A Microfluidic System to Evaluate Intestinal Absorption

Intestinal absorption rates vary with the nature of the substances involved. In-vitro experiments with cell culture inserts are often conducted to evaluate the intestinal absorption rate. These inserts, however, require large amounts of cells, samples, and culture media, and take a long time to evaluate. To overcome these problems, we developed a microchip-based system that mimics the intestine. The microchip was composed of a glass slide, a permeable membrane, and polydimethylsiloxane (PDMS) sheets, which contained microchannels made by photolithography; Caco-2 cells were cultured on the membrane in the microchip. The system was regulated with a microsyringe pump. We conducted permeation tests; cyclophosphamide, which can permeate the intestinal barrier, displayed a high permeability coefficient and Lucifer yellow, which cannot be absorbed at the intestinal wall, displayed a low permeability coefficient. These results were consistent with those obtained using a conventional method, which supports the validity of our new system. The system realized an 80% reduction of cell consumption.

[1]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[2]  Takehiko Kitamori,et al.  Biological cells on microchips: new technologies and applications. , 2007, Biosensors & bioelectronics.

[3]  H. Kimura,et al.  An integrated microfluidic system for long-term perfusion culture and on-line monitoring of intestinal tissue models. , 2008, Lab on a chip.

[4]  Y. Konishi Modulations of Food-derived Substances on Intestinal Permeability in Caco-2 Cell Monolayers , 2003, Bioscience, biotechnology, and biochemistry.

[5]  C. Parish,et al.  New fluorescent dyes for lymphocyte migration studies. Analysis by flow cytometry and fluorescence microscopy. , 1990, Journal of immunological methods.

[6]  Peter Vettiger,et al.  High-aspect-ratio, ultrathick, negative-tone near-UV photoresist and its applications for MEMS , 1998 .

[7]  J. Alsenz,et al.  Development of a 7-Day, 96-Well Caco-2 Permeability Assay with High-Throughput Direct UV Compound Analysis , 2003, Pharmaceutical Research.

[8]  Takehiko Kitamori,et al.  Development of a microchip-based bioassay system using cultured cells. , 2005, Analytical chemistry.

[9]  R. Conradi,et al.  Caco-2 Cell Monolayers as a Model for Drug Transport Across the Intestinal Mucosa , 1990, Pharmaceutical Research.

[10]  Takehiko Kitamori,et al.  Evaluation of effects of shear stress on hepatocytes by a microchip-based system , 2006 .

[11]  Soichi Yabuki,et al.  Microbioassay system for an anti-cancer agent test using animal cells on a microfluidic gradient mixer. , 2006, Analytical sciences : the international journal of the Japan Society for Analytical Chemistry.

[12]  Kiichi Sato,et al.  Microbioassay system for antiallergic drug screening using suspension cells retaining in a poly(dimethylsiloxane) microfluidic device. , 2005, Analytical chemistry.

[13]  Takehiko Kitamori,et al.  Monitoring of intercellular messengers released from neuron networks cultured in a microchip. , 2006, Journal of chromatography. A.