Berkeley Team Uses Nanophotonics for Single-Cell Imaging, Payload Delivery
Researchers with U.S. Department of Energy’s Lawrence Berkeley National Laboratory working with U.C. Berkeley have developed a versatile and less expensive nanowire-based endoscope that can provide high-resolution optical images of the interior of a single living cell.
Peidong Yang, a chemist with Berkeley Lab and UC Berkeley, helped developed the single cell endoscope. (photo by Roy Kaltschmidt).
The Berkeley team’s novel endoscope system was created by attaching a tin oxide nanowire waveguide to the tapered end of an optical fiber. Light travelling along this fiber can be coupled into the nanowire, where it is re-emitted into free space when it reaches the tip.
"By combining the advantages of nanowire waveguides and fiber-optic fluorescence imaging, we can manipulate light at the nanoscale inside living cells for studying biological processes within single living cells with high spatial and temporal resolution," said Peidong Yang, a chemist with Berkeley Lab's Materials Sciences Division, who led this research.
The nanowires used in these experiments were originally developed to study size-dependent novel electronic and optical properties for energy applications, according to the Berkeley researchers. Updates to this technology by Yang’s team allowed the nanowire-based endoscope can also detect optical signals from subcellular regions and, through light-activated mechanisms, can deliver payloads into cells with spatial and temporal specificity, Yang added.
"Previously, we had shown that sub wavelength dielectric nanowire waveguides can efficiently shuttle ultraviolet and visible light in air and fluidic media. By incorporating one of our nanophotonic components into a simple, low-cost, bench-top fiber-optical set-up, we were able to miniaturize our endoscopic system," according to Yang.
To test their nanowire endoscope as a local light source for subcellular imaging, Yang and his co-authors optically coupled it to an excitation laser then waveguided blue light across the membrane and into the interiors of individual HeLa cells, the most commonly used immortalized human cell line for scientific research.
The optical output from the endoscope emission was closely confined to the nanowire tip and thereby offered highly directional and localized illumination," Yang says.
"The insertion of our tin oxide nanowire into the cell cytoplasm did not induce cell death, apoptosis, significant cellular stress, or membrane rupture. Moreover, illuminating the intracellular environment of HeLa cells with blue light using the nanoprobe did not harm the cells because the illumination volume was so small, down to the picolitre-scale."
To deliver payload within a cell using the nanowire endoscope, Yang’s team wanted to overcome limitations of carbon and boron nitride nanotube-based single-cell delivery systems, which can take up to 30 minutes.
Attaching quantum dots to the tin oxide nanowire tip of their endoscope with photo-activated linkers (which can be cleaved by low-power ultraviolet radiation). This approach led to the ability for the nanowire endoscope to release its payload within one minute into the targeted intracellular sites.
"In the future, in addition to optical imaging and cargo delivery, we could also use this nanowire endoscope to electrically or optically stimulate a living cell," Yang says.
The work is appears as "Nanowire-based single-cell endoscopy" in the journal Nature Nanotechnology. Authors include Yang along with Ruoxue Yan, Ji-Ho Park, Yeonho Choi, Chul-Joon Heo, Seung-Man Yang and Luke Lee. This research was supported by the DOE Office of Science and a grant from the National Institutes of Health.