Live Cell Analysis Under Shear Flow

This chapter describes a microfluidic system for live cell analysis that enables precise control over shear stress to emulate physiological conditions encountered in the vasculature and other niches. Data from a number of key application areas are included in the report, including stem cell biology, platelet biology, immune response, and bacterial biofilms. The approach addresses critical limitations of macroscopic approaches like laminar flow chambers or cone and plate assays by providing real-time, high-resolution microscopy datain a low-volume microfluidic format. Utilizing a pneumatic pumping system instead of liquid displacement pumps obviates the need to sterilize components between runs and contributes to higher throughput and parallelization. The microfluidic device is contained within an SBS-standard well plate format that remedies many of the interfacing issues often encountered with hand-made microfluidic devices.

[1]  U. Windberger,et al.  Whole Blood Viscosity, Plasma Viscosity and Erythrocyte Aggregation in Nine Mammalian Species: Reference Values and Comparison of Data , 2003, Experimental physiology.

[2]  Interactions between multiple cell types in parallel microfluidic channels: monitoring platelet adhesion to an endothelium in the presence of an anti-adhesion drug. , 2008, Analytical chemistry.

[3]  P. Lacolley,et al.  In vitro impact of physiological shear stress on endothelial cells gene expression profile. , 2007, Clinical hemorheology and microcirculation.

[4]  J. Sixma,et al.  Functional self-association of von Willebrand factor during platelet adhesion under flow , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[5]  B. Vanhaesebroeck,et al.  Deletion of the p110beta isoform of phosphoinositide 3-kinase in platelets reveals its central role in Akt activation and thrombus formation in vitro and in vivo. , 2010, Blood.

[6]  A. Henrici Studies of Freshwater Bacteria , 1933, Journal of bacteriology.

[7]  R Kujat,et al.  Mechanobiological conditioning of stem cells for cartilage tissue engineering. , 2006, Bio-medical materials and engineering.

[8]  J. Moake,et al.  Platelets and shear stress. , 1996, Blood.

[9]  C. Legrand,et al.  Shear stress modulates tumour cell adhesion to the endothelium. , 2003, Biorheology.

[10]  R. Palmer,et al.  Shear-Enhanced Oral Microbial Adhesion , 2009, Applied and Environmental Microbiology.

[11]  Shaun P Jackson,et al.  The growing complexity of platelet aggregation. , 2007, Blood.

[12]  A. Beaudoin,et al.  Analysis of shear stress and hemodynamic factors in a model of coronary artery stenosis and thrombosis. , 1993, The American journal of physiology.

[13]  A. Groisman,et al.  Microfluidic devices for studies of shear-dependent platelet adhesion. , 2008, Lab on a chip.

[14]  Cristian Ionescu-Zanetti,et al.  Well Plate—Coupled Microfluidic Devices Designed for Facile Image-Based Cell Adhesion and Transmigration Assays , 2010, Journal of biomolecular screening.

[15]  V. Fuster,et al.  Effect of an Eccentric Severe Stenosis on Fibrin(ogen) Deposition on Severely Damaged Vessel Wall in Arterial Thrombosis: Relative Contribution of Fibrin(ogen) and Platelets , 1994, Circulation.

[16]  Roberto Kolter,et al.  Initiation of biofilm formation in Pseudomonas fluorescens WCS365 proceeds via multiple, convergent signalling pathways: a genetic analysis , 1998, Molecular microbiology.

[17]  Qingbo Xu,et al.  HDAC3 is crucial in shear- and VEGF-induced stem cell differentiation toward endothelial cells , 2006, The Journal of cell biology.

[18]  W. Siess,et al.  Rac1-mediated signaling plays a central role in secretion-dependent platelet aggregation in human blood stimulated by atherosclerotic plaque , 2010, Journal of Translational Medicine.

[19]  Peter W Zandstra,et al.  Shear‐Controlled Single‐Step Mouse Embryonic Stem Cell Expansion and Embryoid Body–Based Differentiation , 2005, Stem cells.

[20]  Qizhi Yao,et al.  Shear Stress Induces Endothelial Differentiation From a Murine Embryonic Mesenchymal Progenitor Cell Line , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[21]  N. Savion,et al.  CHAPTER 29 – Impact Cone and Plate(let) Analyzer , 2007 .

[22]  Gerhard Ehninger,et al.  Mesenchymal Stem Cells Can Be Differentiated Into Endothelial Cells In Vitro , 2004, Stem cells.

[23]  M. U. Nollert,et al.  Design Considerations for a Microfluidic Device to Quantify the Platelet Adhesion to Collagen at Physiological Shear Rates , 2009, Annals of Biomedical Engineering.

[24]  Antonella Farsetti,et al.  Epigenetic Histone Modification and Cardiovascular Lineage Programming in Mouse Embryonic Stem Cells Exposed to Laminar Shear Stress , 2005 .

[25]  F. Luscinskas,et al.  Neutrophil Recruitment under Shear Flow: It's All about Endothelial Cell Rings and Gaps , 2009, Microcirculation.

[26]  Danny Bluestein,et al.  Fluid mechanics of arterial stenosis: Relationship to the development of mural thrombus , 1997, Annals of Biomedical Engineering.

[27]  Cheng-Zhong Zhang,et al.  Mechanoenzymatic Cleavage of the Ultralarge Vascular Protein von Willebrand Factor , 2009, Science.

[28]  Caterina Minelli,et al.  A micro-fluidic study of whole blood behaviour on PMMA topographical nanostructures , 2008, Journal of nanobiotechnology.

[29]  A Alexander-Katz,et al.  Shear-induced unfolding triggers adhesion of von Willebrand factor fibers , 2007, Proceedings of the National Academy of Sciences.

[30]  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.

[31]  S. Diamond,et al.  Microfluidic focal thrombosis model for measuring murine platelet deposition and stability: PAR4 signaling enhances shear‐resistance of platelet aggregates , 2008, Journal of thrombosis and haemostasis : JTH.

[32]  Arnan Mitchell,et al.  A shear gradient–dependent platelet aggregation mechanism drives thrombus formation , 2009, Nature Medicine.

[33]  S. Diamond,et al.  Matrix protein microarrays for spatially and compositionally controlled microspot thrombosis under laminar flow. , 2006, Biophysical journal.

[34]  S. Okabe,et al.  Significance of rpoS during maturation of Escherichia coli biofilms , 2008, Biotechnology and bioengineering.

[35]  Carolyn G. Conant,et al.  New Device for High-Throughput Viability Screening of Flow Biofilms , 2010, Applied and Environmental Microbiology.

[36]  Kimiko Yamamoto,et al.  Fluid shear stress induces differentiation of Flk-1-positive embryonic stem cells into vascular endothelial cells in vitro. , 2005, American journal of physiology. Heart and circulatory physiology.

[37]  Force Signaling in Biology , 2009, Science.

[38]  A. Federici,et al.  Activation-independent platelet adhesion and aggregation under elevated shear stress. , 2005, Blood.

[39]  H. Ceri,et al.  The Calgary Biofilm Device: New Technology for Rapid Determination of Antibiotic Susceptibilities of Bacterial Biofilms , 1999, Journal of Clinical Microbiology.

[40]  S. Diamond,et al.  P2Y12 or P2Y1 inhibitors reduce platelet deposition in a microfluidic model of thrombosis while apyrase lacks efficacy under flow conditions. , 2010, Integrative biology : quantitative biosciences from nano to macro.

[41]  Carolyn G. Conant,et al.  Well plate microfluidic system for investigation of dynamic platelet behavior under variable shear loads , 2011, Biotechnology and bioengineering.

[42]  Paul Stoodley,et al.  Bacterial biofilms: from the Natural environment to infectious diseases , 2004, Nature Reviews Microbiology.

[43]  S. Jackson,et al.  Techniques to examine platelet adhesive interactions under flow. , 2004, Methods in molecular biology.

[44]  Scott L Diamond,et al.  A membrane-based microfluidic device for controlling the flux of platelet agonists into flowing blood. , 2008, Lab on a chip.