4.7 Article

Evaluation of the mass transfers of caffeine and vitamin B12 in chloroacetaldehyde treated renal barrier model using a microfluidic biochip

Journal

SENSORS AND ACTUATORS B-CHEMICAL
Volume 174, Issue -, Pages 465-472

Publisher

ELSEVIER SCIENCE SA
DOI: 10.1016/j.snb.2012.08.053

Keywords

Renal barrier model; Microfluidic biochip; Chloroacetaldehyde; Drug permeability; Kidney

Funding

  1. ANR
  2. Universite de Technologie de Compiegne
  3. 189-post grenelle project Activism

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We have analyzed the modification of the mass transfer due to chloroacetaldehyde (CAA) inside a renal barrier model. For that purpose, the Madin-Darby Canine Kidney (MDCK) cell line was cultivated onto a polyethersulfone (PES) membrane. The membrane supporting a junctive cell layer was sandwiched between two polydimethylsiloxane (PDMS) chambers containing a microchannel network. The two compartments of this microfluidic biochip were perfused using two independent fluid circuits. Both circuits were connected to a spectrophotometer in order to perform real time analysis of the solute concentration in each compartment. The caffeine and the vitamin B12 were used as two molecular weight markers (195 Da and 1355 Da respectively). The results have shown that the rate of the mass transfer of the caffeine increased when the CAA concentration increased. Thus as a classical renal function parameters, we showed that the dialysance of the caffeine increased from 170 +/- 40 mu L/cm(2) at 0 mu M, to 200 +/- 15 mu L/cm(2) at 7.6 mu M and to 300 +/- 60 mu L/cm(2) at 76 mu M. On contrary, the transfers of the vitamin B12 were weakly affected at both concentrations in our experimental conditions. This led to find dialysance values equal to 36 +/- 6,42 +/- 6 and 54 +/- 6 mu L/cm(2) at 0 mu M, 7.6 mu M and 76 mu M. These results illustrated a molecular weight and dose response dependent mass transfers. In addition, the augmentation of the CAA concentration was correlated with a desorganization of the tight junction proteins claudin-1 and occludin. This led to demonstrate that the modification of the mass transfer was related to the perturbations of the tight junctions in the tissue. In addition, at the investigated CAA concentrations, the Calcein AM staining has shown that cell viability was maintained. However, at higher CAA concentrations (above 152 mu M), our biochip model was not suitable to perform the mass transfer analysis. This was due to a chemical reaction between the PES material and the CAA leading to the swelling/deterioration of the PES membrane. (C) 2012 Elsevier B.V. All rights reserved.

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