Third Generation DNA Sequencing with a Nanopore - Nanopores: Sensing and Fundamental Biological Interactions - page 306

Fig. 12.9 Current noise spectra measured in nanopores. (a) Noise power spectra of nanopores in
the four membranes measured in 1 M KCl with different effective capacitance. From bottom to
top , a 300 M O resistor, a 7.1 7.3 0.3 nm pore in a MOS membrane, a 1.7 2.8 0.2 nm

pore in a polyimide coated Si 3 N 4 membrane, a 3.0 3.8 0.2 nm pore in ~200 nm Si 3 N 4

membrane, and a 3.3 0.2 nm in 12 nm Si 3 N 4 membrane. The low frequency 1/ f noise,

the high frequency dielectric noise along with the amplifier noise are analyzed for the ~2.4 nm pore
in polyimide coated membrane. The fit to the total noise is shown as a light colored continuous
curve. (b) Noise spectra of a 2.1

4.8

0.2 nm pore in 12 nm nitride membrane for different
electrolyte concentrations. (c) The same noise spectra shown in (c) but offset to show the high
frequency noise without overlap. (d) The rms-current noise vs. bandwidth for the membranes of
(a); the largest contributor to the rms-current noise is dielectric noise prevalent above 1 kHz
frequency. Taken from reference [ 44 ]

2.3

and the electrolyte resistance, R el , so that R el C m > s for the 2.2 nm pore in a

15 nm thick nitride membrane in 100 mM KCl, corresponding to a bandwidth of
Df ¼

1-10 m

pR el C m ~ 100 kHz. If the translocation velocity is high, it becomes
impossible to resolve that portion of the blockade associated with a single base; a
sampling frequency

1/2

16 MHz would be required. More gain can't resolve this
problem due to the concomitant increase in electrical noise.
Motivated to call bases with high fidelity, we along with others have investigated
the noise associated with current measurements in a nanopore. Fig. 12.9a shows the
noise power spectra of four nanopores - with diameters comparable to the DNA
double helix - in different types of membranes: two associated with different nitride
thicknesses 12 nm and 200 nm on a silicon substrate; a third associated with a
composite 30 nm nitride membrane coated with a 4

>

m

m polyimide film on a silicon
substrate; and a fourth associated with a membrane formed from a MOS capacitor;
all measured in 1 M KCl along with the spectrum of a 300 M

resistor, a value
comparable to the resistance of the 2.2 nm pore. The measured noise spectra of all
the nanopore in electrolyte can be analyzed into four components: thermal, 1/f ,
dielectric and amplifier noise contributions. (The light colored continuous trace
represents a sum of all the components fit to a 2.4 nm pore in polyimide coated
membrane.)
We expect that thermal noise associated with pore S t ¼

O

4 k B T=R; resistance,

will be negligible over the band 100 kHz since the noise from the resistor is

below all of the other spectra. We observed at low frequencies that the noise
power density is inversely proportional to the frequency indicative of 1/f noise,
i.e.: S 1 =f ¼ I 2 A=f b ¼ I 2

<

ða=N c Þf b where I is the pore current,

is the Hooge
parameter (an empirically determined proportionality constant that depends on
the type and concentration of charge carriers, N c

a

is the total number of current