Interfacing Biomolecules, Cells and Tissues with Nanowire-based Electrical Devices - Applications of Electrochemistry and Nanotechnology in Biology and Medicine - page 73

from the aqueous environment so that only processes occurring at
the SiNW surface contribute to the electrical signals; and a mated
microfluidic channel (formed between a poly-dimethylsiloxane
(PDMS) mold and the sensor chip) for delivery of solution suspen-
sions onto specific locations on the SiNW-FET surface, Fig. 2A .
The detection capability of nanowire devices was first demon-
strated in 2001 for pH monitoring, as well as selective detection of
strepavidin and calcium ions. 10a Notably, biotin-modified NWs
were able to detect strepavidin down to the picomolar concentra-
tion range. The potential of Si-NW FET devices as a tool for drug
discovery was illustrated in 2005 for the identification of molecu-
lar inhibitors of tyrosine kinases whose constitutive activity is re-
sponsible for chronic myelogenous leukemia. 20
For diagnostic purposes of DNA, NW-based devices were
demonstrated for detection of the activity and inhibition of te-
lomerase, a ribonucleoprotein that is active in 80% of known
human cancers, from unamplified extracts from as few as ten tu-
mor cells, in solutions with relatively high (mM) ionic strength. 15b
In addition, the detection of genetic single mutation associated
with cystic fibrosis was carried out at concentrations down to the
10-fM level, 21 which is 2-5 orders of magnitude better than that
demonstrated for real-time measurements including SPR, 22 nano-
particles enhanced SPR 22 and quartz crystal microbalance 23 for
DNA detection.
In 2004, the limit of biological detection, single particle sensi-
tivity, was achieved by detecting, in real time, the reversible and
selective binding of virus particles to antibody modified NWFETs.
Delivery of a highly diluted virus solution on the order of ~80 aM
or 50 viruses/ml yielded clear conductance changes that were sup-
ported by simultaneous optical imaging of fluorescently labeled
influenza viruses indicating on the binding and unbinding of a sin-
gle virus, 15a Fig. 2B .
Ultimately, the multiplexed real time detection with ultrahigh
sensitivity and exquisite selectivity was demonstrated in 2005 for
the detection of cancer biomarkers, at concentrations down to ~2
fM, 15b Fig. 3A . These results represent a sensitivity limit 10 4 -10 9
times below that afforded by ion sensitive planar FETs. 24 Also, the
detection can be carried out on as little as drop of blood instead of
the milliliters needed for current analyses. The multiplexed detec-
tion of protein biomarkers is especially important in the diagnosis