臺灣博碩士論文加值系統

由於老齡化社會趨勢的增加，於自我照護的階段需要有一個工具，可以快速、方便、準確地檢測出疾病的症狀。而生物傳感器即可做為低成本、高效率的檢測裝置應用在我們的日常生活中。本研究將進一步的利用材料科學，化學科學和電子科學，對於阻抗式及壓電式感測技術進行研究及討論。論文中針對不同換能器的研究，以辨識層，換能器和感測電路三個部分來共同建構生物感測系統。其中根據不同的檢測標的，利用一般表面化學處理程序，將專一性的辨識層有效建構在感測器表面。並因為感測器與辨識層的結合，已成功得到阻抗式感測器對於去氧核糖核酸，蛋白質和動物細胞進行感測及應用。其各感測標的物是透過辨識層的專一性捕捉，及換能器的電子信號轉換而完成特定的感測分析。而另一個部分是利用鋯鈦酸鉛壓電元件，做為新型微重量感測器的研究，主要藉由共振頻率的變化來對於生物分子的重量、大小進行感測。這兩種(阻抗式和壓電式)傳感器的研究在本論文中，皆展現出以微製程技術製備感測晶片，以及訊號讀取電路的系統整合。隨後，本論文也對於感測器實際應用上的考量要素，以不同實驗案例，對於阻抗式及壓電式生物感測器在生物醫學及商品化進行評估及討論。

As the potential threat of an aging society increases, there is great need for a tool that can quickly, conveniently, and accurately detect the symptom of any disease at the self-care stage. Biosensors can essentially serve as a low-cost and highly efficient device for this purpose in addition to other day-to-day applications. This study discusses advances in impedimetric and piezoelectric sensor technology, which draw on the disciplines of materials, chemistry, and electronics. This study shows that a biosensor with a difference transducer consists of three components, a reorganization layer, a transducer, and an output circuit system. According to different detection targets, the reorganization layer of this study follows common immobilization procedures for efficacious attachment on the transducer surface. Based on different immobilization procedures, this study successfully uses the impedance sensor applied in DNA, protein, and animal cells. Then, a “specific reorganization layer” recognizes a specific analyte to show that the electrical signal utilizes a converted impedance sensor. The other part of the study develops a lead zironate titanate (PZT) chip as a novel sensitive gravimetric biosensor by reducing size and using the resonance feature in biomolecule detection. Two types of transducers in this article, impedimetric and piezoelectric, provide the microfabrication technique of sensing chip and readout circuit formation. Subsequently this article discusses a few practical factors in several experiments as different case studies affecting biomedical application and commercialization of impedimetric and piezoelectric biosensors.

Content
中文摘要………………………………………………………………II
Abstract………………………………………………………………III
Content ………………………………………………………………Ⅴ
List of Tables……………………………………………………VIII
List of Figures………………………………………………………IX
Chapter 1 Overview of Biosensor…………………………………1
1.1 Introduction………………………………………………1
1.2 The performance factors of biosensor………………6
1.3 The consideration of biosensor development………7
1.4 Current status of biosensor…………………………9
1.5 Summary……………………………………………………12
Chapter 2
A new PZT piezoelectric sensor for gravimetric applications using the resonance-frequency detection……………………………………………………………14
2.1 Abstract……………………………………………………14
2.2 Introduction………………………………………………15
2.3 Research Methodology………………………………………18
2.3.1 Preparation of Piezoelectric Chip…………………18
2.3.2 Characterization of Piezoelectric Layers…………20
2.3.3 Detection System Fabrication…………………………21
2.4 Results and discussion…………………………………22
2.4.1 Properties of PZT Thin Film …………………………22
2.4.2 Leakage Current Analysis………………………………25
2.4.3 Ferroelectric Hysteresis Properties………………25
2.4.4 Detection System Characterization…………………26
2.5 Summary……………………………………………………31
Chapter 3
Development of a capacitance measurement system for human serum albumin detection……………………………………………33
3.1 Abstract……………………………………………………33
3.2 Introduction………………………………………………34
3.3 The capacitance measurement system fabrication ……………………………………………………35
3.3.1 Micro fabrication of interdigitated chip…………35
3.3.2 SAMs formation and chip preparation………………36
3.3.3 Impedance measurements and Capacitive HSA detection system measurements……………………………………37
3.4 Results and discussion…………………………………38
3.5 Summary……………………………………………………44
Chapter 4
Impedance-based analysis of mouse L929 cells growth was using a novel portable detection system………………………46
4.1 Abstract……………………………………………………46
4.2 Introduction………………………………………………47
4.3 Research Methodology……………………………………49
4.3.1 Chemicals and Materials………………………………49
4.3.2 Cell culture………………………………………………50
4.3.3 Interdigitating microelectrodes fabrication……50
4.3.4 Cells impedace measurement……………………………51
4.3.5 Protable impedance measurement system……………52
4.4 Results and discussion…………………………………53
4.4.1 Physical properties of the biosensor………………53
4.4.2 Equivalent circuit analysis…………………………55
4.4.3 Impedance measurement…………………………………59
4.5 Summary……………………………………………………63
Chapter 5
A capacitance sensor system for oligonucleotide hybridization detection……………………………………………64
5.1 Abstract……………………………………………………64
5.2 Introduction………………………………………………65
5.3 Research Methodology……………………………………67
5.3.1 Preparation of interdigitated chip…………………67
5.3.2 Surface modification……………………………………68
5.3.3 Detection system fabrication…………………………70
5.4 Results and Discussion…………………………………71
5.4.1 Physical properties of the chip……………………71
5.4.2 Surface modification for oligonucleotide detecting ………………………………………………………………72
5.4.3 Automatic capacitance detection system……………75
5.5 Summary……………………………………………………78
Chapter 6 Conclusion and future work…………………………79
6.1 Conclusio…………………………………………………………79
6.2 Future work………………………………………………………82
Reference 84
List of Tables
Table.1-1 Possible bioreceptor molecules and their requirements for structural integrity and signals generated.………………………………………………………………3
Table.2-1 Comparison of sensitivity characteristics of gravimetric sensors…………………………………………………32
Table.3-1 Comparison of detection characteristics of different assay method……………………………………………45
Table.4-1 Result of fitting parameter values in the equivalent circuit for different culture times with an initial cell density of 5 × 104 cells/ml (N≧3)……………57

List of Figures
Fig.1- 1 Biosensor configuration………………………………1
Fig.1- 2 Various biosensor configurations.…………………8
Fig.2- 1 The structure of the PZT piezoelectric sensor (a) the top view of the PZT resonator (b) the cross section of the metal/ferroelectric/metal (MFM) arrangement ………………………………………………………………20
Fig.2- 2 The detection system of experimentation…………22
Fig.2- 3 SEM images of (a) grainy morphology (b) the cross-section of the PZT layer…………………………………24
Fig.2- 4 XRD pattern of PZT (52/48) films are shown……24
Fig.2- 5 Polarization electric (P-E) field hysteresis loop of the PZT chip.………………………………………………26
Fig.2- 6 The PZT resonator frequency characteristic.……29
Fig.2- 7 Schematic diagram of the resonance-frequency detection circuit.…………………………………………………29
Fig.2- 8 Characteristic of the resonance frequency variation from the detection system (a) the hardware of the measurement system (b) the signal was connected to the monitor.………………………………………………………………30
Fig.2- 9 Frequency shift versus of BSA load for piezoelectric sensor…………………………………………………………………31
Fig.3- 1 Schematic procedure of the SAMs for HSA immobilization.………………………………………………………36
Fig.3- 2 A block diagram of the capacitance detection system.…………………………………………………………………38
Fig.3- 3 The Bode plot before and after HSA immobilization.………………………………………………………41
Fig.3- 4 Equivalent circuit model for HSA detection on the chip surface.……………………………………………………41
Fig.3- 5 The capacitance detection system and hardware. ………………………………………………………………42
Fig.3- 6 Impedance changes in HSA detection for different concentrations and times.…………………………………………42
Fig.3- 7 The linear correlation between impedance changes and HSA detection at 5 min with the capacitance detection system.…………………………………………………………………43
Fig.4- 1 Fabrication process of the interdigitating microelectrodes………………………………………………………51
Fig.4- 2 Block diagram of impedance detection system……53
Fig.4- 3 Analysis of the physical properties of the interdigitating electrodes (a) Optical microscopy image of interdigitating chip surface. (b) Capacitance of interdigitating electrodes in air at 500 Hz to 1 MHz.……55
Fig.4- 4 Equivalent circuit model for cell adhesion on the electrode surface.……………………………………………56
Fig.4- 5 Optical microscopy graph of L929 cell growth on the electrode surface at different culture times (initial density: 5 × 104 cells/ml).………………………………………59
Fig.4- 6 Impedance measurement by the detection system (a) The hardware of the measurement system and (b) impedance signal displayed on the monitor.………………60
Fig.4- 7 Change in impedance recorded by the different devices at different cell culture times up to 48 h.………62
Fig.5- 1 A cross- sectional diagram of the interdigitated sensing chip.…………………………………………………………68
Fig.5- 2 Bomolecular structure of hybridized DNA on the silicon chip…………………………………………………………70
Fig.5- 3 A block diagram of the capacitance detection system.…………………………………………………………………71
Fig.5- 4 An interdigitated sensing unit of the array chip. The inset is a sensor array bonded on a PCB board. ………………………………………………………………72
Fig.5- 5 AFM images of the interelectrode area. (a) is the hybridization surface, and (b) is the nonhybridization surface.…………………………………………74
Fig.5- 6 Capacitance measurement using the detection system: (a) hardware of the measurement system, and (b) capacitance signal displayed on the monitor.………………76
Fig.5- 7 Measured capacitances of the interdigitated electrode array for DNA (a) hybridization and (b) nonhybridization monitoring.……………………………………77

Reference
[1]Turner, A.P., “Biosensors sense and sensitivity”, Science 290, pp. 1315–1317, 2000.
[2]Cavalcanti, A., Shirinzadeh, B., Zhang, M., Kretly, L.C., “Nanorobot Hardware Architecture for Medical Defense”, Sensors 8 (5), pp. 2932–2958, 2008.
[3]Bernstein, J., “Uber den zeitlichen verlanf der negativen schwankung des nervenstroms“, The Journal of the Center for Archaeoastronomy 1, pp. 173-207, 1868.
[4]Ehret, R., Baumann, W., Brischwein, M., Schwinde, A., Stegbauer, K., Wolf, B., “On-line control of cellular adhesion with impedance measurements using interdigitated electrode structures”, Medical and Biological Engineering and Computing, 36, pp. 365-370, 1998.
[5]Giaever, I., Keese, C.R. “Use of Electric Fields to Monitor the Dynamical Aspect of Cell Behavior in Tissue Culture”, IEEE Transactions on. Biomedical Engineering, 33, pp. 242-247, 1986.
[6]Cortina, M., Esplandiu, M.J., Alegret, S., Valle M.del, “Urea impedimetric biosensor based on polymer degradation onto interdigitated electrodes”, Sensors and Actuators B. 118, pp. 84-89, 2006.
[7]Clark, L., Lyons, C., “Electrode system for continuous monitoring in cardiovascular surgery”, Annals of the New York Academy of Sciences, 148, pp. 133-153, 1962.
[8]David, F., “Amperometric Oxygen Electrodes”, Current Separations 16(1), pp. 19-22, 1997.
[9]Newman, J.D. and Turner, A. P. F., “Home blood glucose biosensors: a commercial perspective”, Biosensor and Bioelectron., 20, pp.2435-2453, 2005.
[10]Razumiene, J., Gureviciene, V., Vilkanauskyte, A., Marcinkeviciene, L., Bachmatova, I., Meskys, R., Laurinavicius, V., “Improvement of screen-printed carbon electrodes by modification with ferrocene derivative”, Sensors and Actuators B., 95, pp. 378-383, 2003.
[11]Yang, L.H., Li, Y. B., Erf, G.F., “Interidigitated array microelectrode-base electrochemical impedance immunosensor for detection of Escherichia coil O157:H7”, Analytical Chemistry, 76, pp. 1107-1113, 2004.
[12]Giaever and Keese, C.R., “Use of electric fields to monitor the dynamical aspect of cell behavior in tissue culture”, IEEE Transactions on Biomedical Engineering, BME-33(2), pp. 242-247, 1986.
[13]Ehret, R., Baumann, W., Brischwein, M., Schwinde, A., Stegbauer, K. and Wolf, B., “Monitoring of cellular behaviour by impedance measurements on interdigitated electrode structures”, Biosensors and Bioelectronics, 12(1), pp. 29-41, 1997.
[14]Li J., Liu X., Guo M., Liu Y., Liu S., Yao S., “Electrochemical study of breast cancer cells MCF-7 and its application in evaluating the effect of diosgenin”, analytical sciences. 21, pp. 561–564, 2005.
[15]Li, H.N., Ci, Y.X., “Electrochemical method for analyzing intracellular redox activity changes of the etoposide-induced apoptosis in HL-60 cells”, Analytica Chemica Acta, 416, pp. 221–226, 2000.
[16]Feng, J., Luo, G.A., Jian, H.Y., Wang, R.G., An, C.C., “Voltammetric behavior of tumor cells U937 and its usefulness in evaluating the effect of caffeic acid”, Electroanalysis 12, pp. 513–516, 2000.
[17]Tamanaha, C.R. et al, “Magnetic Method for DNA Detection on an Arrayed Solid State Device”, Micro Total Analysis Systems, pp. 444-446, 2001.
[18]Zhang, Ning and David Appella, “Colorimetric Detection of Anthrax DNA with a Peptide Nucleic Acid Sandwich-Hybridization Assay”, Journal of the American Chemical Society, 129 (27), pp. 8424-8425, 2007.
[19]Hintsche, R., Paeschke, M., Uhlig, A., Seitz, R., “Microbiosensor using electrodes made in Si-technology”, Frontiers in biosensonic, pp. 267-283, 1997.
[20]Manfred Paeschke, Frank Dietrich, Albrecht Uhlig, Rainer Hintsche, “Voltammetric Multichannel Measurement using Silicon Fabricated Microelectrode Arrays”, Electroanalysis, 8, pp. 1-8, 1996.
[21]M. Thompson, C. L. Arthur, G. K. Dhaliwal, “Liquid-phase piezoelectric and acoustic transmission studies of interfacial immunochemistry”, Anal. Chem, 58, pp. 1206-1209, 1986.
[22]G. Sauerbreyb, “Verwendung von Schwinquarzen zur Wagung dunner Schichten und zur Mikrowagung“. Zeitschrift fur Physik, 155, pp. 206-222, 1959.
[23]J. F. Scott, C. A. P. de Araujo, L. D. McMillan, H. Yoshimori, H. Watanabe, T. Mihara, M. Azuma, T. Ueda, T. Ueda, D. Ueda and G. Kano, “Ferroelectric thin films in integrated microelectronic devices”, Ferroelectrics, 133, pp. 47-60, 1992.
[24] M. Sayer and K. Sreenivas, “Ceramic thin film: fabrication and applications”, Science, 247, pp. 1056-1060, 1990.
[25]Z. Song, C. Lin, “Microstructure and electrical properties of PbZr0.52Ti0.48O3 ferroelectric films on different Pt bottom electrodes”, Appl. Surf. Sci. 158, pp. 21-27, 2000.
[26]S. J. Martin, H. L. Bandey, and R. W. Cernosek, “Equivalent circuit model for the thickness shear mode resonator with a viscoelastic film near film resonance”, Anal. Chem., 72, pp. 141–149, 2000.
[27]K. Kobayashi, H. Yamada, K. “Matsushige, Dynamic force microscopy using FM detection in various environments”, Appl. Surf. Sci. 188, pp. 430-434, 2002.
[28]W. Hung, S. W. Jiang, Y. R. Li, J. Zhu, Y. Zhang, X. H. Wei, H. Z. Zeng, “Crystallization behavior and domain structure in textured Pb(Zr0.25Ti0.48)O3 thin films by different annealing processes”, Thin Solid Films, 500, pp. 138-143, 2006.
[29]C. D. E. Lakeman and D. A. Payne, “Processing effects in the sol-gel preparation of PZT dried gels, Powders, and Ferroelectric Thin Layers”, J. Am. Ceram. Soc., 75, pp. 3091-3096, 1992.
[30]X. Zheng, Y. Zhou, Z. Yan, “Dependence of Crystalline, Ferroelectric and fracture toughness on annealing in Pb(Zr0.52Ti0.48)O3 thin films deposited by metal organic decomposition”, Mater. Res, 6, pp. 551-556, 2003.
[31]S.Y. Chen, “Texture evolution and electrical properties of oriented PZT thin films”, Mater. Chem. Phys., 45, pp. 159-162, 1996.
[32]P. Juan, Y. Hu, F. Chiu, J.Y. Lee, “The electrical properties of Metal–Ferroelectric (PbZr0.53Ti0.47O3)–Insulator–Silicon (MFIS) capacitors with different insulator materials”, Microelectron. Eng, 80, pp. 309–312, 2005.
[33]S.K. Pandey, A. R. James, R. Raman, S. N. Chatterjee, A. Goyal, C. Prakash, T. C. Goel. “Structural, ferroelectric and optical properties of PZT thin films”, Physica B, 369, pp. 135–142, 2005.
[34]H. Kanai, Y. Yamashita, “Investigation of factors affecting electrical properties of PZT thin film capacitance”, IEEE EI paper, 121-124, 1998.
[35]G. Yi, Z. Wu, M. Sayer, “Preparation of Pb(Zr,Ti)O3 thin films by sol gel processing: electrical, option, and electro-optic properties”, J. Appl. Phys. 64, pp. 2717-2724, 1998.
[36]J. Weber, W. M. Albers, J. Tuppurainen, M. Link, R. Gabl, W. Wersing, M. Schreiter, “Shear mode FBARs as highly sensitive liquid biosensors”, Sens. Actuator A, 128, pp. 84-88, 2006.
[37]R. Cernosek, S. J. Martin, A. R. Hillman, and H. L. Bandey, “Comparison of lumped-element and transmission-line models for thicknessshear-mode quartz resonator sensors”, IEEE Trans. Ultrason., Ferroelect., Freq. Control., 45, pp. 1399–1407, 1998.
[38]Spyridon K., Ioannis L., Ilias K., Georgios I., Theofanis K., Athanasios K.,Konstantinos T., Nikolaos T., Lambros A., “Microalbuminuria: A strong predictor of 3-year adverse prognosis in nondiabetic patients with acute myocardial infarction” , Am. Heart J., 149, 5, pp. 840-845, 2005.
[39]Lewis E. J., Hunsicker L. G., Clarke W. R., “Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes”, N. Engl. J. Med., 345, pp.851–860, 2001.
[40]Riss T., O’Brien M., Morvec R., “Choosing the Right Cell-Based Assay for Your Research”, Cell Notes, 6, pp. 6-12, 2003.
[41]Rica R. de.la. , Cesar F. S., Baldi A., “Polysilicon interdigitated electrodes as impedimetric sensors”, Electrochem. Commun., 8, pp. 1239-1244, 2006.
[42]Ma Z., Masaya K., Ramakrishna S., “Immobilization of Cibacron blue F3GA on electrospun polysulphone ultra-fine fiber surfaces towards developing an affinity membrane for albumin adsorption” , Journal of Membrane Science, 282, 1-2, pp. 237-244, 2006.
[43]Altintas E. B., Denizli A., “Efficient removal of albumin from human serum by monosize dye-affinity beads” , J. Chromatogr. B, 832, 2, pp. 216-223, 2006.
[44]Yang L., Li Y., Griffis C.L., Johnson M.G., “Interdigitated microelectrode (IME) impedance sensor for the detection of viable Salmonella typhimurium”, Biosens. Bioelectron. 19, pp.1139–1147, 2004.
[45]Kassab A., Yavuz H., Odabasi M., Denizli A., “Human serum albumin chromatography by Cibacron Blue F3GA-derived microporous polyamide hollow-fiber affinity membranes”, Journal of hromatography B:Biomedical Sciences and Applications, 746, 2, pp. 123-132, 2000.
[46]Liu Q., Yu J., Xiao L., Tang J. C. On, Zhang Y., Wang P. and Yang M., “Impedance studies of bio-behavior and chemosensitivity of cancer cells by micro-electrode arrays”, Biosensors and Bioelectronics, 24. pp. 1305-1310, 2009.
[47]Stett A., Egert U., Guenther E., Hofmann F., Meyer T., Nisch W., Haemmerle H.,“ Biological application of microelectrode arrays in drug discovery and basic research”, Anal. Bioanal. Chem. 377, pp. 486-495, 2003.
[48]Stenger D.A, Gross G.W., Keefer E.W., Shaffer K. M., Andreadis J. D., Ma W., Pancrazio J.J., “Detection of physiologically active compounds using cell-based biosensors”, Trend. Biotechnol, 19, pp. 304-309, 2001.
[49]Shuilleabhain S. Ni, Mothersill C., Sheehan D., O’Brien N.M., O’Halloran J., Van Pelt F.N.A.M., Davoren M., “In vitro cytotoxicity testing of three zinc metal salts using established fish cell lines”, Toxicol. in Vitro. 18, pp. 365-376, 2004.
[50]White R.E., ”High-Throughput Screening in Drug Metabolism and Pharmacokinetic Support of Drug Discovery”, Phamacol Annu. Rev.Toxicol, 40, pp. 133-157, 2000.
[51]Riss T., O’Brien M., Morvec R., ”Choosing the Right Cell-Based Assay for Your Research”, Cell Notes. 6, pp. 6-12, 2003.
[52]Keese C.R., Giaever I., “A biosensor that monitors cell morphology with electrical fields”, IEEE Eng. Med. Biol., 13, pp. 402-408, 1994.
[53]Rica R. de. la., Cesar F. S., A. Baldi., “Polysilicon interdigitated electrodes as impedimetric sensors”, Electrochemistry Communications, 8, pp. 1239-1244, 2006.
[54]Hsiung L. C., Yang C. H., Chiu C.L., Chen C. L., Wang Y., Lee H., Cheng J. Y., Ho M. C., Wo A. M., “A planar interdigitated ring electrode array via dielectrophoresis for uniform patterning of cells”, Biosensors and Bioelectronics. 24, pp. 869-875, 2008.
[55]Varshney M., Li Y., ”Double interdigitated array microelectrode-based impedance biosensor for detection of viable Escherichia coli O157:H7 in growth medium”, Talanta, 74, pp. 518-525, 2008.
[56]Yang L., Li Y., Erf G. F., ”Interdigitated Array Microelectrode-Based Electrochemical Impedance Immunosensor for Detection of Escherichia coli O157:H7”, Anal. Chem. 76, pp. 1107-1113, 2004.
[57]Varshney M., Li Y., Srinivasan B., Tung S., “A label-free, microfluidics and interdigitated array microelectrode-based impedance biosensor in combination with nanoparticles immunoseparation for detection of Escherichia coli O157:H7 in food samples“, Sensors and Actuators B. 128, pp. 99-107, 2007.
[58]Varshney M., Lin Y., “Interdigitated array microelectrode based impedance biosensor coupled with magnetic nanoparticle–antibody conjugates for detection of Escherichia coli O157:H7 in food samples”, Biosensors and Bioelectronics, 22, pp. 2408-2414, 2007.
[59]Ruan C., Yang L., Li Y., “Immunobiosensor Chips for Detection of Escherichia coli O157:H7 Using Electrochemical Impedance Spectroscopy”, Anal. Chem., 74, pp. 4814-4820, 2002.
[60]Radke S. M., Alocilja E. C., “A microfabricated biosensor for detecting foodborne bioterrorism agents”, IEEE Sensors Journal. 5, pp. 744-750, 2005.
[61]Bang L., Li Y., “AFM and impedance spectroscopy characterization of the immobilization of antibodies on indium–tin oxide electrode through self-assembled monolayer of epoxysilane and their capture of Escherichia coli O157:H7”, Bosensors and Bioelectronics. 20, pp. 1407-1416, 2005.
[62]Berdat D., Marin A., Herrera F., Gijs M. A.M., ”DNA biosensor using fluorescence microscopy and impedance spectroscopy”, Sensors and Actuators B. 118, pp. 53-59, 2006.
[63]Hang T. C., Anthony G., “Frequency dependent and surface characterization of DNA immobilization and hybridization”, Biosensors and Bioelectronics. 19, pp. 1537-1548, 2004.
[64]Yang L., ” Electrical impedance spectroscopy for detection of bacterial cells in suspensions using interdigitated microelectrodes”, Talanta. 74, pp. 1621-1629, 2008.
[65]Yeon J. H., Park J. K., “Cytotoxicity test based on electrochemical impedance measurement of HepG2 cultured in microfabricated cell chip”, Analytical Biochemistry. 341, pp. 308-315, 2005.
[66]Guo M., Chen J., Yun X., Chen K., Nie L., Yao S., “Monitoring of cell growth and assessment of cytotoxicity using electrochemical impedance spectroscopy”, Biochimica et Biophysica Acta. 1760, pp. 432-439, 2006.
[67]Arndt S., Seebach J., Psathaki K., Galla H. J., Wegener J., “Bioelectrical impedance assay to monitor changes in cell shape during apoptosis”, Biosensors and Bioelectronics. 19, pp. 583-594, 2004.
[68]Mishra N. N., Retterer S., Zieziulewicz T. J., Isaacson M., Szarowski D., Mousseau D. E., Lawrence D. A., Turner J. N., “On-chip micro-biosensor for the detection of human CD4+ cells based on AC impedance and optical analysis”, Biosensors and Bioelectronics. 21, pp. 696-704, 2005.
[69]Bouafsoun A., Othmane A., Jaffrezic-Renault N., Kerkeni A., Thoumire O., Prigent A.F., Ponsonnet L., ”Impedance endothelial cell biosensor for lipopolysaccharide detetion”, Materials Science and Engineering C.28, pp. 653-661, 2008.
[70]Wolf P., Rotherme A., Beck-sickinger A. G.,. Robitzki A. A, “Microelectrode chip based real time monitoring of vital MCF-7 mamma carcinoma cells by impedance spectroscopy”, Biosensors and Bioelectronics. 24, pp. 253-259, 2008.
[71]Huang X., Greve D.W., Nguyen D.D., Domach M.M., “Impedance based biosensor array for monitoring mammalian cell behavior”, IEEE Sensors, 1, pp, 304-309, 2003.
[72]Brischwein M., Herrmann S., Vonau W., Berthold F., Grothe H., Motrescu E. R., B. Wolf, “The use of screen printed electrodes for the sensing of cell responses”, AFRICON, pp. 1-5, 2007.
[73]Varshney M., Li Y., ” Interdigitated array microelectrodes based impedance biosensors for detection of bacterial cells”, Biosensors and Bioelectronics. 24, pp. 2951-2960, 2009.
[74]Zou Z., Kai J., Rust M. J., Han J., Ahn C. H., “Functionalized nano interdigitated electrodes arrays on polymer with integrated microfluidics for direct bio-affinity sensing using impedimetric measurement”, Sensors and Actuators A. 136, pp. 518-526, 2007.
[75]Gerwen P. V., Laureyn W., Laureys W., Huyberechts G., Beeck M. O. D., Baert K., Suls J., Sansen W., Jacobs P., Hermans L., Mertens R., “Nanoscaled interdigitated electrode arrays for biochemical sensors”, Sensors and Actuators B. 49, pp. 73-80, 1998.
[76]Laureyn W., Nelis D., Gerwen P. Van, Baert K., Hermans L., Magnee R., Pireaux J. J., Maes G., “Nanoscaled interdigitated titanium electrodes for impedimetric biosensing”, Sensors and Actuators B. 68, pp. 360-370, 2000.
[77]M. Yi, K. H. Jeong, and L. P. Lee, “Theoretical and experimental study towards a nanogap dielectric biosensor”, Biosensors and Bioelectronics. 20, pp. 1320-1326, 2005.
[78]W. Cai, J. R. Peck, D. W. Van der Weide, and R. J. Hamers, “Direct electrical detection of hybridization at DNA-modified silicon surfaces”, Biosensors and Bioelectronics. 19, pp. 1013-1019, 2004.
[79]G. Laurent, L. M. Hagelsieb, D. Lederer, P. E. Lober, D. Flandre, J. Remacle, and J. P. Raskin, “DNA electrical detection based on inductor resonance frequency in standard CMOS technology”, IEEE Solid-State Circuits Conference., pp. 337-340, 2003.
[80]J. Li, C. Xu, Z. Zhang, Y. Wang, H. Peng, Z. Lu, and M. Chan, “A DNA-detection platform with integrated photodiodes on a silicon chip”, Sensors and Actuators B. 106, pp. 378-382, 2005.
[81]F. F. Bier, F. Kleinjung, and F. W. Scheller, “Real-time measurement of nucleic-acid hybridization using evanescent-wave sensors: steps towards the genosensor”, Sensors and Actuators B. 38, pp. 78-82, 1997.
[82]R. de.la.Rica, F. S. Cesar, and A. Baldi, “Polysilicon interdigitated electrodes as impedimetric sensors”, Electrochemistry Communications. 8, pp. 1239-1244, 2006.
[83]S. J. Park, T. A. Taton, C. A. Mirkin, “Array-Based Electrical Detection of DNA with Nanoparticle Probes”, Science. 295, pp. 1503-1506, 2002.
[84]C. A. Mirkin, “Programming the assembly of Two-and Three Dimensional Architecture with DNA and nanoscale Inorganic building blocks,” Inorganic Chemistry”, Inorganic Chemistry. 39, pp. 2258-2272, 2000.
[85]C. Berggren, P. Stålhandske, J. Brundell, and G. Johansson, ” A Feasibility Study of a Capacitive Biosensor for Direct Detection of DNA Hybridization”, Electroanalysis. 11 3, pp. 156-160, 1999.
[86]L. A. Chrisey, G. U. Lee, and C. E. O’Ferrall, “Covalent attachment of synthetic DNA to self-assembled monolayer films,” Nucleic Acids Research. 24, pp. 3031-3039, 1996.
[87] T. Andrew Taton, C. A. Mirkin, and R. L. Letsinger, “Scanometric DNA Array Detection with Nanoparticle Probes”, Science. 289, pp. 1757-1760, 2000.
[88]M. Ikeda, K. Nakazato, H. Mizuta, M. Green, D. Hasko, and H. Ahmed, “Frequency-dependent electrical characteristics of DNA using molecular dynamics simulation”, Nanotechnology. 14, pp. 123-127, 2003.