Sub-terahertz (sub-THz) vibrational spectroscopy for biodetection is based on specific resonance features and vibrational modes or groups of modes at close frequencies that are in the absorption (transmission) spectra of large biological molecules and intact bacterial cells and spores. Improvements in sensitivity, especially in the discriminative capability of sub-THz vibrational spectroscopy for detection, characterization, and identification of bacterial organisms, require higher spectral resolution to resolve the spectral features. Herein we describe a new, continuous-wave and frequency-domain spectroscopy sensor with imaging capability. This spectroscopy system was operated at room temperature in the sub-THz spectral region between 315 and 480 GHz. We present experimental spectra obtained from biological macromolecules and species using this spectrometer, and we compare biological spectra with simulation results using molecular dynamics. Observed, multiple, intense and specific resonances in transmission and absorption spectra from nanogram samples with spectral line widths as small as 0.11 cm provide the conditions for determining reliable discriminative capability and for monitoring interactions between biomaterials and reagents in near real time.