Multi-layered, membrane-integrated microfluidics based on replica molding of a thiol-ene epoxy thermoset for organ-on-a-chip applications.

In this study we have investigated a photosensitive thermoset (OSTEMER 322-40) as a complementary material to readily fabricate complex multi-layered microdevices for applications in life science. Simple, versatile and robust fabrication of multifunctional microfluidics is becoming increasingly important for the development of customized tissue-, organ- and body-on-a-chip systems capable of mimicking tissue interfaces and biological barriers. In the present work key material properties including optical properties, vapor permeability, hydrophilicity and biocompatibility are evaluated for cell-based assays using fibroblasts, endothelial cells and mesenchymal stem cells. The excellent bonding strength of the OSTEMER thermoset to flexible fluoropolymer (FEP) sheets and poly(dimethylsiloxane) (PDMS) membranes further allows for the fabrication of integrated microfluidic components such as membrane-based microdegassers, microvalves and micropumps. We demonstrate the application of multi-layered, membrane-integrated microdevices that consist of up to seven layers and three membranes that specially confine and separate vascular cells from the epithelial barrier and 3D tissue structures.

[1]  Richard Novak,et al.  Rapid fabrication of nickel molds for prototyping embossed plastic microfluidic devices. , 2013, Lab on a chip.

[2]  H. Becker,et al.  Polymer microfluidic devices. , 2002, Talanta.

[3]  D. Beebe,et al.  The present and future role of microfluidics in biomedical research , 2014, Nature.

[4]  H. Andersson,et al.  Microfluidic devices for cellomics: a review , 2003 .

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

[6]  Verena Charwat,et al.  Lab-on-a-chip technologies for stem cell analysis. , 2014, Trends in biotechnology.

[7]  Yoshiya Tanaka,et al.  Interleukin-1β induces differentiation of human mesenchymal stem cells into osteoblasts via the Wnt-5a/receptor tyrosine kinase-like orphan receptor 2 pathway. , 2012, Arthritis and rheumatism.

[8]  Shuvo Roy,et al.  A microfluidic bioreactor with integrated transepithelial electrical resistance (TEER) measurement electrodes for evaluation of renal epithelial cells , 2010, Biotechnology and bioengineering.

[9]  Lucas H. Hofmeister,et al.  Scaling and systems biology for integrating multiple organs-on-a-chip. , 2013, Lab on a chip.

[10]  David Beebe,et al.  Engineers are from PDMS-land, Biologists are from Polystyrenia. , 2012, Lab on a chip.

[11]  Ryutaro Maeda,et al.  A pneumatically-actuated three-way microvalve fabricated with polydimethylsiloxane using the membrane transfer technique , 2000 .

[12]  Frantisek Svec,et al.  Injection molded microfluidic chips featuring integrated interconnects. , 2006, Lab on a chip.

[13]  Michael L Shuler,et al.  Human-on-a-chip design strategies and principles for physiologically based pharmacokinetics/pharmacodynamics modeling. , 2015, Integrative biology : quantitative biosciences from nano to macro.

[14]  D. Ingber,et al.  Microfluidic organs-on-chips , 2014, Nature Biotechnology.

[15]  G. Whitesides,et al.  Rapid Prototyping of Microfluidic Systems in Poly(dimethylsiloxane). , 1998, Analytical chemistry.

[16]  N. Elvassore,et al.  Optimal periodic perfusion strategy for robust long-term microfluidic cell culture. , 2013, Lab on a chip.

[17]  Wouter van der Wijngaart,et al.  Beyond PDMS: off-stoichiometry thiol-ene (OSTE) based soft lithography for rapid prototyping of microfluidic devices. , 2011, Lab on a chip.

[18]  D. Beebe,et al.  Managing evaporation for more robust microscale assays. Part 1. Volume loss in high throughput assays. , 2008, Lab on a chip.

[19]  G. Nash,et al.  Exposure to fluid shear stress modulates the ability of endothelial cells to recruit neutrophils in response to tumor necrosis factor-alpha: a basis for local variations in vascular sensitivity to inflammation. , 2003, Blood.

[20]  J. Ducrée,et al.  A hybrid microfluidic platform for cell-based assays via diffusive and convective trans-membrane perfusion. , 2013, Biomicrofluidics.

[21]  Göran Stemme,et al.  A comparative study of the bonding energy in adhesive wafer bonding , 2013 .

[22]  Arti Ahluwalia,et al.  Allometric Scaling and Cell Ratios in Multi-Organ in vitro Models of Human Metabolism , 2014, Front. Bioeng. Biotechnol..

[23]  A K Capulli,et al.  Approaching the in vitro clinical trial: engineering organs on chips. , 2014, Lab on a chip.

[24]  Mats Johansson,et al.  Functional off‐stoichiometry thiol‐ene‐epoxy thermosets featuring temporally controlled curing stages via an UV/UV dual cure process , 2014 .

[25]  D. Beebe,et al.  PDMS absorption of small molecules and consequences in microfluidic applications. , 2006, Lab on a chip.

[26]  Daniel T Chiu,et al.  Rapid prototyping of thermoset polyester microfluidic devices. , 2004, Analytical chemistry.

[27]  Joe Tien,et al.  Fabrication of microfluidic hydrogels using molded gelatin as a sacrificial element. , 2007, Lab on a chip.

[28]  Christopher Moraes,et al.  On being the right size: scaling effects in designing a human-on-a-chip. , 2013, Integrative biology : quantitative biosciences from nano to macro.

[29]  Jeffrey R. Alcock,et al.  Micro-injection moulding of polymer microfluidic devices , 2009 .

[30]  J. Shuga,et al.  Single-cell multiplex gene detection and sequencing with microfluidically generated agarose emulsions. , 2011, Angewandte Chemie.

[31]  D. Beebe,et al.  Biological implications of polydimethylsiloxane-based microfluidic cell culture. , 2009, Lab on a chip.

[32]  C. Hoyle,et al.  Oxygen Transport Properties of Thiol−Ene Networks , 2009 .

[33]  Aigars Piruska,et al.  The autofluorescence of plastic materials and chips measured under laser irradiation. , 2005, Lab on a chip.

[34]  Zhiyi Zhang,et al.  The fabrication of polymer microfluidic devices using a solid-to-solid interfacial polyaddition , 2009 .

[35]  W. Holnthoner,et al.  Mechanisms of vasculogenesis in 3D fibrin matrices mediated by the interaction of adipose-derived stem cells and endothelial cells , 2014, Angiogenesis.

[36]  Daniel T Chiu,et al.  Disposable microfluidic devices: fabrication, function, and application. , 2005, BioTechniques.

[37]  T. Haraldsson,et al.  Dry transfer bonding of porous silicon membranes to OSTE(+) polymer microfluidic devices , 2012, 2012 IEEE 25th International Conference on Micro Electro Mechanical Systems (MEMS).

[38]  Verena Charwat,et al.  Recent advances and future applications of microfluidic live-cell microarrays. , 2015, Biotechnology advances.

[39]  Verena Charwat,et al.  Microfluidic oxygen imaging using integrated optical sensor layers and a color camera. , 2013, Lab on a chip.

[40]  Daniel T Chiu,et al.  Fabrication of thermoset polyester microfluidic devices and embossing masters using rapid prototyped polydimethylsiloxane molds. , 2003, Lab on a chip.

[41]  T. Haraldsson,et al.  Reaction injection molding and direct covalent bonding of OSTE+ polymer microfluidic devices , 2015 .

[42]  S. Quake,et al.  Monolithic microfabricated valves and pumps by multilayer soft lithography. , 2000, Science.

[43]  K. Ren,et al.  Materials for microfluidic chip fabrication. , 2013, Accounts of chemical research.

[44]  Jerry C. Hu,et al.  Advances in tissue engineering through stem cell‐based co‐culture , 2015, Journal of tissue engineering and regenerative medicine.

[45]  G. Whitesides,et al.  Poly(dimethylsiloxane) as a material for fabricating microfluidic devices. , 2002, Accounts of chemical research.