Biomedical Engineering Reference
In-Depth Information
nanotubes (Davoren et al. 2007), fullerenes, silica (Rao et al. 2004), and quantum dots (Ryman-
Rasmussen et al. 2007). The most commonly tested human and murine inflammatory markers are
the chemokine IL-8, followed by tumor necrosis factor-a (TNF-a), and IL-6.
However, ELISA tests are usually time consuming and require multiple operations. Therefore,
the real-time detection of cytokines has been investigated with surface-immobilized immunoassay
detection on optical sensing instruments, such as the surface plasmon resonance (SPR) or wave-
guide-grating sensors (Battaglia et al. 2005; Kemmler et al. 2009; Yang et al. 2005). These tech-
niques are sensitive to changes in the refractive index at the liquid-solid interface and, thus, allow
the adsorption of monitoring biomolecules at the sensor surface with high sensitivity. Combined
with immunoassays, they allow the sensitive detection of cytokines.
5.4.4 p
aper
-B
ased
B
IoseNsor
for
ros-I
Nduced
dNa o
xIdatIve
d
aMage
B
IoMarkers
d
etectIoN
As mentioned in the previous section, one of the most discussed mechanisms behind the health
effects induced by nanomaterials is their ability to enhance ROS generation. An excessive generation
of ROS can oxidize cellular biomolecules (i.e., DNA) (Valko et al. 2006), leading to oxidative modi-
fications in DNA. 8-Hydroxyguanine and its nucleoside, 8-hydroxy-2′-deoxyguanosine (8-OHdG),
are the most studied DNA damage products due to the relative ease of their measurement and pre-
mutagenic potential (Pulido and Parrish 2003; Risom et al. 2005; Valko et al. 2005, 2006). Elevated
8-OHdG levels have been noted in numerous tumors (Risom et al. 2005; Valko et al. 2006) and, are
thus widely used as a biomarker for oxidative stress and carcinogenesis (Valavanidis et al. 2009).
A novel lateral flow immunoassay (LFIA) has been developed (Zhu et al. 2013) to measure
the concentration of 8-OHdG and, thus, reveals the nanotoxicity at the genomic level. LFIA, also
known as the immunochromatographic test strip, has been widely used as an in-field and point-
of-care diagnostic tool for testing cancer biomarkers (Lin et al. 2008; Liu et al. 2009; Oh et al.
2009; Zeng et al. 2009; Kawde et al. 2010; Yang et al. 2011), proteins (Mao et al. 2008), drugs
(Pattarawarapan et al. 2007; Tang et al. 2009; Wang et al. 2011), hormones (Lu et al. 2005), and
metabolites in biomedical (Liu et al. 2008; Mao et al. 2008, 2009; Dungchai et al. 2010), food, and
environmental settings.
The principle of the immunostrip is mainly based on a competitive-type immunoreaction in the
lateral flow strip. In a typical assay, a sample solution containing a desired concentration of 8-OHdG
is applied to the sample application pad. The sample moves along the strip, due to capillary force,
and is finally captured by specific antibodies through immunoreactions. The accumulation of gold
nanoparticles on the test zone induces a characteristic red band that is visible to the naked eye. This
color change indicates the colorimetric detection of 8-OHdG in a sample and the color intensity is
inversely proportional to the concentration. The LFIA strip provides a simple approach for a rapid
nanotoxicity assessment.
5.5 CONCLUSION
With the increasing number of nanomaterial applications, assessing their toxicity should be the
first important step toward creating safety guidelines for their handling and disposal. Studies of
the biological effects of nanoscale materials that might answer these questions have lagged behind
other aspects of nanotechnology development. In this chapter, we have discussed various biosensing
methods for monitoring nanotoxicity, including techniques for single-cell nanotoxicity testing, such
as carbon fiber microelectrodes and atomic force microscopy, chip-based sensors for nanotoxicity,
and biosensors for nanotoxicity biomarker detections, such as biosensing approaches for inflam-
matory biomarker detections and paper-based biosensors for ROS-induced DNA oxidative damage
biomarker detections.
