Process control in cell culture technology using dielectric spectroscopy

Biotechnology Advances

Volumn 29, Issue 4, 2011, Pages 391-401

  Justice, C ^a   Brix, A ^b,d   Freimark, D ^a   Kraume, M ^c   Pfromm, P ^b   Eichenmueller, B ^d   Czermak, P ^a,b  

^a Giessen Friedberg University of Applied Science   (Germany)

^b 129 Seaton Hall   (United States)

^c TECHNISCHE UNIVERSITÄT BERLIN   (Germany)

^d BOEHRINGER INGELHEIM VETMEDICA INC   (United States)

Author keywords

Biomass monitoring; Cell culture technology; Dielectric spectroscopy; PAT; Process control

Indexed keywords

BIOCHEMICAL PROCESS; BIOLOGICAL CELLS; BIOMASS MONITORING; BIOPHARMACEUTICAL INDUSTRY; BIOPHARMACEUTICALS; CELL-BASED; CULTURE PARAMETERS; DIELECTRIC SENSING; FUTURE APPLICATIONS; IN-LINE MONITORING; INSECT CELL CULTURE; INSECT CELLS; MEDICAL FIELDS; PAT; PROCESS ANALYTICAL TECHNOLOGY; PROCESS MONITORING AND CONTROL; PROCESS OPTIMIZATION; PRODUCT QUALITY; PRODUCTION PROCESS; REAL-TIME PROCESS MONITORING; STEM CELL THERAPY;

CELL CULTURE; CHEMICAL SENSORS; COST REDUCTION; DIELECTRIC DEVICES; DIELECTRIC SPECTROSCOPY; INDUSTRIAL RESEARCH; MAMMALS; OPTIMIZATION; PLANT CELL CULTURE; PROCESS MONITORING; STEM CELLS; TECHNOLOGY;

PROCESS CONTROL;

BIOCHEMISTRY; BIOTECHNOLOGY; CONTROL SYSTEM; COST-BENEFIT ANALYSIS; DISEASE TREATMENT; INSECT; MAMMAL; MONITORING SYSTEM; OPTIMIZATION; PHARMACEUTICAL INDUSTRY; PLANT; SENSOR; SPECTROSCOPY;

ANIMAL; BIOMASS; BIOTECHNOLOGY; CULTURE TECHNIQUE; ELECTROCHEMICAL IMPEDANCE SPECTROSCOPY; INSTRUMENTATION; METHODOLOGY; REVIEW;

ANIMALS; BIOMASS; BIOTECHNOLOGY; CELL CULTURE TECHNIQUES; DIELECTRIC SPECTROSCOPY;

HEXAPODA; MAMMALIA;

EID: 79955590003     PISSN: 07349750     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.biotechadv.2011.03.002     Document Type: Review

References (105)

1. viable biomass probes for disposable bioreactors February 2008, Aber Instruments, Press Release, [cited 15.12.2009]; Available from: http://www.aber-instruments.co.uk.
2. Alexander B.L., Ali R.R., Alton E.W., Bainbridge J.W., Braun S., Cheng S.H., et al. Progress and prospects: gene therapy clinical trials (part 1). Gene Ther 2007, 14(20):1439.
3. Ansorge S., Esteban G., Schmid G. On-line monitoring of infected Sf-9 insect cell cultures by scanning permittivity measurements and comparison with off-line biovolume measurements. Cytotechnology 2007, 55(2-3):115-124.
4. Ansorge S., Esteban G., Schmid G. Multifrequency permittivity measurements enable on line monitoring of changes in intracellular conductivity due to nutrient limitations during batch cultivations of CHO cells. Biotechnol Prog 2010, 26(1):272-283.
5. Arnold W.M. Monitoring of biological cell collection by dielectric spectroscopy. Annular Report Conference on Electrical Insulation and Dielectric Phenomena 2001, [cited 15.12.2009]; Available from: http://ieeexplore.ieee.org/stamp/stamp.jsp?arnumber=00963484.
6. Asami K., Gheorghiu E., Yonezawa T. Real-time monitoring of yeast cell division by dielectric spectroscopy. Biophys J 1999, 76(6):3345-3348.
7. Austin G.D., Watson R.W.J., D'Amore T. Studies of online viable yeast biomass with a capacitance biomass monitor. Ferment Bioindustrial Chem 1994, 43(4):337-341.
8. Baldi L., Hacker D.L., Adam M., Wurm F. Recombinant protein production by large-scale transient gene expression in mammalian cells: state of the art and future perspectives. Biotechnol Lett 2007, 29(5):677-684.
9. Barsoukov E., Macdonald J.R. Impedance spectroscopy: theory, experiment, and applications 2005, Wiley-Interscience.
10. Blute T., Gillies R., Dale B.E. Cell density measurements in hollow fiber bioreactors. Biotechnol Prog 1988, 4:202-209.
11. Boudreau M., Benton T. Bioprocess control: what the next 15 years will bring 14.12.2009 [cited 15.12.2009]; Available from:. http://www.emersonprocess.com/2008.
12. Bragos R., Sarro E., Fontova A., Soley A., Cairo J., Bayes-Genis A., et al. Four versus two-electrode measurement strategies for cell growing and differentiation monitoring using electrical impedance spectroscopy. Conf Proc IEEE Eng Med Biol Soc 2006, 1:2106-2109.
13. Butler M. Animal cell cultures: recent achievements and perspectives in the production of biopharmaceuticals. Appl Microbiol Biotechnol 2005, 68(3):283-291.
14. Cannizzaro C., Gugerli R., Marison I., Von Stockar U. On-line biomass monitoring of CHO perfusion culture with scanning dielectric spectroscopy. Biotechnol Bioeng 2003, 84(5):597-610.
15. Carvell J.P. Viable Biomass Sensor for Bioreactors. BIOforum Europe 2008, 54-55. Darmstadt, Germany.
16. Carvell J.P., Dowd J.E. On-line measurements and control of viable cell density in cell culture manufacturing processes using radio-frequency impedance. Cytotechnology 2006, 50(1-3):35-48.
17. Cerckel I., Garcia A., Degouys V., Dubois D., Fabry L., Miller A.O. Dielectric spectroscopy of mammalian cells. 1. Evaluation of the biomass of HeLa- and CHO cells in suspension by low-frequency dielectric spectroscopy. Cytotechnology 1993, 13(3):185-193.
18. Ceriotti L., Ponti J., Broggi F., Kob A., Drechsler S., Thedinga E., et al. Real-time assessment of cytotoxicity by impedance measurement on a 96-well plate. Sens Actuat B 2007, 123:769-778.
19. Ceriotti L., Ponti J., Colpo P., Sabbioni E., Rossi F. Assessment of cytotoxicity by impedance spectroscopy. Biosens Bioelectron 2007, 22(12):3057-3063.
20. Chew W., Sharratt P. Trends in process analytical technology. Anal Methods 2010, 2(10):1412-1438.
21. Clementschitsch F., Bayer K. Improvement of bioprocess monitoring: development of novel concepts. Microb Cell Fact 2006, 5:19.
22. Cook J.A., Mitchell J.B. Viability measurements in mammalian cell systems. Anal Biochem 1989, 179(1):1-7.
23. Coster H.G.L., Chilcott T.C., Coster A.C.F. Impedance spectroscopy of interfaces, membranes and ultrastructures. Bioelectrochem Bioenerg 1996, 40(2):79-98. 902.
24. Czermak P., Poertner R., Brix A. Special engineering aspects. Cell and tissue reaction engineering 2009, 83-172. Springer- Verlag, Berlin Heidelberg. R. Eibl, D. Eibl, R. Poertner (Eds.).
25. Dalmay C., Cheray M., Pothier A., Lalloué F., Jauberteau M.O., Blondy P. Ultra sensitive biosensor based on impedance spectroscopy at microwave frequencies for cell scale analysis. Sens Actuat A 2009, 1(1):742-745.
26. Daniell H., Streatfield S.J., Wycoff K. Medicalmolecular farming: production of antibodies, biopharmaceuticals and edible vaccines in plants. Trends Plant Sci 2001, 6(5):219-226.
27. Davey C.I., Davey H.M., Kell D.B., Todd R.W. Introduction to the dielectric estimation of cellular biomass in real time, with special emphasis on measurements at high volume fractions. Anal Chim Acta 1993, 279(1):155-161.
28. Davey C.I., Markx G.H., Kell D.B. On the dielectric method of monitoring cellular viability. Pure Appl Chem 1993, 65(9):1921-1926.
29. Davey CI, Guan Y, Kemp RB, Kell DB. Real-time monitoring of the biomass content of animal cell cultures using dielectric spectroscopy. In Animal Cell technology.: Basic Appl. Aspects 8: 61-65.
30. De Beer T.R., Baeyens W.R., Ouyang J., Vervaet C., Remon J.P. Raman spectroscopy as a process analytical technology tool for the understanding and the quantitative in-line monitoring of the homogenization process of a pharmaceutical suspension. Analyst 2006, 131(10):1137-1144.
31. Degouys V., Cerckel I., Garcia A., Harfield J., Dubois D., Fabry L., et al. Dielectric spectroscopy of mammalian cells. 2. Simultaneous in situ evaluation by aperture impedance pulse spectroscopy and low frequency dielectric spectroscopy of the biomass of HTC cells on Cytodex 3. Cytotechnology 1993, 13(3):195-202.
32. Doerner S. Dielektrische und akustische Spektroskopie als prozesstaugliche Analyseverfahren zur Charakterisierung fluid-disperser Systeme. Faculty of Electrical Engineering and Information Technology. Magdeburg: Otto-von-Guericke-Universitaet Magdeburg 2008, 188.
33. Douennebier G., Tups H. FDA PAT Initiative-Eine Anwendersicht zu technischen Moeglichkeiten und aktueller industrieller Umsetzung. ChemIng Technol 2007, 79(12):2019-2028.
34. Dowd J.E., Jubb A., Kwok K.E., Piret J.M. Optimization and control of perfusion cultures using a viable cell probe and cell specific perfusion rates. Cytotechnology 2003, 42(1):35-45.
35. Ducommun P., Bolzonella I., Rhiel M., Pugeaud P., Von Stockar U., Marison I.W. On-line determination of animal cell concentration. Biotechnol Bioeng 2001, 72(5):515-522.
36. Ducommun P., Kadouri A., Von Stockar U., Marison I.W. On-line determination of animal cell concentration in two industrial high-density culture processes by dielectric spectroscopy. Biotechnol Bioeng 2002, 77(3):316-323.
37. Ducommun P., Rueux P.A., Kadouri A., Von Stockar U., Marison I.W. Monitoring of temperature effects on animal cell metabolism in a packed bed process. Biotechnol Bioeng 2002, 77(7):838-842.
38. Dziong D., Kearney R.E., Tabrizian M., Bagnaninchi P. A highly responsive system for on-line in vitro assessment of tissue growth within microporous polymer scaffolds. Conf Proc IEEE Eng Med Biol Soc 2005, 1:1043-1046.
39. Edelstein M.L., Abedi M.R., Wixon J. Gene therapy clinical trials worldwide to 2007-an update. J Gene Med 2007, 9(10):833-842.
40. Ehret R., Baumann W., Brischwein M., Schwinde A., Stegbauer K., Wolf B. Monitoring of cellular behaviour by impedance measurements on interdigitated electrode structures. Biosens Bioelectron 1997, 12(1):29-41.
41. Ehret R., Baumann W., Brischwein M., Schwinde A., Wolf B. On-line control of cellular adhesion with impedance measurements using interdigitated electrode structures. Med Biol Eng Comput 1998, 36(3):365-370.
42. Elias C.B., Zeiser A., Bedard C., Kamen A.A. Enhanced growth of Sf-9 cells to a maximum density of 5.2 Ã-107 cells per mL and production of Î2-galactosidase at high cell density by fed batch culture. Biotechnol Bioeng 2000, 68(4):381-388.
43. Esteban G, Frederic O, Luong B, PROCESS AND SYSTEM FOR ON-LINE AND IN SITU COUNTING OF CELLS IN A BIOLOGICAL CULTURE MEDIUM 2008; United States Patent Application 20080312843; (excessed online 20.01.2011). http://www.freepatentsonline.com/y2008/0312843.html.
44. Esteban G., Ansorge S., Schmid G. On-line viable cell density and physiological states monitoring by dielectric spectroscopy Sf9 growth and infection process. 2006 Conference of Cell Culture Engineering X Canada.; 21.01.2009 2009, [cited 14.12.2009]; Available from: www.fogale.com/Biomass.
45. FDA Guidance for Industry PAT-a framework for innovative pharmaceutical manufacturing and quality assurance 2004, [cited 19.02.2009]; Available from: http://www.fda.gov/cder/OPS/PAT.htm 969.
46. Fehrenbach R., Comberbach M., Petre J.O. On-line biomass monitoring by capacitance measurement. J Biotechnol 1992, 23(3):303-314.
47. Folly R.O.M., Valdman B. Potentiomatric sensor for on line glucose determination. Biotechnol Technol 1996, 10(11):867-870.
48. Gnoth S., Jenzsch M., Simutis R., Lubbert A. Process Analytical Technology (PAT): batch-to-batch reproducibility of fermentation processes by robust process operational design and control. J Biotechnol 2007, 132(2):180-186.
49. Guan Y., Kemp R.B. The viable cell monitor: a dielectric spectroscope for growth and metabolic studies of animal cells on macroporous beads. ESACT Proc. 1997, 15:321-328.
50. Guan Y., Evans P.M., Kemp R.B. Specific heat flow rate: an online monitor and potential control variable of specific metabolic rate in animal cell culture that combines microcalorimetry with dielectric spectroscopy. Biotechnol Bioeng 1998, 58(5):464-477.
51. Guo M., Chen J., Yun X., Chen K., Nie L., Yao S. Monitoring of cell growth and assessment of cytotoxicity using electrochemical impedance spectroscopy. Biochim Biophys Acta 2006, 1760(3):432-439.
52. Heggart H., Margaritis A., Stewart R.J., Pilkington H., Sobczak J., Russell I. Measurement of brewing yeast viability and vitality: A review of methods. Technical quarterly - Master Brewers Assoc Am 2000, 37(4):409-430.
53. Heubach J.F., Graf E.M., Leutheuser J., Bock M., Balana B., Zahanich I., et al. Electrophysiological properties of human mesenchymal stem cells. J Physiol 2004, 554(3):659-672.
54. Hildebrandt C., Bueth H., Cho S. Detection of the osteogenic differentiation of mesenchymal stem cells in 2D and 3D cultures by electrochemical impedance spectroscopy. J Biotechnol 2010, 148(1):83-90.
55. Hoeber R. Eine Methode die elektrische Leitfaehigkeit im Innern von Zellen zu messen. Arch Ges Physiol 1910, 133:237-259.
56. Huang Y.L., Li S.Y., Dremel B.A.A., Bilitewski U., Schmid R.D. On-line determination of glucose concentration throughout animal cell cultures based on chemiluminescent detection of hydrogen peroxide coupled with flow-injection analysis. J Biotechnol 1991, 18(1-2):161-172.
57. Huang X., Greve D.W., Nguyen D.D., Domach M.M. Impedance based biosensor array for monitoring mammalian cell behavior. Sensors 2003, Proceedings of IEEE 2003.
58. Kourti T. The Process Analytical Technology initiative and multivariate process analysis, monitoring and control. Anal Bioanal Chem 2006, 384(5):1043-1048.
59. Kussow C.M., Zhou W., Gryte D.M., Hu W.S. Monitoring of mammalian cell growth and virus production process using on-line oxygen uptake rate measurement. Enzyme Microb Technol 1995, 17(9):779-783.
60. Lee R.M., Choi H., Shin J.S., Kim K., Yoo K.H. Distinguishing between apoptosis and necrosis using a capacitance sensor. Biosens Bioelectron 2009, 24(8):2586-2591.
61. Li F., Hashimura Y., Pendleton R., Harms J., Collins E., Lee B. A systematic approach for scale-down model development and characterization of commercial cell culture processes. Biotechnol Prog 2006, 22(3):696-703.
62. Liu Q., Yu J., Xiao L., Tang J.C.O., Zhang Y., Wang P., et al. Impedance studies of bio-behavior and chemosensitivity of cancer cells by micro-electrode arrays. Biosens Bioelectron 2009, 24(5):1305-1310.
63. Male K.B., Gartu P.O., Kamen A.A., Luong J.H. On-line monitoring of glucose in mammalian cell culture using a flow injection analysis (FIA) mediated biosensor. Biotechnol Bioeng 1997, 55(3):497-504.
64. Malleo D., Nevill J.T., Lee L.P., Morgan H. Continuous differential impedance spectroscopy of single cells. Microfluid Nanofluid 2009, 1-8.
65. Mansfeld F. Electrochemical impedance spectroscopy, Corrosion and Environmental Effects Labs, Dept. of Materials Science and Engineering, University of Southern California, Los Angeles, CA, USA. In: Marcus Philippe, Mansfeld Florian, editors.Analytical methods in corrosion science and engineering; 2006. p. 463-505.
66. Marszalek P., Liu D.S., Tsong T.Y. Schwan equation and transmembrane potential induced by alternating electric field. Biophys J 1990, 58(4):1053-1058.
67. Merten O.W. State-of-the-art of the production of retroviral vectors. J Gene Med 2004, 6:105-124.
68. Miller J.H., Warmflash D. Martian soil biosensors based on dielectric spectroscopy. Institute for Space Systems Operations Annual Report 2006, 21-26. available at http://www.isso.uh.edu/publications/A2006/2006_021_miller.pdf. retrieved February 2011.
69. Myers M.A. Direct measurement of cell numbers in microtitre plate cultures using the fluorescent dye SYBR green I. J Immunol Methods 1998, 212(1):99-103.
70. Nacke T., Land R., Barthel A., Friedrich J., Peyerl P., Helbig M., et al. Process instrumentation for impedance spectroscopy- a modular concept 2008.
71. Negrete A., Kotin R.M. Large-scale production of recombinant adeno-associated viral vectors. Methods Mol Biol 2008, 433:79-95.
72. Negrete A., Esteban G., Kotin R.M. Process optimization of large-scale production of recombinant adeno-associated vectors using dielectric spectroscopy. Applied Microbiology and Biotechnology 2007, 76(4):761-772.
73. Nehring D., Gonzalez R., Poertner R., Czermak P. Experimental and modelling study of different process modes for retroviral production in a fixed bed reactor. J Biotechnol 2006, 122(2):239-253.
74. Noll T., Biselli M. Dielectric spectroscopy in the cultivation of suspended and immobilized hybridoma cells. J Biotechnol 1998, 63(3):187-198.
75. Opel C.F., Li J., Amanullah A. Quantitative modeling of viable cell density, cell size, intracellular conductivity, and membrane capacitance in batch and fed-batch CHO processes using dielectric spectroscopy. Biotechnol Prog 2010, 26:1187-1199.
76. Patel P., Markx G.H. Dielectric measurement of cell death. Enzyme Microb Technol 2008, 43:463-470.
77. Pethig R., Kell D.B. The passive electrical properties of biological systems: their significance in physiology, biophysics and biotechnology. Phys Med Biol 1987, 32(8):933-970.
78. Pickup J.C., Hussain F., Evans N.D., Rolinski O.J., Birch D.J. Fluorescence-based glucose sensors. Biosens Bioelectron 2005, 20(12):2555-2565.
79. Qiu Y., Liao R., Zhang X. Impedance-based monitoring of ongoing cardiomyocyte death induced by tumor necrosis factor-[alpha]. Biophys J 2009, 96(5):1985-1991.
80. Qui Y., Lioa R., Zhang X. Real-timemonitoring primary cardiomyocyte adhesion based on electrochemical impedance spectroscopy and electrical cell-substrate impedance sensing. Anal Chem 2008, 80:990-996.
81. Rahman A.R.A., Register J., Vuppala G., Bhansali S. Cell culture monitoring by impedance mapping using a multielectrode scanning impedance spectroscopy system (CellMap). Physiol Meas 2008, 29(6):227.
82. Rathore A.S., Yu M., Yeboah S., Sharma A. Case study and application of process analytical technology (PAT) towards bioprocessing: use of on-line high-performance liquid chromatography (HPLC) for making real-time pooling decisions for process chromatography. Biotechnol Bioeng 2008, 100(2):306-316.
83. Rengarajan K., Cristol S.M., Mehta M., Nickerson J.M. Quantifying DNA concentrations using fluorometry: a comparison of fluorophores. Mol Vis 2002, 8:416-421.
84. Renneberg R., Lisdat F. Biosensing for the 21st century 2008, Springer Verlag.
85. Ron A., Fishelson N., Croitoriu N., Benayahu D., Shacham-Diamand Y. Theoretical examination of aggregation effect on the dielectric characteristics of spherical cellular suspension. Biophys Chem 2009, 140(1-3):39-50.
86. Rourou S., Gaumon S., Kallel H. On-line monitoring of vero cells cultures during the growth and rabies virus process using biomass spectrometer. Cells Cult 2010, 4:829-832.
87. Rudolph G., Brueckerhoff T., Bluma A., Korb G., Scheper T. Optische Inline-Messverfahren zur Zellzahl- und Zellgroeßenbestimmung in der Bioprozesstechnik. Chem Ing Technol 2007, 79(1-2):42-51.
88. Sarra M., Ison A.P., Lilly M.D. The relationships between biomass concentration, determined by a capacitance-based probe, rheology and morphology of Saccharopolyspora erythraea cultures. J Biotechnol 1996, 51(2):157-165.
89. Schmid G., Zacher D. Evaluation of a novel capacitance probe for on-line monitoring of viable cell densities in batch and fed-batch animal cell culture processes. Animal Cell Technology Meets Genomics, ESACT Proceedings 2005, 2(5):621-624. DOI:10.1007/1-4020-3103-3_125.
90. Stanbridge L.J., Dussupt V., Maitland N.J. Baculoviruses as vectors for gene therapy against human prostate cancer. J Biomed Biotechnol 2003, 3:79-91.
91. Sun T., Morgan H. Single-cell microfluidic impedance cytometry: a review. Microfluid Nanofluid 2010, 8(4):423-443.
92. Teixeira A.P., Oliveira R., Alves P.M., Carrondo M.J.T. Advances in on-line monitoring and control of mammalian cell cultures: Supporting the PAT initiative. Biotechnol Adv 2009, 27(6):726-732.
93. Vojinovic V., Cabral J.M.S., Fonseca L.P. Real-time-bioprocess monitoring Part I: in situ sensors. Sens Actuat B 2006, 114:1083-1091.
94. Walsh G. Biopharmaceutical benchmarks 2006. Nat Biotechnol 2006, 24(7):769-776.
95. Wang M.H., Jang L.S. A systematic investigation into the electrical properties of single HeLa cells via impedance measurements and COMSOL simulations. Biosens Bioelectron 2009, 24(9):2830-2835.
96. Watkins E.J., Pfromm P.H. Capacitance spectroscopy to characterize organic fouling of electrodialysis membranes. J Membr Sci 1999, 162:213-218.
97. Weber C., Pohl S., Poertner R., Pino-Grace P., Freimark D., Wallrapp C., et al. Production Process for Stem Cell Based Therapeutic Implants: Expansion of the Production Cell Line and Cultivation of Encapsulated Cells. Adv Biochem Eng Biotechnol 2010, 123:143-162.
98. Weber C., Pohl S., Poertner R., Pino-Grace P., Pohl S., Wallrapp C., et al. Expansion of human mesenchymal stem cells in a fixed-bed bioreactor system based on non-porous glass carrier- Part A: Inoculation, cultivation, and cell harvest procedure. Int J Artificial Organs 2010, 33(8):512-525.
99. Weber C., Pohl S., Poertner R., Pino-Grace P., Wallrapp C., Geigle P., et al. Expansion of human mesenchymal stem cells in a fixed-bed bioreactor system based on non-porous glass carrier- Part B: Modeling and scale up of the system. Int J Artifal Organs 2010, 33(11):782-795.
100. Wurm F.M. Production of recombinant protein therapeutics in cultivated mammalian cells. Nat Biotechnol 2004, 22(11):1393-1398.
101. Yu N., Atienza J.M., Bernard J., Blanc S., Zhu J., Wang X., et al. Real-time monitoring of morphological changes in living cells by electronic cell sensor arrays: an approach to study G protein-coupled receptors. Anal Chem 2006, 78(1):35-43.
102. Zeiser A., Bedard C., Voyer R., Jardin B., Tom R., Kamen A.A. On-linemonitoring of the progress of infection in Sf-9 insect cell cultures using relative permittivity measurements. Biotechnol Bioeng 1999, 63(1):122-126.
103. Zeiser A., Elias C.B., Voyer R., Jardin B., Kamen A.A. On-line monitoring of physiological parameters of insect cell cultures during the growth and infection process. Biotechnol Prog 2000, 16(5):803-808.
104. Zhuang J., Baldwin W.H., Schoenbach K.H., Kolb J.F. Pulsed electric field induced changes in dielectric properties of biological cells. IEEE 2010.
105. Zipper H., Brunner H., Bernhagen J., Vitzthum F. Investigations on DNA intercalation and surface binding by SYBR Green I, its structure determination and methodological implications. Nucleic Acids Res 2004, 32(12):103.