Nanolens Microscopes Detect Viruses Such as Flu

As the flu spreads like wildfire across the US, quickly diagnosing patients with aches, pains, fever and chills has never been more important. A new optical microscopy method aims to do just that by using tiny liquid lenses that self-assemble around microscopic objects.

When coupled with computer-based computational reconstruction techniques, the portable, cost-effective microscopy platform developed at the University of California, Los Angeles, can detect individual viruses, such as the flu, and nanoparticles, making it potentially useful in the diagnosis of diseases in point-of-care settings or areas with limited medical resources.

This image of an H1N1 flu virus was made using a new nanolens microscope developed at UCLA. Lens-free pixel superresolved holographic detection of individual influenza A (H1N1) viruses. Scale bar shows 10 µm. Images courtesy of UCLA.

Electron microscopy is one of the current gold standards for viewing nanoscale objects. This technology uses an electron beam to outline the shape and structure of nanoscale objects. Other optical imaging-based techniques are also used, but all of them are relatively bulky, require time for the preparation and analysis of samples, and have a limited field of view — typically smaller than 0.2 sq mm — which can make it challenging to view particles in a sparse population, such as low concentrations of viruses.

To overcome these hurdles, Aydogan Ozcan and colleagues at UCLA’s Henry Samueli School of Engineering developed the optical microscopy platform using nanoscale lenses that stick to the objects to be imaged, allowing users to see single viruses and other objects directly and in a relatively inexpensive way. This approach also enables high-volume processing of samples.

Using the nanolens microscope: (a) The experimental setup, (b) Numerical model and scanning electron microscope images of the bead only, and bead-nanolens configuration. (c) Steps of the sample preparation.

“This work demonstrates a high-throughput and cost-effective technique to detect sub-100-nanometer particles or viruses over very large sample areas,” said Ozcan, an associate professor of electrical engineering and bioengineering. “It is enabled by a unique combination of surface chemistry and computational imaging.”

At scales below 100 nm, optical microscopy becomes challenging because of its weak light-signal levels. Using a special liquid composition, nanoscale lenses — typically thinner than 200 nm — self-assemble around objects on a glass substrate.

Detection of individual viruses. Left three columns: Lens-free pixel superresolved holographic detection of individual influenza A (H1N1) viruses. For comparison, right column: Bright-field oil immersion objective lens images of H1N1 viruses, and a single scanning electron microscope image of an H1N1.

A simple light source such as an LED is then used to illuminate the nanolens object assembly. By utilizing a silicon-based sensor array, found in common cellphone cameras, lens-free holograms of the nanoparticles are detected. The holograms are then rapidly reconstructed with the help of a personal computer to detect single nanoparticles on a glass substrate.

The method was used to create images of single polystyrene nanoparticles, as well as adenoviruses and H1N1 influenza viral particles.

The research appeared in Nature Photonics (doi: 10.1038/nphoton.2012.337).

For more information, visit: www.engineer.ucla.edu