples. By applying PCA and using three first principal components, giving 99.66% of variation, it was possible to differentiate samples by their compositions. (C) 2013 Elsevier Ltd. All rights reserved.

关键词： biosensor array Bioelectronic tongue Semi-specific Biochemical oxygen demand (BOD) Industrial wastewater

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Multichannel Boron Doped Nanocrystalline Diamond Ultramicroelectrode arrays: Design, Fabrication and Characterization

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SENSORS 2012年第6期12卷 7669-7681页

作者： Kiran, Raphael Rousseau, Lionel Lissorgues, Gaelle Scorsone, Emmanuel Bongrain, Alexandre Yvert, Blaise Picaud, Serge Mailley, Pascal Bergonzo, Philippe CEA LIST Diamond Sensors Lab F-91191 Gif Sur Yvette France Univ Paris Est ESYCOM EA2552 ESIEE Cite Descartes F-93162 Noisy Le Grand France Univ Bordeaux UMR 5287 INCIA F-33000 Bordeaux France INSERM U968 Inst Vis F-75012 Paris France Univ Paris 06 UMR S968 UPMC Inst Vis F-75012 Paris France CEA LITEN DTS Lab Stockage Elect F-73377 Le Bourget Du Lac France

We report on the fabrication and characterization of an 8 x 8 multichannel Boron Doped Diamond (BDD) ultramicro-electrode array (UMEA). The device combines both the assets of microelectrodes, resulting from conditions in mass transport from the bulk solution toward the electrode, and of BDD's remarkable intrinsic electrochemical properties. The UMEAs were fabricated using an original approach relying on the selective growth of diamond over pre-processed 4 inches silicon substrates. The prepared UMEAs were characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The results demonstrated that the electrodes have exhibited a very fast electrode transfer rate (k(0)) up to 0.05 cm.s(-1) (in a fast redox couple) and on average, a steady state limiting current (in a 0.5 M potassium chloride aqueous solution containing 1 mM Fe(CN)(6)(4-) ion at 100 mV.s(-1)) of 1.8 nA. The UMEAs are targeted for electrophysiological as well as analytical applications.

关键词： ultramicroelectrode boron doped diamond electrochemical impedance spectroscopy biosensor array statistical study of microelectrode arrays

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A spectral imaging array biosensor and its application in detection of leukemia cell

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SENSORS AND ACTUATORS B-CHEMICAL 2011年第2期156卷 760-764页

作者： Fang, Xiangyi Liu, Chunlong Cheng, Xiaoli Wang, Yaoling Yang, Yucong Xi An Jiao Tong Univ MOE Key Lab Nonequilibrium Synth & Modulat Conden Sch Sci Xian 710049 Peoples R China Xi An Jiao Tong Univ Coll Med Affiliated Hosp 1 Haematol Lab Xian 710049 Peoples R China Second Hosp Xian City Xian Peoples R China

A new type of array immunosensor was developed by combining surface plasmon resonance (SPR) and spectral imaging techniques. The system consisted of a monochromator as the wavelength scanning light source, a polarizer, Kretschmann-Raaether attenuated total reflection (ATR) configuration including array sensor chip, and a CCD camera. The images of transmitting light from ATR were recorded versus the wavelength. By averaging gray scales of the pixels in the area of every gold spot from the image series, the complete spectral resonance curve of all sensing spots on the array can be extracted in parallel. The performance of the developed system was evaluated by analyzing interactions of the anti-CD33 monoclonal antibody to its target leukemic cells using 11 cases of human bone marrow specimens. The specimens were also analyzed with flow cytometry method (FCM) for comparison. The initial results measured by the immunosensor array were corresponded with that of FCM, indicating that the developed parallel method might be clinically suitable for immunophenotyping of acute leukemias. The new sensor array system showed the merits of high-throughput, high sensitivity, high specificity, label free and operation convenient. Spots numbers of the array could be increased if suitable technology were adopted for manipulating the micro bio-liquids on the sensor array chip. (C) 2011 Elsevier B.V. All rights reserved.

关键词： Surface plasmon resonance SPR imaging biosensor array High-throughput analysis

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Self-Aligned Process for the Development of Surface Stress Capacitive biosensor arrays

Self-Aligned Process for the Development of Surface Stress C...

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25th Eurosensors Conference

作者： Tsouti, Vasiliki Filippidou, Myrto Boutopoulos, Christos Broutas, Panagiotis Zergioti, Ioanna Chatzandroulis, Stavros NCSR Demokritos Inst Microelect Aghia Paraskevi 15310 Greece Natl Tech Univ Athens Dept Appl Sci Zografos 15780 Greece

The fabrication process of a surface stress based capacitive biosensor array is presented. Flexible membranes and a fixed electrode on the substrate constitute the capacitive biosensors. Probe molecules are immobilized on the membrane surface and the surface stress variations during biological interactions force the membrane to deflect and effectively change the capacitance between the flexible membrane and the fixed substrate. The array consists of 60 sensors and thus is suitable for parallel sensing. Through the presented fabrication process, which is described in detail, sensitive membranes can be created. The process simplicity and the increased sensitivity of the biosensors are related to the use of boron implantation and the consequent self-aligned creation of the conductive membranes after the silicon fusion bonding technique. (C) 2011 Published by Elsevier Ltd.

关键词： biosensor array sensor fabrication capacitive biosensors DNA detection

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Fiber optic enzymatic biosensors and biosensor arrays for measurement of chlorinated ethenes

Fiber optic enzymatic biosensors and biosensor arrays for me...

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作者： Zhong, Zhong Colorado State University

学位级别：Ph.D.

Chlorinated ethenes such as trichloroethylene (TCE), tetrachloroethylene (PCE), three isomers of dichloroethylene (DCEs) and vinyl chloride (VC) are used as solvents and cleaners in a variety of industrial and commercial areas. Chlorinated ethenes have become one of the most common environmental pollutants in groundwater contamination sites due to their widespread usage, moderate solubility compared with other organic pollutants and recalcitrance to natural attenuation. Fiber optic enzymatic biosensor was developed in this study as a continuous, real time and in situ measurement principle. TOM biosensor, first reported enzymatic biosensor, was initiated with toluene measurement in aqueous solution as proof-of-concept experiments. The subsequent success of TOM and TOM-Green in TCE analysis showed great potential of biosensor measurement for chlorinated ethenes, despite the ubiquitous problem for monooxygenase-based biosensor with NADH consumption overtime and after usage. In addition, epoxide toxicity also increased the difficulty of biosensor application for measurement of chlorinated ethenes, although several TOM-Green transformants could mitigate the toxicity with rapid epxoide degradation. Plasmid transformation with was introduced to manipulate the construction of new TOM and TOM-Green transformants with capability of intracellular NADH regeneration. FDH regeneration system was studied for both TOM and TOM-Green cells, while TOM+FDH showed great activity retention and regeneration ability and TOM-Green+FDH was able to retain activity over prolonged storage but failed on regeneration after repeated usage due to the toxicity of TCE epoxide. biosensor array was built with pH-based biosensor to measure a group of haloalkanes. The design concept of biosensor array and detection instrumentation was successful. Linear approach in array data analysis was simple and fast but lacked of accuracy, while nonlinear approach increased the complexity of data analysis to a new l

关键词： biosensor array enzyme biosensor optode toluene o-monooxygenase

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Micro-and Nano-systems for Chemical/Bio-medical Analysis and Diagnostics

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Procedia Engineering 2012年 47卷 1502-1505页

作者： Piotr Grabiec Instytut Technologii Elektronowej (ITE) al.Lotnikow 32/46 02-668 Warsaw Poland

This paper reports selected results of the MNS-DIAG research project. The project is aimed at facilitating access of research teams coming from academia to fully equipped CMOS/MEMS R&D and manufacturing line and thus allowing for inflow of innovative microdevice concepts and development of demonstrators. To address the important grand societal challenges related to well-being and health in the ageing society, the project has been focused on application of micro- and nano-systems for chemical/bio-medical analysis and diagnostics. Out of five demonstrators elaborated within the MNS-DIAG, three are shortly described here, namely, Lab-on-a-chip for oocytes characterization, Micromechanical biosensors array and Integrated MEMS detector for dynamic humidity measurement in medical applications.

关键词： Microsystems Lab-on-a-chip biosensor array Humidity sensor

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Self-Aligned Process for the Development of Surface Stress Capacitive biosensor arrays

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Procedia Engineering 2011年 25卷 835-838页

作者： Vasiliki Tsouti Myrto Filippidou Christos Boutopoulos Panagiotis Broutas Ioanna Zergioti Stavros Chatzandroulis Institute of Microelectronics NCSR “Demokritos” Terma Patriarchou Grigoriou Agia Paraskevi 15310 Greece Department of Applied Sciences National Technical University of Athens Zografou 15780 Greece

关键词： biosensor array sensor fabrication capacitive biosensors DNA detection

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Electrochemical biosensor array for liver diagnosis using silanization technique on nanoporous silicon electrode

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JOURNAL OF BIOSCIENCE AND BIOENGINEERING 2007年第1期103卷 32-37页

作者： Song, Min-Jung Yun, Dong-Hwa Min, Nam-Ki Hong, Suk-In Korea Univ Dept Chem & Biol Engn Seoul 136701 South Korea Korea Univ Dept Control & Instrumentat Engn Yeongi 339700 Choongnam South Korea

An electrochemical biosensor array system was fabricated for the diagnosis and monitoring of liver diseases. Analysis on this array system with multiple samples was performed for point-of-care testing or home-use applications. Cholesterol, bilirubin and aminotransferases present in the serum are well-known biomarkers for liver diseases. For this study, we describe our biosensor array system consisting of cholesterol, bilirubin and glutamate sensors. To immobilize sensing enzymes on the array system, we employed a silanization technique. We observed that porous silicon layers formed on each working electrode notably increase the effective surface area. Sensing electrodes were placed in sampling wells to minimize the cross-interference effect so that multiple sampling would be possible with a low noise current. Compared with traditional analyte measurement procedures, our novel analytical device demonstrated acceptable sensitivities for the analyses of multiple samples and analytes without a marked cross-interference effect. The device sensitivities observed were 0.2656 mu A/mM for cholesterol, 0.15354 mA/mM for bilirubin, 0.13698 mu A/(U/l) for alanine aminotransferase (ALT) and 0.45439 mu A/(U/l) for aspartate aminotransferase (AST).

关键词： cholesterol sensor bilirubin sensor glutamate sensor alanine aminotransferase (ALT)/aspartate aminotransferase (AST) activities biosensor array porous silicon electrochemical biosensor

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Application of peptide nucleic acid towards development of nanobiosensor arrays

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BIOELECTROCHEMISTRY 2010年第2期79卷 153-161页

作者： Singh, Ravindra P. Oh, Byung-Keun Choi, Jeong-Woo Sogang Univ Interdisciplinary Program Integrated Biotechnol Seoul 121742 South Korea Sogang Univ Dept Chem & Biomol Engn Seoul 121742 South Korea

Peptide nucleic acid (PNA) is the modified DNA or DNA analogue with a neutral peptide backbone instead of a negatively charged sugar phosphate. PNA exhibits chemical stability, resistant to enzymatic degradation inside living cell, recognizing specific sequences of nucleic acid, formation of stable hybrid complexes like PNA/DNA/PNA triplex, strand invasion, extraordinary thermal stability and ionic strength, and unique hybridization relative to nucleic acids. These unique physicobiochemical properties of PNA enable a new mode of detection, which is a faster and more reliable analytical process and finds applications in the molecular diagnostics and pharmaceutical fields. Besides, a variety of unique characteristic features, PNAs replace DNA as a probe for biomolecular tool in the molecular genetic diagnostics, cytogenetics, and various pharmaceutical potentials as well as for the development of sensors/arrays/chips and many more investigation purposes. This review paper discusses the various current aspects related with PNAs, making a new hot device in the commercial applications like nanobiosensor arrays. (C) 2010 Elsevier B.V. All rights reserved.

关键词： PNA DNA biosensor array Microarrays Biochips

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