With the new technique, a laser beam is first split into two beams, with one of the beams changed slightly in frequency. The two beams then combine again on the sample that has been labeled with fluorescent molecules. As they interfere at the sample, the frequency difference between the two beams encodes the fluorescence from each pixel, allowing the camera can detect an entire row of pixels at one time. The researchers call the new technique "fluorescence imaging using radiofrequency-tagged emission," or FIRE.
The team says the technique can be applied in flow cytometry, which analyzes cells one by one in a flowing fluid. Unlike current imaging flow cytometers, the FIRE technique can keep up with conventional flow-cytometry speeds and image 50,000 cells per second. While most flow cytometers take only a single-point estimate of a cell's fluorescence, FIRE can create an entire high-resolution, multicolor image of each cell, providing significantly more information to a biologist or clinician.
"This information could be the difference between detecting a rare cancer cell in a blood sample or missing it completely," Diebold said. "We're able to capture images of cells that are blur-free as they flow by at a speed around 100 times faster than state-of-the-art imaging flow cytometers," Diebold said. "This technique really gives you a speed advantage that puts you into a new performance regime relative to current technologies."
The researchers say the technique could also be applied in vivo — for example, in neuroscience research to view neural activity in the brain, making a much larger field of view available to analyze.
"In biology, there are a lot of phenomena that happen at the sub-millisecond time scales, like when the brain fires action potentials with pulses that last around one millisecond" Diebold said. "To resolve a millisecond event, you want to sample that at least twice in that one millisecond, so you need half-millisecond time resolution from your imager.
"A lot these higher-speed fluorescence imaging cameras can get close to single-millisecond time resolution but only over a really small field of view," he said. "They read out pixels serially, one after the other. Our FIRE method gets us well beyond that, as we can simultaneously analyze more than 200 pixels in a row, making a much bigger field of view available at one time."
Jalali also holds a faculty appointment in department of surgery at the David Geffen School of Medicine at UCLA and is a member of the California NanoSystems Institute at UCLA.
The research was partially funded by the Broad Stem Cell Research Center at UCLA.
The UCLA Henry Samueli School of Engineering and Applied Science, established in 1945, offers 28 academic and professional degree programs and has an enrollment of more than 5,000 students. The school's distinguished faculty are leading research to address many of the critical challenges of the 21st century, including renewable energy, clean water, health care, wireless sensing and networking, and cyber-security. Ranked among the top 10 engineering schools at public universities nationwide, the school is home to eight multimillion-dollar interdisciplinary research centers in wireless sensor systems, wireless health, nanoelectronics, nanomedicine, renewable energy, customized computing, the smart grid, and the Internet, all funded by federal and private agencies and individual donors.
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