A Programmable Multifunctional 3D Cancer Cell Invasion Micro Platform.

In the research of cancer cell invasion and metastasis, recreation of physiologically relevant and faithful three-dimensional (3D) tumor models that recapitulate spatial architecture, spatiotemporal control of cell communication and signaling pathways, and integration of extracellular cues remains an open challenge. Here, a programmable multifunctional 3D cancer cell invasion microbuckets-hydrogel (Mb-H) platform is developed by integrating various function-variable microbuckets and extracellular matrix (ECM)-like hydrogels. Based on this Mb-H micro platform, the aggregation of multi-cancer cells is well controlled to form cancer cell spheroids, and the guiding relationship of single-cell migration and collective cell migration during the epithelial-mesenchymal transition (EMT) of cancer cell invasion are demonstrated. By programming and precisely assembling multiple functions in one system, the Mb-H platform with spatial-temporal controlled release of cytokine transforming growth factor beta (TGF-ß) and various functionalized Mb-H platforms with intelligent adjustment of cell-matrix interactions are engineered to coordinate the 3D invasive migration of cancer cell spheroids. This programmable and adaptable 3D cancer cell invasion micro platform takes a new step toward mimicking the dynamically changing (localized) tumor microenvironment and exhibits wide potential applications in cancer research, bio-fabrication, cell signaling, and drug screening.

Real-time impedimetric droplet measurement (iDM).

Droplet-based microfluidic systems require a precise control of droplet physical properties; hence, measuring the morphological properties of droplets is critical to obtain high sensitivity analysis. The ability to perform such measurements in real-time is another demand which has not been addressed yet. In this study, we used coplanar electrodes configured in the differential measurement mode for impedimetric measurement of size and velocity. To obtain the size of the droplets, detailed 3D finite element simulations of the system were performed. The interaction of the non-uniform electric field and the droplet was investigated. Electrode geometry optimization steps were described and design guideline rules were laid out. User-friendly software was developed for real-time observation of droplet length and velocity together with in situ statistical analysis results. A comparison between impedimetric and optical measurement tools is given. Finally, to illustrate the benefit of having real-time analysis, iDM was used to synthesize particles with a predefined monodispersity limit and to study the response times of syringe pump and pressure pump driven droplet generation devices. This analysis allows one to evaluate the 'warm-up' time for a droplet generator system, after which droplets reach the desired steady-state size required by the application of interest.

Evaporation-Induced Biomolecule Detection on Versatile Superhydrophilic Patterned Surfaces: Glucose and DNA Assay.

We introduce a droplet-based biomolecular detection platform using robust, versatile, and low-cost superhydrophilic patterned superhydrophobic surfaces. Benefitting from confinement and evaporation-induced shrinkage of droplets on wetted patterns, we show enrichment-based biomolecular detection using very low sample volumes. First, we developed a glucose assay using fluorescent polydopamine (PDA) based on enhancement of PDA emission by hydrogen peroxide (H2O2) produced in enzyme-mediated glucose oxidation reaction. Incubation in evaporating droplets resulted in brighter fluorescence compared to that in bulk solutions. Droplet assay was highly sensitive toward increasing glucose concentration while that in milliliter-volume solutions resulted in no fluorescence enhancement at similar time scales. This is due to droplet evaporation that increased the reaction rate by causing enrichment of PDA and glucose/glucose oxidase as well as increased concentration of H2O2 generated in shrinking droplet. Second, we chemically functionalized wetted patterns with single-stranded DNA and developed fluorescence-based DNA detection to demonstrate the adaptability of the patterned surfaces for a different class of assay. We achieved detection of glucose and DNA with concentration down to 130 µM and 200 fM, respectively. Patterned superhydrophobic surfaces with their simple production, sensitive response, and versatility present potential for bioanalysis from low sample volumes.