Concept of Bioelectronic Nose - Bioelectronic Nose: Integration of Biotechnology and Nanotechnology - page 6

changes. By the conformational change of the OR, the net charge of the OR protein
subsequently changes [ 45 , 73 ]. The change in charge acts as a gate potential to FET
devices, and the odorants are detected.
Receptor-based bioelectronic noses have many advantages as a practical sen-
sor, although additional studies on protein quality control are still required due to
the complex structure of ORs. Most of all, they have excellent selectivity of ORs,
because the whole protein is used. Therefore, the sensor can precisely discriminate
its ligand from other analogous compounds [ 45 ]. In addition, the mass production
of ORs is possible, and storage is relatively easy [ 61 ]. Furthermore, OR proteins
expressed in E. coli were reported to still be active in dry conditions, which allowed
for a biosensor that detects gaseous odorants to be developed [ 46 ].

1.2.1.2 Cell-Based Bioelectronic Nose

Bioelectronic noses based on cells which express ORs on their surface are classified
as cell-based bioelectronic noses. The cells can generate cellular signals. The bind-
ing event between ORs and odorants triggers the olfactory signaling cascade, and
positive ions flow into the cells from the outside [ 52 , 74 ]. The electrical potential
of the cells consequently changes. The potential change can be measured by vari-
ous sensing methods, such as fluorescent dyes, SPRs, and planar microelectrodes
[ 74 - 78 ].
One of the most important characteristics of cell-based bioelectronic noses is
that the cells containing ORs produce the olfactory signals, which may be identi-
cal to the signals generated by OSNs. Because the isolation and in vitro culture of
OSNs are very difficult, the practical use of OSNs is realistically impossible. There-
fore, as an alternative to OSNs, OR-containing cells have been effectively utilized.
The function of each OR has not yet been fully identified, and has to be elucidated
to understand the mystery of the sense of smell. Cell-based bioelectronic noses can
be effectively used for the identification of the unrevealed function of ORs.

1.2.1.3 Nanovesicle-Based Bioelectronic Nose

The concept of using nanovesicles lies between those of cells and protein. Nanoves-
icles can generate cellular signals similar to those produced by cells. They are pro-
duced from the cell surface by treatment with a chemical compound that destabi-
lizes the cellular membrane [ 79 ]. When nanovesicles are isolated from cells, all
membrane proteins and cytosolic components for the signal transduction are still
contained in the nanovesicles. Therefore, the nanovesicle can have cell-like proper-
ties. In addition, nanovesicles have advantages as a protein-like material in terms of
long-time storage and mass production.
The nanovesicle is especially suitable to be combined with nano-materials by
virtue of its small size. Therefore, nanovesicles have been effectively used for
the functionalization of FETs. The nanovesicle-based bioelectronic nose was first