Magnetic nanotags allow sensitive detection of cancer biomarkers

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The detection of cancer-associated proteins, or biomarkers, in blood samples is a potentially powerful tool for early diagnosis of cancer and monitoring of cancer treatment.

A team led by researchers at Stanford University and the University of California, Santa Cruz, has developed a compact prototype detector that uses magnetic nanotechnology to spot cancer-associated proteins in a human blood serum sample, with much higher sensitivity than current detectors.

In addition to its high sensitivity, the new detector can monitor multiple biomarkers simultaneously. “This ‘multiplex’ capability is important because the use of multiple biomarkers is likely to provide greater accuracy and reliability than single biomarkers for cancer diagnosis and other potential applications,” said Nader Pourmand, Ph.D., one of three principal investigators (PIs) who directed this work. The researchers describe their results in a paper published by Proceedings of the National Academy of Sciences of the United States of America.

“With current detectors, you can detect only one protein at a time,” Dr. Pourmand said. “Instead of the standard fluorescent tags, we used nanosize magnetic beads as tags and were able to detect target molecules with tens to hundreds of times greater sensitivity than standard techniques.”

“This is essentially a proof-of-concept study showing that now we have a chip and a reader that can find multiple biomarkers in a sample at a concentration much lower than the standard that is commercially available,” added Shan Wang, Ph.D., Stanford University, a member of the Center for Cancer Nanotechnology Excellence Focused on Tumor Response, one of eight CCNEs funded by NCI’s Alliance for Nanotechnology in Cancer initiative. Ronald W. Davis, Ph.D., Stanford, was the third investigator in line heading this study.

To tag the cancer proteins with magnetic nanoparticles, the detector subjects blood serum samples to an incubation process that takes place in roughly half an hour. At the heart of the detector is a silicon chip containing 64 embedded sensors whose electrical resistance changes in the presence of a nearby magnetic field. Attached to these sensors are capture antibodies that have the unique ability to latch on to specific cancer-related proteins as they float over the sensors.

During an incubation process in which a test sample is applied to the chip, the antibodies first capture their specific cancer proteins from the sample. Next, a second wave of antibodies attaches to the specific cancer proteins on one end and magnetic nanoparticles on the other end, tethering the captured cancer biomarkers to magnetic “nanotags.” The tags emit a magnetic field that causes a change in the resistance of the underlying sensor, giving the detector a clear signal.

In their paper, the researchers describe detection of very low concentrations of various cancer biomarkers, such as tumor necrosis factor alpha and cancer embryonic antigen. In a multiplex assay involving seven potential cancer biomarkers, concentrations ranging from 5 quadrillionths to 0.1 trillionths of a mole (a standard unit of measurement for molecules) were unambiguously detected simultaneously.

The researchers also estimated that they could detect levels of the protein hCG about 400 times lower than the concentration detectable by current commercial kits known by the acronym ELISA, in which captured proteins are conjugated to color-altering or fluorescent labels.

To properly prepare a patient’s blood sample for use with the detector, a technician must use a centrifuge to separate out the serum, which contains the biomarkers. For this reason, the device would need to be located in a hospital or a private diagnostic lab, Dr. Wang said. Even before that, the device faces clinical utility testing and then must undergo clinical trials to win regulatory approval. To see the device through those steps, Drs. Pourmand and Wang have cofounded the startup company MagArray at the Panorama Institute for Molecular Medicine, a nonprofit incubator in Sunnyvale, California.

Dr. Wang said he is optimistic that the technology could someday save lives by detecting cancer early or by helping doctors select more effective therapy. “The earlier you can detect a cancer, the better chance you have to kill it,” Dr. Wang stated. “This could be especially helpful for lung cancer, ovarian cancer, and pancreatic cancer, because those cancers are hidden in the body.”

This study, which was detailed in the paper “Multiplex protein assays based on real-time magnetic nanotag sensing,” 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 investigator from Brown University also participated in this study. An abstract of this paper is available at the journal’s Web site. View abstract


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