Real-time hardware-based processing of high-precision detector signals for surface plasmon resonance spectroscopy

Surface plasmon resonance (SPR) is fundamentally constrained by small-signal detectability and drift when subtraction is performed in software after digitization. We introduce an SPR detector that executes on-detector amplification and analog differential readout, reducing mechanical components and the reliance on software-based correction. This hardware-native subtraction expands the usable ADC dynamic range and suppresses illumination fluctuations and common-mode disturbances under laboratory conditions. In fixed-angle refractive-index steps (NaCl), the platform resolves , compared to 7,2 10 −6 RIU for a commercial comparator, and improves small-signal SNR by up to 1100-fold while remaining competitive at higher signal levels. In a model IgG–BSA assay, the low noise floor clarifies early binding and equilibrium transitions. By generating intrinsically clean raw signals under controlled laboratory conditions, the hardware-native approach enhances sensitivity and short-term stability for label-free biosensing and reduces the dependence on extensive post-processing. The detector-level differential readout architecture generalizes across platforms and enables compact, robust, high-fidelity SPR in complex environments, with a clear path toward multi-wavelength and arrayed detectors for high-throughput chemical monitoring. • Novel on-chip analog differential readout eliminates software subtraction in SPR. • Achieves 1000-fold SNR improvement in low-signal regimes vs. commercial systems. • Resolves RIU for drift-free refractive index sensing. • Enables clear early binding detection in IgG–BSA assays reducing AI post-processing. • Hardware-native paradigm for robust, compact biosensors in complex environments under laboratory conditions.