We recently introduced an in-liquid sensing concept based on surface acoustic resonance (SAR) in a lab-on-a-chip resonant device with one electrical port. The 185 MHz one-port SAR sensor has a sensitivity comparable to other surface acoustic wave (SAW) in-liquid sensors, while offering a high quality factor (Q) in water, low impedance, and fairly low susceptibility to viscous damping. In this work, we present significant design and performance enhancements of the original sensor presented in part I. A novel ‘lateral energy confinement’ (LEC) design is introduced, where the spatially varying reflectivity of the SAW reflectors enables strong SAW localization inside the sensing domain at resonance. An improvement in mass-sensitivity greater than 100% at resonance is achieved, while the measurement noise stays below 0.5 ppm. Sensing performance was evaluated through real-time measurements of the binding of 40 nm neutravidin-coated SiO2 nanoparticles to a biotin-labeled lipid bilayer. Two complementary sensing parameters are studied, the shift of resonance frequency and the shift of conductance magnitude at resonance.