Simulation of Electronic Sensing of Biomolecules in Translocation Through a Nanopore in a Semiconductor Membrane - Nanopores: Sensing and Fundamental Biological Interactions - page 173

agreement between both methods, thus leading to the model validation. On the
quantitative side, the magnitude of the strand signatures differs by a factor of the
order of 10 2 , mainly due to losses induced by the electrical circuit and the parasitic
capacitors included in the model. In this context, our results still show the resolution
of the 11 bases even in the worse conditions.
Hence, our model enables the optimization of the device by exploring its physical
features (geometry, electrical material properties) or for instance, by adding MOS
amplifiers to the structure to improve the recorded signals. We can already point out
the importance of minimizing the parasitic capacitor value as well as the external
radius of the membrane, which are key parameters in terms of signal magnitude.
Moreover, the results provided by the Spice model can be used, in the electric circuit
domain, as input data for the analysis of analog amplification, numerical conversion
and processing of the electrical signal in the vicinity of the nanopore.
Although these results are encouraging, they are quite coarse assessments as
assumptions such as the fixed conformation of the molecule during the entire
translocation, the constant velocity or the electrical permittivity of the solution
arbitrarily set to water electrical permittivity, have been made. In this respect the
noise induced by ionic stochasticity and the DNA conformation dynamics needs to
be assessed, but this topic is beyond the scope of the chapter.

Acknowledgments This work was funded by NIRT-NSF grant #NSFCCR02-10843, DARPA
grant #392FA9550-04-1-0214, NIH grants ROI-HG003713-01 and P41-PR05969. The authors
gratefully acknowledge the use of the supercomputer time at the National Center for Supercom-
puter Applications provided through Large Resource Allocation Committee grant MCA05S028.
We are grateful to Dr. G. Timp for useful discussion and to Dr. A. Aksimentiev for supplying
NAMD data.

Appendix

Ionic Concentrations

The ionic concentrations in KCl electrolyte solution are similar to electron and hole
concentrations in an intrinsic semiconductor. Because of this similarity, we can
consider the K + Cl - electrolytic solution as an intrinsic semiconductor and introduce
virtual semiconductor parameters, i.e. a virtual energy band gap E geff , virtual
density states of K + ions and Cl - ions, N K þ and N Cl , and virtual effective masses,
m K þ and m Cl for potassium and chlorine ions, respectively [ 38 ]. With these virtual
parameters, we can calculate the ion concentrations of the electrolytic solution as
follows:

;

p

N K þ N Cl

E geff
2 kT

½K þ 0 ¼½Cl 0 ¼

exp (7.20)