Single Nanoparticle Analysis

nanoparticleNanoscale structures mediate many cellular functions, including intracellular transport and intercellular signaling, and engineered nanoparticles are emerging as important tools for disease diagnosis and treatment. Most molecular analysis methods report bulk or average properties of nanoparticle preparations, and do not readily reveal population heterogeneity. However, because of their small size, it is difficult to make quantitative molecular measurements of single nanoparticles. To address this challenge, we are adapting flow cytometry as a sensitive and high speed method for the optical analysis of individual nanoparticles. High efficiency light collection, sensitive detectors, and extended measurement integration times enable the quantitative measurement of individual nanoparticles. We are using these approaches for the analysis of cell-derived membrane vesicles and synthetic model membrane vesicles, as well as to guide the engineering of nanoparticle probes for detection applications.

Selected References:

High throughput single nanoparticle spectroscopy.
David S Sebba, Dakota A Watson and John P Nolan (2009).
ACS Nano 2009; 3:1477-1484.

A trigger channel threshold artifact in nanoparticle analysis.
Nolan, J.P., S.A. Stoner (2013).
Cytometry 83A: 301-305.

Optimization of SERS tag intensity, binding footprint, and emittance.
Nolan, J.P., E. Duggan, D Condello (2014).
Journal of Bioconjugate Chemistry 25: 1233–1242.

Light-scattering detection below the level of single fluorescent molecules for high-resolution charactezation of functional nanoparticles.
Zhu, S., M. Ling, S. Wang, C. Chen, L. Wang, W. Hang, J.P. Nolan, L. Wu, X. Yan (2014).
ACS Nano 8: 10998-11006.

Flow cytometry of extracellular vesicles: pitfalls and prospects.
Nolan, J.P. (2015).
Current Protocols in Cytometry 13.14.1-13.14.16

Multiplex TEM specimen preperation and analysis of plasmonic nanoparticles.
Mulligan, S.K., J.A., Spier, I. Razinkov, A. Cheng, J. Crum, T. Jain, E. Duggan, E. Liu (2015).
Microscopy and Microanalysis (in press).