Detection of charged macromolecules by means of fi eld-effect devices (FEDs): possibilities and limitations - Electrochemical Sensors, Biosensors and Their Biomedical Applications - page 187

● various ssDNA-immobilization methods (adsorption, covalent attachment,
biotin-avidin complexation, linker molecules),
● various densities of the immobilized ssDNA from 3.6

10 5 to 5 10 13

molecules/cm 2 ,
● hybridization-buffer solutions with different electrolyte concentrations (10

M to

1 M), and
● divergent sensor signals reaching from several mV up to

2 V with hybridization

times between several seconds up to several hours.

Most of the experiments for detecting charged macromolecules with FEDs, reported
in literature, have been realized using a transistor structure [11-36]. Recent success-
ful experiments on the detection of charged biomolecules as well as polyelectrolytes
with other types of FEDs, namely semiconductor thin fi lm resistors [39-41], capaci-
tive MIS [42] and EIS structures [43-50], have demonstrated the potential of these
structures - more simple in layout, easy, and cost effective in fabrication - for studying
the molecular interactions at the solid-liquid interface. A summary of results for the
DNA detection with different types of FEDs is given in Table 7.1.
The large diversity of sensor confi gurations and experimental results as well as the
absence of a detailed theory explaining their working principles makes their comparison,
however, quite diffi cult. Controversial effects such as higher signals for sensors with less
density of immobilized ssDNA (0.87 V with 3.8

10 8 molecules/cm 2 ) compared to sen-
sors with more densely packed ssDNA (3 mV with 5 10 13 molecules/cm 2 ), and higher

sensor signals that are observed when fl oating-gate transistors or FEDs without a refer-
ence electrode are used, are only representing two examples in this context.
From the experiments presented in the literature, it is obvious that the adsorp-
tion and binding of charged macromolecules onto the gate surface changes the fl at-
band voltage of FEDs, thus generating a sensor signal. However, which mechanism
is responsible for such a shift of the fl at-band voltage is still under discussion [39,
51, 52]. In most cases, the experimentally observed sensor response is interpreted as
a direct electrostatic detection of charged macromolecules by their intrinsic molecu-
lar charge, fully ignoring the ion concentration and charge redistribution within the
intermolecular spaces (or in the molecular layer) as well as the possible interaction of
small ions with the surface of the underlying gate (insulator) material. An alternative
mechanism based on the detection of the DNA hybridization-induced redistribution
of the counter-ion concentration within the intermolecular spaces or in the molecular
layer has been recently proposed [51]. Thus, there are some open questions regarding
the functional principle of FEDs functionalized with charged macromolecules, and the
source of the experimentally observed signal generation.
In this work, a critical evaluation of the possibilities and limitations of a direct elec-
trical detection of charged macromolecules using a fi eld-effect platform will be given,
mainly focusing on capacitive EIS devices. With these devices it is possible to study
both the geometric capacitance and charge effects induced by the adsorption or bind-
ing of charged macromolecules. Theoretical calculations of the physical model for the
bio-functionalized EIS sensor and experimental results for the detection of the DNA