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Kim,S.-J.; Yokokawa, R.; Lesher-Perez, S.C.; Takayama, S. "Constant flow-driven microfluidic oscillator for different duty cycles." Anal Chem 2011. DOI: 10.1021/ac202866b.
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We designed a normally closed 3-terminal valve constant flow-driven oscillator, building on our previous 4-valve design, this switch to a more electronic circuit analogous design, allowed us to achieve different duty cycles within our device. This paper further characterized the necessary pressures to produce oscillatory behavior within our devices, as well as demonstrated this system to be capable of periodic stimulation/treatment of cultured cells.
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White, J.B.; Takayama, S. "Receptor differential activation and cooperativity better explain cellular preference for different chemoattractant gradient shapes in an EGFR system." Integr. Biol. 2011. DOI:10.1039/C1IB00040C.
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This paper describes a model that explains how cells can fine-tune their migratory response to chemokines. Receptors, especially EGFR, have much different signaling characteristics depending on their degree of oligomerization. We demonstrate how receptor cooperativity and oligomerization can change a cell's migration abilities in vitro which could have implications in how we study cancer metastasis and autoimmunity in vitro.
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Lai, D.; Frampton, J.P.; Sriram, H.; Takayama, S. "Rounded multi-level microchannels with orifices made in one exposure enable aqueous two-phase system droplet microfluidics." Lab Chip 2011. DOI:10.1039/C1LC20560A.
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A one-step exposure to fabricate multi-layer channels for Aqueous Two-Phase System droplets with the lowest interfacial tension to date.
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Mosadegh, B.; Bersano-Begey, T.; Park, J.Y.; Burns, M.A.; Takayama, S. "Next-generation integrated microfluidic circuits." Lab Chip 2011. DOI: 10.1039/C1LC20387H.
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This paper provides a brief overview of microfluidic devices that allow for increased on-chip control of fluid flow through embedded elastomer valves. Parallel instruction, serial instruction, and embedded instruction control schemes are specifically addressed.
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Frampton, J.P.; Lai, D.; Sriram, H.; Takayama, S. "Precisely targeted delivery of cells and biomolecules within microchannels using aqueous two-phase systems." Biomedical Microdevices 2011. DOI: 10.1007/s10544-011-9574-y.
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Small molecule delivery in microfluidic channels has previously been limited by diffusion of the molecules across liquid-liquid interfaces. Aqueous two-phase technology is a biocompatible method that allows for improved spatial resolution when delivering cells, proteins, or small molecules.
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Park, J.Y.; White, J.B.; Walker, N.; Kuo, C.H.; Cha, W.; Meyerhoff, M.E.; Takayama, S. "Response of endothelial cells to extremely slow flows." Biomicrofluidics 2011. DOI: 10.1063/1.3576932.
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This paper describes the effects of extremely slow fluid flow on endothelial cells. Traditional flow studies examine the effects of flow with shear greater than 0.1 dyne/cm2, we utilize an osmotic pump to achieve 10-1000 times smaller shear which can have implications in angiogenesis and developmental biology.
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Douville, N.J.; Li, Z.; Takayama, S.; Thouless, M.D. "Fracture of metal coated elastomers." Soft Matter 2011. DOI: 10.1039/C1SM05140G.
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Strain-induced cracks in gold-coated elastomeric PDMS slabs were examined. These cracks were orders of magnitude deeper than the gold film. We suggest that cracking of the PDMS substrate occurs to release residual energy from failure of the gold film.
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Tavana, H.; Kaylan, K.; Bersano-Begley, T.: Luker, K.E.; Luker, G.D.; Takayama, S. "Rehydration of polymeric, aqueous, biphasic system facilitates high throughput cell exclusion patterning for cell migration studies." Advanced Functional Materials 2011. DOI: 10.1002/adfm.201002559.
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Using aqueous two-phase systems for non-contact cell exclusion printing, we design a novel, high-throughput method for cell migration studies. We validate our "gap migration" platform using known cytoskeletal inhibitors.
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Jovic, A.; Wade, S.M.; Miyawaki, A.; Neubig, R.R.; Linderman, J.J.; Takayama, S. "Hi-Fi transmission of periodic signals amid cell-to-cell variability." Molecular BioSystems 2011. DOI: 10.1039/c1mb05031a.
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This paper combines experimental and theoretical approaches to high fidelity develop techniques for monitoring changes in intracellular calcium oscillations due to extracellular signals (such as G-protein coupled receptor activation).
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Tavana, H.; Mosadegh, B.; Zamankhan, P.; Grotberg, J.B.; Takayama, S. "Microprinted Feeder cells guide embryonic stem cell fate." Biotechnology and Bioengineering 2011. DOI: 10.1002/bit.23190.
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A non-contact, microprinting technique allows for controlled patterning of feeder cell arrays of different sizes on a gel substrate. We demonstrate that feeder cell type can direct fate of overlaid mouse embryonic stem cells.
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Thouless, M.D.; Li, Z.; Douville, N.J.; Takayama, S. "Periodic cracking of films supported on compliant substrates." J. Mechanics and Physics of Solids 2011. DOI:10.1016/j.jmps.2011.04.009.
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Strain can cause patterns of parallel cracks to form in rigid films and their soft substrates. This paper modifies a linear-elastic fracture model to explain this phenomenon.
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Tavana, H.; Zamankhan, P.; Christensen, P.J.; Grotberg, J.B.; Takayama, S. "Epithelium damage and protection during reopening of occluded airway in a physiologic microfluidic pulmonary airway model." Biomed. Microdev. 2011. DOI: 10.1007/s10544-011-9543-5.
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Using a microfluidic device, we study the response of lung airway epithelial cells to stresses generated from repeated exposure to liquid plugs. Addition of surfactant rescues cells from plug-induced cell damage and death. Mathematical modeling confirms the experimental observations.
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Didwania, M.; Didwania, A.; Mehta, G.; Basak, G.W; Yasukawa, S.; Takayama, S.; de Necochea-Campion, R.; Srivastava, A.; Carrier, E. "Artificial Hematopoietic Stem Cell Niche: Bioscaffolds to Microfluids to Mathematical Simulations." Curr. Top. Med. Chem 2011.
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Two recreate an artificial, in vivo-like niche for hematopoietic stem cells, it is necessary to consider the scaffold, the cells themselves, and soluble factors. We describe the states of the art for these three areas and include a mathematical model to aid in design and optimization of an artificial bioreactor.
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Tavana, H.; Takayama, S. "Aqueous biphasic microprinting approach to tissue engineering." Biomicrofluidics 2011, 5. DOI: 10.10631/1.3516658.
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Recent developments have shown aqueous two-phase printing (ATPS) to be a valuable tool for non-contact printing of biomaterials. Since both parts of an ATPS are completely aqueous, yet immiscible, this technique is ideal for spatially patterning delicate molecules or cells without compromising substrate integrity or cell viability.
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Chantiwas, R.; Park, S.; Soper, S. A.; Kim, B.C.; Takayama, S.; Sunkara, V.; Hwang, H.; Cho, Y.-K. "Flexible Fabrication and Applications of Polymer Nanochannels and Nanoslits." Chem. Soc. Rev. 2011. DOI: 10.1039/C0CS00138D.
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This critical review provides an overview of recent advances in polymer-based nanofluidics.
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Torisawa, Y; Mosadegh, B.; Cavnar, S. P.; Ho, M.; Takayama, S. "Transwells with Microstamped Membranes Produce Micropatterned 2D and 3D Co-cultures" Tissue Eng Part C 2011, 17, 61-67.
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Hydrodynamic forces created by a microcontact printed PDMS layer are used to guide cell patterns on the underside of a Transwell co-culture insert. Through co-culture experiments, this paper shows that HepG2 cells inhibit mouse embryonic fibroblast Sox17 formation via direct cell-cell contact and cellular signaling mechanisms.
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Douville, N. J.; Zamankhan, P.; Tung, Y.-C.; Li, R.; Vaughan, B. L.; White, J.; Grotberg, J. B.; Takayama, S. "Combination Fluid and Solid Mechanical Stresses Contribute to Cell Death and Detachment in a Microfluidic Alveolar Model" Lab Chip 2011 11, 609-619.
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This paper describes the importance of mechanical stretch and fluid mechanical stresses in lung injury. In diseased lungs, edematous liquid can fill the airways and impart injurious shear and pressure on alveolar cells; we developed a device to investigate the under-studied contribution of these stresses to alveolar cell death and delamitation.
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Mosadegh, B.; Tavana, H.; Lesher-Perez, S.C.; Takayama, S.
"Patterned deactivation of oxidized polydimethylsiloxane surface for high-density fabrication of normally-closed microfluidic valves" Lab Chip 2011, 11, 734-742. DOI: 10.1142/S0219519410003617.
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Plasma oxidation of PDMS is ubiquitous in microfluidic research. Plasma-induced changes in surface chemistry can be reversed in a spatially-controlled manner by microcontact printing with a second PDMS stamp. Applications in valving and "open microfluidics" are demonstrated.
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Tung, Y.-C.; Hsiao, A.Y.; Allen, S.; Torisawa, Y.; Ho, M.; Takayama, S. "High-throughput spheroid formation, culture, and anti-cancer drug testing using a 384 hanging drop array." Analyst 2011, 136, 473-478. DOI:10.1039/C0AN00609B.
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This paper describes a 384-well format hanging drop cell culture plate that allows for 3D spheroid formation and culture using existing high-throughput screening instruments. Using this platform, we demonstrated anti-cancer drug testing and found differential response of cells cultured in 2D versus 3D for drugs with different modes of action. This user-friendly 3D culture plate provides a simple way to obtain biological insights that are often lost in 2D monolayer cultures.
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