Parallel and Complementary Detection of Proteins by p-type and n-type Silicon Nanowire Transistor Arrays
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Parallel and Complementary Detection of Proteins by p-type and n-type Silicon Nanowire Transistor Arrays Gengfeng Zheng1*, Fernando Patolsky1*, Charles M. Lieber1,2 1 Department of Chemistry and Chemical Biology, 2Division of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138 * These authors contributed equally to this work.
ABSTRACT Label-free, real-time, parallel and complementary electrical detection of proteins is demonstrated by p-type and n-type silicon nanowire field-effect transistors in the same arrays. Composed of hundreds of individually electrically addressable nanowire devices with highly sensitive and reproducible performances, these nanowire arrays can be controllably modified by monoclonal antibodies, and show discrete conductance changes characteristic of highly selective binding and unbinding of target proteins, such as prostate specific antigens (PSA), thus providing a general and powerful platform for high-throughput real-time parallel detection and rapid screening of libraries of biomolecules. Studies show that the PSA proteins can be routinely detected at femtomolar concentrations with high selectivity, and simultaneously incorporation of both p-type and n-type silicon nanowire devices enable discrimination against false positive/negative signals. The integrated complementary nanowire sensor arrays open up substantial opportunities for diagnosis and treatment of complex diseases such as cancer, detection of biological threats, and fundamental proteomic and biophysical studies.
INTRODUCTION Detecting proteins with high selectivity and sensitivity has become an important research subject in both fundamental biology and applied biotechnology. This is especially obvious in the post-genomics era, a time when cataloguing all proteins encoded by the human genome and mapping out their exact interaction networks (a field collectively known as proteomics) have developed into a prominent emphasis in modern high-throughput molecular biology (1,2). One promising approach for the direct electrical detection of proteins uses semiconducting silicon nanowires (SiNWs) or carbon nanotubes configured as field-effect transistors (FETs), which change conductance upon binding of charged macromolecules to receptors linked to the device surfaces (3-6). Here we present the label-free, real time multiplexed detection of protein cancer markers with high selectivity and outstanding sensitivity, using antibody-functionalized nanowire sensors. In this sensor approach, SiNW FETs can be configured into nanosensors by modifying the NW surface with molecular receptors, such as monoclonal antibodies. The binding of charged proteins leads to a SiNW surface potential change and causes depletion or accumulation of carriers in the SiNWs depending on the biomolecule charge as well as the types of SiNWs used. For a p-type (or boron-doped) SiNW, the conductance should decrease/increase when the surface charge of the protein is positive/negative, and vice versa for the n-type (or phosphorus-doped)
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