Biochips – fundamentals and applications - Electrochemical Sensors, Biosensors and Their Biomedical Applications - page 342

and can be used for toxicological testing as well. A multiparametric cell monitoring
system may detect side effects more easily [82]. Arrays are well suited for this appli-
cation when there is only a limited supply of cells or amount of drugs available for
testing [83], especially in the high throughput screening of lead compounds. Although
most protein arrays are based on soluble proteins, progress has been made in array-
ing of functional membrane proteins, which represent the majority of drug targets. By
direct screening of entire proteomes for protein - drug interactions, protein arrays can
aid in determining the selectivity and specifi city of drug leads in further downstream
testing. Second, protein microarray, especially tissue microarray, can be used to predict
the probable toxicity of lead compounds by evaluating the distribution of drug targets
in normal tissue. Finally, protein biochips may be utilized in monitoring drug metabo-
lism and toxicity especially during preclinical pharmacokinetic studies, to supplement
in-vitro and in-vivo model systems. That means biochips can serve as tools to opti-
mally design clinical trials and exclude individuals with potentially deleterious drug-
metabolizing enzyme (DME) profi les.
11.4 ELECTRONIC AND ELECTROCHEMICAL
MICROARRAY BIOCHIPS
Electronic biochips based on the detection of alterations in the electrical properties of
an electrode arising from DNA hybridization and protein bindings have been exten-
sively studied and developed. The electronic detection-based microarrays provide
many advantages inherent in comparison to radioactive or fl uorescent labeling tech-
niques to discern molecular interactions [3, 84-89]. This process offers a detection
technique that is safe, inexpensive, and sensitive, not burdened with complex and oner-
ous regulatory requirements, and can be a miniaturized, small sample-required and
portable device. Electronic biomolecular or cellular sensing transducers, which convert
the biomolecular interaction events into analytical signals, can be amperometric [90],
potentiometric [91], and impedimetric devices [23]. These sensors are mainly based
on detecting electrochemically active labels such as organic dyes, metal complexes,
enzymes or metal nanoparticles [92]. Labelless electronic DNA and protein biosen-
sors are even more attractive for fabrication of electronic biochip arrays. Research and
development of the label-free techniques has been conducted on direct recognition
of target DNA as a dopant within conductive polymer fi lms [93] or by measurements
of impedance spectroscopy [94-96]. Among these label-free techniques, the direct
impedance detection of DNA hybridization provides prominent advantages due to its
simplicity and low cost.
11.4.1 Theoretical consideration
Most electronic biosensors involve the measurements in solutions, and thus the detec-
tion schemes greatly rely on electrochemical methods, which can be used to monitor
electronic signals produced from electrochemical reactions or changes of electronic