Biomedical Engineering Reference
In-Depth Information
Ajayan, 1992; Harmada et al., 1992
). These SWNTs have been used as nanoscale probes and
sensors in electronic (
Niu et al., 1997; Baughman et al., 1999; An et al., 2001
), and in
biological devices (
Mattson et al., 2000, Williams et al., 2002
).
Drouvalakis et al. (2008)
point out other applications of SWNTs, including membrane channels (
Hummer et al.,
2001; Park et al., 2003; Zhu and Schulten, 2003
), molecular tweezers (
Kim and Lieber,
1999
), probes for imaging biomolecules (
Wong et al., 1998; Woolley et al., 2000
), and for
biosensors (
Ng et al., 2001; Chen et al., 2003; Sotiropoulos et al., 2003
).
The authors report that immobilization of proteins on nanotubes is simple. No specific chem-
ical linkages which may alter the peptide conformation and subsequent functionality are
required, as in nanowires (
Zheng et al., 2005
) and self-assembled monolayers (Chou et al.,
2002;
Shen et al., 2005
). Thus, protein bioactivity may be retained (
Fu et al., 2002; Chen
et al., 2003
). They further report that their biosensors using antigen-coated nanotubes may
be used to detect specific autoantibodies in serum. This, they point out, is a critical advan-
tage, especially the detection of specific auto-antibodies in the serum of patients afflicted
with the autoimmune disease, RA.
Arnett et al. (1998)
report that the diagnosis is based on
the detection of biomarkers (Rheumatoid factor, RF) and other clinical features. Studies
(
Schellekens et al., 1998; Girbal-Niehauser et al., 1999; Nakamura, 2000
), show the rele-
vance of citrullinated peptides (citrulline-containing peptides) in RA.
The measurement of these citrullinated peptides,
Drouvalakis et al. (2008)
point out, is per-
formed by Western Blotting and ELISA, using various synthetic cyclic citrullinated peptides
(CCPs) or modified proteins as antigens (Jaroszewski et al., 1996;
Schellekens et al., 1998;
Nogueira et al., 2001
).
Drouvalakis et al. (2008)
also report that their QCM-based
nanosensor, using the peptide-coated nanotube technique, assays human serum, and exhibits
better performance than that exhibited by the gold-standard technique, ELISA, or currently
available microarray technology (
Hueber et al., 2005
).
Drouvalakis et al. (2008)
selected a cohort of RA patients for testing serum (32 samples)
which had been recently diagnosed with RA (less than a year), in accordance with the
ACR criteria. They also used two control groups for comparison:
(a) A normal control group consisting 13 serum samples from a normal group
(b) 11 serum samples from patients who had osteoarthritis (nonautoimmune arthritis)
The authors formed a carbon nanotube film on a QCM sensing device by depositing a total of
100
m
lof50
m
g/ml SWNT suspension in chloroform drop-wise. This was followed by baking
for an hour at 50
C. The next step involved the immobilization of the antigen on top of the
film, using a layer of carboxy-terminated Tween 20 (Tween-COOH) which contained poly-
ethylene glycol (PEG) units and carboxylic acid groups. The PEG minimized NSB and the
carboxylic acid groups provided the subsequent attachment. PEG also served as a spacer;
it separated the antigen from the denaturing effect of the hydrophobic nanotube surface.
