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Development and Application of Cell-Based Biosensors

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Abstract

Biosensors incorporate a biological sensing element that converts a change in an immediate environment to signals conducive for processing. Biosensors have been implemented for a number of applications ranging from environmental pollutant detection to defense monitoring. Biosensors have two intriguing characteristics: (1) they have a naturally evolved selectivity to biological or biologically active analytes; and (2) biosensors have the capacity to respond to analytes in a physiologically relevant manner. In this paper, molecular biosensors, based on antibodies, enzymes, ion channels, or nucleic acids, are briefly reviewed. Moreover, cell-based biosensors are reviewed and discussed. Cell-based biosensors have been implemented using microorganisms, particularly for environmental monitoring of pollutants. Biosensors incorporating mammalian cells have a distinct advantage of responding in a manner that can offer insight into the physiological effect of an analyte. Several approaches for transduction of cellular signals are discussed; these approaches include measures of cell metabolism, impedance, intracellular potentials, and extracellular potentials. Among these approaches, networks of excitable cells cultured on microelectrode arrays are uniquely poised to provide rapid, functional classification of an analyte and ultimately constitute a potentially effective cell-based biosensor technology. Three challenges that constitute barriers to increased cell-based biosensor applications are presented: analytical methods, reproducibility, and cell sources. Possible future solutions to these challenges are discussed. © 1999 Biomedical Engineering Society.

PAC99: 8780-y, 0130Rr, 8717-d

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REFERENCES

  1. Applegate, B. M., S. R. Kermeyer, and G. S. Sayler. A chromosomally based tod-luxCDABE whole-cell reporter for benzene, toluene, ethylbenzene, and xylene (BTEX) sensing. Appl. Environ. Microbiol. 64:2730–2735, 1998.

    Google Scholar 

  2. Baxter, G. T., M. L. Young, D. L. Miller, and J. C. Owicki. Using microphysiometry to study the pharmacology of exogenously expressed m1 and m3 muscarinic receptors. Life Sci. 55:573–583, 1994.

    Google Scholar 

  3. Belkin, S., D. R. Smulski, S. Dadon, A. C. Vollmer, T. K. Van Dyk, and R. A. Larossa. A panel of stress-responsive luminous bacteria for the detection of selected classes of toxicants. Water Research 31:3009–3016, 1997.

    Google Scholar 

  4. Bousse, L. Whole cell biosensors. Sens. Actuators B 34:270–275, 1996.

    Google Scholar 

  5. Bove, M., M. Grattarola, and G. Verreschi. In vitro 2-D networks of neurons characterized by processing the signals recorded with a planar microtransducer array. IEEE Trans. Biomed. Eng. 44:964–977, 1997.

    Google Scholar 

  6. Branch, D. W., J. M. Corey, J. A. Weyhenmeyer, G. J. Brewer, and B. C. Wheeler. Microstamp patterns of biomolecules for high-resolution neuronal networks. Med. Biol. Eng. Comput. 36:135–141, 1998.

    Google Scholar 

  7. Breckenridge, L. J., R. J. A. Wilson, P. Connolly, A. S. G. Curtis, J. A. T. Dow, S. E. Blackshaw, and C. D. W. Wilkinson. Advantages of using microfabricated extracellular electrodes for in vitro neuronal recording. J. Neurosci. Res. 42:266–267, 1995.

    Google Scholar 

  8. Brown, M. J., M. D. Wood, M. C. Coldwell, and D. R. Bristow. Measurement of GABAA receptor function in rat cultured cerebellar granule cells by the Cytosensor microphysiometer. Br. J. Pharmacol. 121:71–76, 1997.

    Google Scholar 

  9. Burlage, R. S., A. V. Palumbo, A. Heitzer, and G. Sayler. Bioluminescent reporter bacteria detect contaminants in soil samples. Appl. Microbiol. Biotechnol. 45:731–740, 1994.

    Google Scholar 

  10. Campanella, L., G. Favero, D. Mastrofini, and M. Tomasetti. Toxicity order of cholanic acids using an immobilized cell biosensor. J. Pharm. Biomed. Anal 14:1007–1013, 1996.

    Google Scholar 

  11. Canepari, M., M. Bove, E. Maeda, M. Cappello, and A. Kawana. Experimental analysis of neuronal dynamics in cultured cortical networks and transitions between different patterns of activity. Biol. Cybern. 77:153–162, 1997.

    Google Scholar 

  12. Cao, L. K., G. P. Anderson, F. S. Ligler, and J. Ezzell. Detection of Yersinia-pestis fraction-1 antigen with a fiber optic biosensor. J. Clin. Microbiol. 33:336–341, 1995.

    Google Scholar 

  13. Cao, C. J., M. E. Eldefrawi, A. T. Eldefrawi, J. W. Burnett, R. J. Mioduszewski, D. E. Menking, and J. J. Valdes. Toxicity of sea nettle toxin to human hepatocytes and the protective effects of phosphorylating and alkylating agents. Toxicon 36:269–281, 1998.

    Google Scholar 

  14. Chen, C. S., M. Mrksich, S. Huang, G. M. Whitesides, and D. E. Ingber. Micropatterned surfaces for control of cell shape, position, and function. Biotechnol. Prog. 14:356–363, 1998.

    Google Scholar 

  15. Cheng, J., E. L. Sheldon, L. Wu, A. Uribe, L. O. Gerrue, J. Carrino, M. J. Heller, and J. P. O'Connell. Preparation and hybridization analysis of DNA/RNA from E. Coli on micro-fabricated bioelectronic chips. Nat. Biotechnol. 16:541–546, 1998.

    Google Scholar 

  16. Clark, P., S. Britland, and P. Connolly. Growth cone guidance and neuron morphology on micropatterned laminin surfaces. J. Cell. Sci. 105:203–212, 1993.

    Google Scholar 

  17. Connolly, P., P. Clark, A. S. G. Curtis, J. A. T. Dow, and C. D. W. Wilkinson. An extracellular microelectrode array for monitoring electrogenic cells in culture. Biosens. Bioelectron. 5:223–234, 1990.

    Google Scholar 

  18. Connolly, P., G. R. Moores, W. Monaghan, J. Shen, S. Britland, and P. Clark. Microelectronic and nanoelectronic interfacing techniques for biological systems. Sens. Actuators B 6:113–121, 1992.

    Google Scholar 

  19. Corey, J. M., B. C. Wheeler, and G. J. Brewer. Compliance of hippocampal neurons to patterned substrate networks. J. Neurosci. Res. 30:300–307, 1991.

    Google Scholar 

  20. Corey, J. M., B. C. Wheeler, and G. J. Brewer. Micrometer resolution silane-based patterning of hippocampal neurons: Critical variables in photoresist and laser ablation processes for substrate fabrication. IEEE Trans. Biomed. Eng. 43:944–955, 1996.

    Google Scholar 

  21. Cornell, B. A., V. L. Braach Maksvytis, L. G. King, P. D. Osman, B. Raguse, L. Wieczorek, and R. J. Pace. A biosensor that uses ion-channel switches. Nature (London) 387:580–583, 1997.

    Google Scholar 

  22. Denyer, M. C. T., M. Riehle, S. T. Britland, and A. Offenhauser. Preliminary study on the suitability of a pharmacological bio-assay based on cardiac myocytes cultured over microfabricated microelectrode arrays. Med. Biol. Eng. Comput. 36:638–644, 1998.

    Google Scholar 

  23. Devine, P. J., N. A. Anis, J. Wright, S. Kim, A. T. Edlefrawi, and M. E. Eldefrawi. A fiberoptic cocaine biosensor. Anal. Biochem. 227:216–224, 1995.

    Google Scholar 

  24. D'Orazio, P. A., T. C. Maley, R. R. McCaffrey, A. C. Chan, D. Orvedahl, D. Blake, S. Degan, J. Benco, C. Murphy, P. G. Edelman, and H. Ludi. Planar (Bio) Sensors for critical care diagnostics. Clin. Chem. 43:1804–1805, 1997.

    Google Scholar 

  25. Dulcey, C. S., J. H. Georger, Jr., V. Krauthamer, D. A. Stenger, T. L. Fare, and J. M. Calvert. Deep UV photochemistry of chemisorbed monolayers; patterned coplanar molecular assemblies. Science 252:551–554, 1991.

    Google Scholar 

  26. Dunn, K. W., S. Mayor, J. N. Myers, and F. R. Maxfield. Applications of ratio fluorescence microscopy in the study of cell physiology. FASEB J. 8:573–582, 1994.

    Google Scholar 

  27. Edman, C. F., D. E. Raymond, D. J. Wu, E. G. Tu, R. G. Sosnowski, W. F. Butler, M. Nerenberg, and M. J. Heller. Electric field directed nucleic acid hybridization on microchips. Nucleic Acids Res. 25:4907–4914, 1997.

    Google Scholar 

  28. Egert, U., B. Schlosshauer, S. Fennrich, W. Nisch, M. Fejtl, T. Knott, T. Müller, and H. Hämmerle. A novel organotypic long-term culture of the rat hippocampus on substrateintegrated multielectrode arrays. Brain Res. Bull. 2:229–242, 1998.

    Google Scholar 

  29. Ehret, R., W. Baumann, M. Brischwein, A. Schwinde, K. Stegbauer, and B. Wolf. Monitoring of cellular behaviour by impedance measurements on interdigitated electrode structures. Biosens. Bioelectron. 12:29–41, 1997.

    Google Scholar 

  30. Elger, C. E., and K. Lehnertz. Seizure prediction by nonlinear time series analysis of brain electrical activity. Eur. J. Neurosci. 10:786–789, 1998.

    Google Scholar 

  31. Evtugyn, G. A., E. P. Rizaeva, E. E. Stoikova, V. Z. Latipova, and H. C. Budnikov. The application of cholinesterase potentiometric biosensor for preliminary screening of toxicity of waste waters. Electroanalysis 9:1–5, 1997.

    Google Scholar 

  32. Feldstein, M. J., J. P. Golden, C. A. Rowe, B. D. MacCraith, and F. S. Ligler. Array biosensor: optical and fluidics systems. Biomed. Microdevices 1:139–153, 1999.

    Google Scholar 

  33. Fernandes, P. B. Technological advances in high-throughput screening. Curr. Opin. Chem. Biol. 2:597–603, 1998.

    Google Scholar 

  34. Finley, M. F. A., M. Kulkarni, and J. E. Huettner. Synapse formation and establishment of neuronal polarity by P19 embryonic carcinoma cells and embyronic stem cells. J. Neurosci. 16:1056–1065, 1996.

    Google Scholar 

  35. Foch-Anderson, F., and P. D'Orazio. Proposal for standardizing direct-reading biosensors for blood glucose. Clin. Chem. 44:655–659, 1998.

    Google Scholar 

  36. Fraichard, A., O. Chassande, G. Bilbaut, C. Dehay, P. Savatier, and J. Samarut. In vitro differentiation of embryonic stem cells into glial cells and functional neurons. J. Cell. Sci. 108:3181–3188, 1995.

    Google Scholar 

  37. Fromherz, P. Extracellular recording with transistors and the distribution of ionic conductances in a cell membrane. Eur. Biophys. J. 28:254–258, 1999.

    Google Scholar 

  38. Fromherz, P., A. Offenhauser, T. Vetter, and J. Weus. A neuron—silicon junction: A Retzius cell of the leech on an insulated-gate field effect transistor. Science 252:1290–1293, 1991.

    Google Scholar 

  39. Gahwiler, B. H., M. Capogna, D. Debanne, R. A. McKinney, and S. M. Thompson. Organotypic slice cultures: a technique has come of age. Trends Neurosci. 20:471–477, 1997.

    Google Scholar 

  40. Gerstein, G. L., and D. H. Perkel. Simultaneously recorded trains of action potentials: analysis and functional interpretation. Science 164:828–830, 1969.

    Google Scholar 

  41. Giaever, I., and C. R. Keese. Use of electric fields to monitor the dynamical aspect of cell behavior in tissue culture. IEEE Trans. Biomed. Eng. 33:242–247, 1986.

    Google Scholar 

  42. Giaever, I., and C. R. Keese. Micromotion of mammalian cells measured electrically. Proc. Natl. Acad. Sci. USA 88:7896–7900, 1991.

    Google Scholar 

  43. Giaever, I., and C. R. Keese. A morphological biosensor for mammalian cells. Nature (London) 366:591–592, 1993.

    Google Scholar 

  44. Gochin, P. M., M. Colombo, G. A. Dorfman, G. L. Gerstein, and C. G. Gross. Neural ensemble coding in inferior temporal cortex. J. Neurophysiol. 71:2325–2337, 1994.

    Google Scholar 

  45. Giuliano, K. A., R. L. DeBiasio, R. T. Dunlay, A. Gough, J. M. Volosky, J. Zock, G. N. Pavlakis, and D. L. Taylor. High-content screening: a new approach to easing key bottlenecks in the drug discovery process. J. Biomol. Screening 2:249–259, 1997.

    Google Scholar 

  46. Graham, C. R., D. Leslie, and D. J. Squirrell. Gene probe assays on a fiber-optic evanescent wave biosensor. Biosens. Bioelectron. 7:487–493, 1992.

    Google Scholar 

  47. Gronert, K., S. P. Colgan, and C. N. Serhan. Characterization of human neutrophil and endothelial cell ligand-operated extracellular acidification rate by microphysiometry: impact of reoxygenation. J. Pharmacol. Exp. Ther. 285:252–261, 1998.

    Google Scholar 

  48. Gross, G. W. Internal dynamics of randomized mammalian neuronal networks in culture. In: Enabling Technologies for Cultured Neuronal Networks, edited by D. A. Stenger and T. M. McKenna. San Diego: Academic, 1994, pp. 277–317.

    Google Scholar 

  49. Gross, G. W., A. Harsch, B. K. Rhoades, and W. Göpel. Odor, drug and toxin analysis with neuronal networks in vitro: Extracellular array recording of network responses. Biosens. Bioelectron. 12:373–393, 1997.

    Google Scholar 

  50. Gross, G. W., B. K. Rhoades, H. M. E Azzazy, and M. C. Wu. The use of neuronal networks on multielectrode arrays as biosensors. Biosens. Bioelectron. 10:553–567, 1995.

    Google Scholar 

  51. Gross, G. W., B. Rhoades, and R. Jordan. Neuronal networks for biochemical sensing. Sens. Actuators B 6:1–8, 1992.

    Google Scholar 

  52. Gross, G. W., B. K. Rhoades, D. L. Reust, and F. U. Schwalm. Stimulation of monolayer networks in culture through thin-film indium-tin oxide recording electrodes. J. Neurosci. Methods 50:131–143, 1993.

    Google Scholar 

  53. Gross, G. W., W. Wen, and J. Lin. Transparent indium-tin oxide patterns for extracellular, multisite recording in neuronal culture. J. Neurosci. Methods 15:243–252, 1985.

    Google Scholar 

  54. Gross, G. W., A. N. Williams, and J. H. Lucas. Recording of spontaneous activity with photoetched microelectrode surfaces from spinal cord neurons in culture. J. Neurosci. Methods 5:13–22, 1982.

    Google Scholar 

  55. Hafeman, D. G., J. W. Parce, and H. M. McConnell. Light-addressable potentiometric sensor for biochemical systems. Science 240:1182–1185, 1988.

    Google Scholar 

  56. Hall, J. M., J. More Smith, J. V. Bannister, and I. J. Higgins. An electrochemical method for detection of nucleic acid hybridisation. Biochem. Mol. Biol. Int. 32:21–28, 1994.

    Google Scholar 

  57. Hampson, R. E., and S. A. Deadwyler. Pitfalls and problems in the analysis of neuronal ensemble recordings during behavioral tasks. In: Methods for Neural Ensemble Recording, edited by M. A. L. Nicolelis. Boca Raton: Chemical Rubber Corp., 1999, pp. 229–248.

    Google Scholar 

  58. Hanbury, C. M., W. G. Miller, and R. B. Harris. Fiber-optic immunosensor for measurement of myoglobin. Clin. Chem. 43:2128–2136, 1997.

    Google Scholar 

  59. Heitzer, A., K. Malachowsky, J. E. Thonnard, P. R. Bienkowski, D. C. White, and G. S. Sayler. Optical biosensor for environmental on-line monitoring of napthalene and salicylate bioavailability with an immobilized bioluminescent catabolic reporter bacterium. Appl. Environ. Microbiol. 60:1487–1494, 1994.

    Google Scholar 

  60. Henderson, D. A. The looming threat of bioterrorism. Science 283:1279–1282, 1999.

    Google Scholar 

  61. Heppner, T. J., and J. F. Fiekers, Soman reversibly decreases the duration of Ca2+ and Ba2+ action potentials in bullfrog sympathetic neurons. Brain Res. 563:303–305, 1991.

    Google Scholar 

  62. Heppner, T. J., and J. F. Fiekers. VX enhances neuronal excitability and alters membrane properties of Rana Catesbeiana sympathetic ganglion neurons. Comp. Biochem. Physiol. 102C:335–338, 1992.

    Google Scholar 

  63. Higashida, H., and S. Furuya. Cholinergic synapse formation between NG108–15 and muscle cells and modulation of transmission. Neurosci. Res. Suppl. 13:S75-S79, 1990.

    Google Scholar 

  64. Hollands, P. Comparative stem cell biology. Int. J. Dev. Biol. 41:245–254, 1997.

    Google Scholar 

  65. Hoogenboom, H. R., A. P. de Bruine, S. E. Hufton, R. M. Hoet, J. W. Arends, and R. C. Roovers. Antibody phage display technology and its applications. Immunotechnology 4:1–20, 1998.

    Google Scholar 

  66. Israel, D. A., W. H. Barry, D. J. Edell, and R. G. Mark. An array of microelectrodes to stimulate and record from cardiac cells in culture. Am. J. Physiol. 247:H669-H674, 1984.

    Google Scholar 

  67. Jardemark, K., C. Farre, I. Jacobson, R. N. Zare, and O. Orwar. Screening of receptor antagonists using agonistactivated patch clamp detection in chemical separations. Anal. Chem. 70:2468–2474, 1998.

    Google Scholar 

  68. Jeanty, G., and R. L. Marty. Detection of paraoxon by continuous flow system based enzyme sensor. Bioelectrochem. Bioenerg. 13:213–218, 1998.

    Google Scholar 

  69. Jimbo, Y., and A. Kawana. Electrical stimulation and recording from cultured neurons using planar electrode array. Bioelectrochem. Bioenerg. 29:193–204, 1992.

    Google Scholar 

  70. Kadlec, R. P., A. P. Zelicoff, and A. M. Vrtis. Biological weapons control; Prospects and implications for the future. J. Am. Med. Assoc. 278:351–356, 1997.

    Google Scholar 

  71. Kampa, I. S., and P. Keffer. The use of a whole-blood bench-top analyzer (Nova 16) in a cardiac STAT intensive care unit. Clin. Chem. 44:884–885, 1998.

    Google Scholar 

  72. Kasianowicz, J. J., E. Brandin, D. Branton, and D. W. Deamer. Characterization of individual polynucleotide molecules using a membrane channel. Proc. Natl. Acad. Sci. USA 93:13770–13773, 1996.

    Google Scholar 

  73. King, J. M. H., P. M. DiGrazia, B. Applegate, R. Burlage, J. Sanseverino, P. Dunbar, F. Larimer, and G. S. Sayler. Rapid, sensitive bioluminescent reporter technology for napthalene exposure and biodegradation. Science 249:778–781, 1990.

    Google Scholar 

  74. Kleinfeld, D., K. H. Kahler, and P. E. Hockberger. Controlled outgrowth of dissociated neurons on patterned substrates. J. Neurosci. 8:4098–4120, 1988.

    Google Scholar 

  75. Klug, M. G., M. H. Soonpaa, G. Y. Koh, and L. J. Field. Genetically selected cardiomyocytes from differentiating embryonic stem cells form stable intracardiac grafts. J. Clin. Invest. 98:216–224, 1996.

    Google Scholar 

  76. Korpan, Y. I., M. V. Gonchar, N. F. Starodub, A. A. Shul'ga, A. A. Sibirny, and A. V. El'skaya. A cell biosensor specific for formaldehyde based on pH-sensitive transistors coupled to methylotrophic yeast cells with genetically adjusted metabolism. Anal. Biochem. 215:216–222, 1993.

    Google Scholar 

  77. Kowolenko, M., C. R. Keese, D. A. Lawrence, and I. Giaever. Measurement of macrophage adherence and spreading with electric fields. J. Immunol. Methods 127:71–77, 1990.

    Google Scholar 

  78. Kowtha, V. C., H. J. Bryant, V. Krauthamer, K. H. Iwasa, and D. A. Stenger. Spontaneous firing of NG108–15 cells induced by transient exposure to ammonium chloride. Cell Mol. Neurobiol. 16:1–9, 1993.

    Google Scholar 

  79. Kumar, P., J. T. Colston, J. P. Chambers, E. D. Rael, and J. J. Valdes. Detection of botulinum toxin using an evanescent wave immunosensor. Biosens. Bioelectron. 9:57–63, 1994.

    Google Scholar 

  80. Kuntzweiler, T. A., S. P. Arneric, and D. L. Donnelly-Roberts. Rapid assessment of ligand actions with nicotinic acetylcholine receptors using calcium dynamics and FLIPR. Drug Dev. Res. 44:14–20, 1998.

    Google Scholar 

  81. Kusterbeck, A. W., G. A. Wemhoff, P. T. Charles, D. A. Yeager, R. Bredehorst, C. W. Vogel, and F. S. Ligler. A continuous flow immunoassay for rapid and sensitive detection of small molecules. J. Immunol. Methods 135:191–197, 1990.

    Google Scholar 

  82. Lacorte, S., N. Ehresmann, and D. Barcelo. Persistence of temephos and its transformation products in rice crop field waters. Environ. Sci. Technol. 30:917–923, 1996.

    Google Scholar 

  83. Larsson, N., T. Ruzgas, L. Gorton, M. Kokaia, P. Kissinger, and E. Csöregi. Design and development of an amperometric biosensor for acetylcholine determination in brain microdialysates. Electrochim. Acta 43:3541–3554 1998.

    Google Scholar 

  84. Ligler, F. S., T. L. Fare, K. D. Seib, J. W. Smuda, A. Singh, P. Ahl, M. E. Ayers, A. Dalziel, and P. Yager. Fabrication of key components of a receptor-based biosensor. Med. Instrum. 22:247–256, 1988.

    Google Scholar 

  85. Ma, W., Q. Y. Liu, D. Jung, P. Manos, J. J. Pancrazio, A. E. Schaffner, J. L. Barker, and D. A. Stenger. Central neuronal synapse formation on micropatterned surfaces. Dev. Brain Res. 111:231–243, 1998.

    Google Scholar 

  86. Ma, W., Q. Y. Liu, D. Maric, R. S. Sathanoori, Y. H. Chang, and J. L. Barker. Basic FGF-responsive telencephalic precursor cells express functional GABAA receptor Cl- channels in vitro. J. Neurobiol. 35:277–286, 1998.

    Google Scholar 

  87. Ma, W., J. J. Pancrazio, M. G. Coulombe, J. Dumm, R. S. Sathanoori, J. L. Barker, V. C. Kowtha, D. A. Stenger, and J. J. Hickman. Neuronal and glial epitopes and transmitte-rsynthesizing enzymes appear in parallel with membrane excitability during neuroblastoma X glioma hybrid differentiation. Dev. Brain Res. 106:155–163, 1998.

    Google Scholar 

  88. Marshall, A., and J. Hodgson. DNA chips: An array of possibilities. Nat. Biotechnol. 16:27–31, 1998.

    Google Scholar 

  89. Marty, J. L., N. Mionetto, and R. Rouillon. Entrapped enzymes in photocrosslinkable gel for enzyme electrodes. Anal. Lett. 25:1389–1398, 1992.

    Google Scholar 

  90. Matsuzawa, M., V. Krauthamer, and R. S. Potember. Directional guidance of neurite outgrowth using substrates patterned with biomaterials. Biosystems 35:199–202, 1995.

    Google Scholar 

  91. Matsuzawa, M., K. Kobayashi, K. Sugioka, and W. Knoll. A biocompatible interface for the geometrical guidance of central neurons in vitro. J. Colloid Interface Sci. 202:213–212, 1998.

    Google Scholar 

  92. McKay, R. Stem cells in the central nervous system. Science 276:66–71, 1997.

    Google Scholar 

  93. Meister, M., J. Pine, and D. A. Baylor. Multi-neuronal signals from the retina: Acquisition and analysis. J. Neurosci. Methods 51:95–106, 1994.

    Google Scholar 

  94. Meusel, M., and T. Vering. Workshop report: concerted action ''Biosensor Stability'' in the EC-program on industrial and materials technologies (BRITE-EURAM). Biosens. Bioelectron. 13:IX-XI, 1998.

    Google Scholar 

  95. Millan, K. M., and S. R. Mikkelsen. Sequence-selective biosensor for DNA based on electroactive hybridization indicators. Anal. Chem. 65:2317–2323, 1993.

    Google Scholar 

  96. Miller, C., Ion Channel Reconstitution. New York: Plenum, 1986.

    Google Scholar 

  97. Minami, H., M. Sugawara, K. Odashima, Y. Umezawa, M. Uto, E. K. Michaelis, and T. Kuwana. Ion channel sensors for glutamic acid. Anal. Chem. 63:2787–2795, 1991.

    Google Scholar 

  98. Mitra, P., C. R. Keese, and I. Giaever. Electrical measurements can be used to monitor the attachment and spreading of cells in tissue culture. Biotechniques 11:504–510 1991.

    Google Scholar 

  99. Mrksich, M., L. E. Dike, J. Tien, D. E. Ingber, and G. M. Whitesides. Using microcontact printing to pattern the attachment of mammalian cells to self-assembled monolayers of alkanethiolates on transparent films of gold and silver. Exp. Cell Res. 235:305–313, 1997.

    Google Scholar 

  100. Narang, U., G. P. Anderson, F. S. Ligler, and J. Burans. Fiber optic-based biosensor for ricin. Biosens. Bioelectron. 12:937–945, 1997.

    Google Scholar 

  101. Nicolelis, M. A. L., L. A. Baccala, R. C. S. Lin, and J. K. Chapin. Sensorimotor encoding by synchronous neural ensemble activity at multiple levels of the somatosensory system. Science 268:1353–1358, 1995.

    Google Scholar 

  102. Nicolelis, M. A. L., and J. K. Chapin. Spatiotemporal structure of somatosensory responses of many-neuron ensembles in the rat ventral posterior medial nucleus of the thalamus. J. Neurosci. 14:3511–3532, 1994.

    Google Scholar 

  103. Nirenberg, M., S. P. Wilson, H. Higashida, A. Rotter, K. Kreuger, N. Busis, R. Ray, J. Kenimer, M. Adler, and H. Fukui. Synapse formation by neuroblastoma hybrid cells. Cold Spring Harbor Symp. Quant. Biol. 48:707–715, 1983.

    Google Scholar 

  104. Niwa, O., T. Horiuchi, R. Kurita, and K. Torimitsu. On-line electrochemical sensor for selective continuous measurement of acetylcholine in cultured brain tissue. Anal. Chem. 70:1126–1132, 1998.

    Google Scholar 

  105. Noiri, E., Y. Hu, W. F. Bahou, C. R. Keese, I. Giaever, and M. S. Goligorsky. Permissive role of nitric oxide in endothelin-induced migration of endothelial cells. J. Biol. Chem. 272:1747–1752, 1997.

    Google Scholar 

  106. Offenhäuser, A., C. Sprössler, M. Matsuzawa, and W. Knoll. Electrophysiological development of embryonic hippocampal neurons from the rat grown on synthetic thin films. Neurosci. Lett. 223:9–12, 1997.

    Google Scholar 

  107. Ogert, R. A., E. J. Brown, B. R. Singh, L. C. Shriver-Lake, and F. S. Ligler. Detection of Clostridium botulinum toxin A using a fibre optic-based biosensor. Anal. Biochem. 205:306–312, 1992.

    Google Scholar 

  108. Ogert, R. A., A. W. Kusterbeck, A. Gregorsy, R. B. Wemhoff, R. Burke, and F. S. Ligler. Detection of cocaine using the flow immunosensor. Anal. Lett 25:1999–2019, 1992.

    Google Scholar 

  109. Oroszlan, P., C. Thommen, M. Wehrli, G. Duveneck, and M. Ehrat. Automated optical sensing system for biochemical assays: a challenge for ELISA. Anal. Meth. Instrum. 1:43–51, 1993.

    Google Scholar 

  110. Orwar, O., K. Jardemark, I. Jacobson, A. Moscho, H. A. Fishman, R. H. Scheller, and R. N. Zare. Patch-clamp detection of neurotransmitters in capillary electrophoresis. Science 272:1779–1782, 1996.

    Google Scholar 

  111. Owicki, J. C., and J. W. Parce. Biosensors based on energy metabolism of living cells: The physical chemistry and cell biology of extracellular acidification. Biosens. Bioelectron. 7:255–272, 1992.

    Google Scholar 

  112. Owicki, J. C., J. W. Parce, K. M. Kercso, G. B. Sigal, V. C. Muir, J. C. Venter, C. M. Fraser, and H. M. McConnell. Continuous monitoring of receptor-mediated changes in the metabolic rates of living cells. Proc. Natl. Acad. Sci. USA 87:4007–4011, 1990.

    Google Scholar 

  113. Paddle, B. M. Biosensors for chemical and biological agents of defense interest. Biosens. Bioelectron. 11:1079–1113, 1996.

    Google Scholar 

  114. Pancrazio, J. J., P. P. Bey, D. S. Cuttino, J. K. Kusel, D. A. Borkholder, K. M. Shaffer, G. T. A. Kovacs, and D. A. Stenger. Portable cell-based biosensor system for toxin detection. Sens. Actuators B 53:179–185, 1998.

    Google Scholar 

  115. Pancrazio, J. J., P. P. Bey, A. Loloee, L. L. Howard, W. M. Gosney, D. A. Borkholder, G. T. A. Kovacs, P. Manos, D. S. Cuttino, and D. A. Stenger. Description and demonstration of a CMOS amplifier-based system with measurement and stimulation capability for bioelectrical signal transduction. Biosens. Bioelectron. 13:971–979, 1998.

    Google Scholar 

  116. Parce, J. W., J. C. Owicki, K. M. Kercso, G. B. Sigal, H. G. Wada, V. C. Muir, L. J. Bousse, K. L. Ross, B. I. Sikic, and H. M. McConnell. Detection of cell-affecting agents with a silicon biosensor. Science 246:243–247, 1989.

    Google Scholar 

  117. Pine, J. Recording action potentials from cultured neurons with extracellular microcircuit electrodes. J. Neurosci. Methods 2:19–31, 1980.

    Google Scholar 

  118. Piunno, P. A., U. J. Krull, R. H. Hudson, M. J. Damha, and H. Cohen. Fiber-optic DNA sensor for fluorometric nucleic acid determination. Clin. Chem. 67:2635–2643, 1995.

    Google Scholar 

  119. Pollard-Knight, D., E. Hawkins, D. Yeung, D. P. Pashby, M. Simpson, A. McDougall, P. Buckle, and S. A. Charles. Immunoassays and nucleic acid determination with a biosensor based on surface plasmon resonance. Ann. Biol. Clin. (Paris) 48:642–646, 1990.

    Google Scholar 

  120. Potyrailo, R. A., R. C. Conrad, A. D. Ellington, and G. M. Hieftje. Adapting selected nucleic acid ligands (aptamers) to biosensors. Anal. Chem. 70:3419–3425, 1998.

    Google Scholar 

  121. Rainina, E. I., E. N. Efremenco, S. D. Varfolomeyev, A. L. Simonian, and J. R. Wild, The development of a new biosensor based on recombinant E. coli for the direct detection of organophosphorous neurotoxins. Biosens. Bioelectron. 11:991–1000, 1996.

    Google Scholar 

  122. Raley-Susman, K. M., K. R. Miller, J. C. Owicki, and R. M. Sapolsky. Effects of excitotoxin exposure on metabolic rate of primary hippocampal cultures: Application of silicon microphysiometry to neurobiology. J. Neurosci. 12:773–780, 1992.

    Google Scholar 

  123. Ramsay, G. DNA chips: State-of-the art. Nat. Biotechnol. 16:40–44, 1998.

    Google Scholar 

  124. Regehr, W. G., J. Pine, and D. B. Rutledge. A long-term in vitro silicon-based microelectrode—neuron connection. IEEE Trans. Biomed. Eng. 35:1023–1031, 1989.

    Google Scholar 

  125. Rippeth, J. J., T. D. Gibson, J. P. Hart, I. C. Hartley, and G. Nelson. Flow-injection detector incorporating a screen-printed disposable amperometric biosensor for monitoring organophosphate pesticides. Analyst (Cambridge, U.K.) 122:1425–1429, 1997.

    Google Scholar 

  126. Rogers, K. R. Biosensors for environmental applications. Biosens. Bioelectron. 10:533–541, 1995.

    Google Scholar 

  127. Rosenmund, C., and G. L. Westbrook. Rundown of N-methyl-D-aspartate channels during whole-cell recording in rat hippocampal-neurons—Role of Ca2+ and ATP. J. Physiol. (London) 470:705–729, 1993.

    Google Scholar 

  128. Rowe, C. A., S. B. Scruggs, M. J. Feldstein, J. P. Golden, and F. S. Ligler. An array immunosensor for simultaneous detection of clinical analytes. Anal. Chem. 71:433–439.

  129. Ryan, M. R., J. P. Lowry, and R. D. O'Neill. Biosensor for neurotransmitter L-glutamic acid designed for efficient use of L-glutamate oxidase and effective rejection of interference. Analyst (Cambridge, U.K.) 122:1419–1424, 1997.

    Google Scholar 

  130. Schiff, S. J., K. Jerger, D. H. Duong, T. Chang, M. L. Spano, and W. L. Ditto. Controlling chaos in the brain. Nature (London) 370:615–620, 1994.

    Google Scholar 

  131. Selifonova, O., R. S. Burlage, and T. Barkay. Bioluminescent sensors for detection of bioavailable Hg(II) in the environment. Appl. Environ. Microbiol. 59:3083–3090, 1993.

    Google Scholar 

  132. Skeen, R. S., W. S. Kisaalita, and B. J. Van Wie. Evaluation of neuron-based sensing with the neurotransmitter serotonin. Biosens. Bioelectron. 5:491–510, 1990.

    Google Scholar 

  133. Skladal, P., and M. Mascini. Sensitive detection of pesticides using amperometric sensors based on cobalt phthalocyanine-modified composite electrodes and immobilized cholinesterases. Biosens. Bioelectron. 7:335–343, 1992.

    Google Scholar 

  134. Smith, T. J., H. S. Wang, M. G. Hogg, R. C. Henrikson, C. R. Keese, and I. Giaever. Prostaglandin E2 elicits a morphological change in cultured orbital fibroblasts from patients with Graves ophthalmopathy. Proc. Natl. Acad. Sci. USA 91:5094–5098, 1994.

    Google Scholar 

  135. So, P., J. T. Francis, T. I. Netoff, B. J. Gluckman, and S. J. Schiff. Periodic orbits: A new language for neuronal dynamics. Biophys. J. 74:2776–2785, 1998.

    Google Scholar 

  136. Stenger, D. A., D. H. Cribbs, and T. L. Fare. Modulation of a gated ion channel admittance in lipid bilayer membranes. Biosens. Bioelectron. 6:425–430, 1991.

    Google Scholar 

  137. Stenger, D. A., J. H. Georger, C. S. Dulcey, J. J. Hickman, A. S. Rudolph, T. B. Nielsen, S. M. McCort, and J. M. Calvert. Coplanar molecular assemblies of amino-and per-fluorinated alkylsilanes: Characterization and geometric definition of mammalian cell adhesion and growth. J. Am. Chem. Soc. 114:8435–8442, 1992.

    Google Scholar 

  138. Stenger, D. A., J. J. Hickman, K. E. Bateman, M. S. Ravenscroft, W. Ma, J. J. Pancrazio, K. M. Shaffer, A. E. Schaffner, D. H. Cribbs, and C. W. Cotman. Microlithographic determination of axonal/dendritic polarity in cultured hippocampal neurons. J. Neurosci. Methods 82:167–173, 1998.

    Google Scholar 

  139. Sticher, P., M. C. M. Jaspers, K. Stemmler, H. Harms, A. J. B. Zehnder, and J. R. van der Meer. Development and characterization of a whole-cell bioluminescent sensor for bioavailable middle chain alkanes in contaminated groundwater samples. Appl. Environ. Microbiol. 63:4053–4060, 1997.

    Google Scholar 

  140. Stoppini, L., S. Duport, and P. Correges. A new extracellular multirecording system for electrophysiological studies: application to hippocampal organotypic cultures. J. Neurosci. Methods 72:23–33, 1997.

    Google Scholar 

  141. Suleiman, A. A., and G. G. Guilbault. Recent developments in piezoelectric immunosensors. A review. Analyst (Cambridge, U.K.) 119:2279–2282, 1994.

    Google Scholar 

  142. Sullivan, E., E. M. Tucker, and I. L. Dale. Measurement of [Ca2+] using the fluorometric imaging plate reader (FLIPR). Methods Mol. Biol. 114:125–133, 1999.

    Google Scholar 

  143. Sutherland, R. M., C. Dähne, J. F. Place, and A. R. Ringrose. Optical detection of antibody-antigen reactions at a glass—liquid interface. Clin. Chem. 30:1533–1538, 1984.

    Google Scholar 

  144. Sutherland, R. M., C. Dähne, J. F. Place, and A. R. Ringrose. Immunoassays at a quartz-liquid—interface: Theory, instrumentation and preliminary application to the fluorescent immunoassay of human immunoglobulin G. J. Immunol. Methods 74:253–265, 1984.

    Google Scholar 

  145. Takahashi, T. Two statistical methods for analyzing multiple neuronal data. Int. J. Neurosci. 88:11–26, 1996.

    Google Scholar 

  146. Thomas, Jr., C. A., P. A. Springer, G. E. Loeb, Y. Berwald-Netter, and L. M. Okun. A miniature microelectrode array to monitor the bioelectric activity of cultured cells. Exp. Cell Res. 74:61–66, 1972.

    Google Scholar 

  147. Thompson, V. S., and C. M. Maragos. Fiber-optic immunosensor for the detection of fumonisin B-1. J. Agric. Food Chem. 44:1041–1046, 1996.

    Google Scholar 

  148. Tiruppathi, C., A. B. Malik, P. J. Del Vecchio, C. R. Keese, and I. Giaever. I. Electrical method for detection of endothelial cell shape change in real time: assessment of endothelial barrier function. Proc. Natl. Acad. Sci. USA 89:7919–7923, 1992.

    Google Scholar 

  149. Tsien, R. Y. Fluorescence measurement and photochemical manipulation of cytosolic free calcium. Trends Neurosci. 11:419–424, 1988.

    Google Scholar 

  150. Vassanelli, S., and P. Fromherz. Neurons from rat brain coupled to transistors. Appl. Phys. A: Mater. Sci. Process. 65:85–88, 1997.

    Google Scholar 

  151. Vassanelli, S., and P. Fromherz. Transistor records of excitable neurons from rat brain. Appl. Phys. A: Mater. Sci. Process. 66:459–463, 1998.

    Google Scholar 

  152. Watts, H. J., D. Yeung, and H. Parkes. Real-time detection and quantification of DNA hybridization by an optical biosensor. Anal. Chem. 67:4283–4289, 1995.

    Google Scholar 

  153. Whelan, J. P., A. W. Kusterbeck, G. A. Wemhoff, R. Bredehorst, and F. S. Ligler. Continuous-flow immunosensor for detection of explosives. Anal. Chem. 65:3561–3565, 1993.

    Google Scholar 

  154. Wilkins, E., and P. Atanasov. Glucose monitoring: state of the art and future possibilities. Med. Eng. Phys. 18:273–288, 1996.

    Google Scholar 

  155. Wolf, B., M. Brischwein, W. Baumann, R. Ehret, and M. Kraus. Monitoring of cellular signalling and metabolism with modular sensor-technique: The PhysioControl-Microsystem (PCM®). Biosens. Bioelectron. 13:501–509, 1998.

    Google Scholar 

  156. Zhang, H. X., and L. G. Sultatos. Biotransformation of the organophosphorous insecticides parathion and methyl parathion in male and female rat livers perfused in situ. Drug Metab. Dispos. 19:473–477, 1991.

    Google Scholar 

  157. Zysk, J. R., and W. R. Baumbach. Homogeneous pharmacologic and cell-based screens provide diverse strategies in drug discovery: somatostatin antagonists as a case study. Comb. Chem. High Throughput Screening 1:171–183, 1998.

    Google Scholar 

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Pancrazio, J.J., Whelan, J.P., Borkholder, D.A. et al. Development and Application of Cell-Based Biosensors. Annals of Biomedical Engineering 27, 697–711 (1999). https://doi.org/10.1114/1.225

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