This talk will focus on the interface of micro-/nano science and cell biology. Even though cell fate (e.g. stem cell differentiation and cancer cell apoptosis) is regulated by interactions with microenvironment cues and intrinsic cellular programs, understanding the functions of microenvironments and manipulating gene expression in stem/cancer cells are hampered by limitations of conventional methods and the lack of extensive knowledge of multiple regulatory signals. If the complex cell behaviors are to be fully investigated, both approaches from nanotechnology-the "top-down" patterning of extracellular matrix (ECM) and signal molecules in combinatorial ways (e.g. ECM compositions, pattern geometry, pattern density and gradient patterns), and the "bottom-up" synthesis of multifunctional nanoparticles and their surface modification with specific signal molecules-should be combined synergistically. To address the aforementioned challenge, our research mainly focuses on three approaches: i) development of combinatorial arrays of microenvironmental signal molecules for investigating cell behaviors; ii) synthesis and utilization of multifunctional nanoparticles as chemotherapeutic reagents against glioblastoma multiforme (GBM); and iii) development of a microfluidic assay platform to identify the optimal conditions for stem cell differentiation and self-renewal. More specifically, we have applied the combinatorial signal arrays to study the temporal/spatial effect of microenvironmental cues on adhesion, growth, differentiation of functional cells (e.g. neural stem cells and glioblastoma cells). Furthermore, novel synthetic approaches for anti-cancer drugs [e.g. Erlotinib and Histone deacetylase inhibitors (HDAC inhibitors)] and modified siRNA to be linked with nanoparticles have been developed. In parallel research efforts, we have developed a high throughput screening method based on microfluidics to study human embryonic stem cell (hESCs) responses toward multiple microenvironmental cues at the single cell level. In this talk, a summary of the results from these efforts and future directions will be discussed.