Biomedical Engineering Reference
In-Depth Information
The detection of nucleic acids (DNA, RNA) by hybridization
to a known complementary sequence (usually in the form of im-
mobilized arrays) is pivotal for clinical diagnostic applications,
such as pathogen and cancer detection, and genomic screening and
profiling. Nucleic acid fragments are biomarkers for diseases, but
since often only a few copies of a particular DNA or RNA frag-
ment are present, the ability to scale hybridization arrays down to a
detection level of a few duplex molecules is highly desirable.
Many efforts have been reported to achieve this sensitivity via
nano-electrochemistry, applied in large-scale arrays of nanostruc-
tured microelectrodes.
186, 187
Zhang and co-workers reported the
detection of 3000 DNA molecules, using a secondary probe strand
labeled with peroxidase, followed by electrochemical detection of
the catalytically produced hydrogen peroxide with an Os-
containing redox hydrogel on a microelectrode.
188
Munge et al.
described the electrochemical detection of as few as 80 DNA cop-
ies (3 per μL), which is the highest electrochemical sensitivity to
date.
189
This was achieved via layer-by-layer electrostatic self-
assembly of alkaline phosphatase enzyme molecules and polyion
layers on a carbon nanotube template. The enzyme catalyzed the
conversion of alpha-naphtyl phosphate to redox-active product
alpha-naphtaphenol. By using a hybridization-controlled sandwich
assay in combination with magnetic nanoparticles to collect the
analyte, a large number of enzyme molecules per analyte strand
were obtained.
1. Sensor Fabrication
One of the limitations of nanoelectrodes is the difficulty of fabrica-
tion. Within the framework of sensor technology, the added re-
quirements of robustness and reproducibility are imposed. As a
result, some very interesting ways to make them have emerged.
(
i
)
Nano Interdigitated Electrode Arrays (nIDEA)
Interdigitated electrodes have many applications within elec-
trical sensing. Typical applications are capacitive sensing, surface
acoustic wave resonators, and with some modification, accelerom-
eters. Jaffrezic-Renault and Dzyadevych provide an excellent re-
view of conductometric sensors for environmental monitoring.
85
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