Computationally Informed Design of a Multi-Axial Actuated Microfluidic Chip Device

This paper describes the computationally informed design and experimental validation of a microfluidic chip device with multi-axial stretching capabilities. The device, based on PDMS soft-lithography, consisted of a thin porous membrane, mounted between two fluidic compartments, and tensioned via a set of vacuum-driven actuators. A finite element analysis solver implementing a set of different nonlinear elastic and hyperelastic material models was used to drive the design and optimization of chip geometry and to investigate the resulting deformation patterns under multi-axial loading. Computational results were cross-validated by experimental testing of prototypal devices featuring the in silico optimized geometry. The proposed methodology represents a suite of computationally handy simulation tools that might find application in the design and in silico mechanical characterization of a wide range of stretchable microfluidic devices.

[1]  Andrea Bacigalupo,et al.  Second‐order computational homogenization of heterogeneous materials with periodic microstructure , 2010 .

[2]  Donald E Ingber,et al.  Microfabrication of human organs-on-chips , 2013, Nature Protocols.

[3]  Yibin Fu,et al.  Nonlinear elasticity : theory and applications , 2001 .

[4]  D. Hurtado,et al.  Gradient flows and variational principles for cardiac electrophysiology: Toward efficient and robust numerical simulations of the electrical activity of the heart , 2014 .

[5]  S. Giannitelli,et al.  Investigating Nonalcoholic Fatty Liver Disease in a Liver-on-a-Chip Microfluidic Device , 2016, PloS one.

[6]  Marco Paggi,et al.  An anisotropic large displacement cohesive zone model for fibrillar and crazing interfaces , 2015 .

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

[8]  Wolfgang A. Wall,et al.  Computational analysis of morphologies and phase transitions of cross-linked, semi-flexible polymer networks , 2015, Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[9]  Kevin Kit Parker,et al.  Cooperative coupling of cell-matrix and cell–cell adhesions in cardiac muscle , 2012, Proceedings of the National Academy of Sciences.

[10]  R. Ogden.  Non-Linear Elastic Deformations , 1984 .

[11]  Yongan Huang,et al.  Microfluidic serpentine antennas with designed mechanical tunability. , 2014, Lab on a chip.

[12]  F. Feyel.  A multilevel finite element method (FE2) to describe the response of highly non-linear structures using generalized continua , 2003 .

[13]  G Puglisi,et al.  Multi-scale modelling of rubber-like materials and soft tissues: an appraisal , 2016, Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[14]  Jong Hwan Sung,et al.  Using PBPK guided “ Body-ona-Chip ” Systems to Predict Mammalian Response to Drug and Chemical Exposure , 2014 .

[15]  Andrew E. Pelling,et al.  A microscale anisotropic biaxial cell stretching device for applications in mechanobiology , 2013, Biotechnology Letters.

[16]  Yi Zheng,et al.  Recent advances in microfluidic techniques for single-cell biophysical characterization. , 2013, Lab on a chip.

[17]  Abel L. Thangawng,et al.  An ultra-thin PDMS membrane as a bio/micro–nano interface: fabrication and characterization , 2007, Biomedical microdevices.

[18]  Wolfgang A Wall,et al.  Consistent finite-element approach to Brownian polymer dynamics with anisotropic friction. , 2010, Physical review. E, Statistical, nonlinear, and soft matter physics.

[19]  Mechanics and Thermomechanics of Rubberlike Solids , 2004 .

[20]  Alberto Rainer,et al.  Microfluidic Organ/Body-on-a-Chip Devices at the Convergence of Biology and Microengineering , 2015, Sensors.

[21]  Marco Rasponi,et al.  Controlled electromechanical cell stimulation on-a-chip , 2015, Scientific Reports.

[22]  E. Yoon,et al.  Quantitative evaluation of cardiomyocyte contractility in a 3D microenvironment. , 2008, Journal of biomechanics.

[23]  R. Ogden,et al.  A New Constitutive Framework for Arterial Wall Mechanics and a Comparative Study of Material Models , 2000 .

[24]  Josue A. Goss,et al.  Muscle on a chip: in vitro contractility assays for smooth and striated muscle. , 2012, Journal of pharmacological and toxicological methods.

[25]  A. Pandolfi,et al.  Theoretical and Numerical Modeling of Nonlinear Electromechanics with applications to Biological Active Media , 2015 .

[26]  Nam-Trung Nguyen,et al.  A polymeric cell stretching device for real-time imaging with optical microscopy , 2013, Biomedical Microdevices.

[27]  D. Gee,et al.  Deformable cell-cell and cell-substrate interactions in semi-infinite domain. , 2013, Journal of biomechanics.

[28]  Wolfgang A. Wall,et al.  Micromechanical simulations of biopolymer networks with finite elements , 2013, J. Comput. Phys..

[29]  Jong Hwan Sung,et al.  Using physiologically-based pharmacokinetic-guided “body-on-a-chip” systems to predict mammalian response to drug and chemical exposure , 2014, Experimental biology and medicine.

[30]  Antoine Barbot,et al.  On-chip Microfluidic Multimodal Swimmer toward 3D Navigation , 2016, Scientific Reports.

[31]  Ichiro Harada,et al.  Design and Construction of an Equibiaxial Cell Stretching System That Is Improved for Biochemical Analysis , 2014, PloS one.

[32]  Christopher S. Chen,et al.  Cooperative contractility: the role of stress fibres in the regulation of cell-cell junctions. , 2015, Journal of biomechanics.

[33]  D. Hurtado,et al.  Computational modeling of non-linear diffusion in cardiac electrophysiology: A novel porous-medium approach , 2016 .

[34]  Chao Lu,et al.  A comprehensive theoretical model for on-chip microring-based photonic fractional differentiators , 2015, Scientific reports.

[35]  Feng Xu,et al.  Engineering cell alignment in vitro. , 2014, Biotechnology advances.

[36]  Donald E Ingber,et al.  Microengineered physiological biomimicry: organs-on-chips. , 2012, Lab on a chip.

[37]  Ricardo Ruiz-Baier,et al.  An augmented velocity–vorticity–pressure formulation for the Brinkman equations , 2015 .

[38]  William H. Press,et al.  Numerical recipes in C , 2002 .

[39]  F. Baaijens,et al.  A thermodynamically motivated model for stress-fiber reorganization , 2016, Biomechanics and modeling in mechanobiology.

[40]  D. Ingber,et al.  Cellular mechanotransduction: putting all the pieces together again , 2006, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[41]  Yong‐Lai Zhang,et al.  Integrated optofluidic-microfluidic twin channels: toward diverse application of lab-on-a-chip systems , 2016, Scientific Reports.

[42]  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.

[43]  J. D. Humphrey,et al.  A homogenized constrained mixture (and mechanical analog) model for growth and remodeling of soft tissue , 2016, Biomechanics and modeling in mechanobiology.

[44]  YongTae Kim,et al.  Organs-on-Chips , 2019, Encyclopedia of Biomedical Engineering.

[45]  Sami Alom Ruiz,et al.  Mechanical tugging force regulates the size of cell–cell junctions , 2010, Proceedings of the National Academy of Sciences.

[46]  Samuel P. Kounaves,et al.  Fabrication and characterization , 1991 .

[47]  A. Pandolfi,et al.  Viscoelectromechanics modeling of intestine wall hyperelasticity , 2016 .

[48]  Chandra Sekhar,et al.  Absence of Detectable Influenza RNA Transmitted via Aerosol during Various Human Respiratory Activities – Experiments from Singapore and Hong Kong , 2014, PloS one.

[49]  R. Bashir,et al.  Development of Miniaturized Walking Biological Machines , 2012, Scientific Reports.

[50]  M. Paggi,et al.  A nonlinear finite thickness cohesive interface element for modeling delamination in fibre-reinforced composite laminates , 2017 .

[51]  Shuichi Takayama,et al.  Individually programmable cell stretching microwell arrays actuated by a Braille display. , 2008, Biomaterials.

[52]  Yiannis Ventikos,et al.  Development of a pneumatically driven active cover lid for multi-well microplates for use in perfusion three-dimensional cell culture , 2015, Scientific Reports.

[53]  A. Pandolfi,et al.  On three- and two-dimensional fiber distributed models of biological tissues , 2014 .

[54]  R. McMeeking,et al.  Simulation of the cytoskeletal response of cells on grooved or patterned substrates , 2015, Journal of The Royal Society Interface.

[55]  D. Ingber,et al.  Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow. , 2012, Lab on a chip.

[56]  Robert M. Wasson.  : An Appraisal , 2007 .

[57]  A. Pandolfi,et al.  Coupled electro-mechanical models of fiber-distributed active tissues. , 2016, Journal of biomechanics.

[58]  Ivonne Sgura,et al.  Fitting hyperelastic models to experimental data , 2004 .

[59]  Yu Sun,et al.  Microfabricated arrays for high-throughput screening of cellular response to cyclic substrate deformation. , 2010, Lab on a chip.

[60]  P. Mozetic,et al.  Combining Type I Interferons and 5-Aza-2'-Deoxycitidine to Improve Anti-Tumor Response against Melanoma. , 2017, The Journal of investigative dermatology.

[61]  A. Bacigalupo.  Second-order homogenization of periodic materials based on asymptotic approximation of the strain energy: formulation and validity limits , 2014, 1401.7855.

[62]  Alfio Quarteroni,et al.  Mathematical modelling of active contraction in isolated cardiomyocytes. , 2014, Mathematical medicine and biology : a journal of the IMA.

[63]  Brian P. Helmke,et al.  A Stretching Device for High-Resolution Live-Cell Imaging , 2010, Annals of Biomedical Engineering.

[64]  Andrea Bacigalupo,et al.  Second-gradient homogenized model for wave propagation in heterogeneous periodic media , 2014 .