Biomedical Engineering Reference
In-Depth Information
crown ether became readily soluble in water and a variety of organic solvents, including
acetone and methanol. Such derivatives could be exploited for further covalent and ionic
functionalization [112]. Biomaterial modification has been considered as another interest-
ing strategy to prepare SWNT stable aqueous dispersion. Wrapping of CNTs with biopoly-
mers (e.g., helical amylase [113] or DNA [32]) or the self-assembly of biomolecules (e.g.,
lipid derivatives [102]) on CNT side walls can provide control over the interfacial proper-
ties and improve the dispersion and homogeneity of the CNTs in water, thus permitting
the assembly of the CNTs into architectures necessary for biosensor applications.
12.4.1.2 Functionalization of Carbon Nanotubes with Biomaterials
Many techniques exist for CNT biofunctionalization including noncovalent and covalent
modification. CNTs can be functionalized by various biomolecules via spontaneous
adsorption, or be immobilized in a more controllable fashion by pretreatment of CNTs.
12.4.1.2.1 Noncovalent Modification
A variety of proteins such as antibodies [115], enzymes [76], and peptides [85] can non-
specifically bind to the CNTs exterior surface without their covalent coupling.
Oligonucleotides can also be nonspecifically bound to the surface and the opened cavity
of CNTs. In fact, both computational and experimental evidences showed that nonspecific
DNA-CNT interactions in water are from the DNA base stacking on the CNT surface, with
the hydrophilic sugar-phosphate backbone pointing to the exterior [114].
12.4.1.2.2 Covalent Binding
Covalent coupling of biomaterials to CNTs is important to meet the specific requirement
demanded by biosensor applications. Biofunctional reagents have been used to modify
the CNT sidewalls with other biomolecules. For example, amide groups produced by
the reaction of the azomethine group and the sidewall of CNTs [116] have been used for
the covalent coupling of amino acids [117] and biologically active peptides for
immunoassays [118].
The oxidatively introduced carboxyl groups represent useful sites for further modifica-
tions, as they enable the covalent coupling of biomolecules through the creation of amide
and ester bonds [112] (Figure 12.13). The carboxylic groups on both ends and sidewalls of
CNTs can covalently tether various organic dyes, DNA, protein, metallic NPs [108], and
even magnetic NPs [109] via carbodiimide coupling or by using heterobifunctional-cou-
pling groups. “Sugar-coated” CNTs generated by derivatized galactoses have been
reported as candidates of biosensing materials for pathogen detection [119,120]. The func-
tionalization of CNTs was based on the carbodiimide-activated amidation of the galactose-
tethered amino groups with CNT-bound carboxylic acids. The high aspect ratio and large
surface area of the CNTs enable the display of abundant sugar arrays, which effectively
captured pathogenic
E. coli
via specific adhesion-receptor interactions.
Also, amine-terminated oligonucleotides have been covalently bound to electrochemi-
cally generated carboxylic acid functional groups at the sidewalls and at the ends of CNTs
[91] (Figure 12.14). The CNT-DNA adduct could then selectively hybridize with comple-
mentary stands while minimizing nonspecific interactions with noncomplementary
strands. The CNT nanoelectrode arrays functionalized with selective DNA probes on the
open end have been considered for promising ultrasensitive DNA biosensors to analyze
both poly G-tagged DNA targets and label-free PCR amplicons [121,122]. Importantly, the
approach to functionalize sidewalls of CNTs with DNA by growing oligonucleotides using
conventional DNA synthesis has made it possible to photolithographically pattern differ-
ent DNA sequences on the CNTs and to fabricate new types of DNA biosensors [123].
