Bridging the gap--biocompatibility of microelectronic materials.

There is an increasing interest in cell-based microelectronic biosensors for high-throughput screening of new products from the biotech pipeline. This requires fundamental knowledge of the biocompatibility of the materials used as the growing support for the cells. Using monolayer-forming Caco-2 cells of human origin, the biocompatibility of silicon wafers coated with various metals, dielectrics and semiconductors was assessed. Besides microscopic inspection, proliferation of cells indicating viability as well as brush border enzyme activity indicating differentiation of adherent growing cells were chosen as parameters to estimate biocompatibility. The type of wafer used for deposition of the coating initially influences the biocompatibility of the final product. Whereas p-doped silicon was fully biocompatible, n-doped silicon reduced the proliferation of cells. Among the different coatings, Al and Ti even increased the cell growth as compared to glass. Culturing the cells for 6 days on coated wafers demonstrated that the differentiation of adhering cells on Ti- and ZrO2-coated wafers was comparable to glass, whereas coatings with Si3N4, Au, Al, and ITO reduced differentiation to 15-35%. In the cases of Au and Si3N4 this effect equilibrated with prolonged culturing. These results demonstrate the importance of a careful selection of the materials used for the production of cell-based biosensors.

[1]  N. Amino,et al.  The analysis of alkaline phosphatase isoenzyme using 4-methylumbelliferyl phosphate as substrate on a cellulose acetate membrane. , 1979, Clinica chimica acta; international journal of clinical chemistry.

[2]  B. Hultberg,et al.  The cell-damaging effects of low amounts of homocysteine and copper ions in human cell line cultures are caused by oxidative stress. , 1997, Toxicology.

[3]  P. Artursson,et al.  Applications of epithelial cell culture in studies of drug transport. , 2002, Methods in molecular biology.

[4]  Axel Buguin,et al.  Un substrat de micropiliers pour étudier la migration cellulaire , 2005 .

[5]  B. Hirst,et al.  P-glycoprotein Potentiates CYP3A4-mediated Drug Disappearance during Caco-2 Intestinal Secretory Detoxification , 2004, Journal of drug targeting.

[6]  Leo Abrahamse,et al.  Comparison of in Vitro Models for the Prediction of Compound Absorption across the Human Intestinal Mucosa , 2004, Journal of biomolecular screening.

[7]  S A Gray,et al.  Design and demonstration of an automated cell-based biosensor. , 2001, Biosensors & bioelectronics.

[8]  Francisco Torrens,et al.  A new topological descriptors based model for predicting intestinal epithelial transport of drugs in Caco-2 cell culture. , 2004, Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques.

[9]  A. Duncan,et al.  Laser microfabricated model surfaces for controlled cell growth. , 2002, Biosensors & bioelectronics.

[10]  B Wolf,et al.  Functional cellular assays with multiparametric silicon sensor chips. , 2003, Lab on a chip.

[11]  David G Castner,et al.  Guided cell patterning on gold-silicon dioxide substrates by surface molecular engineering. , 2004, Biomaterials.

[12]  T. Orfeo,et al.  One hundred and twenty-seven cultured human tumor cell lines producing tumors in nude mice. , 1977, Journal of the National Cancer Institute.

[13]  Michael Wirth,et al.  Lectin-Mediated Drug Targeting: Preparation, Binding Characteristics, and Antiproliferative Activity of Wheat Germ Agglutinin Conjugated Doxorubicin on Caco-2 Cells , 1998, Pharmaceutical Research.

[14]  C. Wilkinson,et al.  A parallel-plate flow chamber to study initial cell adhesion on a nanofeatured surface , 2004, IEEE Transactions on NanoBioscience.

[15]  G Jobst,et al.  Microdevice with integrated dialysis probe and biosensor array for continuous multi-analyte monitoring. , 2003, Biosensors & bioelectronics.

[16]  Michael Wirth,et al.  The lectin-cell interaction and its implications to intestinal lectin-mediated drug delivery. , 2004, Advanced drug delivery reviews.

[17]  Thomas J. Raub,et al.  Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability. , 1989, Gastroenterology.

[18]  Y. Takekuma,et al.  An in vitro system for prediction of oral absorption of relatively water-soluble drugs and ester prodrugs. , 2003, International journal of pharmaceutics.

[19]  S. Chong,et al.  Utility of 96 well Caco-2 cell system for increased throughput of P-gp screening in drug discovery. , 2004, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.