Organic distributed feedback lasers can detect nanoscale materials, and are, therefore, an attractive sensing platform for biological and medical applications. In this paper, we present a model for optimizing such laser sensors, and discuss the advantages of using an organic semiconductor as the laser material in comparison to dyes in a matrix. The structure of the sensor and its operation principle are described. Bulk and surface sensing experimental data using oligofluorene truxene macromolecules and a conjugated polymer for the gain region are shown to correspond to modeled values and is used to assess the biosensing attributes of the sensor. A comparison between organic semiconductor and dye-doped laser sensitivity is made and analyzed theoretically. Finally, experimental and theoretical specific biosensing data are provided, and methods for improving sensitivity are discussed.