Analysis of the mass transfers in an artificial kidney microchip

In this communication we demonstrate a conception of an artificial microkidney using pertinent microtools that more accurately mimic organ functions in vitro. We present a technique to integrate polyethersulfone (PES) membranes usually used in hemodialysis inside a polydimethylsiloxane (PDMS) microchip. The purpose of the microchip is to model glomerular filtration "on-chip". Mass transfer of urea (60 Da), vitamin B12 (1355 Da) and albumin (70,000 Da) are investigated by using two types of membranes (cut-off at 500,000 Da and 40,000 Da) in co-current and counter-current flow conditions. The time of urea, vitamin B12 and albumin removal, and the mechanisms of mass transfer, are controlled either by controlling the pore size of the membranes or by controlling the pressure profiles along the membrane via the flow conditions. An analytical model, which is supported by our data, is put forth. The model allows the extraction of the diffusion coefficients of each molecule through the various membranes studied. Due to the downscaling, the model and the experiments demonstrate that the dialysance in the microchip is expressed by the sum of the diffusion and convection mass transfer components. The results of this work support an analytical model which describes the mass transfer in a microchip modelling a glomerular unit. Coupled with the advantages of the microfluidic biochip (high surface/volume ratio, reduction of the fluid volumes), our data will complete the integration of further cellular functions for the utilisation of the present microchip as a future in vitro model of a miniaturized bio artificial kidney.

[1]  S. Brunet,et al.  Diffusive and convective solute clearances during continuous renal replacement therapy at various dialysate and ultrafiltration flow rates. , 1999, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[2]  Ryutaro Maeda,et al.  A prototype of ultrasonic micro-degassing device for portable dialysis system , 2002 .

[3]  Michael L Shuler,et al.  Incorporation of 3T3‐L1 Cells To Mimic Bioaccumulation in a Microscale Cell Culture Analog Device for Toxicity Studies , 2008, Biotechnology progress.

[4]  A. Mikelić Homogenization theory and applications to filtration through porous media , 2000 .

[5]  L. Griffith,et al.  Tissue Engineering--Current Challenges and Expanding Opportunities , 2002, Science.

[6]  L. Griffith,et al.  A microfabricated array bioreactor for perfused 3D liver culture. , 2002, Biotechnology and bioengineering.

[7]  Cécile Legallais,et al.  A theoretical model to predict the in vitro performance of hemodiafilters , 2000 .

[8]  Y. Sakai,et al.  Development of a biohybrid simulator for absorption and biotransformation processes in humans based on in vitro models of small intestine and liver tissues , 2003, Journal of Artificial Organs.

[9]  Enrique Sanchez-Palencia,et al.  On boundary conditions for fluid flow in porous media , 1975 .

[10]  Aaron Sin,et al.  Development of a Microscale Cell Culture Analog To Probe Naphthalene Toxicity , 2008, Biotechnology progress.

[11]  L. Griffith,et al.  Functional behavior of primary rat liver cells in a three-dimensional perfused microarray bioreactor. , 2002, Tissue engineering.

[12]  M. Weiner,et al.  Acetate transfer across membranes of artificial kidneys in vitro. , 1979, Kidney international.

[13]  Laurent Griscom,et al.  Development of a Renal Microchip for In Vitro Distal Tubule Models , 2007, Biotechnology progress.

[14]  M. Jaffrin,et al.  Simultaneous convective and diffusive mass transfers in a hemodialyser. , 1990, Journal of biomechanical engineering.

[15]  W H Fissell,et al.  Dialysis and Nanotechnology: Now, 10 Years, or Never? , 2006, Blood Purification.

[16]  A. Guillouzo,et al.  Liver cell models in in vitro toxicology. , 1998, Environmental health perspectives.

[17]  Yasuyuki Sakai,et al.  Enhanced cytochrome P450 capacities of Caco-2 and Hep G2 cells in new coculture system under the static and perfused conditions : evidence for possible organ-to-organ interactions against exogenous stimuli , 2004 .

[18]  George M. Whitesides,et al.  Extending Microcontact Printing as a Microlithographic Technique , 1997 .

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

[20]  D. Joseph,et al.  Boundary conditions at a naturally permeable wall , 1967, Journal of Fluid Mechanics.

[21]  M Y Jaffrin,et al.  A one-dimensional model of simultaneous hemodialysis and ultrafiltration with highly permeable membranes. , 1981, Journal of biomechanical engineering.

[22]  Simon A Roberts Drug metabolism and pharmacokinetics in drug discovery. , 2003, Current opinion in drug discovery & development.

[23]  Jeffrey T. Borenstein,et al.  A MEMS-Based Renal Replacement System , 2004 .

[24]  J. De Sutter,et al.  Cytokine removal during continuous hemofiltration in septic patients. , 1999, Journal of the American Society of Nephrology : JASN.

[25]  Anthony Atala,et al.  Methods Of Tissue Engineering , 2006 .

[26]  L M Sweeney,et al.  A cell culture analogue of rodent physiology: Application to naphthalene toxicology. , 1995, Toxicology in vitro : an international journal published in association with BIBRA.

[27]  Teruo Fujii,et al.  Perfusion culture of fetal human hepatocytes in microfluidic environments , 2004 .