Microfluidics and microfabrication technology for highly precise cell manipulation and cultivation

Microfluidic processes are essential techniques not only for manipulating micrometer-size objects like cells, particles, and biomacromolecules, but also for producing micrometer-size objects with highly-controlled morphologies or compositions. First, continuous and rapid separation and accumulation methods for particles or cells using microfluidic devices are introduced. Microfluidic devices have a potential to facilitate rapid and precise particle manipulation, due to accurately fabricated structures close to particle sizes, in micrometer or dimensions. Newly developed methods enable a size- and/or shape-dependent, precise separation of biological cells or soft matters. Next, we present microfluidic devices for preparing functional micrometer-size hydrogel materials having fibrous or particulate morphology. The physical/chemical heterogeneity of the prepared materials allows the incorporated cells to grow differently from the conventional plate cultivation, which is useful for preparing unit structures mimicking the in-vivo tissues. In addition to these materials, here we introduce recently developed several microfluidic/microfabrication techniques, including the preparation processes of microstructured and layered hydrogel plates, micropatterning of ultra-thin hydrogels utilizing local surface modification, micronozzle structures for producing actuating lipid vesicles, and the continuous microfluidic cell processing. These techniques would be useful for rapidly fabricating relatively-large tissue models by assembling the unit materials and/or by employing various conventional/unconventional micromanipulation technologies.