Geometry design of herringbone structures for cancer cell capture in a microfluidic device

Cancer cell detection with high capture efficiency is important for its extensive clinical applications. Herringbone structures in microfluidic devices have been widely adopted to increase the cell capture performance due to its chaotic effect. Given the fact of laminar flow in microfluidic devices, geometry-based optimization acting as a design strategy is effective and can help researchers reduce repetitive trial experiments. In this work, we presented a computational model to track the cell motion and used normalized capture efficiency to evaluate the tumor cell capture performance under various geometry settings. Cell adhesion probability was implemented in the model to consider the nature of ligand–receptor formation and breakage during cell–surface interactions. A facile approach was introduced to determine the two lumped coefficients of cell adhesion probability through two microfluidic experiments. A comprehensive geometric study was then performed by using this model, and results were explained from the fluid dynamics. Although most of the geometric guides agree with the general criterion concluded in the literature, we found herringbone structures with symmetric arms rather than a short arm–long arm ratio of 1/3 are optimal. This difference mainly comes from the fact that our model considers the particulate nature of cells while most studies in the literature optimize the geometry merely relying on mixing effects. Thus, our computational model implemented with cell adhesion probability can serve as a more accurate and reliable approach to optimize microfluidic devices for cancer cell capture.

[1]  Abraham D Stroock,et al.  Investigation of the staggered herringbone mixer with a simple analytical model , 2004, Philosophical Transactions of the Royal Society of London. Series A: Mathematical, Physical and Engineering Sciences.

[2]  Weihong Tan,et al.  Aptamer-enabled efficient isolation of cancer cells from whole blood using a microfluidic device. , 2012, Analytical chemistry.

[3]  I. Mezić,et al.  Chaotic Mixer for Microchannels , 2002, Science.

[4]  Yan Gao,et al.  Recent advances in microfluidic cell separations. , 2013, The Analyst.

[5]  Shunqiang Wang,et al.  Effects of nanopillar array diameter and spacing on cancer cell capture and cell behaviors. , 2014, Nanoscale.

[6]  Dimitri Pappas,et al.  Microfluidics and cancer analysis: cell separation, cell/tissue culture, cell mechanics, and integrated analysis systems. , 2016, The Analyst.

[7]  Antony Thomas,et al.  Influence of Red Blood Cells on Nanoparticle Targeted Delivery in Microcirculation. , 2011, Soft matter.

[8]  Xiaochun Xu,et al.  NanoVelcro Chip for CTC enumeration in prostate cancer patients. , 2013, Methods.

[9]  R. M. Boom,et al.  Flow-induced particle migration in microchannels for improved microfiltration processes , 2013 .

[10]  K. Isselbacher,et al.  Isolation of circulating tumor cells using a microvortex-generating herringbone-chip , 2010, Proceedings of the National Academy of Sciences.

[11]  Xiaojun Feng,et al.  A novel microfluidic mixer based on dual-hydrodynamic focusing for interrogating the kinetics of DNA-protein interaction. , 2013, The Analyst.

[12]  Seungpyo Hong,et al.  Rheologically biomimetic cell suspensions for decreased cell settling in microfluidic devices , 2011, Biomedical microdevices.

[13]  F. Muzzio,et al.  The Kenics Static Mixer : a Three-dimensional Chaotic Flow , 1997 .

[14]  B. Kirby,et al.  Characterization of microfluidic shear-dependent epithelial cell adhesion molecule immunocapture and enrichment of pancreatic cancer cells from blood cells with dielectrophoresis. , 2014, Biomicrofluidics.

[15]  Yu Song,et al.  Biospecies Capture and Detection at Low Concentration , 2012 .

[16]  Gabriel P López,et al.  Microfluidic cell sorting: a review of the advances in the separation of cells from debulking to rare cell isolation. , 2015, Lab on a chip.

[17]  N. Lynn,et al.  Geometrical optimization of helical flow in grooved micromixers. , 2007, Lab on a chip.

[18]  P. Saffman The lift on a small sphere in a slow shear flow , 1965, Journal of Fluid Mechanics.

[19]  Waseem Asghar,et al.  Velocity effect on aptamer-based circulating tumor cell isolation in microfluidic devices. , 2011, The journal of physical chemistry. B.

[20]  Shunqiang Wang,et al.  Highly efficient and selective isolation of rare tumor cells using a microfluidic chip with wavy-herringbone micro-patterned surfaces. , 2016, The Analyst.

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

[22]  Jie Yang,et al.  Computational modeling of magnetic nanoparticle targeting to stent surface under high gradient field , 2014, Computational mechanics.

[23]  Shunqiang Wang,et al.  Generation of Customizable Micro-wavy Pattern through Grayscale Direct Image Lithography , 2016, Scientific Reports.

[24]  Reza Ghodssi,et al.  Real-time monitoring of macromolecular biosensing probe self-assembly and on-chip ELISA using impedimetric microsensors. , 2016, Biosensors & bioelectronics.

[25]  Jie Yang,et al.  Characterization of Nanoparticle Dispersion in Red Blood Cell Suspension by the Lattice Boltzmann-Immersed Boundary Method , 2016, Nanomaterials.

[26]  Eun Sook Lee,et al.  An integrated multifunctional platform based on biotin-doped conducting polymer nanowires for cell capture, release, and electrochemical sensing. , 2014, Biomaterials.

[27]  W. Cai,et al.  Modeling and Simulation of Maximum Power Point Tracker in Ptolemy , 2013 .

[28]  E. B. Nauman,et al.  Static Mixers to Promote Axial Mixing , 2002 .

[29]  Thomas J George,et al.  Capture, release and culture of circulating tumor cells from pancreatic cancer patients using an enhanced mixing chip. , 2014, Lab on a chip.

[30]  J H Myung,et al.  Microfluidic devices to enrich and isolate circulating tumor cells. , 2015, Lab on a chip.

[31]  M Ferrari,et al.  The adhesive strength of non-spherical particles mediated by specific interactions. , 2006, Biomaterials.

[32]  R. Tompkins,et al.  Effect of flow and surface conditions on human lymphocyte isolation using microfluidic chambers. , 2004, Langmuir : the ACS journal of surfaces and colloids.

[33]  R. Skalak,et al.  Design and construction of a linear shear stress flow chamber , 2006, Annals of Biomedical Engineering.

[34]  김병재,et al.  마이크로 채널에서 두 유체 혼합 = Two-fluid mixing in a microchannel , 2003 .

[35]  Piet D. Iedema,et al.  CFD calculation of laminar striation thinning in static mixer reactors , 2001 .

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

[37]  Zhiyi Zhang,et al.  A simplified design of the staggered herringbone micromixer for practical applications. , 2010, Biomicrofluidics.

[38]  Timothy B Lannin,et al.  Parametric control of collision rates and capture rates in geometrically enhanced differential immunocapture (GEDI) microfluidic devices for rare cell capture , 2014, Biomedical microdevices.

[39]  Peng Xue,et al.  Isolation and elution of Hep3B circulating tumor cells using a dual-functional herringbone chip , 2014 .

[40]  J. Aubin,et al.  Design of micromixers using CFD modelling , 2005 .

[41]  D. Hassell,et al.  Investigation of the convective motion through a staggered herringbone micromixer at low Reynolds number flow , 2006 .

[42]  Cheng-Chi Tai,et al.  A fatigue state evaluation system based on the band energy of electroencephalography signals , 2013 .

[43]  Hengzi Wang,et al.  Numerical investigation of mixing in microchannels with patterned grooves , 2003 .

[44]  Shu Yang,et al.  Spatially Selective Nucleation and Growth of Water Droplets on Hierarchically Patterned Polymer Surfaces , 2016, Advanced materials.

[45]  Jason G. Kralj,et al.  Engineering and analysis of surface interactions in a microfluidic herringbone micromixer. , 2012, Lab on a chip.

[46]  Shuang Hou,et al.  Programming Thermoresponsiveness of NanoVelcro Substrates Enables Effective Purification of Circulating Tumor Cells in Lung Cancer Patients , 2014, ACS nano.

[47]  A. Jemal,et al.  Cancer Statistics, 2008 , 2008, CA: a cancer journal for clinicians.