Nanowires Identify Molecular Tumor Markers

Scientists have discovered that molecular markers signifying the presence of cancer in the body are easily identified in blood scanned by special arrays of silicon nanowires--even when these tumor markers comprise only one hundred-billionth of the protein present in a drop of blood.

In addition to this incredible accuracy and sensitivity, the tiny devices also have the potential to pinpoint the precise type of cancer present with a speed not currently available to clinicians. The study, performed by researchers at Harvard University (Boston, MA, USA), was published in the October 2005 issue of the journal Nature Biotechnology and is also available on the journal's web site.

"This is one of the first applications of nanotechnology to healthcare and offers a clinical technique that is significantly better than what exists today,” stated author Dr. Charles M. Lieber, professor of chemistry in Harvard's Faculty of Arts and Sciences. "A nanowire array can test a mere pinprick of blood in just minutes, providing a nearly instantaneous scan for many different cancer markers. It's a device that could open up substantial new possibilities in the diagnosis of cancer and other complex diseases.”

Dr. Lieber and coworkers designed slender nanowires to conduct a small current with antibody receptors for specific cancer markers--such as prostate specific antigen (PSA), PSA-a1-antichymotrypsin, carcinoembryonic antigen (CEA), and mucin-1. When these revealing proteins come into contact with a receptor, they initiate a brief change in conductance that provides a clear indication of the marker's presence. The detectors differentiate among various tumor markers both through the specific receptors used to catch them and because each binds its receptor for a characteristic length of time before dislodging.

"Our results show that these devices are able to distinguish among molecules with near-perfect selectivity,” stated Dr. Lieber, adding that the risk of false readings is minimized by the integration of various control nanowires.
The scientists also included some nanowires in the arrays with nucleic acid receptors for telomerase, an enzyme inactive in most of the body's somatic cells but active in at least 80% of known human cancers. In testing of extracts from as few as 10 tumor cells, these receptors provided real-time tracking of telomerase binding and activity.

According to Dr. Lieber, nanowire arrays could easily be adapted to identify many different tumor markers--more of which are being discovered all the time because of the current growth in proteomics. Widespread use of these tumor markers in healthcare will eventually depend upon the development of methods that allow fast detection of many markers with high selectivity and sensitivity.

"Genomics and proteomics research has elucidated many new biomarkers that have the potential to greatly improve disease diagnosis,” the scientists reported in their article. "The availability of multiple biomarkers is believed to be especially important in the diagnosis of complex diseases like cancer, for which disease heterogeneity makes tests of single markers inadequate. Patterns of multiple cancer markers might, however, provide the information necessary for robust diagnosis of disease … [and] detection of markers associated with different stages of disease pathogenesis could further facilitate early detection.”

Whereas early rounds of cancer testing now only detect whether or not cancer is present, nanowire arrays have the potential to immediately provide details on precisely what kind of cancer is present. Nanowires could also monitor patients' health as the treatment progresses. Because the arrays detect molecules suspended in fluids, drops of blood could be tested directly, in a physician's office, without the need for biochemical manipulation.