Journal
ACS NANO
Volume 14, Issue 2, Pages 2002-2013Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.9b08512
Keywords
interference microscopy; nanoparticle detection; biosensing; computational imaging; label-free; Fourier optics
Categories
Funding
- European Union's Horizon 2020 research and innovation programme [766466]
- National Institutes of Health (NIH) [R21AI135517]
- NIH [5R25GM095480, 5R01A1114814, P01A1120943]
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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 X 100 mu m(2)), enabling simultaneous imaging of more than 10(4) BNPs at a resolution of similar to 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.
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