A Reversibly Sealed, Easy Access, Modular (SEAM) Microfluidic Architecture to Establish In Vitro Tissue Interfaces

Abhyankar, Vinay V.; Wu, Meiye; Koh, Chung-Yan; Hatch, Anson V.; Eddington, ed., David T.

doi:10.1371/journal.pone.0156341

Title: A Reversibly Sealed, Easy Access, Modular (SEAM) Microfluidic Architecture to Establish In Vitro Tissue Interfaces

Journal Article · Thu May 26 00:00:00 EDT 2016 · PLoS ONE

DOI:https://doi.org/10.1371/journal.pone.0156341· OSTI ID:1346605

Abhyankar, Vinay V.; Wu, Meiye; Koh, Chung-Yan; Hatch, Anson V.; Eddington, ed., David T.

Microfluidic barrier tissue models have emerged as advanced in vitro tools to explore interactions with external stimuli such as drug candidates, pathogens, or toxins. However, the procedures required to establish and maintain these systems can be challenging to implement for end users, particularly those without significant in-house engineering expertise. Here we present a module-based approach that provides an easy-to-use workflow to establish, maintain, and analyze microscale tissue constructs. Our approach begins with a removable culture insert that is magnetically coupled, decoupled, and transferred between standalone, prefabricated microfluidic modules for simplified cell seeding, culture, and downstream analysis. The modular approach allows several options for perfusion including standard syringe pumps or integration with a self-contained gravity-fed module for simple cell maintenance. As proof of concept, we establish a culture of primary human microvascular endothelial cells (HMVEC) and report combined surface protein imaging and gene expression after controlled apical stimulation with the bacterial endotoxin lipopolysaccharide (LPS). We also demonstrate the feasibility of incorporating hydrated biomaterial interfaces into the microfluidic architecture by integrating an ultra-thin (< 1 μm), self-assembled hyaluronic acid/peptide amphiphile culture membrane with brain-specific Young’s modulus (~ 1kPa). To highlight the importance of including biomimetic interfaces into microscale models we report multi-tiered readouts from primary rat cortical cells cultured on the self-assembled membrane and compare a panel of mRNA targets with primary brain tissue signatures. As a result, we anticipate that the modular approach and simplified operational workflows presented here will enable a wide range of research groups to incorporate microfluidic barrier tissue models into their work.

View Journal Article

Cite

Export

Save

Research Organization:: Sandia National Lab. (SNL-CA), Livermore, CA (United States); Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: 10027IA-3167; AC04-94AL85000

OSTI ID:: 1346605

Alternate ID(s):: OSTI ID: 1266214

Journal Information:: PLoS ONE, Journal Name: PLoS ONE Vol. 11 Journal Issue: 5; ISSN 1932-6203

Publisher:: Public Library of Science (PLoS)Copyright Statement

Country of Publication:: United States

Language:: English

Citation Metrics:

Cited by: 27 works

Citation information provided by
Web of Science

References (61)

Physical properties of hierarchically ordered self-assembled planar and spherical membranes Carvajal, Daniel; Bitton, Ronit; Mantei, Jason R. Soft Matter, Vol. 6, Issue 8 https://doi.org/10.1039/b923903k	journal	January 2010
Extracellular matrix as a biological scaffold material: Structure and function Badylak, S.; Freytes, D.; Gilbert, T. Acta Biomaterialia, Vol. 5, Issue 1 https://doi.org/10.1016/j.actbio.2008.09.013	journal	January 2009
Advanced Material Strategies for Tissue Engineering Scaffolds Freed, Lisa E.; Engelmayr, George C.; Borenstein, Jeffrey T. Advanced Materials, Vol. 21, Issue 32-33 https://doi.org/10.1002/adma.200900303	journal	September 2009
Development of hyaluronic acid-based scaffolds for brain tissue engineering Wang, Tzu-Wei; Spector, Myron Acta Biomaterialia, Vol. 5, Issue 7 https://doi.org/10.1016/j.actbio.2009.03.033	journal	September 2009
Microengineered physiological biomimicry: Organs-on-Chips Huh, Dongeun; Torisawa, Yu-suke; Hamilton, Geraldine A. Lab on a Chip, Vol. 12, Issue 12 https://doi.org/10.1039/c2lc40089h	journal	January 2012
Self-Assembly and Mineralization of Peptide-Amphiphile Nanofibers Hartgerink, Jeffrey D.; Beniash, Elia; Stupp, Samuel I. Science, Vol. 294, Issue 5547, p. 1684-1688 https://doi.org/10.1126/science.1063187	journal	November 2001
Microfluidic tectonics: A comprehensive construction platform for microfluidic systems Beebe, D. J.; Moore, J. S.; Yu, Q. Proceedings of the National Academy of Sciences, Vol. 97, Issue 25, p. 13488-13493 https://doi.org/10.1073/pnas.250273097	journal	November 2000
Myotubes differentiate optimally on substrates with tissue-like stiffness: pathological implications for soft or stiff microenvironments Engler, Adam J.; Griffin, Maureen A.; Sen, Shamik The Journal of Cell Biology, Vol. 166, Issue 6 https://doi.org/10.1083/jcb.200405004	journal	September 2004
The pressure drop along rectangular microchannels containing bubbles Fuerstman, Michael J.; Lai, Ann; Thurlow, Meghan E. Lab on a Chip, Vol. 7, Issue 11 https://doi.org/10.1039/b706549c	journal	January 2007
c-fos regulates neuronal excitability and survival Zhang, Jianhua; Zhang, Dongsheng; McQuade, Jill Slane Nature Genetics, Vol. 30, Issue 4 https://doi.org/10.1038/ng859	journal	March 2002
Lab-on-a-chip devices: How to close and plug the lab? Temiz, Yuksel; Lovchik, Robert D.; Kaigala, Govind V. Microelectronic Engineering, Vol. 132 https://doi.org/10.1016/j.mee.2014.10.013	journal	January 2015
Arrays of horizontally-oriented mini-reservoirs generate steady microfluidic flows for continuous perfusion cell culture and gradient generation Zhu, Xiaoyue; Yi Chu, Leonard; Chueh, Bor-han The Analyst, Vol. 129, Issue 11 https://doi.org/10.1039/b407623k	journal	January 2004
Microfluidic Arrays of Fluid−Fluid Diffusional Contacts as Detection Elements and Combinatorial Tools Ismagilov, Rustem F.; Ng, Jessamine M. K.; Kenis, Paul J. A. Analytical Chemistry, Vol. 73, Issue 21 https://doi.org/10.1021/ac010502a	journal	November 2001
A microfluidic device for a pharmacokinetic–pharmacodynamic (PK–PD) model on a chip Sung, Jong Hwan; Kam, Carrie; Shuler, Michael L. Lab on a Chip, Vol. 10, Issue 4 https://doi.org/10.1039/b917763a	journal	January 2010
Astrocyte–endothelial interactions at the blood–brain barrier Abbott, N. Joan; Rönnbäck, Lars; Hansson, Elisabeth Nature Reviews Neuroscience, Vol. 7, Issue 1 https://doi.org/10.1038/nrn1824	journal	January 2006
Reconstituting Organ-Level Lung Functions on a Chip Huh, D.; Matthews, B. D.; Mammoto, A. Science, Vol. 328, Issue 5986 https://doi.org/10.1126/science.1188302	journal	June 2010
On chip porous polymer membranes for integration of gastrointestinal tract epithelium with microfluidic ‘body-on-a-chip’ devices Esch, Mandy Brigitte; Sung, Jong Hwan; Yang, Jennifer Biomedical Microdevices, Vol. 14, Issue 5 https://doi.org/10.1007/s10544-012-9669-0	journal	July 2012
Pumpless microfluidic platform for drug testing on human skin equivalents Abaci, Hasan Erbil; Gledhill, Karl; Guo, Zongyou Lab on a Chip, Vol. 15, Issue 3 https://doi.org/10.1039/C4LC00999A	journal	January 2015
Substrate Stiffness Regulates PDGF-Induced Circular Dorsal Ruffle Formation Through MLCK Huynh, John; Bordeleau, Francois; Kraning-Rush, Casey M. Cellular and Molecular Bioengineering, Vol. 6, Issue 2 https://doi.org/10.1007/s12195-013-0278-7	journal	May 2013
Large-Scale, Ultrapliable, and Free-Standing Nanomembranes Kang, Edward; Ryoo, Jihee; Jeong, Gi Seok Advanced Materials, Vol. 25, Issue 15 https://doi.org/10.1002/adma.201204619	journal	February 2013
Molecular mechanisms of mechanotransduction in mammalian sensory neurons Delmas, Patrick; Hao, Jizhe; Rodat-Despoix, Lise Nature Reviews Neuroscience, Vol. 12, Issue 3 https://doi.org/10.1038/nrn2993	journal	February 2011
RNA processing and its regulation: global insights into biological networks Licatalosi, Donny D.; Darnell, Robert B. Nature Reviews Genetics, Vol. 11, Issue 1 https://doi.org/10.1038/nrg2673	journal	January 2010
A novel RING-H2 motif protein downregulated by axotomy: its characteristic localization at the postsynaptic density of axosomatic synapse Nakayama, M.; Miyake, T.; Gahara, Y. The Journal of Neuroscience, Vol. 15, Issue 7 https://doi.org/10.1523/JNEUROSCI.15-07-05238.1995	journal	July 1995
Clear castable polyurethane elastomer for fabrication of microfluidic devices Domansky, Karel; Leslie, Daniel C.; McKinney, James Lab on a Chip, Vol. 13, Issue 19 https://doi.org/10.1039/c3lc50558h	journal	January 2013
A review of microfabrication and hydrogel engineering for micro-organs on chips Verhulsel, Marine; Vignes, Maéva; Descroix, Stéphanie Biomaterials, Vol. 35, Issue 6 https://doi.org/10.1016/j.biomaterials.2013.11.021	journal	February 2014
Streamlining gene expression analysis: integration of co-culture and mRNA purification Berry, Scott M.; Singh, Chandresh; Lang, Jessica D. Integrative Biology, Vol. 6, Issue 2 https://doi.org/10.1039/c3ib40136g	journal	January 2014
Microfabrication of human organs-on-chips Huh, Dongeun; Kim, Hyun Jung; Fraser, Jacob P. Nature Protocols, Vol. 8, Issue 11 https://doi.org/10.1038/nprot.2013.137	journal	October 2013
Multi-cellular 3D human primary liver cell culture elevates metabolic activity under fluidic flow Esch, Mandy B.; Prot, Jean-Matthieu; Wang, Ying I. Lab on a Chip, Vol. 15, Issue 10 https://doi.org/10.1039/C5LC00237K	journal	January 2015
Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow Kim, Hyun Jung; Huh, Dongeun; Hamilton, Geraldine Lab on a Chip, Vol. 12, Issue 12 https://doi.org/10.1039/c2lc40074j	journal	January 2012
Thin collagen film scaffolds for retinal epithelial cell culture Lu, James T.; Lee, Christina J.; Bent, Stacey F. Biomaterials, Vol. 28, Issue 8 https://doi.org/10.1016/j.biomaterials.2006.11.023	journal	March 2007
How multi-organ microdevices can help foster drug development Esch, Mandy B.; Smith, Alec S. T.; Prot, Jean-Matthieu Advanced Drug Delivery Reviews, Vol. 69-70 https://doi.org/10.1016/j.addr.2013.12.003	journal	April 2014
Peptide-amphiphile nanofibers: A versatile scaffold for the preparation of self-assembling materials Hartgerink, J. D.; Beniash, E.; Stupp, S. I. Proceedings of the National Academy of Sciences, Vol. 99, Issue 8, p. 5133-5138 https://doi.org/10.1073/pnas.072699999	journal	April 2002
A bioactive self-assembled membrane to promote angiogenesis Chow, Lesley W.; Bitton, Ronit; Webber, Matthew J. Biomaterials, Vol. 32, Issue 6 https://doi.org/10.1016/j.biomaterials.2010.10.048	journal	February 2011
The elastic modulus of Matrigel™ as determined by atomic force microscopy Soofi, Shauheen S.; Last, Julie A.; Liliensiek, Sara J. Journal of Structural Biology, Vol. 167, Issue 3 https://doi.org/10.1016/j.jsb.2009.05.005	journal	September 2009
PDMS absorption of small molecules and consequences in microfluidic applications Toepke, Michael W.; Beebe, David J. Lab on a Chip, Vol. 6, Issue 12 https://doi.org/10.1039/b612140c	journal	January 2006
A Cell Culture System for the Structure and Hydrogel Properties of Basement Membranes: Application to Capillary Walls Bruggeman, Leslie A.; Doan, Ryan P.; Loftis, Jacqueline Cellular and Molecular Bioengineering, Vol. 5, Issue 2 https://doi.org/10.1007/s12195-012-0221-3	journal	February 2012
From 3D cell culture to organs-on-chips Huh, Dongeun; Hamilton, Geraldine A.; Ingber, Donald E. Trends in Cell Biology, Vol. 21, Issue 12 https://doi.org/10.1016/j.tcb.2011.09.005	journal	December 2011
Elasticity of Native and Cross-Linked Polyelectrolyte Multilayer Films Richert, Ludovic; Engler, Adam J.; Discher, Dennis E. Biomacromolecules, Vol. 5, Issue 5 https://doi.org/10.1021/bm0498023	journal	September 2004
Rapid Prototyping of Microfluidic Systems in Poly(dimethylsiloxane) Duffy, David C.; McDonald, J. Cooper; Schueller, Olivier J. A. Analytical Chemistry, Vol. 70, Issue 23, p. 4974-4984 https://doi.org/10.1021/ac980656z	journal	October 1998
Molecular mechanisms of NCAM function Hinsby, Anders, M. Frontiers in Bioscience, Vol. 9, Issue 1-3 https://doi.org/10.2741/1393	journal	January 2004
Using transcriptomics to guide lead optimization in drug discovery projects: Lessons learned from the QSTAR project Verbist, Bie; Klambauer, Günter; Vervoort, Liesbet Drug Discovery Today, Vol. 20, Issue 5 https://doi.org/10.1016/j.drudis.2014.12.014	journal	May 2015
Generation of Human Pulmonary Microvascular Endothelial Cell Lines Krump-Konvalinkova, Vera; Bittinger, Fernando; Unger, Ronald E. Laboratory Investigation, Vol. 81, Issue 12 https://doi.org/10.1038/labinvest.3780385	journal	December 2001
Integrated Preconcentration SDS−PAGE of Proteins in Microchips Using Photopatterned Cross-Linked Polyacrylamide Gels Hatch, Anson V.; Herr, Amy E.; Throckmorton, Daniel J. Analytical Chemistry, Vol. 78, Issue 14, p. 4976-4984 https://doi.org/10.1021/ac0600454	journal	July 2006
Topographically-patterned porous membranes in a microfluidic device as an in vitro model of renal reabsorptive barriers Frohlich, Else M.; Alonso, José Luis; Borenstein, Jeffrey T. Lab on a Chip, Vol. 13, Issue 12 https://doi.org/10.1039/c3lc50199j	journal	January 2013
Innate immunity and pulmonary host defense Zhang, Ping; Summer, Warren R.; Bagby, Gregory J. Immunological Reviews, Vol. 173, Issue 1 https://doi.org/10.1034/j.1600-065X.2000.917306.x	journal	February 2000
Microfluidic immunoassays as rapid saliva-based clinical diagnostics Herr, A. E.; Hatch, A. V.; Throckmorton, D. J. Proceedings of the National Academy of Sciences, Vol. 104, Issue 13, p. 5268-5273 https://doi.org/10.1073/pnas.0607254104	journal	March 2007
A Theoretical Model Study of the Influence of Fluid Stresses on a Cell Adhering to a Microchannel Wall Gaver, Donald P.; Kute, Stephanie M. Biophysical Journal, Vol. 75, Issue 2 https://doi.org/10.1016/S0006-3495(98)77562-9	journal	August 1998
Brain extracellular matrix Ruoslahti, Erkki Glycobiology, Vol. 6, Issue 5 https://doi.org/10.1093/glycob/6.5.489	journal	January 1996
Cell responses to the mechanochemical microenvironment—Implications for regenerative medicine and drug delivery☆ Rehfeldt, F.; Engler, A.; Eckhardt, A. Advanced Drug Delivery Reviews, Vol. 59, Issue 13 https://doi.org/10.1016/j.addr.2007.08.007	journal	November 2007
Biomimetic tissues on a chip for drug discovery Ghaemmaghami, Amir M.; Hancock, Matthew J.; Harrington, Helen Drug Discovery Today, Vol. 17, Issue 3-4 https://doi.org/10.1016/j.drudis.2011.10.029	journal	February 2012
Endothelium-derived Toll-like receptor-4 is the key molecule in LPS-induced neutrophil sequestration into lungs Andonegui, Graciela; Bonder, Claudine S.; Green, Francis Journal of Clinical Investigation, Vol. 111, Issue 7 https://doi.org/10.1172/JCI16510	journal	April 2003
Regulation and Repair of the Alveolar-Capillary Barrier in Acute Lung Injury Bhattacharya, Jahar; Matthay, Michael A. Annual Review of Physiology, Vol. 75, Issue 1 https://doi.org/10.1146/annurev-physiol-030212-183756	journal	February 2013
Microfabricated Modular Scale-Down Device for Regenerative Medicine Process Development Reichen, Marcel; Macown, Rhys J.; Jaccard, Nicolas PLoS ONE, Vol. 7, Issue 12 https://doi.org/10.1371/journal.pone.0052246	journal	December 2012
Quantitative Analysis of Molecular Absorption into PDMS Microfluidic Channels Wang, Jack D.; Douville, Nicholas J.; Takayama, Shuichi Annals of Biomedical Engineering, Vol. 40, Issue 9 https://doi.org/10.1007/s10439-012-0562-z	journal	April 2012
Lift-off of large-scale ultrathin nanomembranes Miller, Joshua J.; Carter, Robert N.; McNabb, Kelly B. Journal of Micromechanics and Microengineering, Vol. 25, Issue 1 https://doi.org/10.1088/0960-1317/25/1/015011	journal	December 2014
Microfluidic organs-on-chips Bhatia, Sangeeta N.; Ingber, Donald E. Nature Biotechnology, Vol. 32, Issue 8 https://doi.org/10.1038/nbt.2989	journal	August 2014
Integrated DNA and RNA extraction and purification on an automated microfluidic cassette from bacterial and viral pathogens causing community-acquired lower respiratory tract infections Van Heirstraeten, Liesbet; Spang, Peter; Schwind, Carmen Lab Chip, Vol. 14, Issue 9 https://doi.org/10.1039/C3LC51339D	journal	January 2014
Self-Assembly of Large and Small Molecules into Hierarchically Ordered Sacs and Membranes Capito, R. M.; Azevedo, H. S.; Velichko, Y. S. Science, Vol. 319, Issue 5871, p. 1812-1816 https://doi.org/10.1126/science.1154586	journal	March 2008
On Trk for Retrograde Signaling Miller, Freda D.; Kaplan, David R. Neuron, Vol. 32, Issue 5 https://doi.org/10.1016/S0896-6273(01)00529-3	journal	December 2001
Microfluidic Immunoassays Lin, Chun-Che; Wang, Jung-Hao; Wu, Hui-Wen Journal of the Association for Laboratory Automation, Vol. 15, Issue 3 https://doi.org/10.1016/j.jala.2010.01.013	journal	June 2010
Self-assembling peptide amphiphile nanofiber matrices for cell entrapment Beniash, Elia; Hartgerink, Jeffery D.; Storrie, Hannah Acta Biomaterialia, Vol. 1, Issue 4 https://doi.org/10.1016/j.actbio.2005.04.002	journal	July 2005

Similar Records

CCL20, a direct-acting pro-angiogenic chemokine induced by hepatitis C virus (HCV): Potential role in HCV-related liver cancer

Journal Article · Thu Nov 15 00:00:00 EST 2018 · Experimental Cell Research · OSTI ID:1346605

Benkheil, Mohammed; Van Haele, Matthias; Roskams, Tania; +6 more

ADAMTS1 inhibits lymphangiogenesis by attenuating phosphorylation of the lymphatic endothelial cell-specific VEGF receptor

Journal Article · Thu May 01 00:00:00 EDT 2014 · Experimental Cell Research · OSTI ID:1346605

Inagaki, Junko; Takahashi, Katsuyuki; Ogawa, Hiroko; +9 more

Macro- and microvascular endothelial cells in vitro: maintenance of biochemical heterogeneity despite loss of ultrastructural characteristics

Journal Article · Fri Feb 01 00:00:00 EST 1991 · In Vitro Cellular and Developmental Biology; (USA) · OSTI ID:1346605

Stolz, D B; Jacobson, B S

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
microfluidics
RNA extraction
gene expression
lasers
cell cultures
fluidics
RNA isolation
membrane staining

Title: A Reversibly Sealed, Easy Access, Modular (SEAM) Microfluidic Architecture to Establish In Vitro Tissue Interfaces

Citation Formats

References (61)

Similar Records

Related Subjects