A NOVEL NANOCOAXIAL BIOSENSOR FOR DETECTION OF CANCER BIOMARKERS


Year of Award:
2010
Award Type:
R21
Project Number:
CA137681
RFA Number:
RFA-CA-09-008
Technology Track:
Molecular & Cellular Analysis Technologies
PI/Project Leader:
CHILES, THOMAS C.
Other PI or Project Leader:
CAI, DONG ;NAUGHTON, MICHAEL JOSEPH
Institution:
BOSTON COLLEGE
Many cancer therapies are limited and usually ineffective in their success once a tumor has spread beyond the tissue of origin. For many cancer diseases, five- and ten-year survival responses can approach 90% when detected at an early stage, whereas it may drop to 10% or less when detected at a late stage. Tumors release or 'shed' cellular materials and as a consequence many of these so-called 'biomarkers' can be found in the blood and other fluids. Clinical measurement of biomarkers offers the promise of a noninvasive and cost effective screening for early detection of cancer. Measurement of a single cancer biomarker however, is usually not sufficient to achieve the sensitivity required for accurate early-stage cancer screening. Rather, the simultaneous measurement of a panel of biomarkers will be necessary to reach this goal in an overall clinical screening program. Concomitant with the pace of discovery of novel cancer biomarkers, comes a need for low cost, real-time, ultra-sensitive, multiplex biomarker detection. The research described herein will develop and test proof-of- concept of a novel 3-dimensional carbon nanotube-centered 'nanocavity' array (nanocoax) for the quantitative detection of multiple cancer biomarkers. The sensor unit both constitutes a nanoscale capacitor and forms a nanoscale coaxial transmission line built around an aligned internal conductor that, in turn, can be coupled to a biomarker recognition component. In contrast to nanosensors built around 2-dimensional array architecture, the nanocoax design will enable unprecedented sensitivity, selection, combined with proofreading capability for the simultaneous detection of several distinct biomarkers, due to the platform design, which allows 8 2 for a high site density of discrete sensors/chip (10 /cm ). Moreover, the nanocoax biosensor will incorporate a non-optical design based on dielectric impedance spectroscopy detection, enabling label-free measurement and eliminating the need for any sophisticated optical instrumentation. The proposed study will incorporate as a 'model' biomarker, the ovarian cancer biomarker CA125, together with a panel of putative ovarian cancer biomarkers that have recently shown promise for early stage ovarian cancer detection. The specific aims are three- fold: 1) to optimize fabrication and evaluate performance of a single nanocavity; 2), demonstrate proof-of-concept for detection of ovarian cancer biomarker CA125; and 3) demonstrate proof-of- concept for detection of multiple ovarian cancer biomarkers.