Nonlinear electrical impedance spectroscopy of viruses using very high electric fields created by nanogap electrodes

Our living sphere is constantly exposed to a wide range of pathogenic viruses, which can be either known, or of novel origin. Currently, there is no methodology for continuously monitoring the environment for viruses in general, much less a methodology that allows the rapid and sensitive identification of a wide variety of viruses responsible for communicable diseases. Traditional approaches, based on PCR and immunodetection systems, only detect known or specifically targeted viruses. We here describe a simple device that can potentially detect any virus between nanogap electrodes using nonlinear impedance spectroscopy. Three test viruses, differing in shape and size, were used to demonstrate the general applicability of this approach: baculovirus, tobacco mosaic virus (TMV), and influenza virus. We show that each of the virus types responded differently in the nanogap to changes in the electric field strength, and the impedance of the virus solutions differed depending both on virus type and virus concentration. These preliminary results show that the three virus types can be distinguished and their approximate concentrations determined. Although further studies are required, the proposed nonlinear impedance spectroscopy method may achieve a sensitivity comparable to that of more traditional, but less versatile, virus detection systems.

[1]  J. Tiffany,et al.  Models of structure of the envelope of influenza virus. , 1970, Proceedings of the National Academy of Sciences of the United States of America.

[2]  Wayne Einfeld,et al.  Rapid microchip-based electrophoretic immunoassays for the detection of swine influenza virus. , 2008, Lab on a chip.

[3]  The dielectrophoresis of cylindrical and spherical particles submerged in shells and in semi-infinite media , 2004 .

[4]  I Turcu,et al.  Dielectrophoresis: a spherical shell model , 1989 .

[5]  A. Herrmann,et al.  Bending and puncturing the influenza lipid envelope. , 2011, Biophysical journal.

[6]  Hanry Yu,et al.  Label‐free virus identification and characterization using electrochemical impedance spectroscopy , 2014, Electrophoresis.

[7]  Rashid Bashir,et al.  Effects of Dielectrophoresis on Growth, Viability and Immuno-reactivity of Listeria monocytogenes , 2008, Journal of biological engineering.

[8]  Kidong Park,et al.  Electrical capture and lysis of vaccinia virus particles using silicon nano-scale probe array , 2007, Biomedical microdevices.

[9]  M. Giese Micro- and Nanotechnology , 2016 .

[10]  Beate Crossley,et al.  Conventional and future diagnostics for avian influenza. , 2009, Comparative immunology, microbiology and infectious diseases.

[11]  H Morgan,et al.  Separation of submicron bioparticles by dielectrophoresis. , 1999, Biophysical journal.

[12]  Ronghui Wang,et al.  Rapid detection of avian influenza H5N1 virus using impedance measurement of immuno-reaction coupled with RBC amplification. , 2012, Biosensors & bioelectronics.

[13]  Xuanhong Cheng,et al.  Micro- and nanotechnology for viral detection , 2008, Analytical and bioanalytical chemistry.

[14]  Hywel Morgan,et al.  Dielectrophoretic manipulation of rod-shaped viral particles , 1997 .

[15]  Hywel Morgan,et al.  Dielectrophoretic manipulation and characterization of herpes simplex virus-1 capsids , 2001, European Biophysics Journal.

[16]  Samuel Yang,et al.  PCR-based diagnostics for infectious diseases: uses, limitations, and future applications in acute-care settings , 2004, The Lancet Infectious Diseases.

[17]  Brian C. Heinze,et al.  Microfluidic immunosensor for rapid and sensitive detection of bovine viral diarrhea virus , 2009 .

[18]  R F Bey,et al.  ELISA Method for Detection of Influenza A Infection in Swine , 1993, Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc.

[19]  Ryuji Hatsuki,et al.  Direct measurement of electric double layer in a nanochannel by electrical impedance spectroscopy , 2013 .

[20]  Yuze Sun,et al.  Sensitive optical biosensors for unlabeled targets: a review. , 2008, Analytica chimica acta.

[21]  Gengfeng Zheng,et al.  Electrical detection of single viruses. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[22]  S. Burley,et al.  Structure of the Baculovirus nucleocapsid. , 1982, Virology.

[23]  Gwo-Bin Lee,et al.  An integrated microfluidic system for rapid diagnosis of dengue virus infection , 2009, Biosensors and Bioelectronics.

[24]  T. F. Smith,et al.  Real-Time PCR in Clinical Microbiology: Applications for Routine Laboratory Testing , 2006, Clinical Microbiology Reviews.

[25]  Ronghui Wang,et al.  Interdigitated array microelectrode based impedance immunosensor for detection of avian influenza virus H5N1. , 2009, Talanta.

[26]  A. Klug The tobacco mosaic virus particle: structure and assembly. , 1999, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[27]  Katja Fink,et al.  Electrochemical impedance spectroscopy characterization of nanoporous alumina dengue virus biosensor. , 2012, Bioelectrochemistry.

[28]  W. Hassen,et al.  Quantitation of influenza A virus in the presence of extraneous protein using electrochemical impedance spectroscopy , 2011 .

[29]  Rashid Bashir,et al.  Real-time virus trapping and fluorescent imaging in microfluidic devices , 2004 .

[30]  J. Roh,et al.  Analysis of Genes Expression of Spodoptera exigua Larvae upon AcMNPV Infection , 2012, PloS one.

[31]  Steve Tung,et al.  Evaluation study of a portable impedance biosensor for detection of avian influenza virus. , 2011, Journal of virological methods.

[32]  K. Hodneland,et al.  Real-time RT-PCR detection of betanodavirus in naturally and experimentally infected fish from Spain. , 2011, Journal of fish diseases.

[33]  Y. Feldman,et al.  Dielectric spectroscopy of Tobacco Mosaic Virus. , 2003, Biochimica et biophysica acta.

[34]  Kevin W Eliceiri,et al.  NIH Image to ImageJ: 25 years of image analysis , 2012, Nature Methods.