Nanoprojectile Secondary Ion Mass Spectrometry for Nanometrology of Nanoparticles and Their Interfaces

Abstract

Nanoscale molecular characterization plays a crucial role in enhancing our insights into fundamental and materials processes occurring at the nanoscale. However, for many traditional techniques, measurements on different ensembles are mixed and the analytical result reflects the average surface composition or arrangement. Advances in nanometrologies that allow for measurements to be differentiated based on the chemical environment examined are critical for accurate analysis. Here, we present a variant of secondary ion mass spectrometry, SIMS, termed nanoprojectile SIMS, NP-SIMS, capable of nanoscale molecular analysis. The technique examines the sample with a suite, 106–107, of individual gold nanoprojectiles (e.g., Au400 4+) which stochastically probe the surface. Analysis of coemitted ions from each impact allows for the inspection of colocalized moieties within the ejected volume of a single projectile impact (10–15 nm in diameter). If some of these 106–107 measurements arise from nanodomains of similar composition, data can be grouped based on the detected secondary ions. We applied the method to examine a mixture of three different-sized nanoparticles with identical metal cores (3–5 nm in diameter), differing in the length of the attached ligand (decanetiol, tetradecanethiol, and hexadecanethiol). Using NP-SIMS, we determined the relative abundance of the three particles on the surface and isolated measurements based on the impact parameter between the impacting nanoprojectile and the surface particle, demonstrating that measurements occurring near the center of the particle can be differentiated from those at the particle–particle and particle–substrate interfaces. The results suggest that the described methodology is well-suited for molecular analysis of nanoassemblies and may be applied for tracking defects. Here we demonstrate that, using NP-SIMS, ensemble averaging can be avoided and molecular analysis can be undertaken at a scale below 5 nm, allowing for nanoscale molecular analysis of nano-objects and their interfaces.

Nanoprojectile Secondary Ion Mass Spectrometry Enables Multiplexed Analysis of Individual Hepatic Extracellular Vesicles

“…We next compared the level of surface marker expression in cancer cells and normal EVs. To quantify EV markers, we developed a methodology that uses ions characteristic of the target object or the substrate. , We monitored four colocalized Ab@Ln-tags and determined a relative abundance (%) of each tag which correlates to surface expression of the target protein. As seen from Figure B, the analysis of relative abundance (%) revealed that normal EVs had a higher level of CYP2E1 (hepatic marker) concomitant with lower levels of AFP (liver cancer marker) and EpCAM (generic cancer).…”

“…Our team has pioneered the SIMS approach whereby a surface is stochastically bombarded with a suite of individual nanoprojectiles (e.g., ∼ 1 keV/atom Au 400 4+ ) in the event-by-event bombardment detection mode. − A bombardment event generates a crater of ∼10 nm in diameter within an organic layer on the surface; ionized ejecta from each bombardment event are detected, and mass spectra from millions of such events are compiled. This approach has been used by us previously to examine the heterogeneity of biointerfaces, , thin films, , nanoparticles, − and integrated circuits. We have recently demonstrated the feasibility of NP-SIMS for EV analysis using antibodies (Abs)-labeled with halide MS tags and targeting abundant and ubiquitous surface markers, CD63 and CD81 …”

Nanoprojectile Secondary Ion Mass Spectrometry Enables Multiplexed Analysis of Individual Hepatic Extracellular Vesicles

“…To quantify EV markers, we developed a methodology that uses ions characteristic of the target object or the substrate. 34,39 We monitored four co-localized Ab@Ln-tags and determined a relative abundance (%) of each tag which correlates to surface expression of the target protein. As seen from Figure 3B, the analysis of relative abundance (%) revealed that normal EVs had a higher level of CYP2E1 (hepatic marker) concomitant with lower levels of AFP (liver cancer marker) and EpCAM (generic cancer).…”

“…[30][31][32][33] A bombardment event generates a crater of ~10 nm in diameter within an organic layer on the surface; ionized ejecta from each bombardment event are detected and mass spectra from millions of such events are compiled. This approach has been used by us previously to examine the heterogeneity of biointerfaces, 34,35 thin films, 36,37 nanoparticles, [38][39][40] and integrated circuits. We have recently demonstrated the feasibility of NP-SIMS for EV analysis using antibodies (Abs)-labeled with halide MS tags and targeting abundant and ubiquitous surface markers, CD63 and CD81.…”