Biomedical Engineering Reference
In-Depth Information
Fig. 7.8 Voltage traces of the 11 single-nucleotide fragments and the signal of the whole C 3 AC 7
DNA sequence. The contribution from individual nucleotides can be seen in the total trace, and,
thus one can count the number of nucleotides in the strand
(trace #1 on Fig. 7.8 ) corresponds to the first fragment of the DNAwith no phosphate
group in it. The absence of the phosphate group, which is negatively charged, allows
for a positive rise in this trace caused by the positive charge of the sugar ring and the
base in this segment. We also observe that the traces of the DNA fragments overlap
significantly, as the average width of each dip extends over 8-12 ˚ . This means that
in the whole DNA trace the signals from as many as three nearby fragments (and
therefore bases) are mixed, which is to be expected as the Coulomb interaction is a
long range interaction. In addition, the trace #4, which contains the “A” base does
not have any obvious distinct features from other segments containing the “C” bases,
except maybe a slight widening of the signal compared to the nearest fragments,
which may be due to the different distribution of charge on the base as well as to the
different orientation of the base # 4 on the backbone, or, most likely, both.
To study the effect of single nucleotide substitution on the signal induced on the
capacitor structure, we replace one base (# 4) in the C 3 AC 7 strand by C, G, and T
nucleotides respectively, as described in [ 27 , 31 ]. We keep the conformations of the
three resulting strands identical to that of the original strand, with the exception of
the replaced nucleotides. The resulting DNA strands have sequences C 3 CC 7 ,
C 3 GC 7 and C 3 TC 7 , correspondingly. The orientation of their aromatic rings as
well as the backbone structure are identical. The calculated voltage traces for the
four strands obtained by a single base mutation at the fourth place differ in the
vicinity of the fourth base over a position range between
15 and 5 ˚ (results
are not shown). As expected, the traces are identical away from the fourth base as
the DNA conformations there remained the same.
7.5 Circuit Element Modeling of the Membrane
In this section we assess the influence of the membrane capacitances and resistances
on the electrical response of the DNA translocation by using an equivalent electric
circuit based on the membrane geometry and material properties. In this approach,
two external oxide layers have been added to the top and bottom of the membrane
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