Multiplexed Electrical Detection of Single Viruses
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Multiplexed Electrical Detection of Single Viruses 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 We report direct, real-time electrical detection of single virus particles with high selectivity using nanowire field effect transistors. Measurements made with nanowire arrays modified with antibodies for influenza A showed discrete conductance changes characteristic of binding and unbinding in the presence of influenza A but not paramyxovirus or adenovirus. Moreover, simultaneous electrical and optical measurements using fluorescently-labelled influenza A demonstrate conclusively that the conductance changes correspond to binding/unbinding of single viruses at the surface of nanowire devices. In addition, studies of nanowire devices modified with antibodies specific for either influenza or adenovirus show that multiple viruses can be selectively detected in parallel. The possibility of large scale integration of these nanowire devices suggests potential for simultaneous detection of a large number of distinct viral threats at the single virus level. INTRODUCTION One promising approach for the direct electrical detection of viruses [1,2] uses semiconducting nanowires 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]. We have investigated direct, real-time electrical detection of single virus particles using arrays of individually addressable silicon nanowire FETs, which exhibit reproducible high performance properties [7,8]. Nanowire elements within the arrays were functionalized with the same or different virus-specific antibodies as receptors for selective binding, and solutions were delivered to the array using microfluidics. The detection experiments were carried out by monitoring simultaneously the conductance of distinct nanowire elements within the array: when a virus particle binds to the antibody receptor on a nanowire device, the conductance of that device should change from the baseline value, and when the virus unbinds, the conductance should return to the baseline value. For a p-type nanowire the conductance should decrease (increase) when the surface charge of the virus is positive (negative) [3]; the conductance of a second nanowire device at which binding does not occur during this same time period should show no change and can serve as an internal control. Modification of different nanowires within the array with receptors specific for different viruses provides a means for simultaneous detection of multiple viruses.
EXPERIMENTAL DETAILS
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Silicon nanowires were synthesized by chemical vapour deposition using 20 nm gold nanoclusters as catalysts, silane as reactant and diborane as p-type dopant with a B:Si ratio of 1:4000. Arrays of silicon nanowire devi
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