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Using a new type of paramagnetic nanoparticle and a nuclear magnetic resonance (NMR) system built into a microfluidic device, a team of investigators at the Massachusetts General Hospital and Harvard Medical School has created an assay system capable of detecting as few as two cancer cells in 1 microliter of biological fluid. In addition, the new assay requires little sample processing and produces results in less than 15 minutes.
Reporting its work in the Proceedings of the National Academy of Sciences of the United States of America, a research team led by Ralph Weissleder, M.D., Ph.D., co-principal investigator of the MIT-Harvard Center of Cancer Nanotechnology Excellence, describes the methods it developed to create a small but highly magnetic nanoparticle. The new nanoparticle is built around an iron-manganese core and is coated with a small, biocompatible organic molecule to render it soluble in water. This coating also provides attachment points to which the investigators added one of three different monoclonal antibodies, each of which recognizes a specific cancer biomarker.
The investigators also detailed their construction of a microfluidic NMR probe that dramatically improves on the signal-to-noise performance of an earlier probe they had developed. By improving the signal-to-noise properties of their detector, the investigators were able to reduce the sample volume needed for analysis to 1 microliter and increase mass-detection sensitivity by tenfold.
To test their device, the researchers used fine-needle aspirates from human tumors growing in mice as the biosample. Upon obtaining the biosample, the investigators added antibody-labeled magnetic nanoparticles, let them incubate for 5 minutes, washed the aspirates to remove excess nanoparticles, and then injected them into the microfluidic device. Using one antibody-labeled probe, the results were far from optimal, missing as many as 72% of the cancer cells in the sample. However, adding a second antibody-labeled nanoparticle reduced the false-negative rate to 28%, and adding the third antibody-labeled nanoparticle dropped the false-negative rate to almost zero.
About National Cancer Institute
To help meet the goal of reducing the burden of cancer, the National Cancer Institute (NCI), part of the National Institutes of Health, is engaged in efforts to harness the power of nanotechnology to radically change the way we diagnose, treat and prevent cancer.
The NCI Alliance for Nanotechnology in Cancer is a comprehensive, systematized initiative encompassing the public and private sectors, designed to accelerate the application of the best capabilities of nanotechnology to cancer.
Currently, scientists are limited in their ability to turn promising molecular discoveries into benefits for cancer patients. Nanotechnology can provide the technical power and tools that will enable those developing new diagnostics, therapeutics, and preventives to keep pace with today’s explosion in knowledge.
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