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CNPs Inject Fluid into Cells

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PHILADELPHIA, Jan. 18, 2008 -- Carbon nanopipettes (CNPs) thousands of times thinner than a human hair can measure electric current and probe cells without damaging them.

The tiny carbon-based tools were created by University of Pennsylvania (Penn) engineers and physicians to enter and exit cells with minimal intrusion and inject fluids without damaging or inhibiting cell growth.

Glass micropipettes are found in almost every cell laboratory in the world but are fragile at small scales, can cause irreparable cell damage and cannot be used as injectors and electrodes simultaneously. Haim Bau, a professor in the Department of Mechanical Engineering and Applied Mechanics at Penn, and his team developed tiny carbon-based pipettes that can be mass-produced to eliminate the problems associated with glass micropipettes.
CarbonNanopipettes.jpg
(a) From top to bottom: The tip of the carbon nanopipette (CNP) buckles when pushed against the wall of a glass pipette and recovers its initial shape once the force is removed. (b) From top to bottom: A CNP penetrates through the membrane of a smooth muscle cell. The cell is held in place by glass micropipette aspiration. Scale bars, 15 µm. (Image reprinted with permission from IOP Publishing)
Although they range in size from a few tens to a few hundred nanometers, they are far stronger and more flexible than traditional glass micropipettes. If the tip of a carbon nanopipette, or CNP, is pressed against a surface, the carbon tip bends and flexes, then recovers its initial shape. They are rigid enough to penetrate muscle cells, carcinoma cells and neurons.

Researchers believe the pipettes will be useful for concurrently measuring electrical signals of cells during fluid injection. In addition, the pipettes are transparent to x-rays and electrons, making them useful when imaging even at the molecular level. Adding a functionalized protein to the pipette creates a nanoscale biosensor that can detect the presence of proteins.

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“Penn’s Micro-Nano Fluidics Laboratory now mass-produces these pipettes and uses them to inject reagents into cells without damaging the cells,” Bau said. "We are ultimately interested in developing nanosurgery tools to monitor cellular processes and control or alter cellular functions. We feel CNPs will help scientists gain a better understanding of how a cell functions and help develop new drugs and therapeutics."

Just as important as the mechanical properties of carbon nanopipettes, however, is the ease of fabrication, said Michael Schrlau, a doctoral candidate and first author of the study, “Carbon Nanopipettes for Cell Probes and Intracellular Injection,” published in the most recent issue of Nanotechnology. “After depositing a carbon film inside quartz micropipettes, we wet-etch away the quartz tip to expose a carbon nanopipe. We can simultaneously produce hundreds of these integrated nanoscale devices without any complex assembly,” he said.

The next challenge for researchers is fully utilizing the new tools in nanosurgery.

"We will need to go beyond the proof-of-concept, development stage into the utilization stage," Schrlau said. "This includes finding the appropriate collaborations across engineering, life science and medical disciplines."

The research was performed by Bau and Schrlau of the School of Engineering and Applied Science at Penn and by Erica Falls and Barry Ziober of the Department of Otorhinolaryngology at the University of Pennsylvania School of Medicine. The research was supported by an National Science Foundation-Small Business Technology Transfer grant with Vegrandis LLC and the Commonwealth of Pennsylvania through the Nano Technology Institute.

For more information, visit: www.upenn.edu

Published: January 2008
Glossary
cell
1. A single unit in a device for changing radiant energy to electrical energy or for controlling current flow in a circuit. 2. A single unit in a device whose resistance varies with radiant energy. 3. A single unit of a battery, primary or secondary, for converting chemical energy into electrical energy. 4. A simple unit of storage in a computer. 5. A limited region of space. 6. Part of a lens barrel holding one or more lenses.
glass
A noncrystalline, inorganic mixture of various metallic oxides fused by heating with glassifiers such as silica, or boric or phosphoric oxides. Common window or bottle glass is a mixture of soda, lime and sand, melted and cast, rolled or blown to shape. Most glasses are transparent in the visible spectrum and up to about 2.5 µm in the infrared, but some are opaque such as natural obsidian; these are, nevertheless, useful as mirror blanks. Traces of some elements such as cobalt, copper and...
microfluidics
Microfluidics is a multidisciplinary field that involves the manipulation and control of very small fluid volumes, typically in the microliter (10-6 liters) to picoliter (10-12 liters) range, within channels or devices with dimensions on the microscale. It integrates principles from physics, chemistry, engineering, and biotechnology to design and fabricate systems that handle and analyze fluids at the micro level. Key features and aspects of microfluidics include: Miniaturization:...
nano
An SI prefix meaning one billionth (10-9). Nano can also be used to indicate the study of atoms, molecules and other structures and particles on the nanometer scale. Nano-optics (also referred to as nanophotonics), for example, is the study of how light and light-matter interactions behave on the nanometer scale. See nanophotonics.
photonics
The technology of generating and harnessing light and other forms of radiant energy whose quantum unit is the photon. The science includes light emission, transmission, deflection, amplification and detection by optical components and instruments, lasers and other light sources, fiber optics, electro-optical instrumentation, related hardware and electronics, and sophisticated systems. The range of applications of photonics extends from energy generation to detection to communications and...
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