IJAT Vol.12 No.1 pp. 52-63
doi: 10.20965/ijat.2018.p0052


Bioanalytical Method Based on Extended-Gate Field-Effect Transistor Modified by Self-Assembled Monolayer

Taira Kajisa*,† and Toshiya Sakata**

The University of Tokyo Entrepreneur Plaza, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

Corresponding author

**Department of Material Engineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan

June 9, 2017
November 23, 2017
January 5, 2018
field-effect transistor, self-assembled monolayer, extended-gate

In this paper, we introduce semiconductor biosensors for detecting or monitoring various biological substances and for surface chemical technologies tailored to target molecules. To fabricate the semiconductor biosensor best suited to the target biomolecules, the gate electrodes for extended-gate type field-effect transistors (EGFETs), which are separated from semiconductor part, must be constructed by interfacial chemical modification. First, ion-sensitive EGFET was developed by self-assembled monolayer (SAM) modification on gold gate electrode. Polar functional-group-terminated alkanethiol SAM-coated-gate FET showed pH dependency. In particular, carboxy-terminated alkanethiol SAM-coated gate FET showed higher sensitivities from 42 to 56 mV/pH, which was close to the Nernstian response, in a wide range of biological environments. By using the ion-sensitive EGFET, the hydroxyapatite biomineralization process was successfully monitored by increasing the gate surface potential. Furthermore, saccharides were quantified using EGFET by changing the functional group of SAM, with phenylboronic acid as a functional molecule. In conclusion, target-specific surface modification on gate electrodes makes it possible for semiconductor devices to be applied as biosensors.

  1. [1] L. C. J. Qlark, “Monitor and Control of Blood and Tissue Oxygen Tensions,” ASAIO J., Vol.2m No.1, pp. 41-48, 1956.
  2. [2] S. J. Updike, and G. P. Hicks, “The Enzyme Electrode,” Nature, Vol.214, No.5092, pp. 986-988, 1967.
  3. [3] P. Bergveld, “Development of an Ion-Sensitive Solid-State Device for Neurophysiological Measurements,” IEEE Trans. Biomed. Eng., Vol.1, pp. 70-71, 1970.
  4. [4] P. Fromherz and A. Offenhausser, “A Neuron-Silicon Junction: A Retzius Cell of the Leech on an Insulated-Gate Field-Effect Transistor,” Science, Vol.252, No.5010, pp. 1290, 1991.
  5. [5] B. Straub, E. Meyer, and P. Fromherz, “Recombinant Maxi-K Channels on Transistor, a Prototype of Iono-Electronic Interfacing,” Nat. Biotechnol., Vol.19, No.2, pp. 121-124, 2001.
  6. [6] T. Sakata and Y. Miyahara, “DNA Sequencing Based on Intrinsic Molecular Charges,” Angew. Chem. Int. Ed., Vol.45, No.14, pp. 2225-2228, 2006.
  7. [7] T. Sakata, S. Matsumoto, Y. Nakajima, and Y. Miyahara, “Potential Behavior of Biochemically Modified Gold Electrode for Extended-Gate Field-Effect Transistor,” Jpn. J. Appl. Phys., Vol.44, No.4S, p. 2860, 2005.
  8. [8] R. G. Nuzzo and D. L. Allara, “Adsorption of Bifunctional Organic Disulfides on Gold Surfaces,” J. Am. Chem. Soc., Vol.105, No.13, pp. 4481-4483, 1983.
  9. [9] H. O. Finklea, S. Avery, M. Lynch, and T. Furtsch, “Blocking Oriented Monolayers of Alkyl Mercaptans on Gold Electrodes,” Langmuir, Vol.3, No.3, pp. 409-413, 1987.
  10. [10] L H Dubois and R. G. Nuzzo, “Synthesis, Structure, and Properties of Model Organic Surfaces,” Annu. Rev. Phys. Chem., Vol.43, No.1, pp. 437-463, 1992.
  11. [11] L. Strong and G. M. Whitesides, “Structures of Self-Assembled Monolayer Films of Organosulfur Compounds Adsorbed on Gold Single Crystals: Electron Diffraction Studies,” Langmuir, Vol.4, No.3, pp. 546-558, 1988.
  12. [12] C. D. Bain and G. M. Whitesides, “Formation of Monolayers by the Coadsorption of Thiols on Gold: Variation in the Length of the Alkyl Chain,” J. Am. Chem. Soc., Vol.111, No.18, pp. 7164-7175, 1989.
  13. [13] C. D. Bain and G. M. Whitesides, “Modeling Organic Surfaces with Self-Assembled Monolayers,” Angewandte Chemie International Edition in English, Vol.28, No.4, pp. 506-512, 1989.
  14. [14] M. D. Porter, T. B. Bright, D. L. Allara, and C. E. D. Chidsey, “Spontaneously Organized Molecular Assemblies. 4. Structural Characterization of N-Alkyl Thiol Monolayers on Gold by Optical Ellipsometry, Infrared Spectroscopy, and Electrochemistry,” J. Am. Chem. Soc., Vol.109, No.12, pp. 3559-3568, 1987.
  15. [15] P. Bergveld, “Development, Operation, and Application of the Ion-Sensitive Field-Effect Transistor as a Tool for Electrophysiology,” IEEE Trans. Biomed. Eng., Vol.BME-19, No.5, pp. 342-351, 1972.
  16. [16] S. Caras and J. Janata, “Field Effect Transistor Sensitive to Penicillin,” Anal. Chem., Vol.52, No.12, pp. 1935-1937, 1980.
  17. [17] V. Volotovsky and N. Kim, “Determination of Glucose, Ascorbic and Citric Acids by Two-Isfet Multienzyme Sensor,” Sensors Actuators B: Chem., Vol.49, No.3, pp. 253-257, 1998.
  18. [18] K.-Y. Park, S.-B. Choi, M. Lee, B.-K. Sohn, and S.-Y. Choi, “Isfet Glucose Sensor System with Fast Recovery Characteristics by Employing Electrolysis,” Sensors Actuators B: Chem., Vol.83, Nos.1–3, pp. 90-97, 2002.
  19. [19] T. Sakata, M. Kamahori, and Y. Miyahara, “DNA Analysis Chip Based on Field-Effect Transistors,” Japanese J. of Applied Physics Part 1-Regular Papers Brief Communications & Review Papers, Vol.44, No.4B, pp. 2854-2859, 2005.
  20. [20] A. Star, E. Tu, J. Niemann, J. C. P. Gabriel, C. S. Joiner, and C. Valcke, “Label-Free Detection of DNA Hybridization Using Carbon Nanotube Network Field-Effect Transistors,” Proc. Natl. Acad. Sci. U.S.A., Vol.103, No.4, pp. 921-926, 2006.
  21. [21] T. Sakata, I. Makino, S. Kita, and Y. Miyahara, “Electrical Detection of Ovum Membrane Charges Using Biotransistor,” Microelectron. Eng., Vol.85, No.5-6, pp. 1337-1340, 2008.
  22. [22] T. Sakata and Y. Miyahara, “Detection of Molecular Charges at Cell Membrane,” Jpn. J. Appl. Phys., Vol.47, No.1, pp. 368-370, 2008.
  23. [23] T. Sakata and Y. Miyahara, “Noninvasive Monitoring of Transporter-Substrate Interaction at Cell Membrane,” Anal. Chem., Vol.80, No.5, pp. 1493-1496, 2008.
  24. [24] J. M. Rothberg, W. Hinz, T. M. Rearick, J. Schultz, W. Mileski, M. Davey, J. H. Leamon, K. Johnson, M. J. Milgrew, M. Edwards, J. Hoon, J. F. Simons, D. Marran, J. W. Myers, J. F. Davidson, A. Branting, J. R. Nobile, B. P. Puc, D. Light, T. A. Clark, M. Huber, J. T. Branciforte, I. B. Stoner, S. E. Cawley, M. Lyons, Y. Fu, N. Homer, M. Sedova, X. Miao, B. Reed, J. Sabina, E. Feierstein, M. Schorn, M. Alanjary, E. Dimalanta, D. Dressman, R. Kasinskas, T. Sokolsky, J. A. Fidanza, E. Namsaraev, K. J. McKernan, A. Williams, G. T. Roth, and J. Bustillo, “An Integrated Semiconductor Device Enabling Non-Optical Genome Sequencing,” Nature, Vol.475, No.7356, pp. 348-352, 2011.
  25. [25] I. Taniguchi, K. Toyosawa, H. Yamaguchi, and K. Yasukouchi, “Reversible Electrochemical Reduction and Oxidation of Cytochrome-C at a Bis(4-Pyridyl) Disulfide-Modified Gold Electrode,” J. of the Chemical Society-Chemical Communications, Vol.18, pp. 1032-1033, 1982.
  26. [26] C. D. Bain and G. M. Whitesides, “Formation of Two-Component Surfaces by the Spontaneous Assembly of Monolayers on Gold from Solutions Containing Mixtures of Organic Thiols,” J. Am. Chem. Soc., Vol.110, No.19, pp. 6560-6561, 1988.
  27. [27] J. B. Schlenoff, M. Li, and H. Ly, “Stability and Self-Exchange in Alkanethiol Monolayers,” J. Am. Chem. Soc., Vol.117, No.50, pp. 12528-12536, 1995.
  28. [28] P. E. Laibinis, G. M. Whitesides, D. L. Allara, Y. T. Tao, A. N. Parikh, and R. G. Nuzzo, “Comparison of the Structures and Wetting Properties of Self-Assembled Monolayers of N-Alkanethiols on the Coinage Metal Surfaces, Copper, Silver, and Gold,” J. Am. Chem. Soc., Vol.113, No.19, pp. 7152-7167, 1991.
  29. [29] S. Chon and W.-K. Paik, “Adsorption of Self-Assembling Sulfur Compounds through Electrochemical Reactions: Effects of Potential, Acid and Oxidizing Agents,” PCCP, Vol.3, No.16, pp. 3405-3410, 2001.
  30. [30] B. Kong, Y. Kim, and I. S. Choi, “Ph-Dependent Stability of Self-Assembled Monolayers on Gold,” Bull. Korean Chem. Soc, Vol.29, No.9, pp. 1843-1846, 2008.
  31. [31] T. Goda and Y. Miyahara, “Detection of Microenvironmental Changes Induced by Protein Adsorption onto Self-Assembled Monolayers Using an Extended Gate-Field Effect Transistor,” Anal. Chem., Vol.82, No.5, pp. 1803-1810, 2010.
  32. [32] K. M. Towe, “Biomineralization,” Science, Vol.196, No.4296, pp. 1311-1311, 1977.
  33. [33] D. McConnell, W. J. Frajola, and D. W. Deamer, “Relation between the Inorganic Chemistry and Biochemistry of Bone Mineralization,” Science, Vol.133, No.3448, pp. 281-282, 1961.
  34. [34] J. D. Termine, H. K. Kleinman, S. W. Whitson, K. M. Conn, M. L. McGarvey, and G. R. Martin, “Osteonectin, a Bone-Specific Protein Linking Mineral to Collagen,” Cell, Vol.26 (1 Pt 1), pp. 99-105, 1981.
  35. [35] J. P. Gorski and K. Shimizu, “Isolation of New Phosphorylated Glycoprotein from Mineralized Phase of Bone That Exhibits Limited Homology to Adhesive Protein Osteopontin,” J. Biol. Chem., Vol.263, No.31, pp. 15938-15945, 1988.
  36. [36] P. V. Hauschka, J. B. Lian, D. E. Cole, and C. M. Gundberg, “Osteocalcin and Matrix Gla Protein: Vitamin K-Dependent Proteins in Bone,” Physiol. Rev., Vol.69, No.3, pp. 990-1047, 1989.
  37. [37] Q. Zhang, C. Domenicucci, H. A. Goldberg, J. L. Wrana, and J. Sodek, “Characterization of Fetal Porcine Bone Sialoproteins, Secreted Phosphoprotein I (Sppi, Osteopontin), Bone Sialoprotein, and a 23-Kda Glycoprotein. Demonstration That the 23-Kda Glycoprotein Is Derived from the Carboxyl Terminus of Sppi,” J. Biol. Chem., Vol.265, No.13, pp. 7583-7589, 1990.
  38. [38] M. F. Young, J. M. Kerr, K. Ibaraki, A. M. Heegaard, and P. G. Robey, “Structure, Expression, and Regulation of the Major Noncollagenous Matrix Proteins of Bone,” Clin. Orthop. Relat. Res., Vol.281, pp. 275-294, 1992.
  39. [39] T. Iwatsubo, K. Sumaru, T. Kanamori, T. Shinbo, and T. Yamaguchi, “Construction of a New Artificial Biomineralization System,” Biomacromolecules, Vol.7, No.1, pp. 95-100, 2006.
  40. [40] T. Iwatsubo and T. Yamaguchi, “Hypercomplex Gel Changes to Organic/Inorganic Solid Solution by Phase Transition in an Artificial Biomineralization System,” Polym. J, Vol.40, No.10, pp. 958-964, 2008.
  41. [41] A. A. Campbell, G. E. Fryxell, J. C. Linehan, and G. L. Graff, “Surface-Induced Mineralization: A New Method for Producing Calcium Phosphate Coatings,” J. of Biomedical Materials Research, Vol.32, No.1, pp. 111-118, 1996.
  42. [42] J. Aizenberg, A. J. Black, and G. M. Whitesides, “Control of Crystal Nucleation by Patterned Self-Assembled Monolayers,” Nature, Vol.398, No.6727, pp. 495-498, 1999.
  43. [43] Q. Liu, J. Ding, F. K. Mante, S. L. Wunder, and G. R. Baran, “The Role of Surface Functional Groups in Calcium Phosphate Nucleation on Titanium Foil: A Self-Assembled Monolayer Technique,” Biomaterials, Vol.23, No.15, pp. 3103-3111, 2002.
  44. [44] M. Tanahashi and T. Matsuda, “Surface Functional Group Dependence on Apatite Formation on Self-Assembled Monolayers in a Simulated Body Fluid,” J. of Biomedical Materials Research, Vol.34, No.3, pp. 305-315, 1997.
  45. [45] I. Hirata, M. Akamatsu, E. Fujii, S. Poolthong, and M. Okazaki, “Chemical Analyses of Hydroxyapatite Formation on Sam Surfaces Modified with Cooh, Nh2, Ch3, and Oh Functions,” Dental materials J., Vol.29, No.4, pp. 438-445, 2010.
  46. [46] M. Jäger, J. Fischer, A. Schultheis, S. Lensing-Höhn, and R. Krauspe, “Extensive H+ Release by Bone Substitutes Affects Biocompatibility in Vitro Testing,” J. of Biomedical Materials Research Part A, Vol.76A, No.2, pp. 310-322, 2006.
  47. [47] Z.-X. Liu, X.-M. Wang, Q. Wang, X.-C. Shen, H. Liang, and F.-Z. Cui, “Evolution of Calcium Phosphate Crystallization on Three Functional Group Surfaces with the Same Surface Density,” CrystEngComm, Vol.14, No.20, pp. 6695-6701, 2012.
  48. [48] H. Colfen, “Biomineralization: A Crystal-Clear View,” Nat Mater, Vol.9, No.12, pp. 960-961, 2010.
  49. [49] M. A. Rampi, O. J. A. Schueller, and G. M. Whitesides, “Alkanethiol Self-Assembled Monolayers as the Dielectric of Capacitors with Nanoscale Thickness,” Appl. Phys. Lett., Vol.72, No.14, pp. 1781-1783, 1998.
  50. [50] J. C. Sacchettini, L. G. Baum, and C. F. Brewer, “Multivalent Protein-Carbohydrate Interactions. A New Paradigm for Supermolecular Assembly and Signal Transduction,” Biochemistry, Vol.40, No.10, pp. 3009-3015, 2001.
  51. [51] S. Hakomori, “Carbohydrate-to-Carbohydrate Interaction, through Glycosynapse, as a Basis of Cell Recognition and Membrane Organization,” Glycoconjugate J., Vol.21, Nos.3-4, pp. 125-137, 2004.
  52. [52] T. W. Siegel, S. R. Smith, C. A. Ellery, J. R. Williamson, and P. J. Oates, “An Enzymatic Fluorometric Assay for Fructose,” Anal. Biochem., Vol.280, No.2, pp. 329-331, 2000.
  53. [53] M. H. Abraham, H. S. Chadha, R. A. Leitao, R. C. Mitchell, W. J. Lambert, R. Kaliszan, A. Nasal, and P. Haber, “Determination of Solute Lipophilicity, as Log P (Octanol) and Log P (Alkane) Using Poly (Styrene–Divinylbenzene) and Immobilised Artificial Membrane Stationary Phases in Reversed-Phase High-Performance Liquid Chromatography,” J. Chromatogr. A, Vol.766, No.1, pp. 35-47, 1997.
  54. [54] D. Fu, and R. A. Oneill, “Monosaccharide Composition Analysis of Oligosaccharides and Glycoproteins by High-Performance Liquid Chromatography,” Anal. Biochem., Vol.227, No.2, pp. 377-384, 1995.
  55. [55] H. Kwon, and J. Kim, “Determination of Monosaccharides in Glycoproteins by Reverse-Phase High-Performance Liquid Chromatography,” Anal. Biochem., Vol.215, No.2, pp. 243-252, 1993.
  56. [56] K. Anumula, “Quantitative Determination of Monosaccharides in Glycoproteins by High-Performance Liquid Chromatography with Highly Sensitive Fluorescence Detection,” Anal. Biochem., Vol.220, No.2, pp. 275-283, 1994.
  57. [57] Y. B. Vassilyev, O. Khazova, and N. Nikolaeva, “Kinetics and Mechanism of Glucose Electrooxidation on Different Electrode-Catalysts: Part I. Adsorption and Oxidation on Platinum,” J. of electroanalytical chemistry and interfacial electrochemistry, Vol.196, No.1, pp. 105-125, 1985.
  58. [58] B. Beden, F. Largeaud, K. Kokoh, and C. Lamy, “Fourier Transform Infrared Reflectance Spectroscopic Investigation of the Electrocatalytic Oxidation of D-Glucose: Identification of Reactive Intermediates and Reaction Products,” Electrochim. Acta, Vol.41, No.5, pp. 701-709, 1996.
  59. [59] I. Bae, E. Yeager, X. Xing, and C. Liu, “In Situ Infrared Studies of Glucose Oxidation on Platinum in an Alkaline Medium,” J. of electroanalytical chemistry and interfacial electrochemistry, Vol.309, Nos.1-2, pp. 131-145, 1991.
  60. [60] M. Hsiao, R. Adžić, and E. Yeager, “Electrochemical Oxidation of Glucose on Single Crystal and Polycrystalline Gold Surfaces in Phosphate Buffer,” J. Electrochem. Soc., Vol.143, No.3, pp. 759-767, 1996.
  61. [61] R. Adzic, M. Hsiao, and E. Yeager, “Electrochemical Oxidation of Glucose on Single Crystal Gold Surfaces,” J. of electroanalytical chemistry and interfacial electrochemistry, Vol.260, No.2, pp. 475-485, 1989.
  62. [62] C. J. Davis, P. T. Lewis, M. E. McCarroll, M. W. Read, R. Cueto, and R. M. Strongin, “Simple and Rapid Visual Sensing of Saccharides,” Org. Lett., Vol.1, No.2, pp. 331-334, 1999.
  63. [63] K. Koumoto and S. Shinkai, “Colorimetric Sugar Sensing Method Useful in “Neutral” Aqueous Media,” Chem. Lett., Vol.29, No.8, pp. 856-857, 2000.
  64. [64] S. Gao, W. Wang, and B. Wang, “Building Fluorescent Sensors for Carbohydrates Using Template-Directed Polymerizations,” Bioorg. Chem., Vol.29 (5), pp. 308-320, 2001.
  65. [65] N. DiCesare, and J. R. Lakowicz, “Chalcone-Analogue Fluorescent Prfobes for Saccharides Signaling Using the Boronic Acid Group,” Tetrahedron Lett., Vol.43, No.14, pp. 2615-2618, 2002.
  66. [66] J. N. Camara, J. T. Suri, F. E. Cappuccio, R. A. Wessling, and B. Singaram, “Boronic Acid Substituted Viologen Based Optical Sugar Sensors: Modulated Quenching with Viologen as a Method for Monosaccharide Detection,” Tetrahedron Lett., Vol.43, No.7, pp. 1139-1141, 2002.
  67. [67] D. B. Cordes, A. Miller, S. Gamsey, Z. Sharrett, P. Thoniyot, R. Wessling, and B. Singaram, “Optical Glucose Detection across the Visible Spectrum Using Anionic Fluorescent Dyes and a Viologen Quencher in a Two-Component Saccharide Sensing System,” Organic & biomolecular chemistry, Vol.3, No.9, pp. 1708-1713, 2005.
  68. [68] T. Kimura, M. Takeuchi, T. Nagasaki, and S. Shinkai, “Sugar-Induced Color and Orientation Changes in a Cyanine Dye Bound to Boronic-Acid-Appended Poly (L-Lysine),” Tetrahedron Lett., Vol.36, No.4, pp. 559-562, 1995.
  69. [69] M. Takeuchi, T. Mizuno, S. Shinkai, S. Shirakami, and T. Itoh, “Chirality Sensing of Saccharides Using a Boronic Acid-Appended Chiral Ferrocene Derivative,” Tetrahedron: Asymmetry, Vol.11, No.16, pp. 3311-3322, 2000.
  70. [70] M. Lee, T.-I. Kim, K.-H. Kim, J.-H. Kim, M.-S. Choi, H.-J. Choi, and K. Koh, “Formation of a Self-Assembled Phenylboronic Acid Monolayer and Its Application toward Developing a Surface Plasmon Resonance-Based Monosaccharide Sensor,” Anal. Biochem., Vol.310, No.2, pp. 163-170, 2002.
  71. [71] N. Soh, M. Sonezaki, and T. Imato, “Modification of a Thin Gold Film with Boronic Acid Membrane and Its Application to a Saccharide Sensor Based on Surface Plasmon Resonance,” Electroanalysis, Vol.15, No.15-16, pp. 1281-1290, 2003.
  72. [72] Y. Ben-Amram, M. Riskin, and I. Willner, “Selective and Enantioselective Analysis of Mono-and Disaccharides Using Surface Plasmon Resonance Spectroscopy and Imprinted Boronic Acid-Functionalized Au Nanoparticle Composites,” Analyst, Vol.135, No.11, pp. 2952-2959, 2010.
  73. [73] S. Barker, A. Chopra, B. Hatt, and P. Somers, “The Interaction of Areneboronic Acids with Monosaccharides,” Carbohydr. Res., Vol.26, No.1, pp. 33-40, 1973.
  74. [74] G. Springsteen, and B. Wang, “A Detailed Examination of Boronic Acid – Diol Complexation,” Tetrahedron, Vol.58, No.26, pp. 5291-5300, 2002.
  75. [75] J. Yan, G. Springsteen, S. Deeter, and B. Wang, “The Relationship among Pk a, Ph, and Binding Constants in the Interactions between Boronic Acids and Diols – It Is Not as Simple as It Appears,” Tetrahedron, Vol.60, No.49, pp. 11205-11209, 2004.
  76. [76] O. B. Ayyub, M. B. Ibrahim, R. M. Briber, and P. Kofinas, “Self-Assembled Block Copolymer Photonic Crystal for Selective Fructose Detection,” Biosens. Bioelectron., Vol.46, pp. 124-129, 2013.
  77. [77] G. E. K. Branch, D. L. Yabroff, and B. Bettman, “The Dissociation Constants of the Chlorophenyl and Phenetyl Boric Acids1,” J. Am. Chem. Soc., Vol.56, No.4, pp. 937-941, 1934.
  78. [78] S. Soundararajan, M. Badawi, C. M. Kohlrust, and J. H. Hageman, “Boronic Acids for Affinity Chromatography: Spectral Methods for Determinations of Ionization and Diol-Binding Constants,” Anal. Biochem., Vol.178, No.1, pp. 125-134, 1989.
  79. [79] S. J. Angyal, D. Greeves, and V. A. Pickles, “The Stereochemistry of Complex Formation of Polyols with Borate and Periodate Anions, and with Metal Cations,” Carbohydr. Res., Vol.35, No.1, pp. 165-173, 1974.
  80. [80] F. Franks, “Physical Chemistry of Small Carbohydrates-Equilibrium Solution Properties,” Pure Appl. Chem., Vol.59, No.9, pp. 1189-1202, 1987.
  81. [81] G. C. Levy, D. J. Craik, Y.-C. Chou, and R. E. London, “13 C Nmr Relaxation and Conformational Flexibility of the Deoxyribose Ring,” Nucleic Acids Res., Vol.10, No.19, pp. 6067-6083, 1982.
  82. [82] J. T. La Belle, D. K. Bishop, S. R. Vossler, D. R. Patel, and C. B. Cook, “A Disposable Tear Glucose Biosensor – Part 2: System Integration and Model Validation,” J. of Diabetes Science and Technology, Vol.4, No.2, pp. 307-311, 2010.
  83. [83] H. Kaiser, “Die Berechnung Der Nachweisempfindlichkeit,” Spectrochim. Acta, Vol.3, No.1, pp. 40-67, 1947.
  84. [84] B. Peng, J. Lu, A. S. Balijepalli, T. C. Major, B. E. Cohan, and M. E. Meyerhoff, “Evaluation of Enzyme-Based Tear Glucose Electrochemical Sensors over a Wide Range of Blood Glucose Concentrations,” Biosens. Bioelectron., Vol.49, pp. 204-209, 2013.

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