Hand-held mini-microscope allows surgeons to check for complete tumor removal

Scientists have created a pen-sized, hand-held miniature confocal microscope that could be used in the clinic or the operating room to identify cancer cells and guide tumor-resection procedures. Surgeons could use the non-invasive device in real time at the point of care, rather than sending biopsied samples for histological examination, according to results published in the January 2016 issue of Biomedical Optics Express.

“Surgeons don’t have a very good way of knowing when they’re done cutting out a tumor,” said senior author Jonathan Liu, MS, PhD, Director of the Molecular Biophotonics Laboratory and Assistant Professor of Mechanical Engineering at the University of Washington, Seattle, WA. “Being able to zoom and see at the cellular level during the surgery would really help them to accurately differentiate between tumor and normal tissues and improve patient outcomes.”

To develop the device, Dr. Liu and his team collaborated with researchers at Memorial Sloan Kettering Cancer Center in New York, NY, Stanford University School of Medicine in Stanford, CA, and the Barrow Neurological Institute in Phoenix, AZ. Two applications they had in mind for the mini-microscope were detecting oral cancer and guiding brain-tumor resection procedures.

“For brain tumor surgery, there are often cells left behind that are invisible to the neurosurgeon. This device will really be the first to let you identify these cells during the operation and determine exactly how much further you can reduce this residual,” said project collaborator Nader Sanai, MD, Director of the Barrow Brain Tumor Research Center at the Barrow Neurological Institute. “That’s not possible to do today.”

Although other researchers and corporations have developed miniature confocal microscopes for optical sectioning of tissues, these have been hampered by motion artifacts and insufficient resolution. Making miniature microscopes usually requires trade-offs in size, speed, depth, field of view, resolution, image contrast, or sensitivity, Dr. Liu noted.

The mini-microscope described in this study uses dual-axis confocal microscopy, instead of the conventional single-axis confocal design, which reduces background noise and provides clearer, high-contrast imaging of near tissue surfaces (100 μm to 200 μm deep).

This device also employs line-scan imaging, which enables faster frame rates (16 frames/sec, but higher rates are possible) than conventional confocal microscopes that use point-scan imaging (10 frames/sec). A faster frame rate reduces the types of motion artifacts inherent in a hand-held device.

“We feel like this device does one of the best jobs ever—compared to existing commercial devices and previous research devices—of balancing all those tradeoffs,” Dr. Liu said.

The researchers demonstrated in this study that the miniature microscope could capture tongue, kidney, and colon images of mice that compared well with histologic slides of corresponding tissue (at left).

Next, the researchers plan to assess the device in feasibility studies in humans. They hope that after testing the microscope’s performance as a cancer-screening tool, it can be introduced into surgeries or other clinical procedures in the following 2 to 4 years.