Oct. 16, 2000 ITHACA, N.Y. -- Chemical biologists at Cornell University have pioneered a new imaging technique that offers researchers a new way to observe the working of therapeutic drugs within single cancer cells.
The technique, called ion microscopy, promises to open new avenues of cancer research because it offers a high sensitivity for detecting isotopes of elements -- atoms of the same element with different numbers of neutrons.
"Ion microscopy's high sensitivity makes it an ideal tool for localizing anticancer drugs inside tumor cells," says Subhash Chandra, a senior research associate with Cornell's Department of Chemistry and Chemical Biology. He explains that many therapeutic compounds used in cancer treatments contain chemical markers, known as elemental tags, that allow ion microscopes to judge their efficacy.
Chandra was the lead author of a report on the development of the biological and biomedical application of ion microscopy earlier this year in the journal Analytical Chemistry . The subcellular location of transported ions inside normal and cancer cells can be studied with ion microscopy by placing a stable, or nonradioactive, isotope into a laboratory rat's bloodstream, thereby allowing the imaging of cells of the target organ with the transported isotope. The studies described in the journal were performed in cell cultures and on tissues from rats, although, says Chandra, human cell cultures and tissues have been used in studies.
The technique is novel because molecules that have been labeled with either stable or radioactive isotopes can be located within the cell. A researcher using ion microscopy instead of the more common autoradiography (a method that locates radioactively labeled molecules) can use stable isotopes to run studies that would not be possible with radioactively labeled molecules. This shortens imaging time, assuring that the subcellular location of labeled molecules is native to the cell. The form of ion microscopy described in the journal report is called SIMS, for dynamic secondary ion mass spectrometry. This method uses cryogenically prepared, frozen freeze-dried cells in the ion microscope's high vacuum. The advantage of SIMS imaging, Chandra writes in the paper, is that it provides three-dimensional imaging capability for studying the subcellular distribution of elements (or isotopes) and simultaneous analysis of a wide region containing many cells within the same field of view. This is a major advance for biological researchers, providing reproducible observations among a number of cells and ample imaging data.
Further, says Chandra, "The preparation of cells with cryogenic methods preserves the native chemical and structural makeup of the cells for ion microscopy analysis."
The ion microscopy group at Cornell developed a way of growing cells on silicon chips and cryogenically preparing them with a method called "sandwich fracture." This method overcomes compositional and conductive problems and allows cells to be studied for their intracellular chemical composition.
The ion microscope was invented in 1962 and originally was exploited in the semiconductor and electronics industry by such companies as IBM Corp. and Intel Corp. The microscope uses a beam of ions to bombard the sample surface, a process that produces secondary ions by etching off the sample's top layer of atoms. These secondary ions are then filtered. Other microscopic techniques, such as laser scanning confocal microscopy and field emission scanning electron microscopy, are used to help to recognize the location and distribution of ions or molecules in smaller structures, such as cellular organelles.
The other authors of the report, titled "Subcellular Imaging by Dynamic SIMS Ion Microscopy," also members of Cornell's Department of Chemistry and Chemical Biology, were Duane R. Smith, research associate, and Professor Emeritus George H. Morrison. Funding for the research was provided by the National Institutes of Health, the National Science Foundation and the U.S. Department of Energy.
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