Performance and scaling effects in a multilayer microfluidic extracorporeal lung oxygenation device.

Microfluidic fabrication technologies are emerging as viable platforms for extracorporeal lung assist devices and oxygenators for cardiac surgical support and critical care medicine, based in part on their ability to more closely mimic the architecture of the human vasculature than existing technologies. In comparison with current hollow fiber oxygenator technologies, microfluidic systems have more physiologically-representative blood flow paths, smaller cross section blood conduits and thinner gas transfer membranes. These features can enable smaller device sizes and a reduced blood volume in the oxygenator, enhanced gas transfer efficiencies, and may also reduce the tendency for clotting in the system. Several critical issues need to be addressed in order to advance this technology from its current state and implement it in an organ-scale device for clinical use. Here we report on the design, fabrication and characterization of multilayer microfluidic oxygenators, investigating scaling effects associated with fluid mechanical resistance, oxygen transfer efficiencies, and other parameters in multilayer devices. Important parameters such as the fluidic resistance of interconnects are shown to become more predominant as devices are scaled towards many layers, while other effects such as membrane distensibility become less significant. The present study also probes the relationship between blood channel depth and membrane thickness on oxygen transfer, as well as the rate of oxygen transfer on the number of layers in the device. These results contribute to our understanding of the complexity involved in designing three-dimensional microfluidic oxygenators for clinical applications.

[1]  Tatiana Kniazeva,et al.  A microfluidic respiratory assist device with high gas permeance for artificial lung applications , 2011, Biomedical microdevices.

[2]  H. Shiku,et al.  Oxygen Permeability of Surface-modified Poly(dimethylsiloxane) Characterized by Scanning Electrochemical Microscopy , 2006 .

[3]  Erik K. Bassett,et al.  Lung assist device technology with physiologic blood flow developed on a tissue engineered scaffold platform. , 2011, Lab on a chip.

[4]  Robert Langer,et al.  Fabrication of a Hybrid Microfluidic System Incorporating both Lithographically Patterned Microchannels and a 3D Fiber‐Formed Microfluidic Network , 2012, Advanced healthcare materials.

[5]  C. Mavroudis,et al.  Platelet and Leukocyte Activation and Design Consequences for Thoracic Artificial Lungs , 2002, ASAIO journal.

[6]  William R Wagner,et al.  Towards microfabricated biohybrid artificial lung modules for chronic respiratory support , 2009, Biomedical microdevices.

[7]  Teruo Fujii,et al.  Cell Culture in 3-Dimensional Microfluidic Structure of PDMS (polydimethylsiloxane) , 2003 .

[8]  A. Tzafriri,et al.  Luminal flow patterns dictate arterial drug deposition in stent-based delivery. , 2009, Journal of controlled release : official journal of the Controlled Release Society.

[9]  Shuichi Takayama,et al.  Fabrication of microfluidic mixers and artificial vasculatures using a high-brightness diode-pumped Nd:YAG laser direct write method. , 2003, Lab on a chip.

[10]  Ahmad S. Khalil,et al.  Functional endothelialized microvascular networks with circular cross-sections in a tissue culture substrate , 2010, Biomedical microdevices.

[11]  A. Brand Blood transfusions in neonatal cardiac surgery and ECMO , 2009 .

[12]  S Chien,et al.  Effects of hematocrit and plasma proteins on human blood rheology at low shear rates. , 1966, Journal of applied physiology.

[13]  J. Vacanti,et al.  Microfabrication Technology for Vascularized Tissue Engineering , 2002 .

[14]  D. Ingber,et al.  Reconstituting Organ-Level Lung Functions on a Chip , 2010, Science.

[15]  Research highlights. Cell beads for building macroscopic tissues. , 2011, Lab on a chip.

[16]  J D Hellums,et al.  Red blood cell damage by shear stress. , 1972, Biophysical journal.

[17]  Andras Eke,et al.  Oxygen Transport to Tissue XXI , 1999, Advances in Experimental Medicine and Biology.

[18]  Robert W Barber,et al.  Biomimetic design of microfluidic manifolds based on a generalised Murray's law. , 2006, Lab on a chip.

[19]  C D Murray,et al.  The Physiological Principle of Minimum Work: I. The Vascular System and the Cost of Blood Volume. , 1926, Proceedings of the National Academy of Sciences of the United States of America.

[20]  D. Hershey,et al.  Diffusion coefficients for oxygen transport in whole blood , 1968 .

[21]  Shewaferaw S Shibeshi,et al.  The Rheology of Blood Flow in a Branched Arterial System. , 2005, Applied rheology.

[22]  L. Cohn,et al.  Cardiac Surgery in the Adult , 2003 .

[23]  T. Bein,et al.  A new miniaturized system for extracorporeal membrane oxygenation in adult respiratory failure , 2009, Critical care.

[24]  H Koyanagi,et al.  Cardiac Surgery in the Adult , 1997 .

[25]  Joseph A Potkay,et al.  Bio-inspired, efficient, artificial lung employing air as the ventilating gas. , 2011, Lab on a chip.

[26]  E. Edelman,et al.  Luminal Flow Amplifies Stent-Based Drug Deposition in Arterial Bifurcations , 2009, PloS one.