| Compartmentalization combined with regulated exchange and release of biomaterials is the key biological function. At the subcellular level, organelles sequester enzymes and substrates for storage while processing and releasing on demand. At the organism level, appropriate cellular compartmentalization gives rise to tissue organization and higher order function. Man-made bioreaction compartmentalization typically relies on micro-reactors constructed with glass, silicon, hard plastic, or amiphiphilic molecular walls. Reactors with such physical barriers, in return for excellent compartmentalization, lack amenability to molecular and cellular release and exchange as seen in the body. This thesis describes the engineering of multi-compartment bioreactors that utilize stable reagent partitioning within immiscible aqueous solutions. The all aqueous compartmentalization scheme, when combined with a micropatterned surface that pins the liquid-liquid interfaces, enable versatile direct printing of arbitrary multi-compartment bioreactor networks. Additionally, the lack of physical barriers at the liquid-liquid interface between the different aqueous compartments allows use of phase-altering chemicals to trigger rapid and selective mixing of materials between compartments in ways not possible with conventional miroreactors. Specific examples demonstrated include a compartmentalized cascade reaction that utilizes glucose and oxygen as nutrients to catalzye the production of different colored dyes within microcompartments and the localization-enhanced degradation of the microcompartments with a polysaccharide-degrading enzyme. In a separate strategy, a shrinking microreactor platform was created using oil dehydration. These shrinking bioreactors were utilized for micro-scale ATPS phase diagram determination and also adopted for micro-scale self-assembly of CdTe nanoparticles. Finally, surface-templated hydrogel micropatterning was used to compartmentalize cancer cells as well as limit diffusion of chemoattractants. This platform revealed the importance of extracellular matrix-mediated capture and localization of chemoattractants in triggering cancer cell migration that lead to a breakdown of cellular compartmentalization, tissue dis-organization and cancer metastasis. In addition to the specific demonstrations and biological insights obtained, the described macromolecular phase-separation microreactor platforms are versatile in configuration possibilities, particularly when combined with microfabrication technologies, and amenable to further explore materials science and biomedical engineering applications. |
