Noninvasive optical imaging of stem cell differentiation in biomaterials using photonic crystal surfaces

In this chapter, we describe recent advances in the noninvasive optical imaging of stem cells using photonic crystal label-free biosensor surfaces. Technological progress in bioengineering approaches now enables the sophisticated control of live cells in vitro. In such applications, stem cells are often selected as the cell source, as they have the capacity to expand to provide a large pool of cells with varying levels of self-renewal and differentiation potential (stem cells, progenitor cells, terminally differentiated cells) necessary to meet desired therapeutic goals. Precisely engineering stem cell fate decisions, however, has remained a challenge due to the lack of analytical tools that allow dynamic monitoring of heterogeneous stem cell populations in situ in real time at the single-cell level. Currently available technologies such as fluorescence labeling or clonal expansion assays are almost always end-point analyses of ensemble populations of cells that are expensive, labor intensive, and time delayed. New optical imaging tools may increasingly permit label-free imaging of live cells for subcellular-resolution quantification of cellular activities in real time. Noninvasive optical imaging using a nanostructured photonic crystal surface in place of an ordinary glass or plastic substrate for cell growth can be easily integrated into existing bioengineering platforms such as microfluidics or microarrays and can provide a novel, alternative approach to monitor single stem cell activities in vitro. Here, we first detail the principles of photonic crystal enhanced microscopy (PCEM) then offer a detailed rationale for developing new tools that enable monitoring and screening of increasingly small populations of stem cells in vitro. Finally, we close by describing efforts to apply PCEM to characterize stem cell differentiation events via adhesion-based metrics of stem cell differentiation.