Measurements of ligand-binding events to membrane-protein receptors in a near-natural environment display an opportunity in mechanistic studies of membrane receptors. Furthermore, the residence time of drug-target interactions is being increasingly recognized as a key parameter in evaluating drug efficacy, but is hampered by the technical challenge to perform such studies for membrane proteins. However, with membrane proteins embedded in nanoscale lipid vesicles and detection methods with single molecule sensitivity, such information can be gained in a broad dynamic range, as requested in both drug-screening and diagnostic applications. A diverse set of tools with single-nanoparticle sensitivity is now available, to which we recently contributed a concept that enables simultaneous fluorescent and scattering-based label-free imaging of thousands of surface-bound nanoscale entities [Agnarsson B et al., ACS Nano, 2015]. The principle is based on the use of lipid vesicles as enhancer elements in optical waveguide based fluorescence and label-free evanescent-wave scattering microscopy, making the concept compatible with analysis of both water-soluble and cell-membrane bound receptors. The concept is currently evaluated as a diagnostic assay for biomarker detection and in drug-screening applications, previously explored by us using conventional total internal reflection fluorescence (TIRF) microscopy [Gunnarsson et al., Anal Chem (2015)]. The use of scattering microscopy in the context of single-enzyme detection in complex biological fluids will be presented, with focus on single-molecule biomarker detection in cerebrospinal fluid from individuals suffering from Alzheimer’s disease [Angew Chemie, 2015]. A new means to utilize the two-dimensional fluidity of supported cell-membrane derived lipid bilayers in microfluidic designs for nanoparticle size determination and sorting applications will also be presented [Simonnson et al., JACS, 2011 and Pace et al., Anal Chem, 2015].