In a trial, the lens-free microscope invention from the UCLA California Nano Systems Institute enabled a board-certified pathologist to detect cancers and other cellular abnormalities at 99% accuracy

One of our favorite innovators is at it again, this time with a device that could eventually allow pathologists to use a device coupled with a smartphone to view cancer and other abnormalities at the cellular level.

At UCLA, Professor Aydogan Ozcan, Ph.D. is already well known for having invented attachments that use a smartphone’s camera to create a tiny, lens-free microscope. Now Ozcan, who is the Chancellor’s Professor of Electrical Engineering and Bioengineering at the UCLA Henry Samueli School of Engineering and Applied Science, has created an inexpensive smartphone device that produces holographic images of tissue samples that allow pathologists to view cancer and other abnormalities at the cellular level, according to a December 17, 2014, Science Translational Medicine (STM) article.

UCLA Professor Aydogan Ozcan, Ph.D.

UCLA Professor Aydogan Ozcan, Ph.D., holds 30 issued patents (all of which are licensed) and more than 20 pending patent applications for his inventions in nanoscopy, wide-field imaging, lensless imaging, nonlinear optics, fiber optics, and optical coherence tomography. (Picture and caption copyright UCLA.)

This latest device invented by the Professor, with the help of his team at the UCLA California Nano Systems Institute, also images and measures DNA with accuracy equal to a fluorescence microscope, reported a December 23, 2014, ACS Nano article.

“This is a milestone in the work we’ve been doing,” said Ozcan, who is also Associate Director of the UCLA California NanoSystems Institute, a Professor at Howard Hughes Medical Institute, and Founder and Director of Holomic, a private firm specializing in mobile diagnostics innovations. “This is the first time tissue samples have been imaged in 3D using a lens-free, on-chip microscope,” he stated.

DNA imaging techniques using optical microscopy

DNA imaging techniques using optical microscopy have found numerous applications in biology, chemistry and physics, and are based on relatively expensive, bulky and complicated set-ups that limit their use to advanced laboratory settings. Here [Professor Ozcan and his team] demonstrate imaging and length quantification of single molecule DNA strands using a compact, lightweight, and cost-effective fluorescence microscope installed on a mobile phone. (Photo and caption copyright ACS Nano.)

How the Device Illuminates Tissue on a Pathology Slide

The device designed by Ozcan and his team uses a laser, or light-emitting diode, to illuminate a tissue or blood sample on a pathology slide that is inserted into the device. The microchip’s sensor array, which is similar to the chip used in digital cameras in cellphones, captures and records the pattern of shadows created by the sample. These patterns are processed as a series of holograms, forming 3-D images of specimens to provide pathologists a virtual, depth-of-field view. An algorithm color-codes the image reconstruction, improving contrasts in the sample hologram, so abnormalities can be more easily detected.

Blind Test Compares Device Accuracy to Conventional Microscope

In a blind test, a board-certified pathologist used both the lens-free technology and a conventional microscope to analyze sets of tissue specimen images that contained cervical cancer cells, breast cancer cells, and sickle cell anemia blood cells. The pathologist’s diagnoses using the lens-free microscopic images proved accurate 99% of the time, noted the UCLA press release.

“Using this lens-free, on-chip microscope, we successfully imaged invasive carcinoma cells within human breast sections, Papanicolaou smears revealing a high-grade squamous intraepithelial lesion, and sickle cell anemia blood smears over a FOV of 20.5 mm2,” wrote the STM article’s authors. “The resulting wide-field, lens-free images had sufficient image resolution and contrast for clinical evaluation, as demonstrated by a pathologist’s blinded diagnosis of breast cancer tissue samples, achieving an overall accuracy of 99%.”

The lens-free device, however, has another advantage: it produces images that are several hundred times larger in area, or field of view, than those captured by conventional, bright-field optical microscopes, making it possible to process specimens more quickly.

lens-free microscope device

The picture above was created by a lens-free microscope device that uses a smartphone’s camera to holographically create detailed images of tissue samples. It enables pathologists to diagnose cancer at the cellular level. (Image copyright UCLA.)

Previous Lens-free Microscope Uses 3D Holograms to View Tissue Samples

Previously, Ozcan’s team developed a tiny, lens-free microscope called the LUCUS). It combines with a smartphone camera to generate holographic, high-res, 3D images of cells without using optics. And it only costs about $10 to make. (See Dark Daily “Tiny, Simple-to-Use Lensless Microscope Might Soon Find a Place in Pathology,”  June 25, 2010.)

His team also developed custom-designed smartphone attachments and apps that enable users to quickly analyze food samples for allergens, water samples for heavy metals and bacteria, and cell counts in blood samples, as well as to enable Google Glass to be used to process the results of medical diagnostic tests, according to the UCLA press release.

Tiny, Lens-Free Microscope Goes Anywhere

“While mobile healthcare has expanded rapidly with the growth of consumer electronics—cellphones in particular—pathology is still, by and large, constrained to advanced clinical laboratory settings,” stated 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.”

“By providing high-resolution images of large-area pathology samples with 3D digital focus adjustment—lens-free—on-chip microscopy can be useful in resource-limited and point-of-care settings,” the researchers pointed out in the STM article.

This invention may well lead to less expensive and portable technology capable of performing common diagnostic tests on tissue, blood, and other biological specimens. It would be especially useful in remote areas where large numbers of medical laboratory samples need to be examined quickly, such as Ebola-infected countries in West Africa.

—Patricia Kirk

Related Information:

Lens-Free Microscope Can Detect Cancer at the Cellular Level: UCLA Researchers Develop Device That Can Do the Work of Pathology Lab Microscopes

Wide-Field Computational Imaging of Pathology Slides Using Lens-free On-chip Microscopy

Imaging and Sizing of Single DNA Molecules on a Mobile Phone

UCLA Engineers First To Detect and Measure Individual DNA Molecules Using Smartphone Microscope

Portable Lens-Free Holographic Microscopy Brings Pathology Lab Anywhere

Tiny, Simple-to-Use Lensless Microscope Might Soon Find a Place in Pathology

Cue’s Smartphone Device Intended to Give Consumers an Inexpensive Way to Perform Certain Medical Laboratory Tests at Home