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ANALYTICAL CURRENTS Colored, magnetic nanoparticles separate cells Zeev Rosenzweig and colleagues at the University of New Orleans, Tulane University, and Xavier University in Louisiana have created a novel class of nanoparticles with both magnetic and luminescent properties. The nanoparticles can be used to selectively isolate cancer cells, bacteria, and viruses from mixtures, a capability that can benefit clinical diagnoses. The new nanoparticles consist of two distinct components—a superparamagnetic Fe2O3 core and a luminescent quantum dot shell. Because the Fe2O3 core is water-soluble and the quantum dot shells are not, the coupling reaction between the core and shell must occur in an aqueous/organic mixture. The final product, a superparamagnetic nanoparticle with a luminescent quantum dot shell, is completely water-soluble with a diameter of ~20 nm.
The investigators used the nanoparticles to separate breast cancer cells from serum. They modified the nanoparticle surface with an antibody that specifically recognized a molecule on breast cancer cells. To separate the cells from the serum, a permanent magnet was applied to pull down the nanoparticles that were attached to the breast cancer cells. The separated cells could be readily studied by fluorescence microscopy because of the strong luminescence of the nanoparticle quantum dot shell. The investigators envision more applications for these luminescent, superparamagnetic nanoparticles. For one, the quantum dot shells can be created to emit specific wavelengths. Each different-colored nanoparticle can then be modified with an antibody against a specific cancer cell type, bacterium, or virus. Samples can be mixed with these
Fluorescence microscopy of breast cancer cells attached to nanoparticles modified with a breast cancer antibody (10 magnification).
different-colored nanoparticles, and after magnetic separation, the nanoparticle color codes can be used to determine the types of cells present in the samples. (Nano Lett. 2004, 4, 409–413)
Better sensitivity for SPR imaging A notable limitation of using surface plasmon resonance (SPR) imaging to analyze DNA and RNA arrays has been the method’s nanomolar detection limit. Typical genomic samples, however, contain DNA at concentrations of ~20 fM. To drive the detection limit down to 1 fM, a 106 sensitivity enhancement, Robert Corn and colleagues at the University of Wisconsin add a new amplification process based on the enzyme RNase H. RNase H selectively degrades the RNA in an RNA–DNA heteroduplex, yet does not digest single- or double-stranded DNA or single- or double-stranded RNA. After arraying RNA probe molecules on the surface of the SPR chip, the researchers introduce target DNA and RNase H. When the DNA
© 2004 AMERICAN CHEMICAL SOCIETY
binds to a complementary RNA probe, RNase H degrades the probe and the DNA is released, which allows it to bind to another probe. This iterative removal of RNA from the surface is detected by SPR as a change in the percent reflectivity. Using the Y-chromosome gene TSPY as the target DNA and a chip with three probes, the researchers achieved a detection limit of 1 fM in 4 h with a –0.7% reflectivity change for the complementary RNA probe. They noted that the time required to reach a 0.2% reflectivity change increased from 12 ± 2 to 120 ± 25 min as the DNA concentration decreased from 10 pM to 1 fM. It is the integration of the probe loss over time, coupled with the removal of an
(a)
RNA RNA/DNA
DNA RNase H (b)
(c)
(a) When DNA binds to complementary RNA, (b) RNase H digests the RNA and releases the DNA. (c) This iterative process removes many RNA probes for each DNA molecule, thus amplifying the SPR signal. estimated 104 RNA probe molecules for each DNA molecule, that accounts for the sensitivity enhancement. (J. Am. Chem. Soc. 2004, 126, 4086–4087)
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