Quantifying Ligand Adsorption to Nanoparticles Using Tandem Differential Mobility Mass Analysis

Although electrospray-differential mobility analyzers (ES-DMA) have been previously employed to characterize ligand binding to nanoparticles, absolute quantification of surface coverage can be inaccurate at times because of ligand conformational effects. In this Letter, we report a quantitative technique by in-flight coupling of a particle mass analyzer (APM) with ES-DMA, thus enabling a direct quantitative analysis of mass independent of particle size, material, morphology and conformation. We demonstrate the utility of ES-DMA–APM by studying two model complex systems (gold nanoparticle–bovine serum albumin and polystyrene bead–antibody) as a function of concentration and pH. Our results obtained with ES-DMA–APM are in excellent agreement with prior work. We anticipate that this will enhance the capabilities of online quantitative characterization of ligand binding to nanoparticles.