Pathology groups and clinical labs could use the world’s fastest camera to diagnose cancer at earlier stages
There’s a new optical microscope that can detect rogue cancer cells. It was developed by engineers at the University of California Los Angeles (UCLA). The achievement could create new diagnostic capabilities for pathology and clinical laboratory medicine.
New Instrument Detects Circulating Tumor Cells
The target for this new high-speed microscope are Circulating cancer tumor cells (CTC). CTCs are the precursors to metastasis and metastatic cancer accounts for about 90% of cancer mortalities. However, CTCs are difficult to find and identify. Among a billion healthy cells, only a minute number of CTCs exist.
It was the challenge of locating and identifying circulating tumor cells that motivated the researchers at UCLA. To detect such rare cells with statistical accuracy requires an automated, high-throughput instrument, noted a story published at Phys.org. The instrument must be able to examine millions of cells in a reasonably short time. “To catch these elusive cells, the camera must be able to capture and digitally process millions of images continuously at a very high frame rate,” stated Bahram Jalali, Ph.D., in the story.
Jalali is Northrop Grumman Endowed Opto-Electronic Chair in Electrical Engineering at the UCLA Henry Samueli School of Engineering and Applied Science. He also holds joint appointments in the Biomedical Engineering Department, California NanoSystems Institute (CNSI) and the UCLA School of Medicine Department of Surgery.
New Blood-Screening Technology Offers 100X Throughput
The success of Jalili and his colleagues in detecting CTCs came from applying a technology developed earlier. In 2009, Jalali’s team created what it described as “photonic time-stretch camera technology technology” to create the world’s fastest continuous-running camera.
In a paper published in the April 2009 issue of Nature, Jalali and his colleagues described this innovation. “High-speed events require ultrafast, light-sensitive video cameras,” the authors wrote in the abstract. An example of such an event would be certain elements of blood analysis.
Microscopes equipped with digital cameras are currently the gold standard for analyzing cells. However, Jalali pointed out that these digital cameras are neither fast enough nor sensitive enough to detect rogue cancer cells. “It takes time to read the data from the array of pixels, and they become less sensitive to light at high speed,” he observed in the Phys.org story.
Today’s flow cytometry technology has high throughput. However, it relies on single-point light scattering. Also, it does not take a picture and lacks the sensitivity required to detect very rare cells. These include early-stage or pre-metastatic cancer cells. The UCLA team’s high-throughput flow-through optical microscope has the ability to detect rare cells with sensitivity of one part per million in real time, Phys.org reported.
Rapid Real-Time Image Processing Can Reduce Errors
The project required the integration of several cutting-edge technologies and collaboration between academic departments. Jalali and Dino Di Carlo, Ph.D., Associate Professor of Bioengineering at UCLA, led an interdisciplinary team of researchers. They described how they used the new technology to classify cells in blood samples in a paper published in Proceedings of the National Academy of Sciences.
“To show the system’s utility, we demonstrate high-throughput image-based screening of… rare breast cancer cells in blood with an unprecedented throughput of 100,000 particles per second and a record false positive rate of one in a million,” the authors wrote in their abstract. That’s a throughput approximately 100 times higher than conventional imaging-based blood analyzers, Phys.org reported. “This achievement…adds to the significant technology infrastructure being developed at UCLA for cell-based diagnostics,” Di Carlo noted.
“[The] technology can significantly reduce errors and costs in medical diagnosis,” added lead author Keisuke Goda, Ph.D., a UCLA Program Manager at the Department of Electrical Engineering and Department of Bioengineering and a CNSI member. “To further validate the clinical utility of the technology, we are currently performing clinical tests in collaboration with clinicians.”
If the technology kinks can be ironed out, the world’s fastest camera will be a major development for pathologists and clinical laboratory managers. This study is important because preliminary results indicate that the new technology has the potential to quickly enable the detection of rare CTCs from a large volume of cells. This opens the way for early detection of cancer that is statistically accurate, as well as for use in monitoring the efficiency of drug and radiation therapy.
—Pamela Scherer McLeod