Nanogap biosensors for electrical and label-free detection of biomolecular interactions

We demonstrate nanogap biosensors for electrical and label-free detection of biomolecular interactions. Parallel fabrication of nanometer distance gaps has been achieved using a silicon anisotropic wet etching technique on a silicon-on-insulator (SOI) wafer with a finely controllable silicon device layer. Since silicon anisotropic wet etching resulted in a trapezoid-shaped structure whose end became narrower during the etching, the nanogap structure was simply fabricated on the device layer of a SOI wafer. The nanogap devices were individually addressable and a gap size of less than 60 nm was obtained. We demonstrate that the nanogap biosensors can electrically detect biomolecular interactions such as biotin/streptavidin and antigen/antibody pairs. The nanogap devices show a current increase when the proteins are bound to the surface. The current increases proportionally depending upon the concentrations of the molecules in the range of 100 fg ml(-1)-100 ng ml(-1) at 1 V bias. It is expected that the nanogap developed here could be a highly sensitive biosensor platform for label-free detection of biomolecular interactions.

[1]  Young-Pil Kim,et al.  Sublithographic vertical gold nanogap for label-free electrical detection of protein-ligand binding , 2007 .

[2]  Jeong-O Lee,et al.  Single-walled carbon nanotube biosensors using aptamers as molecular recognition elements. , 2005, Journal of the American Chemical Society.

[3]  BARNETT ROSENBERG,et al.  Electrical Conductivity of Proteins , 1962, Nature.

[4]  Paul L. McEuen,et al.  Fabrication of metallic electrodes with nanometer separation by electromigration , 1999 .

[5]  Andreas Manz,et al.  Scaling and the design of miniaturized chemical-analysis systems , 2006, Nature.

[6]  C. Mirkin,et al.  Nanoparticle-Based Bio-Bar Codes for the Ultrasensitive Detection of Proteins , 2003, Science.

[7]  Alexander Star,et al.  Electronic Detection of Specific Protein Binding Using Nanotube FET Devices , 2003 .

[8]  Bong Hyun Chung,et al.  Surface plasmon resonance imaging‐based protein arrays for high‐throughput screening of protein‐protein interaction inhibitors , 2005, Proteomics.

[9]  Bonsang Gu,et al.  A dielectric-modulated field-effect transistor for biosensing. , 2007, Nature nanotechnology.

[10]  Tomoji Kawai,et al.  Electrical conduction through poly(dA)-poly(dT) and poly(dG)-poly(dC) DNA molecules. , 2001, Physical review letters.

[11]  Luke P. Lee,et al.  Theoretical and experimental study towards a nanogap dielectric biosensor. , 2005, Biosensors & bioelectronics.

[12]  Jin Kyeong Kim,et al.  Direct immobilization of protein g variants with various numbers of cysteine residues on a gold surface. , 2007, Analytical chemistry.

[13]  M. Ratner,et al.  Electron Transport in Molecular Wire Junctions , 2003, Science.

[14]  T. Thundat,et al.  Bioassay of prostate-specific antigen (PSA) using microcantilevers , 2001, Nature Biotechnology.

[15]  O. Melnyk,et al.  Combined nanogap nanoparticles nanosensor for electrical detection of biomolecular interactions between polypeptides , 2004 .

[16]  P. Enoksson,et al.  Electrical properties of Si–SiO2–Si nanogaps , 2005, Nanotechnology.

[17]  Marc Tornow,et al.  A silicon-on-insulator vertical nanogap device for electrical transport measurements in aqueous electrolyte solution , 2007 .

[18]  Zhongfan Liu,et al.  Electrochemical approach for fabricating nanogap electrodes with well controllable separation , 2005 .

[19]  Mark A. Reed,et al.  Label-free immunodetection with CMOS-compatible semiconducting nanowires , 2007, Nature.

[20]  D. Armbruster,et al.  Prostate-specific antigen: biochemistry, analytical methods, and clinical application. , 1993, Clinical chemistry.

[21]  C. Cantor,et al.  Molecular cloning and nucleotide sequence of the streptavidin gene. , 1986, Nucleic acids research.

[22]  M. Reed,et al.  Microfabrication of a Mechanically Controllable Break Junction in Silicon , 1995 .

[23]  E. Tamiya,et al.  Label-free immunosensor for prostate-specific antigen based on single-walled carbon nanotube array-modified microelectrodes. , 2007, Biosensors & bioelectronics.

[24]  Ping-Hei Chen,et al.  Ultrasensitive electrical detection of protein using nanogap electrodes and nanoparticle-based DNA amplification. , 2007, Biosensors & bioelectronics.

[25]  Gengfeng Zheng,et al.  Multiplexed electrical detection of cancer markers with nanowire sensor arrays , 2005, Nature Biotechnology.

[26]  Ping-Hei Chen,et al.  Electrical Detection of Protein Using Gold Nanoparticles and Nanogap Electrodes , 2004, Digest of Papers. 2004 International Microprocesses and Nanotechnology Conference, 2004..