CAMBRIDGE, Mass., Sept. 23, 2005 -- Harvard University researchers havefound that molecular markers indicating the presence of cancer in thebody are readily detected in blood scanned by special arrays of siliconnanowires -- even when these cancer markers constitute only onehundred-billionth of the protein present in a drop of blood. Inaddition to this exceptional accuracy and sensitivity, the minusculedevices also promise to pinpoint the exact type of cancer present witha speed not currently available to clinicians.
A paper describing the work will appear in October in the journalNature Biotechnology and is now posted on the journal's web site.
"This is one of the first applications of nanotechnology tohealthcare and offers a clinical technique that is significantly betterthan what exists today," says author Charles M. Lieber, Mark Hyman Jr.Professor of Chemistry in Harvard's Faculty of Arts and Sciences. "Ananowire array can test a mere pinprick of blood in just minutes,providing a nearly instantaneous scan for many different cancermarkers. It's a device that could open up substantial new possibilitiesin the diagnosis of cancer and other complex diseases."
Lieber and his colleagues linked slender nanowires conducting asmall current with antibody receptors for certain cancer markers --such as prostate specific antigen (PSA), PSA-a1-antichymotrypsin,carcinoembryonic antigen and mucin-1. When these telltale proteins comeinto contact with a receptor, it sparks a momentary change inconductance that gives a clear indication of the marker's presence. Thedetectors differentiate among various cancer markers both through thespecific receptors used to snag them and because each binds itsreceptor for a characteristic length of time before dislodging.
"Our results show that these devices are able to distinguish amongmolecules with near-perfect selectivity," Lieber says, adding that therisk of false readings is minimized by the incorporation of variouscontrol nanowires.
The scientists also fitted some nanowires in the arrays withnucleic acid receptors for telomerase, an enzyme inactive in most ofthe body's somatic cells but active in at least 80 percent of knownhuman cancers. In testing of extracts from as few as 10 tumor cells,these receptors allowed real-time monitoring of telomerase binding andactivity.
Lieber says nanowire arrays could easily be scaled up to detectmany different cancer markers -- more of which are being found all thetime, thanks to the current boom in proteomics. Widespread use of thesecancer markers in healthcare will ultimately depend upon thedevelopment of techniques that allow rapid detection of many markerswith high selectivity and sensitivity.
"Genomics and proteomics research has elucidated many newbiomarkers that have the potential to greatly improve diseasediagnosis," the scientists write. "The availability of multiplebiomarkers is believed to be especially important in the diagnosis ofcomplex diseases like cancer, for which disease heterogeneity makestests of single markers inadequate. Patterns of multiple cancer markersmight, however, provide the information necessary for robust diagnosisof disease ... [and] detection of markers associated with differentstages of disease pathogenesis could further facilitate earlydetection."
While initial rounds of cancer testing today identify onlywhether or not cancer is present, nanowire arrays have the potential toimmediately fill in details on exactly what type of cancer is present.Nanowires could also track patients' health as treatment progresses.Because the arrays detect molecules suspended in fluids, drops of bloodcould be tested directly, in a physician's office, without any need forbiochemical manipulation.
Lieber's co-authors are Gengfeng Zheng, Fernando Patolsky, YiCui and Wayne U. Wang, all of Harvard's Department of Chemistry andChemical Biology, Biophysics Program and Division of Engineering andApplied Sciences. The work was supported by the Defense AdvancedResearch Projects Agency and the National Cancer Institute.
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