Design, modeling and characterization of microfluidic architectures for high flow rate, small footprint microfluidic systems.

We propose a strategy for optimizing distribution of flow in a microfluidic chamber for microreactor, lateral flow assay and immunocapture applications. It is aimed at maximizing flow throughput, while keeping footprint, cell thickness, and shear stress in the distribution channels at a minimum, and offering a uniform flow field along the whole analysis chamber. In order to minimize footprint, the traditional tree-like or "rhombus" design, in which distribution microchannels undergo a series of splittings into two subchannels with equal lengths and widths, was replaced by a design in which subchannel lengths are unequal, and widths are analytically adapted within the Hele-Shaw approximation, in order to keep the flow resistance uniform along all flow paths. The design was validated by hydrodynamic flow simulation using COMSOL finite element software. Simulations show that, if the channel is too narrow, the Hele-Shaw approximation loses accuracy, and the flow velocity in the chamber can fluctuate by up to 20%. We thus used COMSOL simulation to fine-tune the channel parameters, and obtained a fluctuation of flow velocity across the whole chamber below 10%. The design was then implemented into a PDMS device, and flow profiles were measured experimentally using particle tracking. Finally, we show that this system can be applied to cell sorting in self-assembling magnetic arrays, increasing flow throughput by a factor 100 as compared to earlier reported designs.

[1]  David Erickson,et al.  Towards numerical prototyping of labs-on-chip: modeling for integrated microfluidic devices , 2005 .

[2]  Arul Jayaraman,et al.  Rapid Fabrication of Bio‐inspired 3D Microfluidic Vascular Networks , 2009 .

[3]  T. Mukherjee,et al.  Institute of Physics Publishing Journal of Micromechanics and Microengineering Systematic Modeling of Microfluidic Concentration Gradient Generators , 2022 .

[4]  Alison Stopeck,et al.  Circulating tumor cells, disease progression, and survival in metastatic breast cancer. , 2004, The New England journal of medicine.

[5]  E. Verpoorte Microfluidic chips for clinical and forensic analysis , 2002, Electrophoresis.

[6]  Peter B Howell,et al.  Toolbox for the design of optimized microfluidic components. , 2006, Lab on a chip.

[7]  S. J. Lee,et al.  Micro total analysis system (μ-TAS) in biotechnology , 2004, Applied Microbiology and Biotechnology.

[8]  G M Whitesides,et al.  Fabrication of topologically complex three-dimensional microfluidic systems in PDMS by rapid prototyping. , 2000, Analytical chemistry.

[9]  Jonathan W. Uhr,et al.  Tumor Cells Circulate in the Peripheral Blood of All Major Carcinomas but not in Healthy Subjects or Patients With Nonmalignant Diseases , 2004, Clinical Cancer Research.

[10]  A. Vincent-Salomon,et al.  Single circulating tumor cell detection and overall survival in nonmetastatic breast cancer. , 2009, Annals of oncology : official journal of the European Society for Medical Oncology.

[11]  Ronald F Renzi,et al.  An integrated microfluidic platform for sensitive and rapid detection of biological toxins. , 2008, Lab on a chip.

[12]  Michael G. Roper,et al.  A fully integrated microfluidic genetic analysis system with sample-in–answer-out capability , 2006, Proceedings of the National Academy of Sciences.

[13]  L. Ceriotti,et al.  New adsorbed coatings for capillary electrophoresis , 2000, Electrophoresis.

[14]  Mehmet Toner,et al.  Isolation and Characterization of Circulating Tumor Cells from Patients with Localized and Metastatic Prostate Cancer , 2010, Science Translational Medicine.

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

[16]  Jean-Louis Viovy,et al.  Use of self assembled magnetic beads for on-chip protein digestion. , 2005, Lab on a chip.

[17]  P. Pilarski,et al.  FISH and chips: chromosomal analysis on microfluidic platforms. , 2007, IET nanobiotechnology.

[18]  David R. Emerson,et al.  Optimal design of microfluidic networks using biologically inspired principles , 2008 .

[19]  C. Cotman,et al.  A microfluidic culture platform for CNS axonal injury, regeneration and transport , 2005, Nature Methods.

[20]  Klavs F. Jensen,et al.  Microfabricated Differential Reactor for Heterogeneous Gas Phase Catalyst Testing , 2002 .

[21]  K. Dorfman,et al.  Contamination-free continuous flow microfluidic polymerase chain reaction for quantitative and clinical applications. , 2005, Analytical chemistry.

[22]  Anne Vincent-Salomon,et al.  Circulating Tumor Cell Detection Predicts Early Metastatic Relapse After Neoadjuvant Chemotherapy in Large Operable and Locally Advanced Breast Cancer in a Phase II Randomized Trial , 2008, Clinical Cancer Research.

[23]  Heinz Schmid,et al.  Controlled particle placement through convective and capillary assembly. , 2007, Langmuir : the ACS journal of surfaces and colloids.

[24]  P. Bongrand,et al.  Direct quantification of the modulation of interaction between cell‐ or surface‐bound LFA‐1 and ICAM‐1 , 2004, Journal of leukocyte biology.

[25]  Hee Chan Kim,et al.  Recent advances in miniaturized microfluidic flow cytometry for clinical use , 2007, Electrophoresis.

[26]  S. Digumarthy,et al.  Isolation of rare circulating tumour cells in cancer patients by microchip technology , 2007, Nature.

[27]  Jean-Louis Viovy,et al.  Self-Assembled Magnetic Matrices for DNA Separation Chips , 2002, Science.

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

[29]  Jean-Louis Viovy,et al.  Wallerian-Like Degeneration of Central Neurons After Synchronized and Geometrically Registered Mass Axotomy in a Three-Compartmental Microfluidic Chip , 2010, Neurotoxicity Research.

[30]  N. Mortensen,et al.  Reexamination of Hagen-Poiseuille flow: shape dependence of the hydraulic resistance in microchannels. , 2004, Physical review. E, Statistical, nonlinear, and soft matter physics.

[31]  Luke P. Lee,et al.  Microfluidics-based systems biology. , 2006, Molecular bioSystems.

[32]  Jean Salamero,et al.  Microfluidic sorting and multimodal typing of cancer cells in self-assembled magnetic arrays , 2010, Proceedings of the National Academy of Sciences.

[33]  H. Wolf,et al.  Nanoparticle printing with single-particle resolution. , 2007, Nature nanotechnology.

[34]  Wei Du,et al.  Microfluidic chips for cell sorting. , 2008, Frontiers in bioscience : a journal and virtual library.