Physicochemical and biological gradients are desirable features for hydrogels to enhance their relevance to biological environments for three-dimensional (3D) cell culture. Therefore, simple and efficient techniques to generate chemical, physical and biological gradients within hydrogels are highly desirable. This work demonstrates a technique to generate biomolecular and mechanical gradients in photocrosslinkable hydrogels by stacking and crosslinking prehydrogel solution in a layer by layer manner. Partial crosslinking of the hydrogel allows mixing of prehydrogel solution with the previous hydrogel layer, which makes a smooth gradient profile, rather than discrete layers. This technique enables the generation of concentration gradients of bovine serum albumin in both gelatin methacryloyl (GelMA) and poly(ethylene glycol) diacrylate hydrogels, as well as mechanical gradients across a hydrogel containing varying gel concentrations. Fluorescence microscopy, mechanical testing, and scanning electron microscopy show that the gradient profiles can be controlled by changing both the volume and concentration of each layer as well as intensity of UV exposure. GelMA hydrogel gradients with different Young's moduli were successfully used to culture human fibroblasts. The fibroblasts migrated along the gradient axis and showed different morphologies. In general, the proposed technique provides a rapid and simple approach to design and fabricate 3D hydrogel gradients for in vitro biological studies and potentially for in vivo tissue engineering applications. RECEIVED
An integrated nano-electromechanical chip (NELMEC) has been developed for the label-free distinguishing of both epithelial and mesenchymal circulating tumor cells (ECTCs and MCTCs, respectively) from white blood cells (WBCs). This nanoelectronic microfluidic chip fabricated by silicon micromachining can trap large single cells (>12 µm) at the opening of the analysis microchannel arrays. The nature of the captured cells is detected using silicon nanograss (SiNG) electrodes patterned at the entrance of the channels. There is an observable difference between the membrane capacitance of the ECTCs and MCTCs and that of WBCs (measured using SiNG electrodes), which is the key indication for our diagnosis. The NELMEC chip not only solves the problem of the size overlap between CTCs and WBCs but also detects MCTCs without the need for any markers or tagging processes, which has been an important problem in previously reported CTC detection systems. The great conductivity of the gold-coated SiNG nanocontacts as well as their safe penetration into the membrane of captured cells, facilitate a precise and direct signal extraction to distinguish the type of captured cell. The results achieved from epithelial (MCF-7) and mesenchymal (MDA-MB231) breast cancer cells circulated in unprocessed blood suggest the significant applications for these diagnostic abilities of NELMEC.
3D hydrogels are powerful, multifunctional materials that are poised to become a building block in next‐generation systems. Modern schemes to print complex 3D hydrogels are advancing rapidly; however, they possess several limitations including—but not limited to—polymer incompatibility or difficulty in imparting continuous heterogeneity in composition or function. Here, a simple strategy of synthesizing programmable hydrogel systems with tunable form and function in 3D is presented. This approach utilizes commercially available stereolithographic printer/resin to fabricate high‐resolution molds followed by the programmed infiltration and gelation of hydrogel prepolymer. This mold is then sacrificed to yield 3D, multifunctional hydrogels exhibiting user‐defined heterogeneity. The approach is compatible with numerous in‐situ gelling polymers and modifiers ranging from interpenetrating networks of organic or synthetic polymers to functional materials possessing dense concentrations of nanomaterials or fluorescent markers. Accessible and versatile, this approach allows the fabrication of complex, multimaterial constructs with tunable 3D environmental responses inaccessible to well‐established hydrogel 3D printing methods.
We report on the hydrogen-assisted deep reactive ion etching of hydrogenated amorphous silicon (a-Si:H) films deposited using radio-frequency plasma enhanced chemical vapor deposition (RF-PECVD). High aspect-ratio vertical and 3D amorphous silicon features, with the desired control over the shaping of the sidewalls, in micro and nano scales, were fabricated in ordered arrays. The suitable adhesion of amorphous Si film to the underlayer allows one to apply deep micro- and nano-machining to these layers. By means of a second deposition of amorphous silicon on highly curved 3D structures and subsequent etching, the fabrication of amorphous silicon rings is feasible. In addition to photolithography, nanosphere colloidal lithography and electron beam lithography were exploited to realize ultra-small features of amorphous silicon. We have also investigated the optical properties of fabricated hexagonally patterned a-Si nanowire arrays on glass substrates and demonstrated their high potential as active layers for solar cells. This etching process presents an inexpensive method for the formation of highly featured arrays of vertical and 3D amorphous silicon rods on both glass and silicon substrates, suitable for large-area applications.
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