Biomedical Engineering Reference
In-Depth Information
Au [174-176]. Subsequent thermal annealing leads to stronger coupling of the metal with
CNTs, and the reduction of the contact resistance. Self-assembly based on molecular
recognition also provides a promising approach for constructing CNTFET systems at
room temperature. In fact, DNA has been used as a scaffold template to pattern SWNT
at a desired address via homologous genetic recombination (such as biotin/avidin, anti-
gen/antibody, and DNA hybridization) [177].
Nonspecific adsorption of proteins including cytochrome C, glucosidase, staphylo-
coccal protein A, human IgG, and streptavidin onto a semiconducting CNT transistor
device has been analyzed by monitoring the conductance change in the nanotubes
[68,69,178]. The proposed mechanism is that the decrease in conductance is due to a
reduction in the charge carriers of
p
-type SWNTs by the noncovalently binding of pro-
tein. For example, the sensitivity for the detection of cytochrome C is around 20 protein
molecules per nanotube, which is in good agreement with a quartz crystal microbalance
(QCM) measurement [179].
Since the nonspecific adsorption of biomolecules on the CNTFET surface is not always
desirable, such binding should be avoided to improve the selectivity and specificity of the
biosensing system. Polymer coating layers including PEI, PEG, polyethyleneoxide, and
Tween on CNTs have been used to capture biomolecules with a high degree of control
and specificity, whereas low-affinity species will be rejected [78,88]. The amino groups in
irreversibly tethered polymer molecules on CNTs permit coupling of biotin or antigen
probes, which still retain their antigenicity for binding their respective streptavidin or
antibody with high specificity. For example, the binding of 10E3 mAbs antibody, a pro-
totype target of the autoimmune response in patients with systemic lupus erythematosus
and mixed connective tissue disease, to a recombinant human autoantigen U1A protein
(a 33-kDa protein, extracted from insect cells) has been monitored in real time electroni-
cally using a CNTFETs-based sensing system [68] (Figure 12.22). For this proposal, U1A
protein was immobilized on Tween-coated CNTs to capture the respective 10E3 mAbs
antibody. The detection limit is lower than 1 nM, which favorably compare with the
detection limit (2.3 nM) based on fluorescence array analysis.
12.5.1.3 Carbon Nanotube-Based Scanning Probe Microscopy Probe Tips for Imaging
Biological Compounds and Biological Sensitive Measurements
Using CNT as atomic force microscopy (AFM) tips has great potential for structural biol-
ogy, such as characterization of larger and more complex biomolecular systems. Since
AFM tips modified by CNTs were first described, carbon nanotube-based tips have shown
great advantages over conventional silicon microfabricated probes, including increased
lateral resolution and damage resistance resulting from reversible elastic buckling to deli-
cate organic and biological samples [181-183]. In addition to measuring topography, the
probe tips can be used to probe the functionality of surface chemical groups and biologi-
cal molecules by using selective chemical-functionalized CNTs [184-188]. The first CNT
AFM tips were fabricated by mechanically attaching CNTs to a commercial cantilever tip
by acrylic adhesive or amorphous carbon under viewing with an optical microscope or a
scanning electron microscope [180]. The manual assembly method to make CNT tips is
conceptually straightforward but has several important limitations, such as low repro-
ducibility. Recently, a “bottom-up” approach in terms of directly growing nanotubes onto
AFM has been reported. In this CVD-based growth approach, well-defined individual
CNT tips can be fabricated by controlling reproducibly the catalyst density used for
growth on the surface (Figure 12.23) [189].
Using nanotube tips, new biological structures have been investigated in the areas of
amyloid-beta protein aggregation and chromatin structure [190]. The reproducibly high
