This content will become publicly available on December 7, 2022
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- Lab on a Chip
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- National Science Foundation
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Serum-Free Manufacturing of Mesenchymal Stem Cell Tissue Rings Using Human-Induced Pluripotent Stem CellsCombination of stem cell technology and 3D biofabrication approaches provides physiological similarity to in vivo tissues and the capability of repairing and regenerating damaged human tissues. Mesenchymal stem cells (MSCs) have been widely used for regenerative medicine applications because of their immunosuppressive properties and multipotent potentials. To obtain large amount of high-quality MSCs without patient donation and invasive procedures, we differentiated MSCs from human-induced pluripotent stem cells (hiPSC-MSCs) using serum-free E6 media supplemented with only one growth factor (bFGF) and two small molecules (SB431542 and CHIR99021). The differentiated cells showed a high expression of common MSC-specific surface markers (CD90, CD73, CD105, CD106, CD146, and CD166) and a high potency for osteogenic and chondrogenic differentiation. With these cells, we have been able to manufacture MSC tissue rings with high consistency and robustness in pluronic-coated reusable PDMS devices. The MSC tissue rings were characterized based on inner diameter and outer ring diameter and observed cell-type-dependent tissue contraction induced by cell-matrix interaction. Our approach of simplified hiPSC-MSC differentiation, modular fabrication procedure, and serum-free culture conditions has a great potential for scalable manufacturing of MSC tissue rings for different regenerative medicine applications.
Assembly of multicomponent structures from hundreds of micron-scale building blocks using optical tweezers
The fabrication of three-dimensional (3D) microscale structures is critical for many applications, including strong and lightweight material development, medical device fabrication, microrobotics, and photonic applications. While 3D microfabrication has seen progress over the past decades, complex multicomponent integration with small or hierarchical feature sizes is still a challenge. In this study, an optical positioning and linking (OPAL) platform based on optical tweezers is used to precisely fabricate 3D microstructures from two types of micron-scale building blocks linked by biochemical interactions. A computer-controlled interface with rapid on-the-fly automated recalibration routines maintains accuracy even after placing many building blocks. OPAL achieves a 60-nm positional accuracy by optimizing the molecular functionalization and laser power. A two-component structure consisting of 448 1-µm building blocks is assembled, representing the largest number of building blocks used to date in 3D optical tweezer microassembly. Although optical tweezers have previously been used for microfabrication, those results were generally restricted to single-material structures composed of a relatively small number of larger-sized building blocks, with little discussion of critical process parameters. It is anticipated that OPAL will enable the assembly, augmentation, and repair of microstructures composed of specialty micro/nanomaterial building blocks to be used in new photonic, microfluidic, andmore »
Hybrid microfluidic systems that are composed of multiple different types of substrates have been recognized as a versatile and superior platform, which can draw benefits from different substrates while avoiding their limitations. This review article introduces the recent innovations of different types of low-cost hybrid microfluidic devices, particularly focusing on cost-effective polymer- and paper-based hybrid microfluidic devices. In this article, the fabrication of these hybrid microfluidic devices is briefly described and summarized. We then highlight various hybrid microfluidic systems, including polydimethylsiloxane (PDMS)-based, thermoplastic-based, paper/polymer hybrid systems, as well as other emerging hybrid systems (such as thread-based). The special benefits of using these hybrid systems have been summarized accordingly. A broad range of biological and biomedical applications using these hybrid microfluidic devices are discussed in detail, including nucleic acid analysis, protein analysis, cellular analysis, 3D cell culture, organ-on-a-chip, and tissue engineering. The perspective trends of hybrid microfluidic systems involving the improvement of fabrication techniques and broader applications are also discussed at the end of the review.
Additive manufacturing (or "three-dimensional (3D) printing") technologies offer unique means to expand the architectural versatility with which microfluidic systems can be designed and constructed. In particular, "direct laser writing (DLW)" supports submicron-scale 3D printing via two-photon (or multi-photon) polymerization; however, such high resolutions are poorly suited for fabricating the macro-to-micro interfaces (i.e., fluidic access ports) critical to microfluidic applications. To bypass this issue, here we present a novel strategy for using DLW to 3D print architecturally complex microfluidic structures directly onto-and notably, fully integrated with-macroscale fused silica tubes. Fabrication and experimental results for this "ex situ DLW (esDLW)" approach revealed effective structure-to-tube sealing, with fluidic integrity maintained during fluid transport from macroscale tubing, into and through demonstrative 3D printed microfluidic structures, and then out of designed outlets. These results suggest that the presented DLW-based printing approach for externally coupling microfluidic structures to macroscale fluidic systems holds promise for emerging applications spanning chemical, biomedical, and soft robotics fields.
Controlled trapping of cells and microorganisms using substrate acoustic waves (SAWs; conventionally termed surface acoustic waves) has proven useful in numerous biological and biomedical applications owing to the label- and contact-free nature of acoustic confinement. However, excessive heating due to vibration damping and other system losses potentially compromises the biocompatibility of the SAW technique. Herein, we investigate the thermal biocompatibility of polydimethylsiloxane (PDMS)-based SAW and glass-based SAW [that supports a bulk acoustic wave (BAW) in the fluid domain] devices operating at different frequencies and applied voltages. First, we use infrared thermography to produce heat maps of regions of interest (ROI) within the aperture of the SAW transducers for PDMS- and glass-based devices. Motile Chlamydomonas reinhardtii algae cells are then used to test the trapping performance and biocompatibility of these devices. At low input power, the PDMS-based SAW system cannot generate a large enough acoustic trapping force to hold swimming C. reinhardtii cells. At high input power, the temperature of this device rises rapidly, damaging (and possibly killing) the cells. The glass-based SAW/BAW hybrid system, on the other hand, can not only trap swimming C. reinhardtii at low input power, but also exhibits better thermal biocompatibility than the PDMS-based SAW systemmore »