Ultrasensitive Label-Free Nanosensing and High-Speed Tracking of Single Proteins

Label-free detection, analysis, and rapid tracking of nanoparticles is crucial for future ultrasensitive sensing applications, ranging from understanding of biological interactions to the study of size-dependent classical-quantum transitions. Yet optical techniques to distinguish nanoparticles direc...

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Bibliographic Details
Published in:Nano letters 2017-02, Vol.17 (2), p.1277-1281
Main Authors: Liebel, Matz, Hugall, James T, van Hulst, Niek F
Format: Article
Language:English
Subjects:
Biosensing Techniques - methods
Diffusion
Fluorescence
Gold - chemistry
Humans
Iron-Binding Proteins - analysis
Microscopy, Interference - methods
Models, Theoretical
Molecular Weight
Nanoparticles - chemistry
Nanostructures - chemistry
Nanotechnology
Protein Binding
Receptors, Cell Surface - analysis
Streptavidin - analysis
Titanium - chemistry
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Summary:Label-free detection, analysis, and rapid tracking of nanoparticles is crucial for future ultrasensitive sensing applications, ranging from understanding of biological interactions to the study of size-dependent classical-quantum transitions. Yet optical techniques to distinguish nanoparticles directly among their background remain challenging. Here we present amplified interferometric scattering microscopy (a-iSCAT) as a new all-optical method capable of detecting individual nanoparticles as small as 15 kDa proteins that is equivalent to half a GFP. By balancing scattering and reflection amplitudes the interference contrast of the nanoparticle signal is amplified 1 to 2 orders of magnitude. Beyond high sensitivity, a-iSCAT allows high-speed image acquisition exceeding several hundreds of frames-per-second. We showcase the performance of our approach by detecting single Streptavidin binding events and by tracking single Ferritin proteins at 400 frames-per-second with 12 nm localization precision over seconds. Moreover, due to its extremely simple experimental realization, this advancement finally enables a cheap and routine implementation of label-free all-optical single nanoparticle detection platforms with sensitivity operating at the single protein level.
ISSN:1530-6984
1530-6992
DOI:10.1021/acs.nanolett.6b05040