In this work, we present a novel biochemical sensing approach based on a plasmonic sensor chip, combined with a specific receptor, excited and interrogated via a custom 3D-printed holder through a transmission-based experimental setup, exploiting polymer optical fibers. The setup is designed to measure a disposable plasmonic chip based on a gold nanograting fabricated on a polymethylmethacrylate substrate. The examined sensor configurations here presented are simulated, realized, and experimentally tested. More specifically, first, a numerical analysis is carried out by changing several sensor parameters, then an experimental optical characterization of different sensor configurations is reported. Finally, to test the biosensing capabilities of the proposed method, as a proof of concept, we deposit on the best sensor configuration a biomimetic receptor specific for bovine serum albumin detection. The experimental results demonstrate that the proposed sensor shows an ultra-low limit of detection, equal to about 37 pmol/L.