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Lens-Free 3-D Microscope Sharp Enough for Pathology

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A computational lens-free, holographic on-chip microscope could provide a faster and cheaper means of diagnosing cancer and other diseases at the cellular level.

Developed by researchers at the University of California, Los Angeles, the compact system illuminates tissue or blood samples with a laser or LED, while a sensor records the pattern of shadows created by the sample.

The device processes these patterns as a series of holograms using the transport-of-intensity equation, multiheight iterative phase retrieval and rotational field transformations. Computer algorithms correct for imaging artifacts and enhance contrast in the reconstructed 3-D images, which can be focused to any depth within the field of view even after image capture.

A tissue sample image created by a new lens-free microscope
A tissue sample image created by a new chip-based, lens-free microscope. Images courtesy of Aydogan Ozcan/UCLA.

With a field of view several hundred times larger than that of an optical microscope, the lens-free device could considerably speed up diagnostic imaging. It is also much smaller than conventional microscopes.

“While mobile health care has expanded rapidly with the growth of consumer electronics — cellphones in particular — pathology is still, by and large, constrained to advanced clinical laboratory settings,” said professor Dr. Aydogan Ozcan. “Accompanied by advances in its graphical user interface, this platform could scale up for use in clinical, biomedical, scientific, educational and citizen-science applications, among others.”

The researchers tested the device using Pap smears that indicated cervical cancer, tissue specimens containing cancerous breast cells and blood samples containing sickle cell anemia.

In a blind test, a board-certified pathologist analyzed sets of specimen images created by the lens-free technology and by conventional microscopes. The pathologist’s diagnoses using the lens-free microscopic images were accurate 99 percent of the time, the researchers said.

“By providing high-resolution images of large-area pathology samples with 3-D digital focus adjustment, lens-free on-chip microscopy can be useful in resource-limited and point-of-care settings,” the researchers wrote in Science Translational Medicine (doi: 10.1126/scitranslmed.3009850).

Funding for the project came from the Presidential Early Career Award for Scientists and Engineers, the National Science Foundation, the National Institutes of Health, the U.S. Army Research Office, the Office of Naval Research and the Howard Hughes Medical Institute.

Smartphone DNA measurements

Ozcan’s lab also recently demonstrated an optomechanical attachment that enables smartphones to perform fluorescence microscopy measurements on DNA.

The 3-D-printed device augments the phone’s camera by creating a high-contrast darkfield imaging setup with an inexpensive external lens, thin-film interference filters, a miniature dovetail stage and a laser diode for oblique excitation of fluorescent labels. The molecules are labeled and stretched on disposable chips that fit into the smartphone attachment.

A smartphone add-on for imaging DNA.
A smartphone add-on enables imaging of DNA in the field.

The device also includes an app that transmits data to a server at UCLA, which measures the lengths of the individual DNA molecules.

This project was funded by the National Science Foundation. The results were published in ACS Nano (doi: 10.1021/nn505821y).

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Mar 2015
Research & TechnologyBiophotonicsAmericasCaliforniaUCLAUniversity of CaliforniaLos Angeleslens-free microscopeMicroscopyAydogan OzcanTech PulseBioScan

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