Nanovesicle-based bioelectronic nose platform mimicking human olfactory signal transduction.

We developed a nanovesicle-based bioelectronic nose (NBN) that could recognize a specific odorant and mimic the receptor-mediated signal transmission of human olfactory systems. To build an NBN, we combined a single-walled carbon nanotube-based field effect transistor with cell-derived nanovesicles containing human olfactory receptors and calcium ion signal pathways. Importantly, the NBN took advantages of cell signal pathways for sensing signal amplification, enabling ≈ 100 times better sensitivity than that of previous bioelectronic noses based on only olfactory receptor protein and carbon nanotube transistors. The NBN sensors exhibited a human-like selectivity with single-carbon-atomic resolution and a high sensitivity of 1 fM detection limit. Moreover, this sensor platform could mimic a receptor-meditated cellular signal transmission in live cells. This sensor platform can be utilized for the study of molecular recognition and biological processes occurring at cell membranes and also for various practical applications such as food screening and medical diagnostics.

[1]  Seunghun Hong,et al.  Universal parameters for carbon nanotube network-based sensors: can nanotube sensors be reproducible? , 2011, ACS nano.

[2]  S. Firestein.  How the olfactory system makes sense of scents , 2001, Nature.

[3]  Hyun Seok Song,et al.  Single‐Carbon‐Atomic‐Resolution Detection of Odorant Molecules using a Human Olfactory Receptor‐based Bioelectronic Nose , 2009 .

[4]  Regine Heller,et al.  Drosophila odorant receptors are both ligand-gated and cyclic-nucleotide-activated cation channels , 2008, Nature.

[5]  Gengfeng Zheng,et al.  Detection, Stimulation, and Inhibition of Neuronal Signals with High-Density Nanowire Transistor Arrays , 2006, Science.

[6]  Oh Seok Kwon,et al.  Polypyrrole nanotubes conjugated with human olfactory receptors: high-performance transducers for FET-type bioelectronic noses. , 2009, Angewandte Chemie.

[7]  Hanns Hatt,et al.  A specific heat shock protein enhances the expression of mammalian olfactory receptor proteins. , 2006, Chemical senses.

[8]  Gordon M. Shepherd,et al.  Discrimination of molecular signals by the olfactory receptor neuron , 1994, Neuron.

[9]  Graeme Milligan,et al.  G Protein-Coupled Receptor Dimerization: Function and Ligand Pharmacology , 2004, Molecular Pharmacology.

[10]  Tai Hyun Park,et al.  Cell-based olfactory biosensor using microfabricated planar electrode. , 2009, Biosensors & bioelectronics.

[11]  June-Ki Park,et al.  100 nm scale low-noise sensors based on aligned carbon nanotube networks: overcoming the fundamental limitation of network-based sensors , 2010, Nanotechnology.

[12]  K. Toko,et al.  Quantification of suppression of bitterness using an electronic tongue. , 2001, Journal of pharmaceutical sciences.

[13]  K. Mikoshiba,et al.  Functional expression of a mammalian odorant receptor. , 1998, Science.

[14]  Horst Vogel,et al.  Investigating cellular signaling reactions in single attoliter vesicles. , 2005, Journal of the American Chemical Society.

[15]  Tai Hyun Park,et al.  "Bioelectronic super-taster" device based on taste receptor-carbon nanotube hybrid structures. , 2011, Lab on a chip.

[16]  M. Bouvier,et al.  Roles of G‐protein‐coupled receptor dimerization , 2004, EMBO reports.

[17]  H. Breer,et al.  Single odors differentially stimulate dual second messenger pathways in lobster olfactory receptor cells , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[18]  P. Fromherz,et al.  Silicon Chip Interfaced with a Geometrically Defined Net of Snail Neurons , 2005 .

[19]  Seunghun Hong,et al.  Highly Selective Environmental Nanosensors Based on Anomalous Response of Carbon Nanotube Conductance to Mercury Ions , 2009 .

[20]  P. Mombaerts,et al.  Molecular biology of odorant receptors in vertebrates. , 1999, Annual review of neuroscience.

[21]  M. Cusick,et al.  Plasma membrane calcium pumps in mouse olfactory sensory neurons. , 2006, Chemical senses.

[22]  Tai Hyun Park,et al.  Recent advances in the development of bioelectronic nose , 2010 .

[23]  Tai Hyun Park,et al.  Bioelectronic nose with high sensitivity and selectivity using chemically functionalized carbon nanotube combined with human olfactory receptor. , 2012, Journal of biotechnology.

[24]  P. Mombaerts.  Seven-transmembrane proteins as odorant and chemosensory receptors. , 1999, Science.

[25]  A. Pisanelli,et al.  Identification of a specific olfactory receptor for 2-isobutyl-3-methoxypyrazine. , 1982, The Biochemical journal.

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

[27]  Dietmar Krautwurst,et al.  Identification of Ligands for Olfactory Receptors by Functional Expression of a Receptor Library , 1998, Cell.

[28]  C. Lieber,et al.  Nanowire Nanosensors for Highly Sensitive and Selective Detection of Biological and Chemical Species , 2001, Science.

[29]  P. Fromherz,et al.  Signal transmission from individual mammalian nerve cell to field-effect transistor. , 2005, Small.

[30]  M. Lee,et al.  Linker-free directed assembly of high-performance integrated devices based on nanotubes and nanowires , 2006, Nature nanotechnology.