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Item A 3D microfluidic device fabrication method using thermopress bonding with multiple layers of polystyrene film(IOP, 2015-05) Cao, Yuanzhi; Bontrager-Singer, Jacob; Zhu, Likun; Department of Mechanical Engineering, School of EngineeringIn this article, we present a fabrication method that is capable of making (3D) microfluidic devices with multiple layers of homogeneous polystyrene (PS) film. PS film was chosen as the primary device material because of its advantageous features for microfluidics applications. Thermopress is used as a bonding method because it provides sufficient bonding strength while requiring no heterogeneous bonding materials. By aligning and sequentially stacking multiple layers (3 to 20) of patterned PS film that were achieved by a craft cutter, complicated 3D structured microfluidic devices can be fabricated by multiple steps of thermopress bonding. The smallest feature that can be achieved with this method is approximately 100 μm, which is limited by the resolution of the cutter (25 μm) as well as the thickness of the PS films. Bonding characteristics of PS films are provided in this article, including a PS film bonding strength test, bonding precision assessment, and PS surface wettability manipulation. To demonstrate the capability of this method, the design, fabrication, and testing results of a 3D interacting L-shaped passive mixer are presented.Item Bioinspired One Cell Culture Isolates Highly Tumorigenic and Metastatic Cancer Stem Cells Capable of Multilineage Differentiation(Wiley, 2020-04-28) Wang, Hai; Agarwal, Pranay; Jiang, Bin; Stewart, Samantha; Liu, Xuanyou; Liang, Yutong; Hancioglu, Baris; Webb, Amy; Fisher, John P.; Liu, Zhenguo; Lu, Xiongbin; Tkaczuk, Katherine H. R.; He, Xiaoming; Medical and Molecular Genetics, School of MedicineItem Creating a capture zone in microfluidic flow greatly enhances the throughput and efficiency of cancer detection(Elsevier, 2019-03) Sun, Mingrui; Xu, Jiangsheng; Shamul, James G.; Lu, Xiongbin; Husain, Syed; He, Xiaoming; Medical and Molecular Genetics, School of MedicineEfficient capture of rare circulating tumor cells (CTCs) from blood samples is valuable for early cancer detection to improve the management of cancer. In this work, we developed a highly efficient microfluidics-based method for detecting CTCs in human blood. This is achieved by creating separate capture and flow zones in the microfluidic device (ZonesChip) and using patterned dielectrophoretic force to direct cells from the flow zone into the capture zone. This separation of the capture and flow zones minimizes the negative impact of high flow speed (and thus high throughput) and force in the flow zone on the capture efficiency, overcoming a major bottleneck of contemporary microfluidic approaches using overlapping flow and capture zones for CTC detection. When the flow speed is high (≥0.58 mm/s) in the flow zone, the separation of capture and flow zones in our ZonesChip could improve the capture efficiency from ∼0% (for conventional device without separating the two zones) to ∼100%. Our ZonesChip shows great promise as an effective platform for the detection of CTCs in blood from patients with early/localized-stage colorectal tumors.Item Differential HDAC6 Activity Modulates Ciliogenesis and Subsequent Mechanosensing of Endothelial Cells Derived from Pluripotent Stem Cells(Elsevier, 2018-07-24) Smith, Quinton; Macklin, Bria; Chan, Xin Yi; Jones, Hannah; Trempel, Michelle; Yoder, Mervin C.; Gerecht, Sharon; Pediatrics, School of MedicineSummary The role of primary cilia in mechanosensation is essential in endothelial cell (EC) shear responsiveness. Here, we find that venous, capillary, and progenitor ECs respond to shear stress in vitro in a cilia-dependent manner. We then demonstrate that primary cilia assembly in human induced pluripotent stem cell (hiPSC)-derived ECs varies between different cell lines with marginal influence of differentiation protocol. hiPSC-derived ECs lacking cilia do not align to shear stress, lack stress fiber assembly, have uncoordinated migration during wound closure in vitro, and have aberrant calcium influx upon shear exposure. Transcriptional analysis reveals variation in regulatory genes involved in ciliogenesis among different hiPSC-derived ECs. Moreover, inhibition of histone deacetylase 6 (HDAC6) activity in hiPSC-ECs lacking cilia rescues cilia formation and restores mechanical sensing. Taken together, these results show the importance of primary cilia in hiPSC-EC mechano-responsiveness and its modulation through HDAC6 activity varies among hiPSC-ECs.