Detection and Digital Resolution Counting of Nanoparticles with Optical Resonators and Applications in Biosensing

The interaction between nanoparticles and the electromagnetic fields associated with optical nanostructures enables sensing with single-nanoparticle limits of detection and digital resolution counting of captured nanoparticles through their intrinsic dielectric permittivity, absorption, and scattering. This paper will review the fundamental sensing methods, device structures, and detection instruments that have demonstrated the capability to observe the binding and interaction of nanoparticles at the single-unit level, where the nanoparticles are comprised of biomaterial (in the case of a virus or liposome), metal (plasmonic and magnetic nanomaterials), or inorganic dielectric material (such as TiO2 or SiN). We classify sensing approaches based upon their ability to observe single-nanoparticle attachment/detachment events that occur in a specific location, versus approaches that are capable of generating images of nanoparticle attachment on a nanostructured surface. We describe applications that include study of biomolecular interactions, viral load monitoring, and enzyme-free detection of biomolecules in a test sample in the context of in vitro diagnostics.M.Á.A. is grateful to Generalitat Valenciana (Spain) (APOSTD/2016/076) for his Postdoctoral fellowship and the financial support from the European Social Fund (ESF). K.D.L. is supported by a Ruth L. Kirschstein Pre-Doctoral Fellowship (NIH F30AI122925). S.L.M. thanks the Department of Science and Technology (DST) and the Council of Scientific and Industrial Research (CSIR) of South Africa. We are also grateful for financial support from the National Science Foundation (grant 1512043) and the National Institutes of Health (R01 AI120683)