Skip to main content
Log in

The cell engineering construction and function evaluation of multi-layer biochip dialyzer

  • Published:
Biomedical Microdevices Aims and scope Submit manuscript

Abstract

We report the fabrication and function evaluation of multi-layer biochip dialyzer. Such device may potentially be applied to the wearable hemodialysis systems. By merging the advantages of microfluidic chip technology with cell engineering, both functions of glomerular filtration and renal tubule physiological activity are integrated in the same device. This device is designed into a laminated structure, in which the chip number of the superimposed layer can be arbitrarily tailored in accordance with the requirements of dialysis capacity. We propose that such structure can overcome the obstacles of large size and detached structure of the traditional hollow fiber dialyzer. To construct this multilayer biochips dialyzer, two types of dialyzer device with two-layered and six-layered chips are assembled, respectively. Cell adhesion and proliferation on three different dialysis membrane materials under static and dynamic conditions are investigated and compared. The filtration capability, re-absorption function and excrete ammonia function of the resulting multi-layer biochip dialyzer are evaluated. The results reveal that the constructed device can perform higher filtration efficiency and also play a role of renal tubule. This methodology may be useful in developing “scaling down” artificial kidneys that can act as wearable or even implantable hemodialysis systems.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • N. Ferrell, R.R. Desai, A.J. Fleischman et al., A microfluidic bioreactor with integrated transepithelial electrical resistance (TEER) measurement electrodes for evaluation of renal epithelial cells. Biotech. Bioeng. 107(4), 707–716 (2010)

    Article  Google Scholar 

  • N. Ferrell, K.B. Ricci, J. Groszek et al., Albumin handling by renal tubular epithelial cells in a microfluidic bioreactor. Biotech. Bioeng. 109(3), 797–803 (2012)

    Article  Google Scholar 

  • X.F. Gao, Y. Tanaka, Y. Sugii et al., Basic structure and cell culture condition of a bioartificial renal tubule on chip towards a cell-based separation microdevice. Anal. Sci. 27, 907–912 (2011)

    Article  Google Scholar 

  • Y. Gu, N. Miki. Microfilter Fabricated with PDMS and PES Membrane Applicable for Implantable Artificial Kidney, Proceedings of the 2nd IEEE International Conference on Nano/Micro Engineered and Molecular Systems, Bangkok, Thailand, 16–19 January 2007

  • Y. Gu, N. Miki, Multilayered microfilter using a nanoporous PES membrane and applicable as the dialyzer of a wearable artificial kidney. J. Micromech. Microeng. 19, 065031 (2009). 8pp

    Article  Google Scholar 

  • A.C. Guyton, J.E. Hall, Urine Formation by the Kidneys, in Human Physiology and Mechanisms of Disease (WB Saunders Company, Philadelphia, 1997), pp. 223–235

    Google Scholar 

  • M. Horie, K. Nishio, K. Fujita et al., Cellular responses by stable and uniform ultrafine titanium dioxide particles in culture-medium dispersions when secondary particle size was 100 nm or less. Toxicol. in Vitro Int. J. Publ. Assoc. BIBRA 24(6), 1629–1638 (2010)

    Article  Google Scholar 

  • W.H. Hőrl, K.M. Koch, R.M. Lindsay, et al., Replacement of Renal Function by Dialysis. (Kluwer Academic Publishers, 2004), 313.

  • D. Huh, B.D. Matthews, A. Mammoto et al., Reconstituting organ-level lung functions on a chip. Science 328, 1662–1668 (2010)

    Article  Google Scholar 

  • H.D. Humes, The bioartificial renal tubule: prospects to improve supportive care in acute renal failure. Ren. Fail. 18, 405–408 (1996)

    Article  Google Scholar 

  • H.D. Humes, Stem cells: the next therapeutic frontier. Trans. Am. Clin. Climatol. Assoc. 116, 167–184 (2005)

    Google Scholar 

  • H.D. Humes, S.M. Mackay, A.J. Funke et al., Tissue engineering of the bioartificial renal tubule assist device: in vitro transport and metabolic characteristics. Kidney Int. 55, 2502–2514 (1999a)

    Article  Google Scholar 

  • H.D. Humes, D.A. Buffington, S.M. Mackay et al., Replacement of renal function in uremic animals with a tissue-engineered kidney. Nat. Biotechnol. 17, 451–455 (1999b)

    Article  Google Scholar 

  • H.D. Humes, W.F. Weitzel, R.H. Bartlett et al., Initial clinical results of the bioartificial kidney containing human cells in ICU patients with acute renal failure. Kidney Int. 66, 1578 (2004)

    Article  Google Scholar 

  • P.J. Hung, P.J. Lee, P. Sabounchi et al., Continuous perfusion microfluidic cell culture array for high-throughput cell-based assays. Biotechnol. Bioeng. 89(1), 1–8 (2005)

    Article  Google Scholar 

  • D. Janasek, J. Franzke, A. Manz, Scaling and the design of miniaturized chemical-analysis systems. Nature 442, 374–380 (2006)

    Article  Google Scholar 

  • K.J. Jang, K.Y. Suh, A multi-layer microfluidic device for efficient culture and analysis of renal tubular cells. Lab Chip 10, 36–42 (2010)

    Article  Google Scholar 

  • K.J. Jang, H.S. Cho, D.H. Kang et al., Fluid-shear-stress-induced translocation of aquaporin-2 and reorganization of actin cytoskeleton in renal tubular epithelial cells. Integr. Biol. 3, 134–141 (2011)

    Article  Google Scholar 

  • S. Joffy, M.H. Rosner, Natriuretic peptides in ESRD. Am. J. Kidney Dis 46(1), 1–10 (2005)

    Article  Google Scholar 

  • M.R. Kaazempur-Mofrad, J.P. Vacanti, N.J. Krebs, et al. A MEMS-based renal replacement system. Solid-State Sensor. 67–70 (2004).

  • D.S. Kim, S.H. Lee, C.H. Ahn et al., Disposable integrated microfluidic biochip for blood typing by plastic microinjection moulding. Lab Chip 6, 794–802 (2006)

    Article  Google Scholar 

  • K.H. Lee, D.J. Kim, B.G. Min et al., Polymeric nanofiber web-based artificial renal microfluidic chip. Biomed. Microdevices 9, 435–442 (2007)

    Article  Google Scholar 

  • A.R. Nissenson, Bottom-up nanotechnology: the human nephron filter. Semin. Dial. 22(6), 661–664 (2009)

    Article  Google Scholar 

  • A.R. Nissenson, C. Ronco, G. Pergamit et al., The human nephron filter: toward a continuously functioning, implantable artificial nephron system. Blood Purif. 23, 269–274 (2005a)

    Article  Google Scholar 

  • A.R. Nissenson, C. Ronco, G. Pergamit et al., Continuously functioning artificial nephron system: the promise of nanotechnology. Hemodial. Int. 9, 210–217 (2005b)

    Article  Google Scholar 

  • N. Ozgen, M. Terashima, T. Aung et al., Evaluation of long-term transport ability of a bioartificial renal tubule device using LLC-PK1 cells. Nephrol. Dial. Transplant. 19, 2198–2207 (2004)

    Article  Google Scholar 

  • K.C. Popat, L. Leoni, C.A. Grimes et al., Influence of engineered titania nanotubular surfaces on bone cells. Biomaterials 28, 3188–3197 (2007)

    Article  Google Scholar 

  • M. Sato, T. Ohashi, Biorheological views of endothelial cell responses to mechanical stimuli. Biorheology 42(6), 421–441 (2005)

    Google Scholar 

  • Y. Sekiguchi, T. Dohi, H. Funakubo. Application of NiTi shape memory alloy to use a micro-pump for portable or wearable artificial kidney system. Meeting of the Society for Biomaterials. 592, (1982).

  • J.H. Seo, D.J. Kim, S.U. Son et al., Separation of blood cells and plasma in microchannel. Solid-State Sensors Actuators Microsyst. 2, 1684–1687 (2005)

    Google Scholar 

  • B.S. Smith, S. Yoriya, L. Grissom et al., Hemocompatibility of titania nanotube arrays. J. Biomed. Mater. Res. A 95A(2), 350–360 (2010)

    Article  Google Scholar 

  • S. Song, A.K. Singh, T.J. Shepodd et al., Microchip dialysis of proteins using in situ photopatterned nanoporous polymer membranes. Anal. Chem. 76(8), 2367–2373 (2004)

    Article  Google Scholar 

  • M. Tanaka, A. Takayama, E. Ito et al., Effect of pore size of self-organized honeycomb-patterned polymer films on spreading, focal adhesion, proliferation, and function of endothelial cells. J. Nanosci. Nanotechnol. 7(3), 763–772 (2007)

    Article  Google Scholar 

  • G.M. Whitesides, The origins and the future of microfluidics. Nature 442, 368–373 (2006)

    Article  Google Scholar 

  • P. Yager, T. Edwards, E. Fu et al., Microfluidic diagnostic technologies for global public health. Nature 442, 412–418 (2006)

    Article  Google Scholar 

  • S.H. Ye, J. Watanabe, M. Takai et al., Design of functional hollow fiber membranes modified with phospholipid polymers for application in total hemopurification system. Biomaterials 26(24), 5032–5041 (2005)

    Article  Google Scholar 

Download references

Acknowledgments

This work was financed by the National Natural Science Foundation of China (21173090 and 30970717), and the Special Fund for Strategic Emerging Industry Development of Shenzhen (JCYJ20120618100557119). Technical assistance from the Analytical and Testing Center of HUST is gratefully acknowledged.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Wen Zhu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhu, W., Li, J. & Liu, J. The cell engineering construction and function evaluation of multi-layer biochip dialyzer. Biomed Microdevices 15, 781–791 (2013). https://doi.org/10.1007/s10544-013-9764-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10544-013-9764-x

Keyword

Navigation