High-throughput, high-resolution interferometric light microscopy of biological nanoparticles

Date
2020-01
Advisor
Instructor
Source Title
ACS Nano
Print ISSN
1936-0851
Electronic ISSN
Publisher
American Chemical Society
Volume
14
Issue
22
Pages
2002 - 2013
Language
English
Type
Article
Journal Title
Journal ISSN
Volume Title
Abstract

Label-free, visible light microscopy is an indispensable tool for studying biological nanoparticles (BNPs). However, conventional imaging techniques have two major challenges: (i) weak contrast due to low-refractive-index difference with the surrounding medium and exceptionally small size and (ii) limited spatial resolution. Advances in interferometric microscopy have overcome the weak contrast limitation and enabled direct detection of BNPs, yet lateral resolution remains as a challenge in studying BNP morphology. Here, we introduce a wide-field interferometric microscopy technique augmented by computational imaging to demonstrate a 2-fold lateral resolution improvement over a large field-of-view (>100 × 100 μm2 ), enabling simultaneous imaging of more than 104 BNPs at a resolution of ∼150 nm without any labels or sample preparation. We present a rigorous vectorial-optics-based forward model establishing the relationship between the intensity images captured under partially coherent asymmetric illumination and the complex permittivity distribution of nanoparticles. We demonstrate high-throughput morphological visualization of a diverse population of Ebola virus-like particles and a structurally distinct Ebola vaccine candidate. Our approach offers a low-cost and robust label-free imaging platform for high-throughput and high-resolution characterization of a broad size range of BNPs.

Course
Other identifiers
Book Title
Keywords
Interference microscopy, Nanoparticle detection, Biosensing, Computational imaging, Label-free, Fourier optics
Citation
Published Version (Please cite this version)