Simulation of Electronic Sensing of Biomolecules in Translocation Through a Nanopore in a Semiconductor Membrane - Nanopores: Sensing and Fundamental Biological Interactions - page 172

quite similar voltage dips and the shoulder. However, one of the advantages of the
Spice model over multi-physics simulations [ 19 , 31 ] is the ability to analyze the
signal response as a function of parameters external to the nanopore.
7.7 Conclusion
We performed a three-dimensional multi-scale/multi-material numerical simulation
of the quasi-electrostatic characteristics of a novel solid state nano-biophysical device
which can be used as a DNA detector. The simulation demonstrates the possibility of
a nanopore device to function as a DNA detector. In particular, we show that the DNA
translocation causes electrodes' voltage to exhibit changes in excess of 10mV that can
be recorded experimentally. From the recorded voltage trace we also show the
possibility to measure DNA length and observe fine features that correspond to single
nucleotides.
These experiments and simulations are only the first step in our exploration of
the nanopore-capacitor mechanism of DNA single molecule electrical sequencing.
Only one DNA snapshot was analyzed with respect to the electric response of the
nanopore and was presented in this work. Several other DNA snapshots that were
also analyzed (but not presented) produced similar results. The analysis of more
realistic stochastic DNA translocation is a subject of our current research.
We also studied the electrical signals produced on a capacitor membrane
containing a narrower 1 nm nanopore by single stranded DNAs with a single base
mutation. The calculated maximum voltage due to the different bases varies from
2 to 9 mV, which is experimentally detectable. Signals from individual nucleotides
can be identified in the recorded voltage traces, suggesting a 1 nm diameter pore in
a capacitor can be used to accurately count the number of nucleotides in a DNA
strand. Our data show the possibility of distinguishing DNAs with different
sequences in the ideal situation when the strands have the same conformation.
However, the influence of stochastic DNA translocation on the induced signal is an
important issue for realistic modeling of the nanopore - DNA system. The stochas-
tic “wiggling” of the DNA, although restricted by the nanopore, may reduce the
resolution of single nucleotides or even make nucleotides indistinguishable. This
issue is currently under investigation and will be the subject of a subsequent
publication. Nevertheless, our results are an important milestone in DNA detection
because techniques could be used to reduce or annihilate DNA stochastic move-
ment in a nanopore. One of such recently proposed techniques involves wrapping
DNA on a carbon nanotube [ 20 ], which is then lowered into a pore to detect bases.
Another approach for reducing the effect of the DNA stochastic motion on the
recorded voltage, is the method of “DNA flossing” through a nanopore to sample
segments of the molecule and collect the average reading [ 37 ].
In order to assess the influence of the membrane capacitances and resistances on
the signal level we developed a SPICE circuit model and compared our results with
the multi-scale model described in [ 19 , 31 ] to point out a good qualitative