Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A single cell endoscope

21.12.2011
Berkeley Lab researchers use nanophotonics for optical look inside living cells

An endoscope that can provide high-resolution optical images of the interior of a single living cell, or precisely deliver genes, proteins, therapeutic drugs or other cargo without injuring or damaging the cell, has been developed by researchers with the U.S. Department of Energy (DOE)'s Lawrence Berkeley National Laboratory (Berkeley Lab). This highly versatile and mechanically robust nanowire-based optical probe can also be applied to biosensing and single-cell electrophysiology.

A team of researchers from Berkeley Lab and the University of California (UC) Berkeley attached a tin oxide nanowire waveguide to the tapered end of an optical fibre to create a novel endoscope system. Light travelling along the optical fibre can be effectively coupled into the nanowire where it is re-emitted into free space when it reaches the tip. The nanowire tip is extremely flexible due to its small size and high aspect ratio, yet can endure repeated bending and buckling so that it can be used multiple times.

"By combining the advantages of nanowire waveguides and fibre-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," says Peidong Yang, a chemist with Berkeley Lab's Materials Sciences Division, who led this research. "We've shown that our 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, who also holds appointments with the University of California Berkeley's Chemistry Department and Department of Materials Science and Engineering, is the corresponding author of a paper in the journal Nature Nanotechnology describing this work titled "Nanowire-based single-cell endoscopy." Co-authoring the paper were Ruoxue Yan, Ji-Ho Park, Yeonho Choi, Chul-Joon Heo, Seung-Man Yang and Luke Lee.

Despite significant advancements in electron and scanning probe microscopy, visible light microscopy remains the workhorse for the study of biological cells. Because cells are optically transparent, they can be noninvasively imaged with visible light in three-dimensions. Also, visible light allows the fluorescent tagging and detection of cellular constituents, such as proteins, nucleic acids and lipids. The one drawback to visible light imaging in biology has been the diffraction barrier, which prevents visible light from resolving structures smaller than half the wavelength of the incident light. Recent breakthroughs in nanophotonics have made it possible to overcome this barrier and bring subcellular components into view with optical imaging systems. However, such systems are complex, expensive and, oddly enough, bulky in size.

"Previously, we had shown that subwavelength dielectric nanowire waveguides can efficiently shuttle ultraviolet and visible light in air and fluidic media," Yang says. "By incorporating one of our nanophotonic components into a simple, low-cost, bench-top fibre-optical set-up, we were able to miniaturize our endoscopic system."

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."

Having demonstrated the biocompatibility of their nanowire endoscope, Yang and his co-authors next tested its capabilities for delivering payloads to specific sites inside a cell. While carbon and boron nitride nanotube-based single-cell delivery systems have been reported, these systems suffer from delivery times that range from 20-to-30 minutes, plus a lack of temporal control over the delivery process. To overcome these limitations, Yang and his co-authors attached quantum dots to the tin oxide nanowire tip of their endoscope using photo-activated linkers that can be cleaved by low-power ultraviolet radiation. Within one minute, their functionalized nanowire endoscope was able to release its quantum dot cargo into the targeted intracellular sites.

"Confocal microscopy scanning of the cell confirmed that the quantum dots were successfully delivered past the fluorescently labeled membrane and into the cytoplasm," Yang says. "Photoactivation to release the dots had no significant effect on cell viability."

The highly directional blue laser light was used to excite one of two quantum dot clusters that were located only two micrometers apart. With the tight illumination area and small separation between the light source and the dots, low background fluorescence and high imaging contrast were ensured.

"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 nanowires used in these experiments were originally developed to study size-dependent novel electronic and optical properties for energy applications.

This research was supported by the DOE Office of Science and a grant from the National Institutes of Health.

Lawrence Berkeley National Laboratory addresses the world's most urgent scientific challenges by advancing sustainable energy, protecting human health, creating new materials, and revealing the origin and fate of the universe. Founded in 1931, Berkeley Lab's scientific expertise has been recognized with 13 Nobel prizes. The University of California manages Berkeley Lab for the U.S. Department of Energy's Office of Science. For more, visit www.lbl.gov.

DOE's Office of Science is the single largest supporter of basic research in the physical sciences in the Unites States, and is working to address some of the most pressing challenges of our time. For more information, please visit the Office of Science website at science.energy.gov.

Lynn Yarris | EurekAlert!
Further information:
http://www.lbl.gov

More articles from Life Sciences:

nachricht Seeing on the Quick: New Insights into Active Vision in the Brain
15.08.2018 | Eberhard Karls Universität Tübingen

nachricht New Approach to Treating Chronic Itch
15.08.2018 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

Im Focus: World record: Fastest 3-D tomographic images at BESSY II

The quality of materials often depends on the manufacturing process. In casting and welding, for example, the rate at which melts solidify and the resulting microstructure of the alloy is important. With metallic foams as well, it depends on exactly how the foaming process takes place. To understand these processes fully requires fast sensing capability. The fastest 3D tomographic images to date have now been achieved at the BESSY II X-ray source operated by the Helmholtz-Zentrum Berlin.

Dr. Francisco Garcia-Moreno and his team have designed a turntable that rotates ultra-stably about its axis at a constant rotational speed. This really depends...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

Early opaque universe linked to galaxy scarcity

15.08.2018 | Physics and Astronomy

Molecular switch detects metals in the environment

15.08.2018 | Materials Sciences

Seeing on the Quick: New Insights into Active Vision in the Brain

15.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>