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

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

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.

关键词： biosensor array sensor fabrication capacitive biosensors DNA detection

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Bioelectronic tongue for the simultaneous determination of urea, creatinine and alkaline ions in clinical samples

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biosensorS & BIOELECTRONICS 2008年第6期23卷 795-802页

作者： Gutierrez, Manuel Alegret, Salvador del Valle, Manel Univ Barcelona Dept Chem Sensors & Biosensors Grp Bellaterra 08193 Spain

Urea and creatinine biosensors based on urease and creatinine deiminase, respectively, covalently immobilized onto ammonium selective electrodes, were included in an array together with sensors sensitive to ammonium, potassium and sodium. Generic sensors to alkaline ions were also included. All the sensors used were of all-solid-state type, employing polymeric membranes and having rather nonspecific response characteristics. A response model based on artificial neural networks was built and tested for the simultaneous determination of urea, creatinine, ammonium, potassium and sodium. The results show that it is possible to obtain a good multivariate calibration model. In this way, the developed bioelectronic tongue was successfully applied to multidetermination of the five species in raw and spiked urine samples. Predicted concentrations showed a good agreement with reference methods of analysis, allowing a simple direct method for determining urea and creatinine in real samples. At the same time, this method permitted to obtain the concentrations of the alkaline interferences (endogenous ammonium, potassium and sodium) without the need of eliminating them. (C) 2007 Elsevier B.V. All rights reserved.

关键词： biosensor array potentiometric electronic tongue urea creatinine artificial neural networks

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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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State of the Art in the Field of Electronic and Bioelectronic Tongues - Towards the Analysis of Wines

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ELECTROANALYSIS 2009年第23期21卷 2509-2520页

作者： Zeravik, Jiri Hlavacek, Antonin Lacina, Karel Skladal, Petr Masaryk Univ Fac Sci Dept Biochem CS-61137 Brno Czech Republic

This review compares various types of (bio)electronic tongues. The design and principles of potentiometric and voltammetric electronic tongues are discussed together with applications in food and environmental analysis. Different approaches towards bioelectronic tongue are presented. Several methods for evaluation and interpretation of the measured data are described. Finally, the potential of such devices for analysis of wine is discussed.

关键词： Electronic tongue Bioelectronic tongue Sensor array biosensor array Electrochemical sensor Amperometry Voltammetry Potentiometry biosensors

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Submicron giant magnetoresistive sensors for biological applications

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SENSORS AND ACTUATORS A-PHYSICAL 2005年第1期120卷 1-6页

作者： Wood, DK Ni, KK Schmidt, DR Cleland, AN Univ Calif Santa Barbara Dept Phys Santa Barbara CA 93106 USA

We have fabricated submicron giant magnetoresistive (GMR) structures and evaluated their sensitivity for biomagnetic applications. GMR devices were fabricated using electron beam lithography, with minimum dimensions below 100 nm. We developed a new characterization technique for these sensors, using a scanned nanoscale magnetic probe and monitoring the resulting response of the sensors. The magnetic field from the scanned probe is similar to that generated by the magnetic particles used to tag bioanalytes. The devices demonstrated extremely high magnetic field resolution. Noise measurements, combined with a local field sensitivity from the scanned probe measurements, predict a sensitivity of 2 x 10(-16) emu/Hz(1/2) for a magnetic particle 100 nm above the sensor surface. This corresponds to detection of single 100 rim commercially available magnetic labels, which are the lowest size scale of labels now used in biological studies, with a signal-to-noise of unity. Additionally, we predict detection of single 200 nm magnetic labels with a position sensitivity of 93 nm/Hz(1/2) allowing proximity detection for particles not directly bound to the sensor surface, with a corresponding signal-to-noise of 10. (c) 2004 Elsevier B.V. All rights reserved.

关键词： giant magnetoresistance nanoscale sensor electron beam lithography biomagnetic label biosensor array magnetic field sensor

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A steady-state and flow-through cell for screen-printed eight-electrode arrays

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ANALYTICA CHIMICA ACTA 2005年第2期531卷 165-172页

作者： Dock, E Christenson, A Sapelnikova, S Krejci, J Emnéus, J Ruzgas, T Lund Univ Dept Analyt Chem SE-22100 Lund Sweden BVT Technol AS CZ-61700 Brno Czech Republic

An electrochemical cell has been developed enabling amperometric steady-state- and flow-injection measurements with screen-printed arrays consisting of eight working electrodes (circle divide = 1 mm) arranged radially around a printed Ag/AgCl reference electrode in the centre. The cell contained a rotator, providing similar hydrodynamics over all the working electrodes in the array, which was manually centered under the rotator. The reproducibility of steady-state measurements with eight-electrode platinum or gold arrays in this cell was studied by measuring and comparing currents from ferricyanide reduction at each electrode in the array. It was found that the relative standard deviation (R.S.D.) for the currents at different electrodes on one array was below 5%. Similar R.S.D. was found if measurements were compared between several arrays. This indicates that manual insertion/positioning of the eight-electrode array in the cell and hydrodynamics at the electrodes provided measurement reproducibility similar to the reproducibility of manufacturing eight-electrode platinum or gold arrays by screen-printing. A comparative study was performed between screen-printed and through mask sprayed carbon arrays. It was found that the reproducibility of the sprayed arrays was similar to that of the platinum or gold screen-printed arrays, with R.S.D. values below 6% regarding the variation between electrodes within the same array and the variation between different arrays. To enable flow-injection measurements, a tube (0.4 mm inner diameter) was inserted into a hole drilled through the centre of the steady-state cell rotator. This construction made it possible to inject the solution into the cell through the tube (not rotating), while the rotator was spinning over the eight-electrode array. It was found that this combination of flow-injection and mixing by a rotator provided a uniform current response over the array electrodes and that, at optimum conditions, the R.S.D. values

关键词： electrode array steady-state measurements screen-printed electrode flow-through cell biosensor array

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Prediction of wastewater quality using amperometric bioelectronic tongues

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biosensorS & BIOELECTRONICS 2016年 75卷 375-382页

作者： Czolkos, Ilja Dock, Eva Tonning, Erik Christensen, Jakob Winther-Nielsen, Margrethe Carlsson, Charlotte Mojzikova, Renata Skladal, Petr Wollenberger, Ulla Norgaard, Lars Ruzgas, Tautgirdas Emneus, Jenny Tech Univ Denmark DTU Nanotech Dept Micro & Nanotechnol DK-2800 Lyngby Denmark AkzoNobel Ind Coatings AB S-20517 Malmo Sweden Fiberline Composites AS DK-5500 Middelfart Denmark Umetrics AB S-21134 Malmo Sweden DHI Water & Environm Dept Environm Risk Assessment DK-2970 Horsholm Denmark AnoxKaldnes AB S-22647 Lund Sweden Palacky Univ Olumouc Fac Dent & Med Dept Biol Olomouc 77515 Czech Republic Masaryk Univ Inst Biochem CS-61137 Brno Czech Republic Univ Potsdam Inst Biochem & Biol Analyt Biochem D-14476 Golm Germany Univ Copenhagen Dept Food Sci Fac Sci DK-1958 Frederiksberg Denmark Malmo Univ Fac Hlth & Soc Dept Biomed Sci S-20506 Malmo Sweden

Wastewater samples from a Swedish chemi-thermo-mechanical pulp (CTMP) mill collected at different purification stages in a wastewater treatment plant (WWTP) were analyzed with an amperometric enzyme-based biosensor array in a flow-injection system. In order to resolve the complex composition of the wastewater, the array consists of several sensing elements which yield a multidimensional response. We used principal component analysis (PCA) to decompose the array's responses, and found that wastewater with different degrees of pollution can be differentiated. With the help of partial least squares regression (PLS-R), we could link the sensor responses to the Microtox (R) toxicity parameter, as well as to global organic pollution parameters (COD, BOD, and TOC). From investigating the influences of individual sensors in the array, it was found that the best models were in most cases obtained when all sensors in the array were included in the PLS-R model. We find that fast simultaneous determination of several global environmental parameters characterizing wastewaters is possible with this kind of biosensor array, in particular because of the link between the sensor responses and the biological effect onto the ecosystem into which the wastewater would be released. In conjunction with multivariate data analysis tools, there is strong potential to reduce the total time until a result is yielded from days to a few minutes. (C) 2015 Elsevier B.V. All rights reserved.

关键词： biosensor array Electronic tongue Amperometric sensor Screen-printed electrode Multivariate data analysis Chemometrics Wastewater Toxicity Phenolic compounds

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Potentiometric bioelectronic tongue for the analysis of urea and alkaline ions in clinical samples

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biosensorS & BIOELECTRONICS 2007年第9-10期22卷 2171-2178页

作者： Gutierrez, Manuel Alegret, Salvador del Valle, Martel Univ Autonoma Barcelona Dept Chem Sensors & Biosensors Grp E-08193 Barcelona Spain

Urea biosensors based on urease covalently immobilized on to ammonium and hydrogen ion-selective electrodes were included in arrays together with ammonium, potassium, sodium, hydrogen and generic response to alkaline sensors. Response models based on artificial neural network (ANN) and partial least squares (PLS1) were built, tested and compared for the simultaneous determination of urea, ammonium, potassium and sodium. The results show that it is possible to obtain good ANN and PLS calibration models for simultaneous determination of these four species, but with better prediction capability when the ANN are used. The developed bioelectronic tongue was applied to multidetermination in urine samples. The ANN model showed again better agreement with reference methods, allowing a simple direct determination of urea in the real samples without the necessity of eliminating the alkaline interferences, or compensating endogenous ammonium. (c) 2006 Elsevier B.V. All rights reserved.

关键词： biosensor array electronic tongue urea artificial neural networks partial least squares

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Ultrasensitive optical biosensing detection and multiple therapy based on an NIR-II thermoelectric nanoheterojunction

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CHEMICAL ENGINEERING JOURNAL 2024年 499卷

作者： Shang, Hongyuan Ding, Meili Zhang, Xiaofei Zhang, Aiping Du, Jinwen Zhang, Ruiping Shanxi Med Univ Shanxi Bethune Hosp Dept Radiol Hosp 3 Taiyuan 030032 Peoples R China Shanxi Med Univ Shanxi Engn Res Ctr Characterist Drug Dev Sch Pharm Shanxi Prov Key Lab Drug Synth & Novel Pharmaceut Taiyuan 030001 Peoples R China Taiyuan Municipal 2 Peoples Hosp Stomatol Dept Taiyuan 030002 Peoples R China Shanxi Med Univ Shanxi Prov Peoples Hosp Hosp 5 Radiol Dept Taiyuan 030001 Peoples R China

An one-to-all optical diagnostic and therapeutic agent, referring to a single nanocatalyst synchronously displaying multiple optical biosensor and therapeutic modes, is still a remarkable promise because of its outstanding capability in tumor. However, nanocatalyst activity is significantly weakened by the limited light absorption property and catalytic efficiency. Here, a unique pyroelectric nanocatalyst, In2S3-CuInS2@red blood cell membrane (In2S3-CIS@RM), with excellent pyroelectric/photothermal conversion capability for boosted peroxidasemimicking catalytic activity, is rationally developed. The In2S3-CIS@RM displays catalytic capacity by reacting Cu+ with H2O2 to produce highly toxic & sdot;OH, promoted by 808 nm near-infrared (NIR) light-mediated photothermal/pyroelectric therapy. By synergizing this three-modal effect, cancer suppression is realized with an obvious cancer inhibition rate after the introduction of In2S3-CIS@RM into the HepG2 cells and following 808 nm laser irradiation. Meanwhile, an optical biosensor array is constructed through In2S3-CIS@RM-triggered chromogenic reaction for a fast and accurate analysis of five antioxidants. Interestingly, this biosensor array is verified to be effective for accurate monitoring of invasive cancer in early cancer occurrence, benefiting from the superior catalytic activity of In2S3-CIS@RM and abnormal levels of antioxidants in cancer cells. Thus, this study provides an avenue for developing an NIR laser-activatable one-to-all optical diagnostic and therapeutic nanosystem.

关键词： Multifunctional thermoelectric nanosystem Tumor therapy biosensor array Photothermal effect Peroxidase-mimicking activity

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An electrochemiluminescent imaging strategy based on CRISPR/Cas12a for ultrasensitive detection of nucleic acid

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ANALYTICA CHIMICA ACTA 2024年 1324卷 343040页

作者： Luo, Sijian Wu, Jie Zhong, Min Sun, Jun Ao, Hang Cao, Xu Liu, Jinbo Ju, Huangxian Southwest Med Univ Sichuan Prov Engn Technol Res Ctr Mol Diag Clin Di Dept Lab Med Mol Diag Clin Dis Key Lab LuzhouAffiliated Hosp Luzhou 646000 Sichuan Peoples R China Nanjing Univ Sch Chem & Chem Engn State Key Lab Analyt Chem Life Sci Nanjing 210023 Peoples R China

Background: Persistent infection with human papillomavirus (HPV) significantly contributes to the development of cervical cancer. Thus, it is urgent to develop rapid and accurate methods for HPV detection. Herein, we present an ultrasensitive CRISPR/Cas12a-based electrochemiluminescent (ECL) imaging technique for the detection of HPV-18 DNA. Result: The ECL DNA sensor array is constructed by applying black hole quencher (BHQ) and polymer dots (Pdots) co-labeled hairpin DNA (hpDNA) onto a gold-coated indium tin oxide slide (Au-ITO). The ECL imaging method involves an incubation process of target HPV-18 with a mixture of crRNA and Cas12a to activate Cas12a, followed by an incubation of the active Cas12a with the ECL sensor. This interaction causes the indiscriminate cleavage of BHQ from Pdots by digesting hpDNA on the sensor surface, leading to the restoration of the ECL signal of Pdots. The ECL brightness readout demonstrates superior performance of the ECL imaging technique, with a linear detection range of 10 fM-500 pM and a limit-of-detection (LOD) of 5.3 fM. Significance: The Cas12a-based ECL imaging approach offers high sensitivity and a broad detection range, making it highly promising for nucleic acid detection applications.

关键词： Electrochemiluminescent imaging biosensor array CRISPR/Cas12a Polymer dots HPV-18

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