This research attempted to develop “label-free” biosensor for the detection of cardiovascular risk biomarker, C-reactive protein (CRP). An electrospun Polystyrene (PS)/ Polyaniline (PANI) nanofiber was used as the sensing element of the biosensor and coupled with electrical measurement system. High aspect ratio and porosity of nanoscale fiber provides size matched confinement for tiny biomolecule immobilization, which leads to rapid transduction and enhancement in signal strength. Nanofiber mat was integrated with a gold microelectrode interdigitated chip and microfluidic chamber to create a lab-on-chip platform. Results demonstrated that nanotextured fiber with appropriate chemical and electrical functionality can be used as sensing element of an electrochemical biosensor for detection of biomolecules at very low concentration. CRP was successfully detected at 100 fg/ml concentration from human serum suggesting the potential of this lab-on-chip platform for early detection of any cardiovascular risk. A large dynamic linear range of 100 fg/ml-1 μg/ml was achieved in human serum for detection of CRP. Less than 10% cross-reactivity with human albumin suggests the selective detection capability of the proposed biosensor.