Abstract
We have developed a microfluidic bioassay system that mimics glomerular filtration and tubular secretion in the kidney. The system consists of a peristaltic micropump (heart), a dialysis component (renal corpuscle), and a secretion component (renal proximal tubule). Analytes were separated by size using a dialysis membrane in the dialysis component. Model cells were cultured on a membrane in the secretion component, and active transport mediated by P-glycoprotein (P-gp) was confirmed using the P-gp substrate rhodamine 123 with or without the P-gp inhibitor quinidine sulfate. The system achieved both size separation and selective transport by P-gp on a single microchip. This proof-of-concept model may find applications in drug excretion assays, including studies of drug-drug interactions during tubular secretion.
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References
K. M. Morrissey, S. L. Stocker, M. B. Wittwer, L. Xu, and K. M. Giacomini, Annu. Rev. Pharmacol. Toxicol., 2013, 53, 503.
G. T. Tucker, Brit. J. Clin. Pharmacol., 1981, 72, 761.
L. F. Prescott, Brit. J. Anaesth., 1972, 44, 246.
R. Bendayan, Pharmacotherapy, 1996, 76, 971.
A. Skardal, T. Shupe, and A. Atala, Drug Discov. Today, 2016, 27, 1399.
D. Huh, G. A. Hamilton, and D. E. Ingber, Trends Cell Biol., 2011, 27, 745.
R. Paoli and J. Samitier, Micromachines, 2016, 7, 126.
K. J. Jang and K. Y. Suh, Lab Chip, 2010, 70, 36.
K. J. Jang, A. P. Mehr, G. A. Hamilton, L. A. McPartlin, S. Y. Chung, K. Y. Suh, and D. E. Ingber, Integr Biol., 2013, 5, 1119.
C. M. Sakolish and G. J. Mahler, RSC Adv., 2017, 7, 4216.
Y. Imura, E. Yoshimura, and K. Sato, Anal. Chem., 2013, 85, 1683.
Y. Sakuta, K. Tsunoda, and K. Sato, Anal. Sci., 2017, 33, 391.
M. F. Fromm, R. B. Kim, C. M. Stein, G. R. Wilkinson, and D. M. Roden, Circulation, 1999, 99, 552.
L. Barthe, M. Bessouet, J. F. Woodley, and G. Houin, Int. J. Pharmaceut., 1998, 773, 255.
K. M. Morrissey, S. L. Stocker, M. B. Wittwer, L. Xu, and K. M. Giacomini, Annu. Rev. Pharmacol. Toxicol., 2013, 53, 503.
N. Sugihara, K. Toyama, A. Michihara, K. Akasaki, H. Tsuji, and K. Furuno, Toxicology, 2006, 223, 156.
C. Albrecht, J. I. Elliott, A. Sardini, T. Litman, B. Stieger, P. J. Meier, and C. F. Higgins, Biochim. Biophys. Acta Biomembranes, 2002, 7567, 133.
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This work was supported in part by the Asahi Glass Foundation and the Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant Number JP15H03823).
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Sakuta, Y., Takehara, I., Tsunoda, KI. et al. Development of a Microfluidic System Comprising Dialysis and Secretion Components for a Bioassay of Renal Clearance. ANAL. SCI. 34, 1073–1078 (2018). https://doi.org/10.2116/analsci.18P141
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DOI: https://doi.org/10.2116/analsci.18P141