Digital microfluidics for spheroid-based invasion assays.

Cell invasion is a key process in tissue growth, wound healing, and tumor progression. Most invasion assays examine cells cultured in adherent monolayers, which fail to recapitulate the three-dimensional nuances of the tissue microenvironment. Multicellular cell spheroids have a three-dimensional (3D) morphology and mimic the intercellular interactions found in tissues in vivo, thus providing a more physiologically relevant model for studying the tissue microenvironment and processes such as cell invasion.

Digital microfluidics for automated hanging drop cell spheroid culture.

Cell spheroids are multicellular aggregates, grown in vitro, that mimic the three-dimensional morphology of physiological tissues. Although there are numerous benefits to using spheroids in cell-based assays, the adoption of spheroids in routine biomedical research has been limited, in part, by the tedious workflow associated with spheroid formation and analysis. Here we describe a digital microfluidic platform that has been developed to automate liquid-handling protocols for the formation, maintenance, and analysis of multicellular spheroids in hanging drop culture.

Fluorinated liquid-enabled protein handling and surfactant-aided crystallization for fully in situ digital microfluidic MALDI-MS analysis.

A droplet (digital) microfluidic device has been developed that enables complete protein sample preparation for MALDI-MS analysis. Protein solution dispensing, disulfide bond reduction and alkylation, tryptic digestion, sample crystallization, and mass spectrometric analysis are all performed on a single device without the need for any ex situ sample purification. Fluorinated solvents are used as an alternative to surfactants to facilitate droplet movement and limit protein adsorption onto the device surface.