A Macro‐to‐Micro Interface for Performing Comprehensive Microfluidic Cell Culture Assays

A new design of a macro‐to‐micro interface that can be used for simple and reliable control of comprehensive microfluidic cell culture processes is introduced making microfluidic procedures easily accessible to biological laboratories. The novel macro‐to‐micro interface is evaluated by adapting a workflow for single‐cell, cell pair, and cell cluster encapsulation into hydrogel beads acting as 3D microenvironment with subsequent long‐term cultivation. For the first time, the coupling of single‐cell time‐lapse microscopy data with phenotypic (immunofluorescence) and genotypic (single‐molecule RNA fluorescence in situ hybridization) endpoint measurements as well as downstream compatibility in a single chip is shown. The presented platform will be a valuable tool for performing studies of dynamic biological processes coupled to a multiparametric endpoint characterization at the single‐cell level as well as for gaining more detailed mechanistic insights into gene function relationships and the behavior of biological systems. A novel macro‐to‐micro interface for performing comprehensive microfluidic cell culture processes is introduced. Time‐lapse microscopy data of single‐cells encapsulated into hydrogel beads are coupled to phenotypic (Immunofluorescence, IF) and genotypic (single‐molecule RNA fluorescence in situ hybridization, smRNA FISH) endpoint measurements thereby providing mechanistic insights into gene function relationships. The presented platform allows in‐depth analysis of biological systems and makes microfluidic procedures accessible to biological laboratories.