Invited Paper BN+NM-TuM9
“Body-On-A-Chip”: Combining Microfabrication, Cell Cultures, and Mathematical Models

Tuesday, November 1, 2011, 10:40 am, Room 105

We seek to understand the response of the human body to various pharmaceuticals. Our platform technology is an in vitro system that combines microfabrication and cell cultures and is guided by a computer model of the body. We called this in vitro system a micro cell culture analog (microCCA) or a “Body-on-a-Chip”. A microCCA device contains mammalian cells cultured in interconnected micro-chambers to represent key body organs linked through the circulatory system and is a physical representation of a physiologically based pharmacokinetic model. ^{(1, 2)} MicroCCAs can reveal toxic effects that result from interactions between organs as well as provide realistic, inexpensive, accurate, rapid throughput toxicological studies that do not require animals. The advantages of operating on a microscale include the ability to mimic physiological relationships more accurately as the natural length scale is order of 10 to 100 microns.

We have used a microCCA to test potential combination therapies (Tegafur and uracil) for colon cancer. ⁽³⁾ Tegafur is a prodrug for 5-FU and uracil an inhibitor of DPD, an enzyme which deactivates 5-FU. Simple microwell plates cannot probe this system, but the microCCA predicts the types of responses observed experimentally. A “pumpless” system that would be easy to utilize has been demonstrated with Tegafur also.⁽⁴⁾ We have coupled these body modules with a micro model of the GI tract to examine the response to oral exposure of drugs, chemicals, or nanoparticles. ⁽⁵⁾

Overall, we believe that in vitro, microfabricated devices with cell cultures provide a viable alternative to animal models to predict toxicity and efficacy in response to pharmaceuticals.

References

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2. Khamsi, R. Meet the Stripped Down Rat. Nature (2005), 435(5 May):12-13.

3. Sung, J.H. and M.L. Shuler. A Micro Cell Culture Analog (microCCA) with 3-D Hydrogel Culture of Multiple Cell Lines to Assess Metabolism-Dependent Cytotoxicity of Anti-Cancer Drugs.

Lab Chip (2009), 9:1385-1394.

4. Sung, J.H., C. Kam, and M.L. Shuler. A microfluidic device for pharmacokinetic-pharmacodynamic (PK-PD) model on a chip. Lab Chip (2010) 10: 446-455.

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