A reconfigurable biosensor with different spectral sensitivities could provide new opportunities to increase the label-free selectivity and sensitivity for biomolecules. Here, we propose and numerically demonstrate a phase change chalcogenide material (Ge ₂ Sb ₂ Te ₅ )-based photonic crystal fiber (PCF) sensor for tunable and enhanced refractive index sensing at near infrared (NIR) wavelengths. In order to achieve this, we integrate a thin hybrid sensing layer of Au/Ge ₂ Sb ₂ Te ₅ with D-shaped PCF. By switching the structural phase of Ge ₂ Sb ₂ Te ₅ from amorphous to crystalline, we realize tunable and enhanced refractive index sensing with a large figure of merit (FOM) for the sensing range from 1.35 to 1.40, which covers most known analytes such as proteins, cancer cells, glucose and viruses or DNA/RNA. The obtained average bulk refractive index sensitivity is 17,600 nm/RIU and 8,000 nm/RIU for crystalline and amorphous phase, respectively. The observed large tunable differential response of the proposed sensor offers a promising opportunity to design an assay for the selective detection of higher and lower molecular weight biomolecules through future artificial intelligence-based sensing.