Solid-State Nanopore Sensors for Nucleic Acid Analysis - Nanopores: Sensing and Fundamental Biological Interactions - page 18

10 3 M) where the effects of surface charge are dominant
and Debye layer overlap in the nanopore is indeed expected. P-type unipolar
behavior was observed suggesting that K + ions are the majority carriers in these
TiO 2 gated nanopores. Studies by Kalman et al. focused on integrating a Au
electrode into a conical nanopore [ 42 ]. By modulating the electric potential applied
to the gate, one alters the distribution of ions in the overlapping Debye layer in the
pore and thus the potential distribution in the pore. Using this approach Kalman
et al. were able to manipulate the current through the device from the rectifying
behavior synonymous with conical nanopores to a near linear type behavior as seen
in structurally symmetric nanopores. The mechanism for this change in transport
behavior was accredited to the enhancement of concentration polarization induced
by the gate. The manipulation of surface charge through the chemical modification
of solid-state nanopores will be discussed in subsequent sections.

low salt concentrations ( <

1.3.5 Noise in Solid-State Nanopores

Electrical noise in ionic current measurements involving solid-state nanopores
limits the utility of these systems in wide spread nucleic acid based diagnostics.
Two dominant sources of noise have been documented in the literature; a low
frequency current fluctuation with 1 /f characteristics (flicker noise) and a high-
frequency background noise component associated with the relatively high capaci-
tance of the insulating membrane on the support chip (dielectric noise) [ 16 , 35 , 79 ,
80 , 82 , 86 , 87 ]. Minimizing these respective noise components is integral to
improving the sensitivity and signal to noise ratio of nanopore sensors.

1.3.5.1 1/f Noise in Solid-State Nanopores

1/ f noise has been observed in many physical and biological systems. 1/ f noise is
present in the form of fluctuations in the voltages or currents of semiconductors, the
voltage across nerve membranes and synthetic membranes and in the resistance of
aqueous ionic solutions [ 45 ]. The power spectrum, denoted by S(f) , is proportional
to the reciprocal of the frequency in a narrow bandwidth as illustrated in eq. 1.1 .

constant
j a

Sðf Þ¼ where 0 <a< 2 (1.1)

Hoogerheide et al. studied the 1/ f noise characteristics of Si 3 N 4 nanopores as a
function of pH and electrolyte ionic strength and concluded that 1/ f noise originates
from surface charge fluctuations at the nanopore surface [ 35 ]. The model presented
was based on protonization of surface functional groups and was sensitive to as few
as tens of active surface groups in the nanopore. In contrast, Smeets et al. concluded
that low frequency noise was predominantly due to the number of charge carriers