The ability to distinguish and isolate rare cells from among a large population of assorted cells has become increasingly important for the early detection of disease and for monitoring disease treatments.
Circulating cancer tumor cells are a perfect example. Typically, there are only a handful of them among a billion healthy cells, yet they are precursors to metastasis, the spread of cancer that causes about 90 percent of cancer mortalities. Such “rogue” cells are not limited to cancer — they also include stem cells used for regenerative medicine and other cell types.
Unfortunately, detecting such cells is difficult. Achieving good statistical accuracy requires an automated, high-throughput instrument that can examine millions of cells in a reasonably short time. Microscopes equipped with digital cameras are currently the gold standard for analyzing cells, but they are too slow to be useful for this application. Now, a new optical microscope developed by UCLA engineers could make the tough task a whole lot easier.
“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 Bahram 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 current flow-cytometry method has high throughput, but since it relies on single-point light scattering, as opposed to taking a picture, it is not sensitive enough to detect very rare cell types, such as those present in early-stage or pre-metastasis cancer patients.
To overcome these limitations, an interdisciplinary team of researchers led by Jalali and Dino Di Carlo, a UCLA associate professor of bioengineering, with expertise in optics and high-speed electronics, microfluidics, and biotechnology, has developed a high-throughput flow-through optical microscope with the ability to detect rare cells with sensitivity of one part per million in real time.