Novel designs and technologies for cell engineering

Microfl uidic devices, such as lab-on-a-chip systems, are highly advantageous for cell engineering and cell based assays. It is a particularly useful approach for development of the in vitro cellular systems mimicking the in vivo environment. In this paper, a novel lab-on-a-chip device for three-dimensional human cell culture and anticancer drug testing is presented. Cells were cultured as Multicellular Tumor Spheroids (MCTS) — the best cancer tumor model developed so far. Diff erent designs were tested and novel technique of microfabrication in poly(dimethylsiloxane) was developed. MCTS were cultured in a system of polymeric microwells, with the network of microfl uidic channels for culture medium fl ow. Design included optimal shear stress and proper nutrients supply for cultured cells. Final design provided MCTS culture for four weeks with the homeostasis-like state achievement, which is characteristic for the in vivo situation.

[1]  Christopher S. Chen,et al.  Engineering cellular microenvironments to improve cell-based drug testing. , 2002, Drug discovery today.

[2]  T. A. Desai,et al.  Micro- and nanoscale structures for tissue engineering constructs. , 2000, Medical engineering & physics.

[3]  K. Cunningham,et al.  The role of shear stress in the pathogenesis of atherosclerosis , 2005, Laboratory Investigation.

[4]  Francesco Pampaloni,et al.  Three-dimensional tissue models for drug discovery and toxicology. , 2009, Recent patents on biotechnology.

[5]  Matthieu Piel,et al.  Microfluidic tools for cell biological research. , 2010, Nano today.

[6]  Toshihiro Akaike,et al.  Enhanced liver functions of hepatocytes cocultured with NIH 3T3 in the alginate/galactosylated chitosan scaffold. , 2006, Biomaterials.

[7]  Juergen Friedrich,et al.  Experimental anti-tumor therapy in 3-D: Spheroids – old hat or new challenge? , 2007, International journal of radiation biology.

[8]  T. Park,et al.  Integration of Cell Culture and Microfabrication Technology , 2003, Biotechnology progress.

[9]  L. Griffith,et al.  Capturing complex 3D tissue physiology in vitro , 2006, Nature Reviews Molecular Cell Biology.

[10]  Vincent Gau,et al.  Antimicrobial susceptibility testing using high surface-to-volume ratio microchannels. , 2010, Analytical chemistry.

[11]  Dorota Stadnik,et al.  Miniaturized tools and devices for bioanalytical applications: an overview , 2009, Analytical and bioanalytical chemistry.

[12]  Detlev Belder,et al.  Rapid replication of master structures by double casting with PDMS. , 2009, Lab on a chip.

[13]  J. Vacanti,et al.  Microfabrication Technology for Vascularized Tissue Engineering , 2002 .

[14]  D. Beebe,et al.  Biological implications of polydimethylsiloxane-based microfluidic cell culture. , 2009, Lab on a chip.

[15]  Shuichi Takayama,et al.  Micro- and nanotechnologies for studying cellular function. , 2003, Current topics in medicinal chemistry.

[16]  G. Whitesides,et al.  Poly(dimethylsiloxane) as a material for fabricating microfluidic devices. , 2002, Accounts of chemical research.

[17]  R. Kwapiszewski,et al.  Microfluidic devices as tools for mimicking the in vivo environment , 2011 .

[18]  Tobias Schmelzle,et al.  Engineering tumors with 3D scaffolds , 2007, Nature Methods.

[19]  Steffen Hauptmann,et al.  Comparison of protein expression profiles between monolayer and spheroid cell culture of HT‐29 cells revealed fragmentation of CK18 in three‐dimensional cell culture , 2002, Electrophoresis.

[20]  D. Beebe,et al.  Microenvironment design considerations for cellular scale studies. , 2004, Lab on a chip.

[21]  Kenneth M. Yamada,et al.  Cell interactions with three-dimensional matrices. , 2002, Current opinion in cell biology.

[22]  Teruo Fujii,et al.  Cell Culture in 3-Dimensional Microfluidic Structure of PDMS (polydimethylsiloxane) , 2003 .

[23]  G. Whitesides,et al.  Fabrication of microfluidic systems in poly(dimethylsiloxane) , 2000, Electrophoresis.

[24]  Peter P Gray,et al.  Effect of shear stress on expression of a recombinant protein by Chinese hamster ovary cells. , 2003, Biotechnology and bioengineering.

[25]  M. Miyazaki,et al.  A Practical Method for Rapid Microchannel Fabrication in Polydimethylsiloxane by Replica Molding without Using Silicon Photoresist , 2006 .

[26]  G. Garcı́a-Cardeña,et al.  A new in vitro model to evaluate differential responses of endothelial cells to simulated arterial shear stress waveforms. , 2002, Journal of biomechanical engineering.

[27]  John P. Puccinelli,et al.  Thermal aging and reduced hydrophobic recovery of polydimethylsiloxane , 2006 .

[28]  André Guillouzo,et al.  Evolving concepts in liver tissue modeling and implications for in vitro toxicology , 2008, Expert opinion on drug metabolism & toxicology.

[29]  Artur Dybko,et al.  ‘Lab-on-a-chip’ for cell engineering: towards cellular models mimicking in vivo , 2011 .

[30]  Kenneth M. Yamada,et al.  Modeling Tissue Morphogenesis and Cancer in 3D , 2007, Cell.

[31]  R. Sutherland Cell and environment interactions in tumor microregions: the multicell spheroid model. , 1988, Science.

[32]  Hwan-You Chang,et al.  Recent advances in three‐dimensional multicellular spheroid culture for biomedical research , 2008, Biotechnology journal.

[33]  Chih-Ming Ho,et al.  Surface molecular property modifications for poly(dimethylsiloxane) (PDMS) based microfluidic devices , 2009, Microfluidics and nanofluidics.

[34]  Tomoyuki Yasukawa,et al.  A multicellular spheroid array to realize spheroid formation, culture, and viability assay on a chip. , 2007, Biomaterials.