Optical microscope detects rare cancer cells

Ashley N. Paddock, ashley.paddock@photonics.com

A new optical microscope easily detects rare cells in real time and could help doctors diagnose diseases earlier or monitor treatments. The ability to distinguish and isolate rare cells – such as circulating cancer tumor cells and stem cells – from a large population of assorted cells has become increasingly important for disease detection. Typically, there are only a handful of these “rogue” cells among a billion healthy ones, but because they are precursors to metastasis – the spread of cancer that causes about 90 percent of cancer mortalities – it is important to be able to find them.

To detect such cells requires an automated high-throughput instrument that can examine millions of cells in a reasonably short time. Currently, microscopes equipped with digital cameras are used to analyze cells, but they are too slow to be useful for this application.

Now, Bahram Jalali and Dino Di Carlo from the University of California, Los Angeles, have devised a high-throughput flow-through optical microscope that can detect rare cells with sensitivity of one part per million in real time. The instrument is equipped with photonic time-stretch camera technology developed by Jalali’s group in 2009 to create the quickest continuous-running camera in the world.

Optical microscope with world’s fastest camera. Courtesy of UCLA.

“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,” said Jalali, who holds the Northrop Grumman Endowed Opto-Electronic Chair in Electrical Engineering at the UCLA Henry Samueli School of Engineering and Applied Science. “Conventional CCD and CMOS cameras are not fast and sensitive enough. It takes time to read the data from the array of pixels, and they become less sensitive to light at high speed.”

The team described how it integrated the camera with real-time image processing and advanced microfluidics for the classification of cells in blood samples in Proceedings of the National Academy of Sciences (doi 10.1073/pnas.1204718109). The new blood-screening technology delivers throughput of 100,000 cells per second, roughly a hundredfold increase in rate when compared with conventional imaging-based blood analyzers.

This study illustrates the detection of rare breast cancer cells in blood in real time with an unprecedented low false-positive rate of one cell in a million. Initial results show that this method can quickly detect rare circulating tumor cells from large volumes of blood samples, opening the door for statistically accurate early cancer detection and for monitoring the efficacy of drug and radiation therapies. The results were obtained by mixing cancer cells grown in a laboratory with various proportions of blood to emulate real patient blood.

The team is conducting clinical trials to assess the efficacy of the technology, which can significantly reduce errors and costs in medical diagnosis. It also could be used for water-quality monitoring and urine analysis.

The research was funded by the US Congressionally Directed Medical Research Programs, the Burroughs Wellcome Fund and NantWorks LLC.

For more on the camera technology developed by Bahram Jalali’s group, see “Full Steam Ahead with the Fastest Camera in the World.”