Comprehensive characterization of nanomaterials for medical applications is a challenging and complex task due to the multitude of parameters which need to be taken into consideration in a broad range of conditions. Routine methods such as dynamic light scattering or nanoparticle tracking analysis provide some insight into the physicochemical properties of particle dispersions. For nanomedicine applications the information they supply can be of limited use. For this reason, there is a need for new methodologies and instruments that can provide additional data on nanoparticle properties such as their interactions with surfaces. Nanophotonic force microscopy has been shown as a viable method for measuring the force between surfaces and individual particles in the nano-size range. Here we outline a further application of this technique to measure the size of single particles and based on these measurement build the distribution of a sample. We demonstrate its efficacy by comparing the size distribution obtained with nanophotonic force microscopy to established instruments, such as dynamic light scattering and differential centrifugal sedimentation. Our results were in good agreement to those observed with all other instruments. Furthermore, we demonstrate that the methodology developed in this work can be used to study complex particle mixtures and the surface alteration of materials. For all cases studied, we were able to obtain both the size and the interaction potential of the particles with a surface in a single measurement.
IntroductionNanotechnology for medical applications has been a topic of much scientific interest for several decades due to its potential to address existing challenges in patient treatment 1,2 . In particular, the use of nanoparticles (NPs) as components in the design of targeted drug delivery has been an exciting concept. The field is now facing serious challenges partly due to the reduced circulation lifetime of NPs compared to more conventional approaches [3][4][5] . One of the main obstacles is that as NPs enter into living organisms they adsorb biomolecules forming a layer, known as the biomolecular corona. The NPbiomolecular complex has been shown to have a strong correlation with the "identity" of the materials and determine their biodistribution [6][7][8] . Mechanistic details of the interaction between this complex and cell/tissue surfaces in the body remain unclear, in part due to the lack of reliable methods to measure the physicochemical properties of materials in real exposure conditions. This includes, but is not limited to, accurate size of the particle-protein complex, NP-surface interaction at different conditions and the diffusivity of NPs close to a surface. Such information combined with other advanced characterization methods to study the accessible epitopes on the biomolecular corona could help elucidate the interaction mechanisms between NPs and the cell surface. The most commonly property used to characterize a NP dispersion is its size distribution. For biological ...