In this manuscript, a new approach in surface plasmon resonance microscopy is presented. The method provides optical real-time detection of single nanoparticles on surfaces. The potential of the method is demonstrated recording spherical dielectric particles as small as 40 nm in diameter and single HIV virus-like particles having diameters of ∼100 nm both immobilized on functionalized surfaces. The surface plasmon resonance signal in the binding spots was found to be almost linearly proportional to the size of the particles and, therefore, surpasses the intensity of Mie scattering on spherical particle (dependence ∼ r −6 ) by orders of magnitude for small objects. The physical reason leading to this strong effect is discussed.

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