Detection of charged macromolecules by means of fi eld-effect devices (FEDs): possibilities and limitations - Electrochemical Sensors, Biosensors and Their Biomedical Applications - page 195

However, all reported results on DNA-FEDs that are based on the mechanism of
a direct electrostatic detection by their intrinsic molecular charge have some princi-
pal limitations due to the so-called counter-ion screening effect, which is also well
known from immuno-modifi ed FETs proposed by Schenck already in 1978 (see, e.g.,
[56]). It has been intensively debated whether it would be possible to detect an anti-
body-antigen affi nity-binding reaction with an FET, or not [3, 54]. As a result of these
discussions, it was generally accepted that the screening of protein charges by small
inorganic counter-ions present in the electrolyte solution will result in macroscopically
nearly uncharged layers and prevent successful measurements of immunospecies with
FETs. Under ideal conditions (i.e. a truly capacitive interface at which the immuno-
logical binding sites can be immobilized, a nearly complete antibody coverage, highly
charged antigens, and a very low ionic strength), the theoretically expected signal
should be on the order of 10 mV or less [3].
The charge distribution in the immediate vicinity of the interface will play a criti-
cal role in transferring the hybridization-induced signal to the FED. Only effects of
charge-density changes that occur directly at the surface of the FED or within the order
of the Debye length λ D from the surface can be detected as a measurable biosensor

signal (see also Eq. (3)):

εε kT

zqI

el 0

λ D (3)

2

22

ε el the dielectric constant of the electrolyte,
z is the valency of the ions in the electrolyte, and I represents the ionic strength, which
for a 1:1 salt, can be replaced by the electrolyte concentration n 0 .
Figure 7.5 clarifi es this effect for a 10-bases DNA molecule attached normally to
the surface of the FED. Note, with increasing ionic strength of the electrolyte, the frac-
tion of DNA charge, which remains in the double layer and thus will be mirrored in the
space-charge region of the FED, is decreased. For example, under physiological con-
ditions with

Here, ε 0 is the permittivity of vacuum,

0.8 nm, most of the DNA charge will be at a distance greater than
the Debye length from the surface, which makes its detection more diffi cult or even
impossible. If ssDNA molecules are, furthermore, immobilized using additional linker
molecules or spacers extending from the insulating layer of the FED, the DNA hybridi-
zation-induced charge changes will be still smaller. On the other hand, if the DNA mol-
ecules lie more or less fl at on the surface, a higher hybridization signal can be expected.
The screening of the charge associated with the probe- or target-DNA molecules by
small counter-ions (cations) present in the solution is a major obstacle also in detecting
the DNA hybridization. According to Manning's counter-ion condensation theory [57,
58], monovalent cations reduce the DNA charge by 76% and divalent cations by 88%:
the more diffuse ionic layer will compensate the remaining charge. Consequently, the
counter-ion condensation effect will mask or reduce the expected hybridization sig-
nal and prevent successful measurements, especially in high ionic strength solutions.
Higher salt concentrations of the electrolyte solution should result in a bigger screening
of the molecular charges and thus in a smaller sensor signal. In the most unfortunate

λ D