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      Label-free biomarker detection from whole blood

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          Abstract

          Label-free nanosensors can detect disease markers to provide point-of-care diagnosis that is low-cost, rapid, specific and sensitive. 1- 13 However, detecting these biomarkers in physiological fluid samples is difficult because of problems like biofouling and nonspecific binding, and the resulting need to use purified buffers greatly reduces the clinical relevance of these sensors. Here, we overcome this limitation by using distinct components within the sensor to perform purification and detection. A microfluidic purification chip captures multiple biomarkers simultaneously from blood samples and releases them, after washing, into purified buffer for sensing by a silicon nanoribbon detector. This two-stage approach isolates the detector from the complex environment of whole blood, and reduces its minimum required sensitivity by effectively pre-concentrating the biomarkers. We show specific and quantitative detection of two model cancer antigens from a 10 uL sample of whole blood in less than 20 minutes. This study marks the first use of label-free nanosensors with physiologic solutions, positioning this technology for rapid translation to clinical settings.

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          Most cited references25

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          Cancer Statistics, 2008

          Each year, the American Cancer Society estimates the number of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute, Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. Incidence and death rates are age-standardized to the 2000 US standard million population. A total of 1,437,180 new cancer cases and 565,650 deaths from cancer are projected to occur in the United States in 2008. Notable trends in cancer incidence and mortality include stabilization of incidence rates for all cancer sites combined in men from 1995 through 2004 and in women from 1999 through 2004 and a continued decrease in the cancer death rate since 1990 in men and since 1991 in women. Overall cancer death rates in 2004 compared with 1990 in men and 1991 in women decreased by 18.4% and 10.5%, respectively, resulting in the avoidance of over a half million deaths from cancer during this time interval. This report also examines cancer incidence, mortality, and survival by site, sex, race/ethnicity, education, geographic area, and calendar year, as well as the proportionate contribution of selected sites to the overall trends. Although much progress has been made in reducing mortality rates, stabilizing incidence rates, and improving survival, cancer still accounts for more deaths than heart disease in persons under age 85 years. Further progress can be accelerated by supporting new discoveries and by applying existing cancer control knowledge across all segments of the population.
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            The case for early detection.

            Early detection represents one of the most promising approaches to reducing the growing cancer burden. It already has a key role in the management of cervical and breast cancer, and is likely to become more important in the control of colorectal, prostate and lung cancer. Early-detection research has recently been revitalized by the advent of novel molecular technologies that can identify cellular changes at the level of the genome or proteome, but how can we harness these new technologies to develop effective and practical screening tests?
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              Label-free immunodetection with CMOS-compatible semiconducting nanowires.

              Semiconducting nanowires have the potential to function as highly sensitive and selective sensors for the label-free detection of low concentrations of pathogenic microorganisms. Successful solution-phase nanowire sensing has been demonstrated for ions, small molecules, proteins, DNA and viruses; however, 'bottom-up' nanowires (or similarly configured carbon nanotubes) used for these demonstrations require hybrid fabrication schemes, which result in severe integration issues that have hindered widespread application. Alternative 'top-down' fabrication methods of nanowire-like devices produce disappointing performance because of process-induced material and device degradation. Here we report an approach that uses complementary metal oxide semiconductor (CMOS) field effect transistor compatible technology and hence demonstrate the specific label-free detection of below 100 femtomolar concentrations of antibodies as well as real-time monitoring of the cellular immune response. This approach eliminates the need for hybrid methods and enables system-scale integration of these sensors with signal processing and information systems. Additionally, the ability to monitor antibody binding and sense the cellular immune response in real time with readily available technology should facilitate widespread diagnostic applications.
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                Author and article information

                Journal
                101283273
                34218
                Nat Nanotechnol
                Nature nanotechnology
                1748-3387
                1748-3395
                3 December 2009
                13 December 2009
                February 2010
                1 August 2010
                : 5
                : 2
                : 138-142
                Affiliations
                [1 ] Yale University, School of Engineering and Applied Science, Department of, Biomedical, New Haven, CT 06511
                [2 ] Yale University, School of Engineering and Applied Science, Department of, Electrical, New Haven, CT 06511
                [3 ]Cornell Nanofabrication Facility, Cornell University, Ithaca, NY 14853
                [4 ]Harvard University, School of Engineering and Applied Science, Department of Bioengineering, Cambridge, MA 02138
                [5 ] Yale University, School of Engineering and Applied Science, Department of, Applied Physics, New Haven, CT 06511
                [6 ] Yale University, School of Engineering and Applied Science, Department of, Chemical Engineering, New Haven, CT 06511
                Author notes

                Reprints and permission information is available online at http://npg.nature.com/reprintsandpermissions/. Correspondence and requests for materials should be addressed to M.A.R. and T.M.F.

                Article
                nihpa155229
                10.1038/nnano.2009.353
                2818341
                20010825
                a209fd95-d77c-41a0-97c8-e70b0454893d

                Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

                History
                Funding
                Funded by: National Institute of Biomedical Imaging and Bioengineering : NIBIB
                Award ID: R01 EB008260-03 ||EB
                Categories
                Article

                Nanotechnology
                Nanotechnology

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