“Label-Free” Imaging Approach Monitors Nanotubes in Cells, Blood for Biomedical Research

The structures have potential applications in drug delivery to treat diseases and imaging for cancer research. Two types of nanotubes are created in the manufacturing process, metallic and semiconducting. Until now, however, there has been no technique to see both types in living cells and the bloodstream, according to Dr. Ji-Xin Cheng, an associate professor of biomedical engineering and chemistry at Purdue University (West Lafayette, IN, USA) .

The imaging technique, called transient absorption, employs a pulsing near-infrared laser to deposit energy into the nanotubes, which then are probed by a second near-infrared laser. The researchers have overcome major hurdles in using the imaging technology, detecting, and monitoring the nanotubes in live cells and laboratory mice, Dr. Cheng reported. “Because we can do this at high speed, we can see what’s happening in real time as the nanotubes are circulating in the bloodstream,” he said.

Findings were described online in a research article December 4, 2011, in the journal Nature Nanotechnology. The imaging technique is “label-free,” meaning it does not require that the nanotubes be marked with dyes, making it potentially useful for research and medicine, according to Dr. Cheng. “It’s a fundamental tool for research that will provide information for the scientific community to learn how to perfect the use of nanotubes for biomedical and clinical applications,” he said.

The traditional imaging technique utilizes luminescence, which is limited because it detects the semiconducting nanotubes but not the metallic ones. One hurdle in using the transient absorption imaging system for living cells was to remove the interference caused by the background glow of red blood cells, which is brighter than the nanotubes.

The researchers resolved this problem by separating the signals from red blood cells and nanotubes in two separate “channels.” Light from the red blood cells is somewhat delayed compared to light emitted by the nanotubes. The two kinds of signals are “phase separated” by restricting them to different channels based on this delay.

Researchers utilized the technique to see nanotubes circulating in the blood vessels of mice earlobes. “This is important for drug delivery because you want to know how long nanotubes remain in blood vessels after they are injected,” Dr. Cheng said. “So you need to visualize them in real time circulating in the bloodstream.”

The structures, called single-wall carbon nanotubes, are formed by rolling up a one-atom-thick layer of graphite called graphene. The nanotubes are intrinsically hydrophobic; therefore, some of the nanotubes used in the research were coated with DNA to make them water-soluble, which is required for them to be transported in the bloodstream and into cells.

The researchers also have captured images of nanotubes in the liver and other organs to examine their distribution in mice, and they are using the imaging technique to study other nanomaterials such as graphene.

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