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.
This work, which is detailed in the paper “Rapid detection and profiling of cancer cells in fine-needle aspirates,” was supported by the NCI Alliance for Nanotechnology in Cancer, a comprehensive initiative designed to accelerate the application of nanotechnology to the prevention, diagnosis, and treatment of cancer. An abstract is available at the journal’s Web site.