Handheld Mini-Microscope Could ID Cancer Cells in Real-Time
Identifying cancer cells is not a quick or simple process, and waiting for the results to find out whether you or a loved one have cancer or not is extremely stressful as it can take days and sometimes even weeks – until now that is.
According to results published in the January 2016 issue of Biomedical Optics Express, Researchers at the University of Washington, Memorial Sloan Kettering Cancer Center, Stanford University, and the Barrow Neurological Institute have been working on a hand-held miniature confocal microscope that could be used in the clinic or the operating room to identify cancer cells and guide tumour-resection procedures.
Biopsies and tumour removals typically require sending intra-operative tissue samples to the pathology lab for evaluation under a microscope. This takes time and is often detrimental to the patients, resulting in the removal of healthy tissues, longer time under anesthesia, and other concerns.
Surgeons could use the non-invasive device in real-time at the point of care, rather than sending biopsied samples for histological examination, thereby saving time and saving the patient a lot of stress.
“Surgeons don’t have a very good way of knowing when they’re done cutting out a tumour,” 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.”
Two specific applications the researchers 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.”
The device relies on dual-axis confocal microscopy to peer up to a half millimeter under the surface without taking a slice of the tissue.
It does this process rapidly using mirrors that sweep a light beam across the area of the tissue being analyzed, capturing what it’s seeing to a nearby computer that further analyzes the data.
The researchers believe they can get it to work fast enough to avoid smudging during handheld operation, a necessity if the microscope is to be used during actual surgeries.
There are many other uses for this type of microscope; for instance, dentists who find a suspicious-looking lesion in a patient’s mouth often wind up cutting it out and sending it to a lab to be biopsied for oral cancer. Most come back benign.
That process subjects patients to an invasive procedure and overburdens pathology labs. A miniature microscope with high enough resolution to detect changes at a cellular level could be used in dental or dermatological clinics to better assess which lesions or moles are normal and which ones need to be biopsied.
“Trying to see beneath the surface of tissue is like trying to drive in a thick fog with your high beams on – you really can’t see much in front of you,” Liu said. “But there are tricks we can play to see more deeply into the fog, like a fog light that illuminates from a different angle and reduces the glare.”
The microscope also employs a technique called line scanning to speed up the image-collection process. It uses micro-electrical-mechanical — also known as MEMS — mirrors to direct an optical beam which scans the tissue, line by line, and quickly builds an image.
Imaging speed is particularly important for a handheld device, which has to contend with motion jitter from the human using it. If the imaging rate is too slow, the images will be blurry.
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).
The handheld microscope, roughly the size of a pen, combines technologies in a novel way to deliver high-quality images at faster speeds than existing devices. Researchers expect to begin testing it as a cancer-screening tool in clinical settings next year.