Detection of charged macromolecules by means of fi eld-effect devices (FEDs): possibilities and limitations - Electrochemical Sensors, Biosensors and Their Biomedical Applications - page 186

The detection of molecular interactions at the solid-liquid interface is of great inter-
est for a wide variety of applications, ranging from biomedical implants and drug-carrier
systems up to biosensors, DNA arrays, and protein-chip technology. Moreover, a deep
understanding of the adsorption and binding of charged macromolecules onto charged
surfaces is important not only for sensor applications, but also for the fundamental
understanding of many key physiological processes. More than 400 diseases can be
detected by molecular analysis of nucleic acids, and a growing demand of DNA diag-
nosis in genetics, medicine, and drug discovery can be prediced [9]. Typically, DNA-
detection principles are based on a DNA-hybridization event, where an unknown
single-stranded DNA (ssDNA) is identifi ed by its complementary DNA (cDNA) mol-
ecule. As a result of the hybridization event, a double-stranded DNA (dsDNA) helix
structure with the two complementary strands is formed: Due to the unique comple-
mentary nature of the bases pairs' binding reaction (adenine-thymine (A-T), cytosine-
guanine (C-G)), the hybridization event is highly effi cient and specifi c, even in the
presence of a mixture of additional non-complementary nucleic acids. The hybridiza-
tion reaction occurs best if all the bases along both the probe and complementary tar-
get DNA molecules are fully matching. Therefore, genosensors and DNA chips should
have a sensitivity high enough to detect even a single mismatch (single nucleotide
polymorphism) with high reliability.
In the techniques actually employed for DNA-hybridization detection, the readout
of the DNA-hybridization event requires the labeling of DNA molecules (either the
analyte DNA or the immobilized ssDNA) with various markers (radiochemical, enzy-
matic, fl uorescent, redox, etc.). In spite of their high sensitivity, selectivity and low
detection limits, all these techniques, however, suffer from being time-consuming,
expensive, and complex to implement (e.g. [10]). A label-free detection is thus highly
desirable. The direct electrical detection of intrinsic charges of biomolecules with
bio-functionalized semiconductor devices would circumvent the obstacles of labe-
ling. Therefore, recently different research groups have devoted considerable effort to
realize a label-free electronic detection of charged biomolecules, such as DNA, pro-
teins, and peptides, by their intrinsic molecular charge using the fi eld-effect platform
[11-47]. Moreover, a possibility of potentiometric detection of single nucleotide poly-
morthisms by means of a genetic fi eld-effect transistor has been experimentally dem-
onstrated [29, 30]. Due to the inherent miniaturization and compatibility with advanced
micro- and nano-fabrication technologies, these devices offer a new challenge of DNA
chips with direct electronic readout for a label-free, fast, simple, and inexpensive real-
time analysis of nucleic acid samples.
Results from a DNA-hybridization detection achieved with FEDs differ in:

● the set-up of the FED (capacitive EIS and MIS structure, depletion-/enhance-
ment-mode FET, Au or Pt fl oating-gate FET, extending-gate FET, FET devices
with or without reference electrode, poly-Si and hydrogenated amorphous Si
(a-Si:H) thin fi lm transistor),
● the different gate-insulator materials (SiO 2 , silanized SiO 2 , SiO 2 -Si 3 N 4 , SiO 2 -
Ta 2 O 5 , SiO 2 -poly-L-lysine) with different thicknesses (from 2 nm to 100 nm),