Wide-Field Imaging of Nanoparticles and Viruses

Professor Aydogan Ozcan at the University of California, Los Angeles talks to AZoNano about Wide-field imaging of nanoparticles and viruses.

Please can you briefly explain how your new optical microscopy method works?

We developed a new computational optical microscopy platform by using nanoscale lenses that stick to the objects that need to be imaged. This lets users see single viruses and other objects in a relatively inexpensive way and allows for the processing of a high volume of samples.

In this approach, a simple light source, such as a light-emitting diode (LED) is used to illuminate the nano-lens object assembly. By utilizing a silicon-based sensor array, which is also found in cell-phone 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.

What are the main challenges with optical microscopy and how has your research aimed to overcome these obstacles?

Electron microscopy is one of the current gold standards for viewing nanoscale objects. This technology uses a beam of electrons to outline the shape and structure of nanoscale objects. Other optical imaging–based techniques are used as well, 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 square millimeters — which can make viewing particles in a sparse population, such as low concentrations of viruses, challenging.

To overcome these issues we created a wide-field imaging technique that uses lensfree holographic on-chip imaging and self-assembled nano-lenses to detect individual sub-100nm objects over very large imaging areas, e.g., >20 mm^2.

How does your method benefit the end-user of the microscopy platform?

Ultra-wide field of view, ease of use, field-portability and cost-effectiveness.

How does this platform compare to existing nanoscale imaging techniques?

While our technique does not offer the high resolution of electron microscopy, it has a much wider field of view — more than 20 square millimeters — and can be helpful in finding nanoscale objects in samples that are sparsely populated.

What type of nanoscale objects can be identified using this technique?

We have used the new technique to create images of single polystyrene nanoparticles, as well as adenoviruses and H1N1 influenza viral particles.

What existing microscopy techniques have been combined to build this platform?

This platform is enabled by a unique combination of surface chemistry and computational on-chip imaging techniques that are based on partially coherent digital in-line holography and pixel super-resolution.

How cost-effective is the new technique?

The components that are used in this imaging modality are rather cost-effective since they are already found in modern digital electronic devices, including cell phones or digital cameras. As an example, the CMOS imager that is used in this work can be purchased with less than $10 at high volumes, and is already installed in some cell phone camera units.

How is this optical microscopy method useful in the diagnosis of diseases?

Because of its compactness, field-portability as well as cost-effectiveness, such a computational microscope that can detect individual viruses over extremely large areas could be rather useful for telemedicine applications by, for example, quantification of viral load in bodily fluids including blood.

Do you plan to commercialize your platform? If so, how far away is the product from market?

A Los Angeles based start-up company (Holomic LLC) that I co-founded has licensed more than 20 different IP applications on lensfree computational microscopy tools from my lab at UCLA, through our Office of Intellectual Property. In early 2014, a prototype of a high-resolution lensfree microscope can be in the market (subject to change in plans).

How do you plan on expanding this research area?

We would like to bring specificity to this unique nano-imaging and sensing platform through its integration with micro-fluidic systems.

Where can we find further information?

Further information on this research can be found on our research group website.

About Professor Aydogan Ozcan

Dr. Aydogan Ozcan received his Ph.D. at Stanford University Electrical Engineering Department. After a short post-doctoral fellowship at Stanford University, he was appointed as a research faculty at Harvard Medical School, Wellman Center for Photomedicine in 2006. Dr. Ozcan joined UCLA in the summer of 2007, where he is currently an Associate Professor leading the Bio- and Nano-Photonics Laboratory at the Electrical Engineering and Bioengineering Departments.

Dr. Ozcan gave more than 130 invited talks and is also the author of one book, the co-author of more than 260 peer reviewed research articles in major scientific journals and conferences. In addition, Dr. Ozcan is the founder and a member of the Board of Directors of Holomic LLC.

Prof. Ozcan received several major awards including the 2011 Presidential Early Career Award for Scientists and Engineers (PECASE), which is the highest honor bestowed by the United States government on science and engineering professionals in the early stages of their independent research careers.

Dr. Ozcan is elected Fellow of SPIE, and is a Senior Member of IEEE, a Member of LEOS, EMBS, OSA, and BMES.