As basic science research has increased in both complexity and scale, so too has the importance of cost-effective and generalizable techniques for the interrogation of cells and tissues. Over the past few decades, several technologies have been leveraged to meet this demand, recently including photonic crystal (PC) biosensors. This work describes the application of PC biosensors to cell microscopy, resulting in a label-free imaging technique capable of measuring cell attachment and attachment modulation. The approach uses a photonic crystal optical resonator surface incorporated into conventional microplate wells and a microscope-based detection instrument that measures shifts in the resonant coupling conditions caused by localized changes in dielectric permittivity at the cell-sensor interface. Four model systems are demonstrated for studying cancer cells, primary cardiac muscle cells, and stem cells. Each experiment yielded information regarding cell attachment density without the use of potentially cytotoxic labels, enabling study of processes including growth, development, differentiation, and death in the same cells for periods lasting several days. After demonstrating this technology in several systems typical of cell biology problems, PC biosensors were applied toward the investigation of tumor immunity. In particular, it has remained difficult for immunologists to study how tumor cells interact with components of the innate immune system, especially in the context of specific apoptotic recognition. The final chapter details the use of PC biosensors in detecting these types of interactions between two distinct cell types, the first reported use of label-free biosensors to detect such cellular changes
