A microfluidic chip with gravity‐induced unidirectional flow for perfusion cell culture

Perfusion flow is one of the essential elements and advantages of organ‐on‐a‐chip technology. For example, microfluidics have enabled implementation of perfusion flow and recapitulation of fluidic environment for vascular endothelial cells. The most prevalent method of implementing flow in a chip is to use a pump, which requires elaborate manipulation and complex connections, and accompanies a large amount of dead volume. Previously we devised a gravity‐induced flow system which does not require tubing connections, but this method results in bidirectional flow to enable recirculation, which is somewhat different from physiological blood flow. Here, we have developed a novel microfluidic chip that enables gravity‐induced, unidirectional flow by using a bypass channel with geometry different from the main channel. Human umbilical vein endothelial cells were cultured inside the chip and the effect of flow direction was examined. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2701, 2019

[1]  N. Jeon,et al.  Hybrid polymer microfluidic platform to mimic varying vascular compliance and topology. , 2017, Lab on a chip.

[2]  Michael Doran,et al.  A novel multishear microdevice for studying cell mechanics. , 2009, Lab on a chip.

[3]  Paolo Righettini,et al.  Design of a cone-and-plate device for controlled realistic shear stress stimulation on endothelial cell monolayers , 2016, Cytotechnology.

[4]  Kidong Park,et al.  Measurement of cell traction force with a thin film PDMS cantilever , 2017, Biomedical microdevices.

[5]  K. Sze,et al.  Development of a micromanipulator-based loading device for mechanoregulation study of human mesenchymal stem cells in three-dimensional collagen constructs. , 2010, Tissue engineering. Part C, Methods.

[6]  Andreas Hierlemann,et al.  Adding the 'heart' to hanging drop networks for microphysiological multi-tissue experiments. , 2015, Lab on a chip.

[7]  Nam-Trung Nguyen,et al.  Microfluidic gut-on-a-chip with three-dimensional villi structure , 2017, Biomedical microdevices.

[8]  Sang-Hoon Lee,et al.  Spheroid-based three-dimensional liver-on-a-chip to investigate hepatocyte-hepatic stellate cell interactions and flow effects. , 2013, Lab on a chip.

[9]  D. Ingber,et al.  Microfluidic organs-on-chips , 2014, Nature Biotechnology.

[10]  Mandy B. Esch,et al.  Modular, pumpless body-on-a-chip platform for the co-culture of GI tract epithelium and 3D primary liver tissue. , 2016, Lab on a chip.

[11]  Majid Ebrahimi Warkiani,et al.  Flow-induced stress on adherent cells in microfluidic devices. , 2015, Lab on a chip.

[12]  Tai Hyun Park,et al.  Microtechnology‐based organ systems and whole‐body models for drug screening , 2016, Biotechnology journal.

[13]  Kangsun Lee,et al.  Design of pressure-driven microfluidic networks using electric circuit analogy. , 2012, Lab on a chip.

[14]  Douglas A Lauffenburger,et al.  Microfluidic shear devices for quantitative analysis of cell adhesion. , 2004, Analytical chemistry.

[15]  F. Sonntag,et al.  A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents. , 2015, Lab on a chip.

[16]  Jong Hwan Sung,et al.  Organ‐on‐a‐chip technology and microfluidic whole‐body models for pharmacokinetic drug toxicity screening , 2013, Biotechnology journal.

[17]  S. Bolz,et al.  A microfluidic platform for probing small artery structure and function. , 2010, Lab on a chip.

[18]  Jong Hwan Sung,et al.  A microfluidic device with 3-d hydrogel villi scaffold to simulate intestinal absorption. , 2013, Journal of nanoscience and nanotechnology.

[19]  Megan L. McCain,et al.  Ensembles of engineered cardiac tissues for physiological and pharmacological study: heart on a chip. , 2011, Lab on a chip.

[20]  Xingyu Jiang,et al.  A microfluidic flow-stretch chip for investigating blood vessel biomechanics. , 2012, Lab on a chip.

[21]  J. Collins,et al.  Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip , 2015, Proceedings of the National Academy of Sciences.

[22]  N. Arslan,et al.  Steady and disturbed flow effects on human umbilical vein endothelial cells (HUVECs) in vascular system: an experimental study. , 2010, Acta of bioengineering and biomechanics.

[23]  Jong Hwan Sung,et al.  Microfluidic Gut-liver chip for reproducing the first pass metabolism , 2017, Biomedical Microdevices.

[24]  W. K. Tucker,et al.  Endothelial Nuclear Patterns in the Canine Arterial Tree with Particular Reference to Hemodynamic Events , 1972, Circulation research.

[25]  Brendon M. Baker,et al.  Endothelial Cell Sensing of Flow Direction , 2013, Arteriosclerosis, thrombosis, and vascular biology.

[26]  Shinji Sugiura,et al.  Microfluidic perfusion culture chip providing different strengths of shear stress for analysis of vascular endothelial function. , 2014, Journal of bioscience and bioengineering.

[27]  Jong Hwan Sung,et al.  Construction of 3D multicellular microfluidic chip for an in vitro skin model , 2017, Biomedical microdevices.

[28]  Mandy B. Esch,et al.  Microfabricated mammalian organ systems and their integration into models of whole animals and humans. , 2013, Lab on a chip.

[29]  Jong Hwan Sung,et al.  A microfluidic device for a pharmacokinetic-pharmacodynamic (PK-PD) model on a chip. , 2010, Lab on a chip.

[30]  B L Langille,et al.  Relationship between Blood Flow Direction and Endothelial Cell Orientation at Arterial Branch Sites in Rabbits and Mice , 1981, Circulation research.

[31]  D. Beebe,et al.  Physics and applications of microfluidics in biology. , 2002, Annual review of biomedical engineering.

[32]  Joohyung Lee,et al.  Phenotype Transformation of Aortic Valve Interstitial Cells Due to Applied Shear Stresses Within a Microfluidic Chip , 2017, Annals of Biomedical Engineering.

[33]  Hui Zhao,et al.  Integrated microfluidic chip for endothelial cells culture and analysis exposed to a pulsatile and oscillatory shear stress. , 2009, Lab on a chip.

[34]  D. Ingber,et al.  A human breathing lung‐on‐a‐chip , 2010, Annals of the American Thoracic Society.

[35]  Yuzhi Zhang,et al.  Distinct endothelial phenotypes evoked by arterial waveforms derived from atherosclerosis-susceptible and -resistant regions of human vasculature. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Sanghyo Kim,et al.  Continuous oxygen supply in pump-less micro-bioreactor based on microfluidics , 2015, BioChip Journal.