Abstract: A system and method for molecule detection uses a surface plasmon resonance (SPR) system with detection spots having fixed nanostructures. An SPR assembly may be combined with a digital microfluidic control system such as an electrowetting-on-dielectric (EWOD) chip. The microfluidic system individually directs sample droplets to different detection spots of the SPR assembly, thus allowing the SPR examination of different samples or sample reactions on the same surface. The nanostructures at the detection spots enhance the sensitivity of the SPR signals.