A study of electrochemical biosensor for analysis of three-dimensional (3D) cell culture.

Cell culture has a fundamental role not only in regenerative medicine but also in biotechnology, pharmacology, impacting both drug discovery and manufacturing. Although cell culture has been generally developed for only two-dimensional (2D) culture systems, three-dimensional (3D) culture is being spotlighted as the means to mimic in vivo cellular conditions. In this study, a method for cytotoxicity assay using an electrochemical biosensor applying 3D cell culture is presented. In order to strengthen the advantage of a 3D cell culture, the experimental condition of gelation between several types of sol-gels (alginate, collagen, matrigel) and cancer cells can be optimized to make a 3D cell structure on the electrode, which will show the reproducibility of electrical measurement for long-term monitoring. Moreover, cytotoxicity test results applying this method showed IC(50) value of A549 lung cancer cells to erlotinib. Thus, this study evaluates the feasibility of application of the electrochemical biosensor for 3D cell culture to cytotoxicity assay for investigation of 3D cell response to drug compounds.

[1]  J. Kolesar,et al.  Isolation and characterization of erlotinib-resistant human non-small cell lung cancer A549 cells. , 2011, Oncology letters.

[2]  Frank J. Millero,et al.  Investigation of metal sulfide complexes in sea water using cathodic stripping square wave voltammetry , 1994 .

[3]  K. F. Weibezahn,et al.  Cyclic AMP response in cells exposed to electric fields of different frequencies and intensities , 1994, Radiation and environmental biophysics.

[4]  Silvana Andreescu,et al.  Advanced electrochemical sensors for cell cancer monitoring. , 2005, Methods.

[5]  E. Giovannetti,et al.  Molecular Mechanisms Underlying the Synergistic Interaction of Erlotinib, an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, with the Multitargeted Antifolate Pemetrexed in Non-Small-Cell Lung Cancer Cells , 2008, Molecular Pharmacology.

[6]  Alok R Ray,et al.  Three-dimensional chitosan scaffold-based MCF-7 cell culture for the determination of the cytotoxicity of tamoxifen. , 2005, Biomaterials.

[7]  Shang-Tian Yang,et al.  Microbioreactors for high-throughput cytotoxicity assays. , 2008, Current opinion in drug discovery & development.

[8]  Gundula Piechotta,et al.  Electrical biochip technology—a tool for microarrays and continuous monitoring , 2003, Analytical and bioanalytical chemistry.

[9]  Emmanuel M. Drakakis,et al.  A Real-Time Multi-Channel Monitoring System for Stem Cell Culture Process , 2008, IEEE Transactions on Biomedical Circuits and Systems.

[10]  T. Matsue,et al.  Monitoring the cellular activity of a cultured single cell by scanning electrochemical microscopy (SECM). A comparison with fluorescence viability monitoring. , 2003, Biosensors & bioelectronics.

[11]  Jeong-Suong Yang,et al.  Comparison of the sensitivity of thiolated aptamer based biosensor according to the condition of electrode substrates , 2010 .

[12]  Kuo-Chien Tsao,et al.  Serum total homocysteine increases with the rapid proliferation rate of tumor cells and decline upon cell death: a potential new tumor marker. , 2002, Clinica chimica acta; international journal of clinical chemistry.

[13]  M. S. Cooper,et al.  Gap junctions increase the sensitivity of tissue cells to exogenous electric fields. , 1984, Journal of theoretical biology.

[14]  G. Giaccone,et al.  The multilayered postconfluent cell culture as a model for drug screening. , 2000, Critical reviews in oncology/hematology.

[15]  Giovanni De Micheli,et al.  Targeting of multiple metabolites in neural cells monitored by using protein-based carbon nanotubes , 2011 .

[16]  M. Mehrvar,et al.  Recent Developments, Characteristics, and Potential Applications of Electrochemical Biosensors , 2004, Analytical sciences : the international journal of the Japan Society for Analytical Chemistry.

[17]  Yosi Shacham-Diamand,et al.  Novel integrated electrochemical nano-biochip for toxicity detection in water. , 2005, Nano letters.

[18]  Shuichi Takayama,et al.  High-throughput 3D spheroid culture and drug testing using a 384 hanging drop array. , 2011, The Analyst.

[19]  Li Wang,et al.  Correlation between cell growth rate and glucose consumption determined by electrochemical monitoring , 2011 .

[20]  H. Kimura,et al.  Cell-Based Microfluidic Biochip for Electrochemical Real-Time Monitoring of Glucose and Oxygen , 2007, TRANSDUCERS 2007 - 2007 International Solid-State Sensors, Actuators and Microsystems Conference.

[21]  Chu Zhang,et al.  Hyaluronic acid-based hydrogels as 3D matrices for in vitro evaluation of chemotherapeutic drugs using poorly adherent prostate cancer cells. , 2009, Biomaterials.

[22]  Li Xie,et al.  Microelectronic cell sensor assay for detection of cytotoxicity and prediction of acute toxicity. , 2006, Toxicology in vitro : an international journal published in association with BIBRA.

[23]  I. Mian,et al.  Tissue architecture: the ultimate regulator of breast epithelial function. , 2003, Current opinion in cell biology.

[24]  Ivan Martin,et al.  New dimensions in tumor immunology: what does 3D culture reveal? , 2008, Trends in molecular medicine.

[25]  R. Perez-soler,et al.  Schedule-Dependent Cytotoxic Synergism of Pemetrexed and Erlotinib in Human Non–Small Cell Lung Cancer Cells , 2007, Clinical Cancer Research.

[26]  M. Bissell,et al.  Interaction with basement membrane serves to rapidly distinguish growth and differentiation pattern of normal and malignant human breast epithelial cells. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[27]  D Miklavcic,et al.  Theoretical evaluation of the distributed power dissipation in biological cells exposed to electric fields. , 2000, Bioelectromagnetics.

[28]  Tai Hyun Park,et al.  Enhancement of cellular olfactory signal by electrical stimulation , 2009, Electrophoresis.

[29]  M. Poupon,et al.  Distinctive alterations of invasiveness, drug resistance and cell–cell organization in 3D-cultures of MCF-7, a human breast cancer cell line, and its multidrug resistant variant , 2004, Clinical & Experimental Metastasis.

[30]  Dan Du,et al.  A disposable impedance sensor for electrochemical study and monitoring of adhesion and proliferation of K562 leukaemia cells , 2007 .

[31]  M. Gu,et al.  Electrochemical detection of 17β-estradiol using DNA aptamer immobilized gold electrode chip , 2007 .

[32]  N. Kotov,et al.  Three-dimensional cell culture matrices: state of the art. , 2008, Tissue engineering. Part B, Reviews.

[33]  Elise C. Fear,et al.  Modeling assemblies of biological cells exposed to electric fields , 1998 .

[34]  Nadia Nikolaus,et al.  Protein Detection with Aptamer Biosensors , 2008, Sensors.

[35]  I. Willner,et al.  Probing Biomolecular Interactions at Conductive and Semiconductive Surfaces by Impedance Spectroscopy: Routes to Impedimetric Immunosensors, DNA‐Sensors, and Enzyme Biosensors , 2003 .