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.

Public Health Relevance

The early detection of cancer, while the disease is in a pre- malignant stage, provides the best opportunity for effective treatment and cure. This research proposal seeks to specifically build and test a highly sensitive nanoscale biosensor platform for the detection of so-called cancer biomarkers, which are indicators of cancer cells and are present in blood and fluids. The technology developed herein will provide a commercial, low cost, miniaturized sensor with unprecedented sensitivity and combined with simultaneous detection of multiple cancer biomarkers, which in turn, will increase the accuracy of cancer disease diagnosis and enable more effective treatment.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZCA1-SRLB-R (O1))
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Sorbara, Lynn R
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Boston College
Schools of Arts and Sciences
Chestnut Hill
United States
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Rizal, Binod; Merlo, Juan M; Burns, Michael J et al. (2015) Nanocoaxes for optical and electronic devices. Analyst 140:39-58
Archibald, Michelle M; Rizal, Binod; Connolly, Timothy et al. (2015) A nanocoaxial-based electrochemical sensor for the detection of cholera toxin. Biosens Bioelectron 74:406-10
Rizal, Binod; Archibald, Michelle M; Connolly, Timothy et al. (2013) Nanocoax-based electrochemical sensor. Anal Chem 85:10040-4
Zhao, Huaizhou; Rizal, Binod; McMahon, Gregory et al. (2012) Ultrasensitive chemical detection using a nanocoax sensor. ACS Nano 6:3171-8
Cai, Dong; Ren, Lu; Zhao, Huaizhou et al. (2010) A molecular-imprint nanosensor for ultrasensitive detection of proteins. Nat Nanotechnol 5:597-601