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Introduction: Three-dimensional (3D) cell cultures are identified as more accurate and representative models of human cancers than conventional two-dimensional monolayer cell cultures. However, currently established 3D culturing techniques are technically challenging, time- and resource-consuming, and performed using traditional laboratory tissue culturing equipment. In recent years, microfluidics has been introduced into biomedical research, allowing cells and tissues to be cultured in microfabricated devices. The current challenge is to adapt existing 3D cell culturing techniques to microfluidic devices, allowing for the fabrication of low-cost, rapid evaluation devices to facilitate biomedical research and clinical application. The aim of this review was to evaluate microfluidics and 3D cell culture research with particular relevance to oncological research. Methods: Journal articles were acquired from different scientific databases and were identified using specific keywords. Three-Dimensional Cell Culturing Microfluidic Concepts: Various 3D cell culturing microfluidic devices have been designed, based on existing 3D cell culturing methods. This includes non-cell adherent-based devices, matrix-embedding, hanging drop, and droplet-based culturing methods. These platforms facilitate the culturing, treatment, and analysis of 3D spheroids, while simultaneously scaling down traditional experimental requirements. Limitations and Future Perspectives: Beyond superficial analysis, a major drawback in the current scope of 3D cell culturing microfluidic devices is the inability to extract spheroids for examining histology. Polydimethylsiloxane is the preferred material to fabricate devices but may need revision for commercializing microfluidic platforms in the future. Integrating 3D bioprinting and organoid cultures could potentially improve the quality of 3D models in microfluidic devices. Conclusion: 3D spheroids are an effective representation of in vivo cancers and microfluidics has streamlined the culture, treatment, and analysis of 3D models. Considerable improvements have been made in combining the two entities, but further work is required to manufacture 3D cell culturing microfluidic devices on a commercial scale. \ud \ud

Although it is widely recognised that enzymes play a significant role in sculpting complex silica skeletons in marine sponges, the potential for exploiting enzymes in materials synthesis has not yet been fully harnessed. In this work we show that the digestive enzyme papain can self-assemble into monolayers on oxide surfaces, where they then drive the formation of crystalline titanium dioxide nanoparticles. This dual functionality of thin film formation and mineralization promotion has the potential to enable the construction of hierarchical inorganic/organic structures in the form of continuous amorphous titania/protein films which can be refined to 93% anatase post annealing. Additional control over the film thickness is afforded by layer-by-layer processing using a simple dip-coating approach. Papain's TiO₂-mineralizing activity displays complex kinetics that deviates from the native Michaelis–Menten kinetic activity, yet deactivation studies demonstrate that this activity relies upon residues that are essential for catalytic site function. These parameters provide unique insight into enzymatic biomineralization, allowing a flexible route to achieving bioengineered titania heterostructures, and potentially providing a green-chemistry solution to photovoltaic cell development.

As crystallization processes are often rapid, it can be difficult to monitor their growth mechanisms. In this study, we made use of the fact that crystallization proceeds more slowly in small volumes than in bulk solution to investigate the effects of the soluble additives Mg(2+) and poly(styrene sulfonate) (PSS) on the early stages of growth of calcite crystals. Using a "Crystal Hotel" microfluidic device to provide well-defined, nanoliter volumes, we observed that calcite crystals form via an amorphous precursor phase. Surprisingly, the first calcite crystals formed are perfect rhombohedra, and the soluble additives have no influence on the morphology until the crystals reach sizes of 0.1-0.5 μm for Mg(2+) and 1-2 μm for PSS. The crystals then continue to grow to develop morphologies characteristic of these additives. These results can be rationalized by considering additive binding to kink sites, which is consistent with crystal growth by a classical mechanism.

From biomineralization to synthesis, organic additives provide an effective means of controlling crystallisation processes. There is growing evidence that these additives are often occluded within the crystal lattice, where this promises an elegant means of creating nanocomposites and tuning physical properties. Here, we use the incorporation of sulfonated fluorescent dyes to gain new understanding of additive occlusion in calcite (CaCO3), and to link morphological changes to occlusion mechanisms. We demonstrate that these additives are incorporated within specific zones, as defined by the growth conditions, and show how occlusion can govern changes in crystal shape. Fluorescence spectroscopy and lifetime imaging microscopy also show that the dyes experience unique local environments within different zones. Our strategy was then extended to simultaneously incorporate mixtures of dyes, whose fluorescence cascade creates calcite nanoparticles that fluoresce white. This offers a simple strategy for generating biocompatible and stable fluorescent nanoparticles whose output can be tuned as required.