Absolute Quantification of Nanoparticle Interactions with Individual Human B Cells by Single Cell Mass Spectrometry.

We report on the absolute quantification of nanoparticle interactions with individual human B cells using quadrupole-based inductively coupled plasma mass spectrometry (ICP-MS). This method enables the quantification of nanoparticle-cell interactions at single nanoparticle and single cell levels. We demonstrate the efficient and accurate detection of individually suspended B cells and found an ∼100-fold higher association of colloidally stable positively charged nanoparticles with single B cells than neutrally charged nanoparticles. We confirmed that these nanoparticles were internalized by individual B cells and determined that the internalization occurred via energy-dependent pathways consistent with endocytosis. Using dual analyte ICP-MS, we determined that >80% of single B cells were positive for nanoparticles. Our study demonstrates an ICP-MS workflow for the absolute quantification of nanoparticle-cell interactions with single cell and single nanoparticle resolution. This unique workflow could inform the rational design of various nanomaterials for controlling cellular interactions, including immune cell-nanoparticle interactions.

Quantifying Chemical Composition and Reaction Kinetics of Individual Colloidally Dispersed Nanoparticles.

To control a nanoparticle's chemical composition and thus function, researchers require readily accessible and economical characterization methods that provide quantitative in situ analysis of individual nanoparticles with high throughput. Here, we established dual analyte single-particle inductively coupled plasma quadrupole mass spectrometry to quantify the chemical composition and reaction kinetics of individual colloidal nanoparticles. We determined the individual bimetallic nanoparticle mass and chemical composition changes during two different chemical reactions: (i) nanoparticle etching and (ii) element deposition on nanoparticles at a rate of 300+ nanoparticles/min. Our results revealed the heterogeneity of chemical reactions at the single nanoparticle level. This proof-of-concept study serves as a framework to quantitatively understand the dynamic changes of physicochemical properties that individual nanoparticles undergo during chemical reactions using a commonly available mass spectrometer. Such methods will broadly empower and inform the synthesis and development of safer, more effective, and more efficient nanotechnologies that use nanoparticles with defined functions.