Fabrication of a chemiresistive biosensor for detection of biomolecules is demonstrated on a high surface area, flexible electro-spun nylon fiber mat. For the first time, the –OH functionalized conducting copolymer of 3,4-ethylenedioxythiophene (EDOT) and 3-thiopheneethanol (3-TE) is synthesized and conformally deposited on the electro-spun mats by oxidative chemical vapor deposition (oCVD). The free –OH functional groups of the copolymer are available for immobilization of analyte specific biomolecules. Here, avidin and biotin molecules are employed as the analyte-specific molecule and analyte respectively for their high specificity to each other. The sensitivities of avidin immobilized conducting copolymer on electro-spun mats are tested against micro-molar to nano-molar concentrations of biotin in aqueous solutions. Application of electro-spun fiber mat in this case enhances the sensor response 6 times when compared to a flat substrate and also significantly lowers the response time. In addition to the experimental studies, current work also includes modeling of the kinetics of the change of response for the biotin-avidin interactions as a function of time. Most importantly, this fabrication technique promises an extremely sensitive and field deployable method for the detection of other biomolecules, for example, food pathogens.